Heparin - ClinicalKey

28/10/2019 Heparin- ClinicalKey
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Heparin
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Descripción
Heparin is a parenteral anticoagulant widely used in clinical medicine. It is a glycosaminoglycan composed of chains
of alternating residues of D-glucosamine and an uronic acid; its molecular weight ranges from 5,000—30,000
daltons, with a mean of 15,000 daltons (about 50 monosaccharide chains). Commercially, heparin is derived from
porcine or bovine tissue, and is available as the calcium or sodium salt. Full therapeutic doses of heparin prolong
clotting time; however, bleeding time is usually unaffected by heparin. The response to heparin is variable since only
about one-third of the molecules have anticoagulant activity, and its activity and clearance is dependent upon the
length and size of the heparin molecules. The preferential clearance of larger molecules in vivo leads to
accumulation of lower-molecular weight species that have a reduced ratio of antithrombin to antifactor Xa activity.
Compared with low molecular weight heparins, unfractionated heparin produces a less predictable anticoagulant
response due primarily to its reduced bioavailability after subcutaneous administration of low doses, its dose-
dependent clearance, and differences among patients in the nonspecific binding of heparin to proteins and cells.
Heparin was discovered in 1916 and was approved by the FDA in 1939.
Mecanismos de acción
Heparin exerts its anticoagulant action by accelerating the activity of antithrombin III (ATIII) to inactivate
thrombin; however, heparin does not lyse existing clots. Approximately one-third of heparin molecules contain a
unique pentasaccharide sequence with high-affinity binding to ATIII. The interaction of heparin with ATIII produces
a conformational change in ATIII, which accelerates the ability of ATIII to inactivate thrombin (factor IIa), factor Xa,
and factor IXa. Of these enzymes, thrombin is the most sensitive to inhibition by heparin/ATIII. Heparin catalyzes
the ATIII inactivation of thrombin by acting as a template to which both thrombin and ATIII bind to form a ternary
complex. The inactivation of factor Xa does not require the heparin/ATIII complex formation and occurs via binding
of ATIII to factor Xa. Heparin molecules must be greater than 18 monosaccharides to bind to thrombin and ATIII
simultaneously. Therefore, smaller heparin molecules (i.e., < 18 monosaccharides) are unable to accelerate the
inactivation of thrombin by ATIII, but retain their ability to catalyze the inhibition of factor Xa by ATIII. Heparin is
unable to inactivate fibrin-bound (i.e., surface) thrombin or factor Xa bound to phospholipid surfaces within the
prothrombinase complex. The inability of heparin to inactivate surface-bound thrombin and factor Xa may explain
its limited efficacy in patients with unstable angina, high-risk coronary angioplasty, and coronary thrombolysis. At
doses higher than those required to stimulate the activity of ATIII, heparin catalyzes the inactivation of thrombin by
heparin cofactor II, which does not require interaction with ATIII.25334 Heparin also stimulates the inhibition of
thrombin by plasminogen activator inhibitor I, protein C inhibitor, and protease nexin-1 and inhibition of factor Xa
by tissue factor pathway inhibitor; however, these proteins are only present in the serum in very small quantities as
compared to ATIII.
https://www-clinicalkey-es.aure.unab.edu.co/#!/content/drug_monograph/6-s2.0-289 1/85
High doses of heparin also interfere with platelet aggregation, which, in turn, prolongs the bleeding time, although
commonly used therapeutic doses heparin do not affect bleeding time. High-molecular-weight heparin fractions
have a greater effect on platelet function. It has been shown that the platelet-aggregating activity of heparin can be
directly related to its molecular weight.
Fibroblast growth factors (FGF) bind to heparin with high-affinity. Heparin potentiates the effects of FGF by
promoting the binding of these factors to their receptors, a transmembrane tyrosine kinase. Fibroblast growth
factors stimulate angiogenesis. As opposed to its anticoagulation effects, the activity of heparin on FGF is due to the
degree of sulfation and not the size of the molecule.
The variability of anticoagulant response in individuals given fixed doses of heparin is thought to be due to
differences between patients in their plasma concentrations of neutralizing plasma proteins and/or heparin-binding
proteins (e.g., histidine-rich glycoprotein, vitronectin, lipoproteins, fibronectin, fibrinogen, platelet factor 4, and von
Willebrand factor). The response of the aPTT ratio to heparin may be decreased in patients with high levels of factor
VIII. These patients may have therapeutic plasma heparin levels at the usual dose of heparin when measured using
anti-Xa activity or by protamine sulfate titration, but require very high doses of heparin (> 50,000 International
Units/day) to achieve an aPTT > 1.5-times control. Patients with acquired antithrombin deficiency (< 25% normal
concentration) may not respond to heparin.
Pharmacokinetics
Heparin is given parenterally, either intravenously or subcutaneously. Because heparin is highly negatively charged,
it binds to a variety of plasma proteins (e.g., histidine-rich glycoprotein, vitronectin, lipoproteins, fibronectin,
fibrinogen, platelet factor 4, and von Willebrand factor) some of which are acute-phase reactant proteins that are
elevated in acute illness or are released from platelet and endothelial cells as part of the clotting process. The
variability in plasma levels of heparin-binding proteins in patients with thromboembolic diseases is responsible for
the unpredictable anticoagulant effect of heparin. The nonspecific binding of heparin to proteins and cells may also
account for its poor bioavailability when administered subcutaneously in doses of less than 35,000 units/24 hours.
When doses more than 35,000 units/24 hours are given, bioavailability is almost complete due to saturation of
heparin-binding sites. Because of its large molecular size, heparin does not cross the placenta and is not distributed
into breast milk.
Heparin appears to be cleared and metabolized by the reticuloendothelial system. Heparin is metabolized by a rapid,
zero-order mechanism, followed by slower first-order renal clearance. In the zero-order phase, heparin is bound to
the surface of cells (such as macrophages and endothelial cells) where it is internalized and depolymerized. Because
this process is saturable, the plasma half-life of heparin increases from 30 to 150 minutes as the administered dose
increases from 25 units/kg to 400 units/kg.
Affected cytochrome P450 isoenzymes: none
•Route-Specific Pharmacokinetics
Intravenous Route
After intravenous administration, response is almost immediate. The anticoagulation half-life of heparin is 1, 2.5,
and 5 hours when heparin 100, 400, or 800 units/kg, respectively, is given intravenously.
Subcutaneous Route
Individual response after subcutaneous injection varies, but anticoagulant activity is generally delayed for 1 to 2
hours. The nonspecific binding of heparin to proteins and cells may also account for its poor bioavailability when
administered subcutaneously in doses of less than 35,000 units/24 hours. When doses more than 35,000 units/24
hours are given, bioavailability is almost complete due to saturation of heparin-binding sites.
•Special Populations
Pediatrics
Neonates
Premature neonates (n = 25, gestational age 25 to 36 weeks) had a significantly shorter plasma half-life (35.5 to 41.6
minutes), larger volume of distribution (57.8 to 81 mL/kg), and faster clearance (1.37 to 1.49 mL/kg/minute) after
an IV bolus dose of 100 units/kg compared to adults receiving an IV bolus dose of 75 units/kg (half-life = 63.3
minutes, Vd = 36.6 mL/kg, CL = 0.43 mL/kg/minute).51861
Geriatric
Following similar doses of heparin, elderly patients (e.g., older than 60 years of age) may have higher plasma levels
of heparin and longer activated partial thromboplastin times compared with younger patients.
Other
Pulmonary embolism
The half-life of heparin may be shorter in patients with pulmonary embolism.
Last revised: May 16, 2017
Indicaciones y Dosificación
acute myocardial infarction
antiphospholipid antibody syndrome
arterial thromboembolism
arterial thromboembolism prophylaxis
cerebral thromboembolism
coronary artery thrombosis prophylaxis
deep venous thrombosis (DVT)
deep venous thrombosis (DVT) prophylaxis
disseminated intravascular coagulation (DIC)
intravascular catheter occlusion prophylaxis
mural thrombosis
mural thrombosis prophylaxis
percutaneous coronary intervention (PCI)
periprocedural anticoagulation
prosthetic heart valves
pulmonary embolism
pulmonary embolism prophylaxis
thrombosis prophylaxis
unstable angina
Converting to Oral Anticoagulants
When converting from heparin to warfarin, continue therapeutic heparin therapy for several days after warfarin
initiation until the INR (prothrombin time) is within a stable therapeutic range. At that point, heparin may be
discontinued without tapering. NOTE: Heparin may prolong the one-stage prothrombin time. When heparin is
given with warfarin, prothrombin time is most accurate at least 5 hours after the last IV dose or 24 hours after the
last subcutaneous dose of heparin.
When converting from heparin to oral anticoagulants other than warfarin, stop the heparin infusion immediately
after administering the first dose of oral anticoagulant. If the patient is receiving intermittent IV heparin,
discontinue heparin and administer the oral anticoagulant 0 to 2 hours before the time that the next dose of
heparin would have been administered.56872
For the treatment of deep venous thrombosis (DVT) or pulmonary embolism; for the treatment of
arterial thromboembolism including cerebral thromboembolism; or for the treatment of mural
thrombosis
Intravenous Infusion dosage (weight-based)
Adults:
80 units/kg IV bolus, then maintenance infusion of 18 units/kg/hour IV continuous infusion. If the aPTT is less than
35 (1.2 times normal), increase infusion rate by 4 units/kg/hour and rebolus with 80 units/kg IV. If aPTT is 35 to 45
(1.2 to 1.5 times normal), increase infusion rate by 2 units/kg/hour and rebolus with 40 units/kg IV. If aPTT is 46 to
70 (1.5 to 2.3 times normal), maintain infusion. If aPTT is 71 to 90 (2.3 to 3 times normal), decrease infusion rate by
2 units/kg/hour. If aPTT is more than 90 (more than 3 times normal), hold infusion for 1 hour and decrease rate by
3 units/kg/hour. Repeat aPTT every 6 hours for the first 24 hours, then every morning, unless it is outside the
therapeutic range.23706 Patients should be treated for 5 days or more and oral anticoagulation should be overlapped
for 4 to 5 days or more. Heparin can be discontinued on day 5 to 6 if the INR has been within the therapeutic range
for 2 consecutive days. Patients with massive PE or severe iliofemoral thrombosis should be offered a longer period
of heparin therapy (about 10 days).25332
Pregnant females:
Full dose heparin as a continuous IV infusion should be given for 5 to 10 days, followed by full dose heparin
subcutaneously until term. Subcutaneous heparin should be given every 12 hours and adjusted to prolong the aPTT
into the therapeutic range. Heparin should be discontinued 24 hours for average risk recurrence of DVT or 4 to 6
hours for patients at high risk for recurrence (e.g., proximal DVT within less than 2 weeks) before elective induction
of labor.25402
Children and Adolescents:
75 to 100 units/kg IV load then 20 units/kg/hour IV as an initial maintenance dose. Adjust dose to maintain aPTT
60 to 85 seconds, assuming this reflects an antifactor Xa level of 0.3 to 0.7 units/mL.41347 49232
Neonates and Infants:
Intermittent intravenous dosage
Adults:
5,000 to 10,000 units IV every 4 to 6 hours or 100 units/kg IV every 4 hours. Dosage should be adjusted according
to coagulation test results.
Infants, Children, and Adolescents:
Initially, 50 units/kg IV as a loading dose then 100 units/kg IV every 4 hours. Adjust dosage according to aPTT
results.51874 Continuous infusion is preferred over intermittent administration in pediatric patients.
Subcutaneous dosage
Adults:
8,000 to 10,000 units subcutaneous every 8 hours or 15,000 to 20,000 units subcutaneous every 12 hours.
For thrombosis prophylaxis
for thrombosis prophylaxis, including arterial thromboembolism prophylaxis, during

extracorporeal circulation in patients undergoing open heart or other cardiovascular surgery
Intravenous dosage
Adults:
Initially, at least 150 units/kg IV. For procedures expected to last less than 60 minutes, doses up to 300 units/kg IV
may be used. For procedures expected to last longer than 60 minutes, doses up to 400 units/kg IV may be used.
Further dosage should be based on coagulation test results (e.g., activated clotting time (ACT)).
for thrombosis prophylaxis, including arterial thromboembolism prophylaxis, during hemodialysis
Intravenous dosage
Adults:
2,000 to 5,000 units IV bolus at the initiation of dialysis, followed by 10 to 20 units/kg/hour IV infusion directly
into the arterial port of the dialysis circuit or repeated bolus doses as needed to maintain the activated clotting time
(ACT) or whole blood partial thromboplastin time (WBPTT) at about 150% of baseline. The extent of anticoagulation
is based on risk factors for bleeding and co-existing conditions. In patients at moderate risk for bleeding,
administration of lower loading doses and lower maintenance infusion rates can be used to maintain the ACT or
WBPTT at about 115% to 125% of baseline.
for coronary artery thrombosis prophylaxis during percutaneous coronary intervention (PCI) in
patients not receiving abciximab therapy
Intravenous dosage
Adults:
60 to 100 units/kg IV bolus; maintain the activated clotting time (ACT) within 250 to 300 seconds by the HemoTec
device or 300 to 350 seconds by the Hemochron device.25124 Postprocedural heparin is not routinely given for
uncomplicated PCI. Early femoral sheath removal is recommended (e.g., when the ACT falls to less than 150 to 180
seconds) to reduce access site complications.
Adolescents, Children, Infants, and Neonates:
100 units/kg IV bolus is recommended for pediatric patients requiring cardiac catheterization via an artery. For
prolonged procedures, further doses may be necessary; however, specific recommendations are not available.49232
for coronary artery thrombosis prophylaxis during percutaneous coronary intervention (PCI) in
patients receiving abciximab concomitantly
Intravenous dosage
Adults:
50 to 70 units/kg IV bolus; maintain the activated clotting time (ACT) at 200 seconds or more with either the
HemoTec or Hemochron device.25124 Remove femoral sheaths after the procedure when the ACT falls to less than
150 to 180 seconds.
for deep venous thrombosis (DVT) prophylaxis
Subcutaneous dosage
General medical patients with risk factors for DVT (e.g., cancer, bed rest, heart failure, severe lung disease):
5,000 units subcutaneously every 8 to 12 hours, however, some clinicians use 7,500 units subcutaneously every 12
hours or LMWH.
Moderate risk adults undergoing surgery (e.g., minor procedure, with additional risk factors; non-major surgery
for patients 40—60 years with no risk factors; major surgery in patients younger than 40 years with no risk
factors:
5,000 units subcutaneously every 8 to 12 hours, starting 1 to 2 hours before surgery, LMWH, intermittent pneumatic
compression, or elastic stockings.25329
Higher risk adults or geriatric undergoing surgery (e.g., non-major surgery in patients > 60 years or with
additional risk factors; major surgery in patients older than 40 years or with additional risk factors):
5,000 units subcutaneously every 8 hours, LMWH, or intermittent pneumatic compression (IPC). In all higher-risk
general surgery patients, the use of mechanical prophylaxis with elastic stockings (ES) or IPC is recommended
initially. In very high-risk general surgery patients with multiple risk factors, combination of pharmacologic (i.e.,
heparin or LMWH) and mechanical (i.e., ES or IPC) prophylaxis is recommended.25329
Female adults undergoing major gynecologic surgery for benign disease, no additional risk factors:
5,000 units subcutaneous every 12 hours, starting 1 to 2 hours prior to surgery.25329
Female adults undergoing extensive gynecological surgery for malignancy:
5,000 units subcutaneously every 8 hours, starting 1 to 2 hours prior to surgery.25329
Adults undergoing major open urologic procedure (including high-risk):
5,000 units subcutaneously every 8 to 12 hours, starting 1 to 2 hours prior to surgery, LMWH, elastic stockings (ES),
or intermittent pneumatic compression (IPC). For patients at highest risk, heparin 5,000 units subcutaneously every
8 to 12 hours in combination with ES with or without IPC.25329
Adults undergoing elective hip replacement surgery:
5,000 units subcutaneously every 8 to 12 hours, starting 1 to 2 hours before surgery, as an alternative for
LMWH.25329 49700 Treatment should continue for a minimum of 10 to 14 days after surgery; up to 35 days is
recommended. The use of an intermittent pneumatic compression device (IPCD) during the hospital stay is
encouraged.49700
Adults undergoing hip-fracture surgery:
5,000 units subcutaneously every 8 to 12 hours, starting 1 to 2 hours before surgery, as an alternative to
LMWH.25329 49700 Treatment should continue for a minimum of 10 to 14 days after surgery; up to 35 days is
recommended. The use of an intermittent pneumatic compression device (IPCD) during the hospital stay is
encouraged.49700
Adults undergoing neurosurgery:
5,000 units subcutaneously every 8 to 12 hours, starting 1 to 2 hours before surgery, as an alternative to elastic
stockings (ES) or intermittent pneumatic compression (IPC) alone; however, use must be balanced with the
clinically important risk of intracranial bleeding. Low-dose heparin may be offered in combination with ES or IPC
for patients at high-risk and may be more effective than either modality alone.25329
Adults with acute myocardial infarction:
7,500 units subcutaneously every 12 hours until fully ambulatory for all patients not receiving heparin for another
reason.25330
Adults with acute ischemic stroke and impaired mobility:
5,000 units subcutaneously every 8 to 12 hours, LMWH, or a heparinoid, if not contraindicated.30259 Low-dose
heparin should be restricted for 24 hours after thrombolytic administration.30259 Low-dose heparin may be used
safely in combination with aspirin.30259 For patient with contraindications to anticoagulant therapy, intermittent
pneumatic compression devices or elastic stockings are recommended.30259
for deep venous thrombosis (DVT) prophylaxis in pregnant females
Subcutaneous dosage
Pregnant females with a history of DVT with a transient risk factor; no current risk factors:
Surveillance and post partum anticoagulation.25402
Pregnant females with an episode of idiopathic DVT; thrombophilia (confirmed laboratory abnormality); no
current long-term anticoagulation:
Options include surveillance, heparin 5,000 units subcutaneously every 12 hours, adjusted dose heparin
subcutaneously every 12 hours to maintain a target anti-Xa level of 0.1 to 0.3 units/mL, or LMWH with postpartum
anticoagulation.25402
Pregnant females, no prior DVT; thrombophilia (confirmed laboratory abnormality); no current long-term
anticoagulation:
Options include surveillance, heparin 5,000 units subcutaneously every 12 hours, or LMWH with postpartum
anticoagulation. Indication for active prophylaxis is strongest in antithrombin-deficient women.25402
Pregnant females with 2 or more episodes of DVT, and/or long-term anticoagulation (e.g., single episode of DVT,
idiopathic or associated with thrombophilia):
Options include adjusted dose heparin subcutaneously every 12 hours to maintain a target anti-Xa level of 0.1 to 0.3
units/mL or LMWH with postpartum, long-term anticoagulation.25402
Pregnant females with mechanical heart valves:
Adjusted doses of heparin subcutaneously every 12 hours throughout pregnancy to maintain a mid-interval aPTT at
2 times control or more or anti-Xa concentration maintained at 0.35 to 0.7 units/mL. Or, at the 13th week of
pregnancy, change to warfarin until the middle of the third trimester then restart heparin or LMWH until delivery.
Long-term anticoagulation should resume postpartum.25402
for thrombosis prophylaxis and/or for pulmonary embolism prophylaxis in patients at increased
risk after sustaining an acute MI (e.g., Q-wave infarction, severe LV dysfunction, CHF, history of
systemic or pulmonary embolism, 2D echo evidence of mural thrombus, or atrial fibrillation)
Intravenous or Subcutaneous dosage
Adults:
In patients not receiving thrombolytic therapy, 75 units/kg IV bolus, followed by 1,250 units/hour IV, with a target
aPTT of 1.5 to 2 times control (also see dosage for treatment of an evolving acute MI). For patients who have received
heparin following thrombolytic therapy (see acute myocardial infarction indication for initial heparin dosage
recommendations following thrombolytic therapy), continue IV heparin or change to subcutaneous heparin (initial
dose about 17,500 units every 12 hours) beyond 48 hours to maintain the aPTT 1.5 to 2 times control, LMWH, or
convert to oral anticoagulation.25330
for mural thrombosis prophylaxis in patients with an acute transmural anterior myocardial
infarction
Subcutaneous dosage
Adults:
12,500 units subcutaneously every 12 hours for 10 days after an acute anterior MI. When compared to 5,000 units
subcutaneously every 12 hours, left ventricular mural thrombosis was observed less frequently in the high-dose
heparin group. There was no difference in the frequency of hemorrhagic complications between the 2 groups.24752
for arterial thromboembolism prophylaxis in patients with prosthetic heart valves
Intravenous or Subcutaneous dosage
Adults:
80 units/kg IV bolus, then initial maintenance infusion of 18 units/kg/hour IV continuous infusion or 17,500 to
20,000 units subcutaneously every 12 hours, adjusted to prolong the aPTT 1.5 to 2 times control. Heparin (or
LMWH) should be given initially with oral anticoagulants until the INR is within the therapeutic range for 2
consecutive days.
Pregnant females:
Adjust doses of heparin subcutaneously every 12 hours throughout pregnancy to maintain a mid-interval aPTT at 2
times control or more or anti-Xa level maintained at 0.35 to 0.7 units/mL. Or, at the 13th week of pregnancy, change
to warfarin until the middle of the third trimester then restart heparin or LMWH until delivery. Long-term
anticoagulation should resume postpartum.25402
For intravascular catheter occlusion prophylaxis
NOTE: The amount of heparin solution in each single dose is sufficient to prevent clotting within the lumen of the
indwelling catheter for up to 24 hours. If the catheter is used for withdrawal of repeated blood samples for
laboratory tests and the presence of heparin is likely to interfere with the test, the in situ heparin flush should be
cleared from the catheter by aspirating and discarding a volume of solution equivalent to that of the indwelling
catheter before the desired blood sample is drawn. If the drug to be administered is incompatible with heparin, the
entire catheter or lumen should be flushed with sterile water or normal saline before and after the medication is
administered. Following the second flush, the heparin flush solution may be reinstilled into the set.51863
to maintain patency of single and multiple-lumen catheters
Intravenous catheter
Adults:
Use heparin 100 units/mL. Instill enough volume to fill the lumen of the catheter (usually 2 to 5 mL) to the tip.
Catheters should be flushed daily, with additional flushes given when stagnant blood is observed in the catheter.
This solution should be replaced each time the catheter or lumen is used for drug or blood administration, and after
blood withdrawal from the catheter.
Infants, Children, and Adolescents weighing more than 10 kg†:
In general, heparin 100 units/mL is used for pediatric patients weighing more than 10 kg. Instill enough volume to
fill the lumen of the catheter. Catheters should be flushed at least daily; certain types of catheters are more prone to
clotting and require more frequent flushing. Refer to site-specific guidelines for details. Additional flushes should be
administered when stagnant blood is observed in the catheter. This solution should be replaced each time the
catheter or lumen is used for drug or blood administration, and after blood withdrawal from the catheter.
Infants and Children weighing less than 10 kg†:
In general, heparin 10 units/mL is used for infants and small children (e.g., weight less than 10 kg). Instill enough
volume to fill the lumen of the catheter. Catheters should be flushed at least daily; certain types of catheters are more
prone to clotting and require more frequent flushing. Refer to site-specific guidelines for details. Additional flushes
should be administered when stagnant blood is observed in the catheter. This solution should be replaced each time
the catheter or lumen is used for drug or blood administration, and after blood withdrawal from the catheter.
Neonates†:
0.5 units/kg/hour IV infused through the line is recommended for maintaining central venous access line patency in
neonates. Use only preservative free solutions.49232
to maintain patency of peripheral catheters (i.e., heparin locks)
Intravenous catheter
Adults:
Use heparin 100 units/mL. Instill enough volume to fill the lumen of the catheter. This solution should be replaced
each time the catheter or lumen is used for drug or blood administration, and after blood withdrawal from the
catheter.
Infants, Children, and Adolescents weighing more than 10 kg†:
In general, heparin 100 units/mL is used for pediatric patients weighing more than 10 kg. Instill enough volume to
fill the lumen of the catheter. Catheters should be flushed at least daily; certain types of catheters are more prone to
clotting and require more frequent flushing. Refer to site-specific guidelines for details. Additional flushes should be
administered when stagnant blood is observed in the catheter. This solution should be replaced each time the
catheter or lumen is used for drug or blood administration, and after blood withdrawal from the catheter.
Infants and Children weighing less than 10 kg†:
In general, heparin 10 units/mL is used for infants and small children (e.g., weight less than 10 kg). Instill enough
volume to fill the lumen of the catheter. Catheters should be flushed at least daily; certain types of catheters are more
prone to clotting and require more frequent flushing. Refer to site-specific guidelines for details. Additional flushes
should be administered when stagnant blood is observed in the catheter. This solution should be replaced each time
the catheter or lumen is used for drug or blood administration, and after blood withdrawal from the catheter.
Neonates†:
0.5 units/kg/hour IV infused through the line is recommended for maintaining central venous access line patency in
neonates. Use only preservative free solutions.49232
to maintain patency of arterial lines
Intraarterial catheter
Adults:
Use a final heparin concentration of 1 unit/mL (range: 0.5 to 2 units/mL). In order to avoid large total doses and
systemic effects, use 0.5 units/mL in patients receiving multiple lines containing heparin.
Infants, Children, and Adolescents†:
Use a final heparin concentration of 0.5 units/mL to run at 1 mL/hour IV.49232
Neonates†:
Use a final heparin concentration of 0.5 units/mL running at a rate of 1 mL/hour IV for peripheral arterial catheters.
A final heparin concentration of 0.25 to 1 unit/mL with a total heparin dose of 25 to 200 units/kg/day IV is
recommended to maintain patency of umbilical artery catheters (UAC). Use only preservative free solutions.49232
to maintain line patency in patients receiving total parenteral nutrition (TPN)
TPN solution additive
Adults:
A final heparin concentration of 1 unit/mL may be added to TPN solutions intended for central or peripheral
administration.
Adolescents and Children†:
A final heparin concentration of 1 unit/mL may be added to TPN solutions intended for central or peripheral
administration.
Neonates and Infants†:
A final concentration of heparin of 0.5 to 1 unit/mL added to peripheral or central TPN solutions. Lower
concentrations may be used in small infants receiving larger TPN volumes to avoid systemic heparin effects.
For the prevention of pregnancy loss and/or thrombosis in patients with antiphospholipid antibody
syndrome (APLA)
in pregnant women with APLA and >= 2 early pregnancy losses, or >= 1 late pregnancy loss, or
preeclampsia, or intrauterine growth restriction (IUGR), or abruption
Subcutaneous dosage
Adult females:
Antepartum aspirin and heparin 5000 Units subcutaneous every 12 hours or adjusted doses of heparin subcutaneous
every 12 hours to maintain a anti-Xa level of 0.1—0.3 Units/mL, or LMWH.25402
in pregnant women with thrombophilic defects and recurrent miscarriages; a miscarriage during or
after the second trimester; or preeclampsia, intrauterine growth restriction (IUGR), or abruption
Subcutaneous dosage
Adult females:
Consider low-dose aspirin with either heparin 5000 Units subcutaneous every 12 hours or adjusted doses of heparin
subcutaneous every 12 hours to maintain a anti-Xa level of 0.1—0.3 Units/mL, or LMWH. Give anticoagulants
postpartum.25402
in pregnant women with APLA and a history of venous thrombosis, with current long-term
anticoagulation
Subcutaneous dosage
Adult females:
Adjusted doses of heparin subcutaneous every 12 hours to maintain a anti-Xa level of 0.1—0.3 Units/mL or LMWH.
Give anticoagulants postpartum. Resume long-term oral anticoagulation therapy postpartum.25402
in women with antiphospholipid antibodies and no previous venous thrombosis and no pregnancy
losses
Subcutaneous dosage
Adult females:
Options include surveillance, heparin 5000 Units subcutaneous every 12 hours, prophylactic LMWH, or low-dose
aspirin.25402
For the treatment of disseminated intravascular coagulation (DIC)
Continuous Intravenous Infusion dosage
Adults:
The use and the dosing of heparin in the management of DIC are controversial. For selected patients (i.e., those with
clinically overt thromboembolism or extensive deposition of fibrin), low doses of heparin 300 to 1,000 units/hour or
15 units/kg/hour IV infusion have shown some benefit. Patients with antithrombin III levels less than 25% may not
respond to heparin. In general, heparin should be continued until fibrinogen levels are more than 100 mg/dL and
platelet counts are more than 100,000/mm3 .
Children and Adolescents:
Neonates and Infants:
For the treatment of unstable angina
NOTE: In 2009, the USP adopted new reference standards and manufacturing controls for heparin that result in a
10% reduction in the potency. This change in heparin potency may have clinical significance in situations that
require dosage adjustments and more frequent monitoring, especially when aggressive anticoagulation is needed,
including pediatric patients undergoing extracorporeal membrane oxygenation, adults and children undergoing
cardiopulmonary bypass, and the treatment or prevention of life-threatening thromboses. Healthcare providers
should exercise clinical judgement when deciding what dose to administer and continue to individualize heparin
dosing. Higher doses may be required to achieve and maintain the desired anticoagulant effect in some patients.40305
Intravenous dosage
Adults:
The American College of Chest Physicians (ACCP) recommends that all patients hospitalized for the treatment of
unstable angina receive aspirin PO and heparin 75 Units/kg IV bolus, followed by an initial maintenance dose of
1250 Units/hour IV, with a target of prolonging the aPTT to 1.5—2 times control.25330 Heparin therapy should be
maintained for at least 48 hours, or until the unstable pattern resolves. Clinical practice guidelines for the diagnosis
and management of unstable angina recommend maintaining an aPTT of 1.5—2.5 times control.24978 An initial IV
infusion of 15—18 Units/kg/hour has also been recommended.24979
For the treatment of an evolving acute myocardial infarction (AMI) (i.e., coronary artery
thrombosis†) in patients who have received thrombolytic therapy with alteplase (tPA), reteplase (r-
PA), or tenecteplase (TNK-tPA).
NOTE: In 2009, the USP adopted new reference standards and manufacturing controls for heparin that result in a
10% reduction in the potency. This change in heparin potency may have clinical significance in situations that
require dosage adjustments and more frequent monitoring, especially when aggressive anticoagulation is needed,
including pediatric patients undergoing extracorporeal membrane oxygenation, adults and children undergoing
cardiopulmonary bypass, and the treatment or prevention of life-threatening thromboses. Healthcare providers
should exercise clinical judgement when deciding what dose to administer and continue to individualize heparin
dosing. Higher doses may be required to achieve and maintain the desired anticoagulant effect in some patients.40305
Intravenous dosage
Adults:
60 Units/kg IV bolus (Max: 4000 Units) given simultaneously with initial dose of thrombolytic therapy followed by
heparin 12 Units/kg/hour IV (Max: 1000 Units/hour) adjusted to keep the aPTT at 1.5—2 times control (50—70
seconds) for 48 hours.25330 All AMI patients without contraindications and who are not receiving heparin for
another reason should receive not less than low-dose heparin (7500 Units subcutaneous every 12 hours) or LMWH
until ambulation to prevent venous thrombosis.25330 Heparin therapy should be maintained for longer than 48
hours only in patients with a high risk of systemic or venous thromboembolism (e.g., anterior MI, CHF, previous
embolus, atrial fibrillation).24869 25330
for patients receiving streptokinase or anistreplase (APSAC) concurrently
Intravenous dosage
Adults:
If streptokinase (SK) or anistreplase (APSAC) is used, heparin should be given only in those patients who are at high
risk for systemic emboli (e.g. large anterior MI, atrial fibrillation, previous embolus, or known LV thrombus) (See
standard dosage). Heparin should not be given <= 4 hours after fibrinolytic therapy and should be given when the
aPTT is < 70 (goal aPTT 50—70 seconds).25330 After 48 hours, consideration may be given to subcutaneous heparin
administration (initial dose about 17,500 Units every 12 hours to maintain aPTT 1.5—2 times control), LMWH, or
oral anticoagulants.25330 If the patient has no risk factors and SK or APSAC is the thrombolytic that was used,
therapeutic heparin is not recommended.25330
Subcutaneous dosage (streptokinase only)
Adults:
12,000 Units subcutaneous every 12 hours for at least 48 hours. Heparin should not be given <= 4 hours after
fibrinolytic therapy and should be given when the aPTT is < 70 (goal aPTT 50—70 seconds).25330
For periprocedural anticoagulation† (bridge therapy) in patients with atrial fibrillation, mechanical
heart valve, or venous thrombosis who require an interruption in oral anticoagulant therapy
for patients taking direct-acting oral anticoagulants (DOACs) who require multiple procedures
and/or are unable to tolerate oral medications post-procedure
Subcutaneous dosage
Adults:
5,000 to 7,500 units subcutaneously twice daily may be sufficient. DOACs have short half-lives; hence, alternative
anticoagulation during temporary interruption is not needed in the majority of situations.51785 63236
for patients taking warfarin at moderate or high risk for thromboembolism and with no significant
bleed risk
Intravenous dosage
Adults:
80 units/kg IV bolus followed by 18 units/kg/hour continuous IV infusion; adjust infusion rate to attain aPTT 1.5 to
2 times the control.51249 51785 Stop warfarin approximately 5 days prior to procedure and initiate heparin 24 hours
or more after the first missed dose of warfarin. Guidelines recommend starting heparin when INR is less than 2 in
those with nonvalvular atrial fibrillation, or if INR is not measured, after omitting 2 to 3 doses of warfarin.
Discontinue heparin 4 to 6 hours prior to procedure if the aPTT is within normal range. If necessary, residual
anticoagulation can be assessed by checking the aPTT. In most cases, warfarin can be restarted in the first 12 to 24
hours after the procedure at the patient’s usual therapeutic dose; post-procedural bridging can be considered in
patients with moderate or high risk of stroke or thromboembolic events.51785 63236
Subcutaneous dosage
Adults:
5,000 to 7,500 units subcutaneously twice daily (low-dose prophylactic regimen) as an alternative to intravenous
heparin therapy. Stop warfarin approximately 5 days prior to procedure and initiate heparin 24 hours or more after
the first missed dose of warfarin. Guidelines recommend starting heparin when INR is less than 2 in those with
nonvalvular atrial fibrillation, or if INR is not measured, after omitting 2 to 3 doses of warfarin. Discontinue heparin
4 to 6 hours prior to procedure if the aPTT is within normal range. If necessary, residual anticoagulation can be
assessed by checking the aPTT In most cases, warfarin can be restarted in the first 12 to 24 hours after the procedure
at the patient’s usual therapeutic dose; post-procedural bridging can be considered in patients with moderate or high
risk of stroke or thromboembolic events.51785 63236
Therapeutic Drug Monitoring:
The activated partial thromboplastin time (aPTT) is usually used to monitor heparin therapy since it is sensitive to
the inhibitory effects of heparin on thrombin, factor Xa and factor IXa; although, only about 40% of the variation
in plasma heparin levels is actually reflected by changes in aPTT. An aPTT ratio of 1.5—2.5 times baseline is
traditionally regarded as the therapeutic target in the clinical treatment of thromboembolic disease with heparin.
However, because the activity of thromboplastin reagents differ, the therapeutic aPTT range varies among
different brands and lots of reagents.23474 Therefore, the American College of Chest Physicians recommends that
the therapeutic range for each aPTT reagent be calibrated to be equivalent to a plasma heparin concentration (by
protamine titration) of 0.2—0.4 International Units/ml or to an anti-factor Xa concentration of about 0.3—0.6
International Units/ml.25334 Alternatively, heparin treatment can be monitored by a chromogenic anti-factor Xa
heparin assay with a targeted range of 0.3—0.7 International Units/ml. In patients with a subtherapeutic aPTT
response despite high doses of heparin, further increases in heparin dosage may not be necessary if the heparin
level is therapeutic (i.e., 0.3—0.7 International Units/ml by anti-factor Xa assay). Potency does not differ between
calcium and sodium salts of heparin.
Dosage should be adjusted to produce a therapeutic aPTT or heparin concentration by protamine titration at 6
hours after a SC or IV dose or infusion rate change. The measurement of anti-factor Xa levels, if available,
approximately 4 hours after SC injection has been recommended.
The aPTT is sensitive over a heparin range of 0.1—1 International Units/ml. However, in high-risk angioplasty
patients or in patients having cardiac bypass surgery the aPTT is unsuitable for monitoring heparin dosage since
these patients often require heparin levels > 1 International Units/ml (5 International Units/ml for CABG
patients). For these procedures, the activated clotting time (ACT) is usually used to monitor heparin therapy since
this test shows a graded response to heparin concentrations in the range of 1—5 International Units/ml.
Maximum Dosage Limits:
NOTE: Since heparin-induced bleeding has been related to dose in addition to other patient specific factors, it would
seem to be prudent to limit the dose of heparin, especially in high-risk patients.
Maximum Dosage Limits:
•Adults
Maintain the aPTT below levels that correlate with heparin concentrations of 0.4 units/mL (by protamine titration)
or an anti-factor Xa concentration of 0.7 units/mL.
•Geriatric
•Adolescents
•Children
•Infants
•Neonates
Patients with Hepatic Impairment Dosing
It appears that hepatic impairment does not affect the elimination of heparin; however, patients with hepatic disease
may have increased risk of bleeding during heparin therapy.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage
adjustments are needed.
Last revised: July 2, 2018
Administración
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Use extreme caution during the preparation, dispensing, and administration of any heparin-containing products
for pediatric patients. Heparin injection is available in various concentrations, and the inadvertent administration
of the incorrect concentration could result in devastating consequences. Fatal hemorrhages have occurred in
pediatric patients (including neonates) due to medication errors in which concentrated 1 mL heparin injection
vials were administered rather than 1 mL 'catheter lock flush' vials.
Administer intravenously or subcutaneously. Intramuscular injection can produce large hematomas caused by
accidental puncture of veins and, therefore, should be avoided. There is evidence that administration by
intermittent IV injection is associated with more bleeding than when administered by continuous infusion.
Therefore, if administered intravenously, a continuous infusion is preferred.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever
solution and container permit.41347 56872
Intravenous Administration
Intermittent IV injection:
Administer IV either undiluted or in 50 to 100 mL of 0.9% Sodium Chloride Injection.41347 56872
Continuous IV infusion:
Dilute desired dose in a prescribed amount of 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or
Lactated Ringer's Injection. Invert container at least 6 times after diluting to ensure adequate mixing. Periodically
mix during the infusion.
Administer IV bolus doses over 10 minutes in pediatric patients.
Infuse intravenously via an electronic infusion pump. Adjust rate based on aPTT or plasma heparin
concentration (by protamine titration or anti-factor Xa assay).56872
Subcutaneous Administration
Using a 25 to 27 gauge needle that is 3/8 to 5/8 inches in length, inject by deep subcutaneous injection into the
lower abdomen; do not aspirate or massage injection site. Take care not to inject intradermally. Rotate injection
sites frequently.
The initial dose should be sufficiently high to counteract the reduced bioavailability from subcutaneous
administration. If an immediate effect is required, the initial dose should be proceeded by an IV bolus injection.
Parámetros de monitorización
hemoglobin/hematocrit
partial thromboplastin time (PTT)
platelet count
Contraindicaciones
aneurysm
asthma
benzyl alcohol hypersensitivity
bleeding
breast-feeding
coagulopathy
corn hypersensitivity
disseminated intravascular coagulation (DIC)
diverticulitis
endocarditis
fever
geriatric
head trauma
hemophilia
heparin hypersensitivity
heparin-induced thrombocytopenia (HIT)
hepatic disease
hypertension
hypotension
infants
infection
inflammatory bowel disease
intracranial bleeding
intramuscular administration
intramuscular injections
lumbar puncture
menstruation
myocardial infarction
neonates
neoplastic disease
peptic ulcer disease
porcine protein hypersensitivity
pregnancy
premature neonates
renal disease
spinal anesthesia
sulfite hypersensitivity
surgery
thrombocytopenia
thrombophlebitis
vaginal bleeding
Do not use therapeutic heparin when appropriate blood coagulation tests for monitoring cannot be performed at
appropriate intervals. Discontinue heparin immediately if the coagulation test is excessively prolonged or
hemorrhage occurs. Monitor platelet counts, hematocrit, and occult blood in stool throughout the course of therapy,
regardless of the route of administration. (_WPS/RefShow.aspx?rid=51862)51862
Use caution when interpreting the clinical implications of elevated hepatic enzymes in patients receiving heparin.
Significant elevations in aminotransferases (AST and ALT) have occurred in a high percentage of patients (including
healthy subjects) who received heparin. (_WPS/RefShow.aspx?rid=51862)51862
Heparin may prolong the one-stage prothrombin time. Hence, when given with warfarin, allow at least 5 hours after
the last IV dose or 24 hours after the last subcutaneous dose of heparin to elapse before blood is drawn to obtain an
accurate prothrombin time. (_WPS/RefShow.aspx?rid=56872)56872
Heparin is contraindicated in patients with known heparin hypersensitivity; reserve heparin in these patients for
clearly life-threatening situations. Heparin is derived from porcine tissue; therefore, use of heparin is
contraindicated in patients with porcine protein hypersensitivity. Because heparin is derived from animal tissue,
monitor for signs and symptoms of hypersensitivity when it is used in patients with a history of allergy.56872
Heparin solutions containing dextrose may be contraindicated in patients with corn hypersensitivity. Some heparin
preparations contain sulfites, which can induce a life-threatening allergic response in some patients. Use such
heparin products with extreme caution in patients with known sulfite hypersensitivity; sulfite sensitivity reactions
tend to occur more frequently in patients with asthma.41675 Some heparin preparations contain benzyl alcohol as a
preservative; avoid these formulations in patients with benzyl alcohol hypersensitivity.51862
Heparin is contraindicated in patients with severe thrombocytopenia and in those with a history of heparin-induced
thrombocytopenia (HIT), heparin-induced thrombocytopenia and thrombosis (HITT), or thrombocytopenia with
pentosan polysulfate. Heparin may be used safely in patients with mild nonimmune thrombocytopenia (platelets
more than 100,000/mm3 ), which may remain stable or reverse with continued treatment. However, use an
alternative anticoagulant and avoid all sources of heparin in patients with a history of immune-mediated HIT
because these patients can develop thrombotic complications during heparin therapy. Because it may not be possible
to differentiate asymptomatic, nonimmune thrombocytopenia from immune-mediated thrombocytopenia, monitor
the platelet count closely. If the platelet count falls below 100,000/mm3 or recurrent thrombosis develops, promptly
discontinue heparin, evaluate for HIT and HITT, and, if necessary, administer an alternative anticoagulant.
Thrombosis in association with thrombocytopenia may indicate white-clot syndrome, which can lead to severe
thromboembolic complications. HIT or HITT can occur up to several weeks after the discontinuation of heparin
therapy; evaluate patients presenting with thrombocytopenia or thrombosis after heparin discontinuation for HIT or
HITT. Avoid future heparin use in patients with a diagnosis of HIT or HITT, especially within 3 to 6 months of
diagnosis and while patients test positive for antibodies. (_WPS/RefShow.aspx?rid=41675)41675 (_WPS/RefShow.aspx?
rid=51862)51862 (_WPS/RefShow.aspx?rid=56872)56872
Heparin is contraindicated in patients with uncontrollable bleeding (with the exception of bleeding associated with
disseminated intravascular coagulation).41347 Avoid use of heparin in the presence of major bleeding, unless the
benefits of therapy outweigh the potential risks. Fatal hemorrhages have occurred with the use of heparin.56872
Hemorrhage can occur at virtually any site in patients receiving heparin. Blood coagulation tests should be
performed before and regularly during therapy. Consider the possibility of a hemorrhagic event with an unexplained
fall in hematocrit, hypotension, or any other unexplained symptom. Use heparin with extreme caution in a patient
with conditions that might increase the risk of hemorrhage. These may include subacute bacterial endocarditis;
dissecting aortic aneurysm; peptic ulcer disease; diverticulitis; inflammatory bowel disease; liver disease;
coagulopathy; hemophilia; thrombocytopenia; menstruation; threatened abortion or other abnormal vaginal
bleeding; severe hypertension; head trauma; major surgery or trauma, especially involving eye, brain, or spinal cord;
during or immediately after a lumbar puncture or spinal anesthesia; tube drainage of stomach or small intestine;
and increased capillary permeability. Patients with hereditary antithrombin III deficiency receiving antithrombin III
therapy are also at risk for hemorrhage with concurrent heparin use; reduce the heparin dose during concomitant
use to reduce the risk of bleeding.56872 Monitor all patients receiving heparin closely for easy bruising or petechiae,
which can precede signs of hemorrhage such as nosebleed, hematuria, or tarry stools.
In patients with acute intracranial bleeding, the American College of Chest Physicians (ACCP) recommends the
initial use of pneumatic compression devices for prevention of DVT and PE.30259 In stable patients, low-dose
subcutaneous heparin may be initiated as soon as the second day after the onset of intracranial hemorrhage
(ICH).30259 This represents a Grade 2C recommendation by ACCP, and assumes a relatively low degree of risk
aversion.30259 30260
Increased resistance to heparin is frequently encountered in patients with fever, thrombosis, thrombophlebitis,
infection with thrombosing tendencies, myocardial infarction, neoplastic disease, postsurgical patients, and patients
with antithrombin III deficiency. Monitor coagulation tests closely in such patients; heparin dose adjustments based
on anti-factor Xa concentrations may be necessary.41347 56872
Use heparin cautiously in patients with underlying hepatic disease as these patients often have coagulopathies and
are at increased risk for anticoagulant-associated bleeding.51288 56872 Patients with inherited antithrombin
deficiency usually have antithrombin concentrations 40% to 60% of normal but may have resistance to heparin and
require higher doses to achieve the desired therapeutic response.51290 Patients with acquired antithrombin
deficiency, as seen with severe hepatic disease (e.g., cirrhosis), renal disease (e.g., nephrotic syndrome), or
disseminated intravascular coagulation (DIC), may not respond to heparin.51290 51291
When using heparin lock flush solutions to maintain catheter patency, the 100 unit/mL concentration should not be
used in neonates or in infants who weigh less than 10 kg because of the risk of systemic anticoagulation. While
systemic anticoagulation is not common with the use of heparin flushes for line patency in general, clinicians should
use caution and carefully monitor small infants and other at risk patients receiving multiple flushes per day
regardless of the heparin concentrations used. Extreme caution should be used during the preparation, dispensing,
and administration of heparin flushes, heparin-containing fluids, and therapeutic doses of heparin for pediatric
patients. Heparin injection is available in a wide range of concentrations. Fatal hemorrhages have occurred in
pediatric patients (including neonates) due to medication errors in which concentrated 1 mL heparin injection vials
were administered rather than 1 mL 'catheter lock flush' vials. To confirm correct vial choice during preparation and
prior to administration, carefully inspect labels of heparin injection vials. Use preservative-free heparin formulations
in neonates. Multiple dose vials contain benzyl alcohol as a preservative and should be avoided in this population. A
'gasping syndrome' characterized by CNS depression, metabolic acidosis, and gasping respirations has been
associated with benzyl alcohol dosages more than 99 mg/kg/day in neonates. However, the minimum amount of
benzyl alcohol at which toxicity may occur is unknown and low-birth weight and premature neonates may be more
likely to develop toxicity. Normal therapeutic heparin doses would deliver benzyl alcohol at amounts lower than
those reported with 'gasping syndrome'; however, the clinician should be aware of the toxic potential, especially if
other drugs containing benzyl alcohol are administered.51862
Geriatric patients, especially females, may have higher plasma concentrations of heparin and longer activated partial
thromboplastin time (aPTT) compared to patients younger than 60 years of age following similar doses. A higher
incidence of bleeding in elderly patients older than 60 years, especially females, has been reported. Elderly patients
may require lower doses of heparin.56872
Heparin is not intended for intramuscular administration. Severe large hematomas caused by accidental puncture of
an IM vein may occur.41347 Avoid intramuscular injections of other medications to patients receiving heparin. IM
injections may cause bleeding, bruising, or hematomas.
In published reports, heparin exposure during pregnancy did not result in increased risk of adverse maternal or fetal
outcomes in humans. No teratogenicity was seen in animal studies where animals were given approximately 10 times
the maximum recommended human dose during organogenesis; however, increased resorptions were reported.
Consider the benefits and risks of heparin to a pregnant woman and possible risks to the fetus when using heparin
during pregnancy.56872 Heparin does not cross the placental barrier. When indicated, use only preservative-free
heparin formulations; benzyl alcohol has been associated with serious adverse events and death, particularly in
neonates and infants.41347
There are no data on the presence of heparin in human milk, the effects on the breast-fed infant, or the effects on
milk production. Due to its large molecular weight, heparin is not likely to be excreted in human breast milk, and
any heparin in milk would not be orally absorbed by a nursing infant. Consider the developmental and health
benefits of breast-feeding along with the mother's clinical need for heparin and any potential adverse effects on the
breast-fed infant from heparin or from the underlying maternal condition. When indicated, use only preservative-
free heparin formulations; benzyl alcohol has been associated with serious adverse events and death, particularly in
neonates and infants.41347 56872
Last revised: September 27, 2019
Interacciones
Abciximab
Acetaminophen; Aspirin, ASA; Caffeine
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
Ado-Trastuzumab emtansine
Aliskiren; Valsartan
Alprostadil
Alteplase
Altretamine
Amiloride
Amiloride; Hydrochlorothiazide, HCTZ
Aminosalicylate sodium, Aminosalicylic acid
Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
Amlodipine; Valsartan
Anagrelide
Angiotensin-converting enzyme inhibitors
Antithrombin III
Antithymocyte Globulin
Apixaban
Aprotinin
Argatroban
Arsenic Trioxide
Aspirin, ASA
Aspirin, ASA; Butalbital; Caffeine
Aspirin, ASA; Butalbital; Caffeine; Codeine
Aspirin, ASA; Caffeine; Dihydrocodeine
Aspirin, ASA; Caffeine; Orphenadrine
Aspirin, ASA; Carisoprodol
Aspirin, ASA; Carisoprodol; Codeine
Aspirin, ASA; Dipyridamole
Aspirin, ASA; Omeprazole
Aspirin, ASA; Oxycodone
Aspirin, ASA; Pravastatin
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
Azelastine; Fluticasone
Beclomethasone
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
Betamethasone
Betrixaban
Bismuth Subsalicylate
Bismuth Subsalicylate; Metronidazole; Tetracycline
Bivalirudin
Budesonide
Budesonide; Formoterol
Caplacizumab
Carbenicillin
Cardiac glycosides
Celecoxib
Cetirizine
Cetirizine; Pseudoephedrine
Chlorambucil
Choline Salicylate; Magnesium Salicylate
Ciclesonide
Cilostazol
Clofarabine
Clopidogrel
Collagenase
Corticorelin, Ovine
Corticosteroids
Corticotropin, ACTH
Cortisone
Cytarabine, ARA-C
Dabigatran
Dalteparin
Danaparoid
Danazol
Dasatinib
Decitabine
Deferasirox
Defibrotide
Deflazacort
Denileukin Diftitox
Desirudin
Desloratadine
Desloratadine; Pseudoephedrine
Desmopressin
Dexamethasone
Dextran
Diclofenac
Diclofenac; Misoprostol
Diflunisal
Diphenhydramine; Ibuprofen
Diphenhydramine; Naproxen
Dipyridamole
Drospirenone
Drospirenone; Estradiol
Drospirenone; Ethinyl Estradiol
Drospirenone; Ethinyl Estradiol; Levomefolate
Drotrecogin Alfa
Edoxaban
Eltrombopag
Enoxaparin
Eplerenone
Epoprostenol
Eptifibatide
Esomeprazole; Naproxen
Esterified Estrogens; Methyltestosterone
Estramustine
Etodolac
Famotidine; Ibuprofen
Fenoprofen
Fexofenadine
Fexofenadine; Pseudoephedrine
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements)
Floxuridine
Fludrocortisone
Flunisolide
Fluorouracil, 5-FU
Flurbiprofen
Fluticasone
Fluticasone; Salmeterol
Fluticasone; Umeclidinium; Vilanterol
Fluticasone; Vilanterol
Folate analogs
Fondaparinux
Formoterol; Mometasone
Garlic, Allium sativum
Ginger, Zingiber officinale
Ginkgo, Ginkgo biloba
Green Tea
Guarana
Hemin
Hydrochlorothiazide, HCTZ; Spironolactone
Hydrochlorothiazide, HCTZ; Triamterene
Hydrochlorothiazide, HCTZ; Valsartan
Hydrocodone; Ibuprofen
Hydrocortisone
Hydroxyurea
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
Ibritumomab Tiuxetan
Ibrutinib
Ibuprofen
Ibuprofen; Oxycodone
Ibuprofen; Pseudoephedrine
Icosapent ethyl
Iloprost
Imatinib
Indocyanine Green
Indomethacin
Inotersen
Interferon Alfa-2a
Interferon Alfa-2b
Interferon Alfa-2b; Ribavirin
Interferon Alfa-n3
Interferon Alfacon-1
Intravenous Lipid Emulsions
Kava Kava, Piper methysticum
Ketoprofen
Ketorolac
Lansoprazole; Naproxen
Lepirudin
Levocetirizine
Lithium
Lomustine, CCNU
Loratadine
Loratadine; Pseudoephedrine
Magnesium Salicylate
Meclofenamate Sodium
Mefenamic Acid
Meloxicam
Methoxsalen
Methylprednisolone
Methylsulfonylmethane, MSM
Methyltestosterone
Mifepristone
Miltefosine
Mometasone
Mycophenolate
Nabumetone
Nandrolone Decanoate
Naproxen
Naproxen; Pseudoephedrine
Naproxen; Sumatriptan
Natural Antineoplastics
Nebivolol; Valsartan
Nelarabine
Nicotine
Nintedanib
Nitroglycerin
Nonsteroidal antiinflammatory drugs
Obinutuzumab
Omacetaxine
Oritavancin
Orlistat
Oxandrolone
Oxaprozin
Palifermin
Pentosan
Phentermine; Topiramate
Photosensitizing agents
Piperacillin
Piperacillin; Tazobactam
Piroxicam
Porfimer
Potassium
Potassium Phosphate
Potassium Phosphate; Sodium Phosphate
Potassium-sparing diuretics
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
Prasugrel
Prednisolone
Prednisone
Protamine
Reteplase, r-PA
Rivaroxaban
Rofecoxib
Sacubitril; Valsartan
Salicylates
Salsalate
Sedating H1-blockers
Selective serotonin reuptake inhibitors
Serotonin norepinephrine reuptake inhibitors
Sodium Hyaluronate, Hyaluronic Acid
Sodium Iodide
Spironolactone
Streptokinase
Sulfinpyrazone
Sulindac
Telavancin
Tenecteplase
Terfenadine
Tetracyclines
Thrombolytic Agents
Ticagrelor
Ticarcillin
Ticarcillin; Clavulanic Acid
Ticlopidine
Tinzaparin
Tipranavir
Tirofiban
Tolmetin
Tolvaptan
Topiramate
Trazodone
Treprostinil
Tretinoin, ATRA
Triamcinolone
Triamterene
Urokinase
Valdecoxib
Valsartan
Vasopressin, ADH
Verteporfin
Vilazodone
Vorapaxar
Vorinostat
Vortioxetine
Warfarin
Abciximab: (Moderate) The use of abciximab within 7 days of use an oral anticoagulant is contraindicated unless the
patient's prothrombin time is less than or equal to 1.2 times the control value. Because abciximab inhibits platelet
aggregation, additive effects may be seen when abciximab is given in combination with other agents that affect
hemostasis such as other platelet inhibitors (e.g. aspirin, ASA, clopidogrel, dipyridamole, ticlopidine), thrombolytic
agents (e.g. alteplase, reteplase, streptokinase), and anticoagulants (e.g., heparin, warfarin). However, in clinical
trials with abciximab, aspirin and heparin were administered concomitantly. The bleeding risk is significantly
increased with concurrent abciximab and thrombolytic therapy; the risks of combination therapy should be weighed
against the potential benefits. The GUSTO V study evaluated reduced-dose reteplase in combination with full dose
abciximab, in comparison to full dose reteplase alone in patients with acute myocardial infarction (MI); all patients
received concurrent aspirin and heparin therapy. The combination regimen was associated with a two-fold increase
in moderate to severe non-intracranial bleeding complications, including spontaneous GI bleeding. In addition,
large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Although NSAIDs lacks platelet inhibitory effects, an increased risk for GI bleeding is possible when NSAIDs are
administered during abciximab therapy. 1582 5170 6562
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) An additive risk of bleeding may be seen in patients receiving
platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin and heparin,
heparin is frequently administered in combination with low-dose aspirin therapy to patients who have had an acute
myocardial infarction and in other disease states. In addition, large doses of salicylates (>= 3-4 g/day) can cause
hypoprothrombinemia, an additional risk factor for bleeding. 28440 41347
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) An additive risk of bleeding may be
seen in patients receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug interaction between
aspirin and heparin, heparin is frequently administered in combination with low-dose aspirin therapy to patients
who have had an acute myocardial infarction and in other disease states. In addition, large doses of salicylates (>= 3-
4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. 28440 41347
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) An additive risk of bleeding may be seen in
patients receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin
and heparin, heparin is frequently administered in combination with low-dose aspirin therapy to patients who have
had an acute myocardial infarction and in other disease states. In addition, large doses of salicylates (>= 3-4 g/day)
can cause hypoprothrombinemia, an additional risk factor for bleeding. 28440 41347
Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of anticoagulants with ado-trastuzumab

emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding,
with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically
necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving
anticoagulation therapy, others had no known additional risk factors. 53295
Aliskiren; Valsartan: (Minor) Concomitant use of valsartan with other drugs that may increase potassium
concentrations, such as heparin, may lead to increases in serum potassium. 29130
Alprostadil: (Moderate) Caution is advised with the concomitant administration of alprostadil injection for dilation
of the ductus arteriosis and heparin infusions. Coadministration resulted in a 140% increase in partial
thromboplastin time and a 120% increase in thrombin time in a study of 12 healthy volunteers receiving alprostadil
90 mcg infusion over 3 hours and heparin 5000 units. Monitor patients for increased bleeding if these agents are
used together. 30848
Alteplase: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and
anticoagulants. 28469
Altretamine: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be
seen in patients receiving concomitant anticoagulants. 4661
Amiloride: (Moderate) Simultaneous use of a potassium-sparing diuretic with heparin can increase the risk of
hyperkalemia, especially in the presence of renal impairment. Monitoring of serum potassium is recommended as
indicated. 2173 5873
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Simultaneous use of a potassium-sparing diuretic with heparin
can increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitoring of serum
potassium is recommended as indicated. 2173 5873
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) An additive risk of bleeding may be seen in patients
receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin and
heparin, heparin is frequently administered in combination with low-dose aspirin therapy to patients who have had
an acute myocardial infarction and in other disease states. In addition, large doses of salicylates (>= 3-4 g/day) can
cause hypoprothrombinemia, an additional risk factor for bleeding. 28440 41347
Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Minor) Concomitant use of valsartan with other drugs that
may increase potassium concentrations, such as heparin, may lead to increases in serum potassium. 29130
Amlodipine; Valsartan: (Minor) Concomitant use of valsartan with other drugs that may increase potassium
Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive
risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as other
anticoagulants. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an
additional risk factor for bleeding. An in vivo interaction study in humans demonstrated that a single 1 mg dose of
anagrelide administered concomitantly with a single dose of aspirin 900 mg was well tolerated; there was no effect
on bleeding time, PT, or PTT. However, aspirin alone produced a marked inhibition of platelet aggregation ex vivo;
anagrelide enhanced the platelet inhibition effects of aspirin slightly. Patients may be at increased risk of bleeding if
anagrelide is administered with aspirin. 5170 6912
Angiotensin-converting enzyme inhibitors: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors decrease

aldosterone secretion, leading to small increases in serum potassium levels. Drugs that increase serum potassium
concentration, such as heparin, should be given cautiously to patients taking ACE inhibitors. Frequently monitor
serum potassium. Hyperkalemia can cause serious, sometimes fatal, arrhythmias. 28634
Antithrombin III: (Major) As a regulator of hemostasis, antithrombin III (AT III) may increase bleeding risk in
patients receiving heparin concomitantly. The anticoagulant effect of heparin is enhanced by concurrent treatment
with AT III in patients with hereditary AT III deficiency. In addition, the half-life of AT III may be altered during
concomitant administration with anticoagulants. Thus, in order to avoid bleeding, the heparin dosage may need to
be reduced during treatment with AT III. Coagulation tests (aPTT and anti-Factor Xa, when appropriate) should be
performed regularly and especially in the first hours following the start or withdrawal of AT III therapy to ensure
appropriate anticoagulation. 30131 34885
Antithymocyte Globulin: (Moderate) Drugs that can cause thrombocytopenia, such as antithymocyte globulin, may
lead to an increased risk of bleeding when given concurrently with anticoagulants. 30137 41851
Apixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if apixaban
and other anticoagulants are used concomitantly. If switching from apixaban to another anticoagulant, discontinue
apixaban and start the other anticoagulant at the usual time of the next dose of apixaban. If switching from another
anticoagulant to apixaban, discontinue the other anticoagulant and start apixaban at the usual time of the next dose
of the other anticoagulant. Coadministration of apixaban and other anticoagulants may increase the risk of bleeding.
52739
Aprotinin: (Moderate) If an activated clotting time is used to determine the effectiveness of heparin anticoagulation,
the prolongation of ACT by aprotinin may lead to an overestimation of the degree of anticoagulation, thereby leading
to inadequate anticoagulation. 5204
Argatroban: (Major) An additive risk of bleeding may be seen in patients receiving other anticoagulants in
combination with heparin. 29402 41347
Arsenic Trioxide: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
antineoplastic agents and anticoagulants concomitantly. 5208 5279
Aspirin, ASA: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g.
aspirin, ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is frequently
administered in combination with low-dose aspirin therapy to patients who have had an acute myocardial infarction
and in other disease states. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia,
an additional risk factor for bleeding. 28440 41347
Aspirin, ASA; Butalbital; Caffeine: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet
inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is
frequently administered in combination with low-dose aspirin therapy to patients who have had an acute myocardial
infarction and in other disease states. In addition, large doses of salicylates (>= 3-4 g/day) can cause
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) An additive risk of bleeding may be seen in patients
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) An additive risk of bleeding may be seen in patients receiving
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) An additive risk of bleeding may be seen in patients receiving
Aspirin, ASA; Carisoprodol: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) An additive risk of bleeding may be seen in patients receiving
Aspirin, ASA; Dipyridamole: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet
hypoprothrombinemia, an additional risk factor for bleeding. 28440 41347 (Moderate) Because dipyridamole is a
platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other
agents that affect hemostasis. 5168 6926
Aspirin, ASA; Omeprazole: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet
Aspirin, ASA; Oxycodone: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet
Aspirin, ASA; Pravastatin: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) An additive
risk of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-
drug interaction between aspirin and heparin, heparin is frequently administered in combination with low-dose
aspirin therapy to patients who have had an acute myocardial infarction and in other disease states. In addition,
large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
28440 41347
Azelastine; Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including
intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium
concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. 54506
Beclomethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) An additive risk of
bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug
interaction between aspirin and heparin, heparin is frequently administered in combination with low-dose aspirin
therapy to patients who have had an acute myocardial infarction and in other disease states. In addition, large doses
of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. 28440 41347
Betamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Betrixaban: (Major) Avoid concurrent use of betrixaban with heparin due to the increased bleeding risk. Monitor
patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and other anticoagulants are
used concomitantly. Coadministration of betrixaban and other anticoagulants may increase the risk of bleeding.
41347 62037
Bismuth Subsalicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors
(e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is frequently
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) An additive risk of bleeding may be seen in patients
Bivalirudin: (Major) An additive risk of bleeding may be seen in patients receiving or other anticoagulants in
Budesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from
sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid
status if sodium-containing drugs and corticosteroids must be used together. 54506
Budesonide; Formoterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Caplacizumab: (Moderate) Assess and monitor closely for bleeding with concomitant use of caplacizumab and
anticoagulants. Concomitant use of caplacizumab with any anticoagulant may increase the risk of bleeding. Interrupt
caplacizumab use if clinically significant bleeding occurs. 63940
Carbenicillin: (Moderate) Some penicillins (e.g., carbenicillin) can inhibit platelet aggregation, which may increase
the risk of bleeding with any anticoagulants. Clinically important bleeding of this type is relatively rare. The
concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR
thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora
may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients
for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and
upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin. 28549 57681 57682 6644 6645
Cardiac glycosides: (Minor) Digitalis (e.g., cardiac glycosides like digoxin or digitoxin) may partially counteract the
anticoagulant actions of heparin, according to the product labels. However, this interaction is not of clinical
significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical
parameters of the patient. 56872
Celecoxib: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs).
Monitor clinical and laboratory response closely during concurrent use. 29732 40621 49946
Cetirizine: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the
product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the
partial thromboplastin time (aPTT) and other clinical parameters of the patient. 56872
Cetirizine; Pseudoephedrine: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin,
according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is
adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient. 56872
Chlorambucil: (Moderate) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be
seen in patients receiving concomitant anticoagulants. 4757 5170
Choline Salicylate; Magnesium Salicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving
Ciclesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Cilostazol: (Moderate) The safety of cilostazol has not been established with concomitant administration of
anticoagulants. Because cilostazol is a platelet aggregation inhibitor, concomitant administration with similar acting
drugs could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and
combinations of these agents should be approached with caution. Patients on anticoagulants should be monitored
for changes in response to anticoagulation therapy if cilostazol is administered concurrently. 5167
Clofarabine: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen
in patients receiving concomitant anticoagulants. 5170 5279
Clopidogrel: (Moderate) Because clopidogrel inhibits platelet aggregation, a potential additive risk for bleeding
exists if clopidogrel is given in combination with other agents that affect hemostasis such as anticoagulants. In
healthy volunteers receiving heparin, clopidogrel does not alter the effect of heparin on coagulation parameters or
require adjustment of the heparin dose. In addition, heparin has no effect on inhibition of platelet aggregation
induced by clopidogrel. Nevertheless, the safety of this combination has not been established and concomitant
administration of clopidogrel with heparin should be undertaken with caution. 28434 28435
Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking anticoagulants is advised. The
efficacy and safety of administering injectable collagenase to a patient taking an anticoagulant within 7 days before
the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection
site. 38955
Corticorelin, Ovine: (Major) The use of a heparin solution to maintain IV cannula patency during corticorelin
stimulation tests is not recommended. A possible interaction between corticorelin and heparin may have been
responsible for a major hypotensive reaction that occurred after corticorelin administration. 46912
Corticosteroids: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Corticotropin, ACTH: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Cortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Cytarabine, ARA-C: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of
bleeding may be seen in patients receiving concomitant anticoagulants. 5208
Dabigatran: (Major) Based on the pharmacology of dabigatran, other oral anticoagulants and thrombolytic agents
could cause additive risk of bleeding when given concurrently with dabigatran. 41347 42121
Dalteparin: (Major) An additive risk of bleeding may be seen in patients receiving other anticoagulants (e.g.,
heparin) in combination with dalteparin. 40620 41347
Danaparoid: (Severe) An additive risk of bleeding may be seen in patients receiving other anticoagulants (e.g.,
heparin, warfarin) in combination with danaparoid. Monitoring of anticoagulant therapy by prothrombin time and
Thrombotest is unreliable within 5 hours after danaparoid administration. 6910
Danazol: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of
bleeding when used concurrently with anticoagulants. 3946
Dasatinib: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is
necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of
hemorrhage. 60087
Decitabine: (Moderate) Due to the thrombocytopenic effects of antineoplastic agents, an additive risk of bleeding
may be seen in patients receiving concomitant anticoagulants. 5279 9105
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking
deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric
hemorrhage including anticoagulants. 31807
Defibrotide: (Severe) Coadministration of defibrotide with antithrombotic agents like anticoagulants is

contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if
coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic
agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of
defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic
agent have abated. 60681
Deflazacort: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Denileukin Diftitox: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
antineoplastic agents in combination with anticoagulants. 5279 6880
Desirudin: (Major) Any agent which may enhance the risk of hemorrhage should generally be discontinued before
initiating desirudin therapy, including anticoagulants. If coadministration cannot be avoided, close clinical and
laboratory monitoring should be conducted. During prophylaxis of venous thromboembolism with desirudin,
concomitant treatment with heparins [including unfractionated and low-molecular weight heparins (LMWHs)] or
dextrans is not recommended. The effects of desirudin and unfractionated heparins on prolongation of aPTT are
additive. 29598 41347
Desloratadine: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to
the product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to
the partial thromboplastin time (aPTT) and other clinical parameters of the patient. 56872
Desloratadine; Pseudoephedrine: (Minor) Antihistamines may partially counteract the anticoagulant actions of
heparin, according to the product labels. However, this interaction is not likely of clinical significance since heparin
therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient. 56872
Desmopressin: (Minor) Desmopressin has been shown to have an additive effect on the anticoagulant activity of
heparin. Caution should be used when coadministering these agents. 6927
Dexamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Dextran: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with
caution in patients on anticoagulants concurrently. 49553
Diclofenac: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Diclofenac; Misoprostol: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs
(NSAIDs). Monitor clinical and laboratory response closely during concurrent use. 29732 40621 49946
Diflunisal: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Diphenhydramine; Ibuprofen: (Moderate) An additive risk of bleeding may be seen in patients receiving
anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal
antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. 29732
40621 49946
Diphenhydramine; Naproxen: (Moderate) An additive risk of bleeding may be seen in patients receiving
40621 49946
Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding
if dipyridamole is given in combination with other agents that affect hemostasis. 5168 6926
Drospirenone: (Minor) Chronic heparin therapy may predispose a patient to develop hyperkalemia; this risk may be
increased in patients receiving drospirenone concomitantly. Monitoring of serum potassium during the 1st month of
concurrent therapy with drospirenone is recommended. 4716
Drospirenone; Estradiol: (Minor) Chronic heparin therapy may predispose a patient to develop hyperkalemia; this
risk may be increased in patients receiving drospirenone concomitantly. Monitoring of serum potassium during the
1st month of concurrent therapy with drospirenone is recommended. 4716
Drospirenone; Ethinyl Estradiol: (Minor) Chronic heparin therapy may predispose a patient to develop
hyperkalemia; this risk may be increased in patients receiving drospirenone concomitantly. Monitoring of serum
potassium during the 1st month of concurrent therapy with drospirenone is recommended. 4716
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Chronic heparin therapy may predispose a patient to
develop hyperkalemia; this risk may be increased in patients receiving drospirenone concomitantly. Monitoring of
serum potassium during the 1st month of concurrent therapy with drospirenone is recommended. 4716
Drotrecogin Alfa: (Major) Treatment with drotrecogin alfa should be carefully considered in patients who are
receiving or have received any anticoagulants. There is an additive risk of beeding. 5205
Edoxaban: (Major) Avoid concurrent use of edoxaban with heparin due to the increased bleeding risk. Monitor
patients closely and promptly evaluate any signs or symptoms of bleeding if edoxaban and other anticoagulants are
used concomitantly. Coadministration of edoxaban and other anticoagulants may increase the risk of bleeding.
Long-term concomitant treatment with edoxaban and other anticoagulants is not recommended; short-term use
may be necessary for patients transitioning to or from edoxaban. 41347 58685
Eltrombopag: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g.,
warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in
patients receiving these drugs when eltrombopag is discontinued. 40392
Enoxaparin: (Major) An additive risk of bleeding may be seen in patients receiving enoxaparin in combination with
other anticoagulants. If coadministration of 2 or more anticoagulants is necessary, patients should be closely
monitored for evidence of bleeding. 29732
Eplerenone: (Minor) Heparin may potentially increase the risk of hyperkalemia in patients receiving eplerenone.
Monitor serum potassium if eplerenone is used concurrently with drugs with potential to induce hyperkalemia. 2173
4707
Epoprostenol: (Moderate) When used concurrently with anticoagulants, epoprostenol may increase the risk of
bleeding. 4892
Eptifibatide: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as
anticoagulants, may be associated with an increased risk of bleeding. In addition, large doses of salicylates (>= 3 to 4
g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. In clinical trials with eptifibatide,
aspirin and heparin were administered concomitantly. Eptifibatide has been administered with a thrombolytic agent
in a small number of patients. In the IMPACT II study, 15 patients received a thrombolytic agent with the 135/0.5
dosing regimen, 2 of whom experienced a major bleed. In the PURSUIT study, 40 patients who received eptifibatide
(180 mcg/kg bolus, then 2 mcg/kg/min) also received a thrombolytic agent, 10 of whom experienced a major bleed.
In another acute MI study (n=181), eptifibatide (180 mcg/kg bolus, then up to 2 mcg/kg/min for up to 72 hours) was
administered concomitantly with streptokinase (1.5 mU over 60 min). At the highest studied infusion rates (1.3 to 2
mcg/kg/min), eptifibatide was associated with an increase in the incidence of bleeding and transfusions compared to
the incidence seen with streptokinase alone. 1728 1729 5170 6890
Esomeprazole; Naproxen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants
in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory
drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. 29732 40621 49946
Esterified Estrogens; Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants
through reduction of procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored,
especially when methyltestosterone treatment is initiated or discontinued. 29883
Estramustine: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
Etodolac: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Famotidine; Ibuprofen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Fenoprofen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Fexofenadine: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to
Fexofenadine; Pseudoephedrine: (Minor) Antihistamines may partially counteract the anticoagulant actions of
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Drug interactions with fish oil, omega-3 fatty
acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However,
because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used
concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may
be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In
one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin
therapy were administered various doses of fish oil supplements to determine the effect on INR determinations.
Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily.
Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no
statistically significant difference in INRs between the placebo or treatment period within each group. There was
also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding
episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have
a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in
INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil,
omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish
oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving
warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of
warfarin adjusted accordingly. 26860 29141 29579 30541
Floxuridine: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
Fludrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Flunisolide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Fluorouracil, 5-FU: (Major) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
antineoplastic agents and anticoagulants concomitantly. 5208
Flurbiprofen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Fluticasone; Salmeterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high
doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources,
including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium
Fluticasone; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Folate analogs: (Moderate) Due to the thrombocytopenic effects of folate analogs, when used as antineoplastic
agents, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. 40129 51786
Fondaparinux: (Major) Discontinue heparin before starting fondaparinux due to the increased bleeding risk, unless
these agents are essential. If coadministration is necessary, monitor patients closely and promptly evaluate any signs
or symptoms of bleeding. 40227 41347
Formoterol; Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Garlic, Allium sativum: (Moderate) Garlic produces clinically significant antiplatelet effects so additive risk of
bleeding may occur if anticoagulants are given in combination. Avoid concurrent use of herbs which interact with
anticoagulants when possible. If garlic dietary supplements are taken, monitor the INR or other appropriate
parameters to attain clinical and anticoagulant endpoints. In regard to warfarin, published data are limited to a
random case report; however, the product labeling for warfarin includes garlic as having potential for interaction
due to additive pharmacologic activity. A case of spontaneous spinal epidural hematoma, attributed to dysfunctional
platelets from excessive garlic use in a patient not receiving concomitant anticoagulation, has been reported. 25588
25600 28470 28549 63043
Ginger, Zingiber officinale: (Moderate) Additive bleeding may occur if anticoagulants are given in combination with
ginger, zingiber officinale. Ginger inhibits thromboxane synthetase (platelet aggregation inducer) and is a
prostacyclin agonist. Patients taking ginger and an anticoagulant should be monitored closely for bleeding. 28470
28836 28837 29137
Ginkgo, Ginkgo biloba: (Major) Ginkgo, Ginkgo biloba is reported to inhibit platelet aggregation and several case
reports describe bleeding complications with Ginkgo biloba, with or without concomitant drug therapy. Since ginkgo
produces clinically-significant antiplatelet effects, it should be used cautiously in patients drugs that inhibit platelet
aggregation or pose a risk for bleeding, such as anticoagulants. Ginkgo, Ginkgo biloba is reported to inhibit platelet
aggregation and several case reports describe bleeding complications with Ginkgo biloba, with or without
concomitant drug therapy. Since ginkgo produces clinically-significant antiplatelet effects, it should be used
cautiously in patients drugs that inhibit platelet aggregation or pose a risk for bleeding, such as anticoagulants (e.g.,
warfarin), aspirin, ASA or other platelet inhibitors, or thrombolytic agents. A patient who had been taking aspirin
325 mg/day PO for 3 years following coronary-artery bypass surgery, developed spontaneous bleeding into his eye
after taking a standardized extract of Ginkgo biloba (Ginkoba commercial product) 40 mg PO twice daily for one
week. The patient stopped taking the ginkgo but continued taking the aspirin with no recurrence of bleeding over a
3-month period. Other clinical data exist that describe spontaneous subdural hematomas associated with chronic
ginkgo biloba ingestion. 25081 25082 25083 25273 28470
Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that
the use of green tea may increase the risk of bleeding if co-administered with anticoagulants (e.g., enoxaparin,
heparin, warfarin, and others) thrombolytic agents, or platelet inhibitors (e.g., aspirin, clopidogrel, cilostazol and
others). Caution and careful monitoring of clinical and/or laboratory parameters are warranted if green tea is
coadministered with any of these agents. Exogenous administration or occult sources of vitamin K may decrease or
reverse the activity of warfarin; stability of the diet can be an important factor in maintaining anticoagulation goals.
Occult sources of vitamin K include green tea and green tea dietary supplements. Published data are limited in
regard to this interaction. A patient with previous INRs of 3.2. and 3.79 on a dose of 7.5mg daily of warfarin (goal
INR 2.5 to 3.5) had an INR of 1.37. One month later, the patient's INR was 1.14. The patient admitted that he had
started consuming 0.51 gallon of green tea daily approximately one week prior to the INR of 1.37. The patient denied
noncompliance and other changes in diet, medications, or health. The patient discontinued green tea and one week
later his INR was 2.55. While the amount of vitamin K in a single cup of brewed green tea may not be high (0.03
mcg/100 g), the actual amount may vary from cup to cup depending on the amount of tea leaves used, the length of
time the tea bags are allowed to brew, and the volume of tea consumed. Additionally, if a patient drinks multiple
cups of tea per day, the amount of vitamin K could reach significance. It is recommended that patients on warfarin
maintain a stable intake of green tea. 367 6434 6440 6529 6581
Guarana: (Major) Guarana has been shown to possess minor antiplatelet activity and, therefore, concurrent use of
guarana and anticoagulants or platelet inhibitors should be avoided. 30208 30209
Hemin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies,
concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by
hemin has not been established. 6701 6702
Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Simultaneous use of a potassium-sparing diuretic with

heparin can increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitoring of serum
Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Simultaneous use of a potassium-sparing diuretic with

heparin can increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitoring of serum
Hydrochlorothiazide, HCTZ; Valsartan: (Minor) Concomitant use of valsartan with other drugs that may increase
potassium concentrations, such as heparin, may lead to increases in serum potassium. 29130
Hydrocodone; Ibuprofen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants
in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory
drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. 29732 40621 49946
Hydrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Hydroxyurea: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
antineoplastic agents and anticoagulants concomitantly. 5208 5279
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) An additive risk
of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug
interaction between aspirin and heparin, heparin is frequently administered in combination with low-dose aspirin
therapy to patients who have had an acute myocardial infarction and in other disease states. In addition, large doses
of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. 28440 41347
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90
ibrutumomab tiuxetan with drugs that interfere with coagulation such as anticoagulants; the risk of bleeding may be
increased. If coadministration with anticoagulants is necessary, monitor platelet counts more frequently for evidence
of thrombocytopenia. 41826 (Moderate) Use potassium phosphates cautiously with heparin, as both drugs increase
serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients
with impaired renal function. Patients should have serum potassium concentration determinations at periodic
intervals. 57713 57714 57715
Ibrutinib: (Moderate) The concomitant use of ibrutinib and anticoagulant agents such as heparin may increase the
risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy
including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were
fatal. The mechanism for bleeding with ibrutinib therapy is not well understood. 56410
Ibuprofen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Ibuprofen; Oxycodone: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Ibuprofen; Pseudoephedrine: (Moderate) An additive risk of bleeding may be seen in patients receiving
40621 49946
Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA).
Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used
concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may
be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In
one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin
therapy were administered various doses of fish oil supplements to determine the effect on INR determinations.
Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily.
Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no
statistically significant difference in INRs between the placebo or treatment period within each group. There was
also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding
episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a
statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR
from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-
3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1
gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin
that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of
warfarin adjusted accordingly. 3535 5879 6320 7299
Iloprost: (Moderate) When used concurrently with anticoagulants, inhaled iloprost may increase the risk of bleeding.
7537
Imatinib: (Major) Due to the thrombocytopenic effects of imatinib an additive risk of bleeding may be seen in
patients receiving concomitant anticoagulants. In addition, large doses of salicylates (>= 3-4 g/day) can cause
hypoprothrombinemia, an additional risk factor for bleeding. The manufacturer recommends that patients who
require anticoagulation while receiving imatinib should receive low-molecular weight heparin or standard heparin
instead of warfarin. 4966 5170
Indocyanine Green: (Moderate) Heparin products that contain sodium bisulfite may reduce the absorption peak of
indocyanine green. Collection of blood samples for analysis should be performed with anticoagulants that do not
contain sodium bisulfite. 48809
Indomethacin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Inotersen: (Moderate) Use caution with concomitant use of inotersen and anticoagulants due to the potential risk of
bleeding from thrombocytopenia. Consider discontinuation of anticoagulants in a patient taking inotersen with a
platelet count of less than 50,000 per microliter. 63624
Interferon Alfa-2a: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
antineoplastic agents in combination with anticoagulants. 5279
Interferon Alfa-2b: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
Interferon Alfa-2b; Ribavirin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients
receiving antineoplastic agents in combination with anticoagulants. 5279
Interferon Alfacon-1: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
Interferon Alfa-n3: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
Intravenous Lipid Emulsions: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements)
or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty
acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants,
platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that
combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized,
double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses
of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week
treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for
INR determinations and adverse reactions. There was no statistically significant difference in INRs between the
placebo or treatment period within each group. There was also no difference in INRs found between groups. One
episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil
supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients
receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin
therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day.
The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related
effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy
should have their INR monitored more closely and the dose of warfarin adjusted accordingly. 26860 29141 29579 30541
Kava Kava, Piper methysticum: (Moderate) Kava kava, Piper methysticum does appear to have some anti-
thrombotic activity. Persons who are receiving anticoagulants should not take kava kava without first discussing use
with their health care professional. Kava kava, Piper methysticum exhibits antithrombotic activity and also inhibits
CYP isozymes important in warfarin clearance such as CYP2C9, 2C19, 1A2 and 3A4. Avoid concurrent use of herbs
which interact with warfarin when possible. If these herbal products are taken concurrently with warfarin, monitor
INR and adjust warfarin dosage to attain clinical and anticoagulant endpoints. 28836 28837
Ketoprofen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Ketorolac: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Lansoprazole; Naproxen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Lepirudin: (Major) An additive risk of bleeding may be seen in patients receiving other anticoagulants in
Levocetirizine: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to
Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may
affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and
therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For
patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be
carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium
consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment.
Supplemental oral sodium and fluid should be only be administered under careful medical supervision. 28654 55943
Lomustine, CCNU: (Moderate) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an
additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. 5170 5279 7668
Loratadine: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the
Loratadine; Pseudoephedrine: (Minor) Antihistamines may partially counteract the anticoagulant actions of
Magnesium Salicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors
(e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is frequently
Meclofenamate Sodium: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Mefenamic Acid: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Meloxicam: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Methoxsalen: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of
photosensitizing agents used in photodynamic therapy. 6625
Methylprednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs such as
increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM.
Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians
should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants such as
warfarin until data confirming the safety of MSM in patients taking these drugs are available. During one of the
available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using
anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume
methylsulfonylmethane, MSM while receiving warfarin should be observed for increased bleeding. 32984 32986
Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants through reduction of
procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored, especially when
methyltestosterone treatment is initiated or discontinued. 29883
Mifepristone: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants
is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these
circumstances. When mifepristone is used chronically for other conditions, such as Cushing's disease, an interaction
with heparin is not expected; however, follow usual cautions and monitor as per standard of care. 28003 48697
Miltefosine: (Moderate) Caution is advised when administering miltefosine with anticoagulants, as use of these
drugs together may increase risk for bleeding. Miltefosine, when administered for the treatment of visceral
leishmaniasis, has been associated with thrombocytopenia; monitor platelet counts in patients receiving treatment
for this indication. In addition, monitor closely for increased bleeding if use in combination with an anticoagulant.
56867
Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Mycophenolate: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents
which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
4873
Nabumetone: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Nandrolone Decanoate: (Moderate) Androgens can enhance the effects of anticoagulants. Dosage of the
anticoagulant may have to be decreased in order to maintain prothrombin time at the desired therapeutic level.
When anabolic steroid or androgen therapy is started or stopped in patients on anticoagulant therapy, close
monitoring is required. Additionally, nandrolone decanoate may generate a pharmacodynamic interaction with
warfarin by independently affecting the activity of circulating coagulation proteins. Androgens reduce the amount or
activity of circulating coagulant proteins thereby enhancing the anticoagulant effect of warfarin. 23809
Naproxen: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Naproxen; Pseudoephedrine: (Moderate) An additive risk of bleeding may be seen in patients receiving
40621 49946
Naproxen; Sumatriptan: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in
Natural Antineoplastics: (Moderate) Due to the risk of bleeding with natural antineoplastics, patients should receive
other agents that may increase the risk of bleeding, such as anticoagulants. 5279 6639
Nebivolol; Valsartan: (Minor) Concomitant use of valsartan with other drugs that may increase potassium
Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen
in patients receiving concomitant anticoagulants. 8493
Nicotine: (Minor) Nicotine may partially counteract the anticoagulant actions of heparin, according to the product
labels. However, this interaction is not likely of clinical significance in most patients since heparin therapy is
Nintedanib: (Moderate) Nintedanib is a VEGFR inhibitor and may increase the risk of bleeding. Monitor patients
who are taking anticoagulants closely and adjust anticoagulation therapy as necessary. Use nintedanib in patients
with known risk of bleeding only if the anticipated benefit outweighs the potential risk. 58203
Nitroglycerin: (Minor) At high doses, nitroglycerin may interfere with the anticoagulant effect of heparin.
Intravenous nitroglycerin can induce heparin resistance. Monitor for lack of heparin efficacy if these drugs are
administered concurrently. However, this interaction is not likely of clinical significance since heparin therapy is
adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient. 56872 61121
Nonsteroidal antiinflammatory drugs: (Moderate) An additive risk of bleeding may be seen in patients receiving
40621 49946
Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all
events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding
concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially
during the first cycle. 56353
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and anticoagulants when the platelet count is less
than 50,000 cells/microliter due to an increased risk of bleeding. 52213
Oritavancin: (Severe) Use of intravenous unfractionated heparin for 120 hours (5 days) after oritavancin
administration is contraindicated. Although oritavancin has no effect on the coagulation cascade, it does interfere
with some coagulation tests by binding to and preventing activation of coagulation by phospholipid reagents
commonly used in laboratory tests. The activated partial throboplastin time (aPTT) is artificially elevated for up to
120 hours (5 days) after oritavancin dosing. Consider use of an alternate anticoagulant, as appropriate. For patients
who require aPTT monitoring within 120 hours (5 days) after oritavancin use, a non-phospholipid dependent
coagulation test, such as Factor Xa, which is chromogenic, may be considered. 57741
Orlistat: (Moderate) Patients on chronic stable doses of anticoagulants, like heparin, should be monitored closely for
changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR,
and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in
patients treated concomitantly with orlistat and anticoagulants. 27971 60877
Oxandrolone: (Moderate) An increased effect of anticoagulants may occur with oxandrolone; the anticoagulant
dosage may need adjustment downward with oxandrolone initiation or adjustment upward with oxandrolone
discontinuation to maintain the desired clinical effect. Oxandrolone suppresses clotting factors II, V, VII, and X,
which results in an increased prothrombin time. An increase in plasminogen-activator activity, and serum
concentrations of plasminogen, protein C, and antithrombin III have occurred with several 17-alpha-alkylated
androgens. For example, concurrent use of oxandrolone and warfarin may result in unexpectedly large increases in
the INR or prothrombin time (PT). A multidose study of oxandrolone (5 or 10 mg PO twice daily) in 15 healthy
individuals concurrently treated with warfarin resulted in significant increases in warfarin half-life and AUC; a 5.5-
fold decrease in the mean warfarin dosage from 6.13 mg/day to 1.13 mg/day (approximately 80 to 85% dose
reduction) was necessary to maintain a target INR of 1.5. According to the manufacturer, if oxandrolone therapy is
initiated in a patient already receiving warfarin, the dose of warfarin may need to be decreased significantly to
reduce the potential for excessive INR elevations and associated risk of serious bleeding events. The patient should
be closely monitored with frequent evaluation of the INR and clinical parameter, and the dosage of warfarin should
be adjusted as necessary until a stable target INR is achieved. Careful monitoring of the INR and necessary
adjustment of the warfarin dosage are also recommended when the androgen therapy is changed or discontinued.
28549 47397
Oxaprozin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Palifermin: (Moderate) The co-administration of palifermin and unfractionated heparin may result in a 4 to 5-fold
increase in palifermin exposure; however, this interaction does not appear to affect the pharmacodynamics of either
drug. If heparin is used to maintain an IV line, rinse the line with saline prior to and after palifermin administration.
The palifermin AUC value was increased by 5-fold and the mean clearance was decreased by 80% after a single 60
mcg/kg dose of palifermin was administered with therapeutic levels of unfractionated heparin compared with no
heparin in 27 healthy subjects. The activated partial thromboplastin time (aPTT) was not affected by this interaction.
The palifermin AUC value was increased by 425% and the palifermin clearance, volume of distribution, and half-life
was decreased by 76.5%, 73.1%, and 38.8%, respectively, following the administration of palifermin 40 mcg/kg/day
for 3 days in combination with therapeutic levels of unfractionated heparin compared with no heparin in 31 healthy
subjects. Palifermin administration results in a dose-dependent epithelial cell proliferation that may be assessed by
Ki67 immunohistochemical staining. In this study, the pharmacokinetics of palifermin did not affect Ki67 expression
in buccal biopsies. The co-administration of palifermin and low-molecular weight heparins (LMWHs), such as
enoxaparin and dalteparin, is expected to have a similar interaction. 54912
Pentosan: (Major) Pentosan is a weak anticoagulant. Pentosan has 1/15 the anticoagulant activity of heparin. An
additive risk of bleeding may be seen in patients receiving other anticoagulants (e.g., heparin, warfarin) in
combination with pentosan. 40043 41347
Phentermine; Topiramate: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin,
dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more
frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe
bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or
coagulation. 28378
Photosensitizing agents: (Minor) Drugs that decrease clotting, such as anticoagulants, could decrease the efficacy of
photodynamic therapy. 6625 6751
Piperacillin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the
risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The
8348
Piperacillin; Tazobactam: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may
increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively
rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an
increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the
intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR.
Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially
during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin. 28549
57681 57682 6749 6750 8348
Piroxicam: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Porfimer: (Minor) Drugs that decrease clotting, such as anticoagulants, could decrease the efficacy of photodynamic
therapy. 6625 6751
Potassium Phosphate: (Moderate) Use potassium phosphates cautiously with heparin, as both drugs increase serum
potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with
impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
57713 57714 57715
Potassium Phosphate; Sodium Phosphate: (Moderate) Use potassium phosphates cautiously with heparin, as both
drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly
patients or patients with impaired renal function. Patients should have serum potassium concentration
determinations at periodic intervals. 57713 57714 57715
Potassium: (Moderate) In some cases, heparin can cause hyperkalemia. Chronic heparin therapy may predispose a
patient to develop hyperkalemia, especially patients with renal impairment and those receiving potassium-
containing medications, such a potassium salts. Monitoring of serum potassium is recommended as indicated. 25529
Potassium-sparing diuretics: (Moderate) Simultaneous use of a potassium-sparing diuretic with heparin can
increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitoring of serum potassium is
recommended as indicated. 2173 5873
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Prasterone (DHEA) is contraindicated

for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone
is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial
infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these
conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the
human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production
of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several
anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone
or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors,
including aspirin, ASA should be monitored for side effects or the need for dosage adjustments. 30054
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone (DHEA) is contraindicated for

use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is
also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial
infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these
conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the
human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production
of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several
anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone
or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors,
including aspirin, ASA should be monitored for side effects or the need for dosage adjustments. 30054
Prasugrel: (Moderate) Based on the mechanism of actions of prasugrel and unfractionated heparin or low-molecular
weight heparins (LMWHs), patients receiving these medications in combination may be at increased risk of
bleeding. The concurrent use of prasugrel and a single 100 unit/kg intravenous dose of heparin did not disrupt
coagulation or the inhibition of platelet aggregation; however, the bleeding time increased compared with
monotherapy of either medication. Use caution when administering prasugrel with medications that may increase
the risk of bleeding, such as unfractionated heparin or LMWH. 36055
Prednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Prednisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids
Protamine: (Severe) Upon contact with heparin, protamine forms a salt, neutralizing the anticoagulant effect of both
drugs. Protamine, a strongly basic compound, forms complexes with heparin sodium or heparin calcium, which are
acidic compounds. Formation of this complex can result in disruption of the heparin-antithrombin III complex
responsible for the anticoagulant activity of heparin. Protamine is used therapeutically to reverse the activity of
heparins. 6862
Reteplase, r-PA: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and
Rivaroxaban: (Major) Due to the increased bleeding risk, avoid concurrent use of rivaroxaban with heparin; the
safety of concomitant use has not been studied. If heparin is used during therapeutic transition periods, closely
observe patients and promptly evaluate any signs or symptoms of blood loss. 41347 44854
Rofecoxib: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Sacubitril; Valsartan: (Minor) Concomitant use of valsartan with other drugs that may increase potassium
Salicylates: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin,
ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is frequently administered
in combination with low-dose aspirin therapy to patients who have had an acute myocardial infarction and in other
disease states. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional
risk factor for bleeding. 28440 41347
Salsalate: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin,
ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is frequently administered
in combination with low-dose aspirin therapy to patients who have had an acute myocardial infarction and in other
disease states. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional
risk factor for bleeding. 28440 41347
Sedating H1-blockers: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin,
according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is
Selective serotonin reuptake inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the
concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like heparin. Case reports and
epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin
reuptake and gastrointestinal bleeding. 28260 28269 28270 28343 32127 47184
Serotonin norepinephrine reuptake inhibitors: (Moderate) Advise patients of the increased bleeding risk associated
with the concomitant use of serotonin norepinephrine reuptake inhibitors (SNRIs) and anticoagulants like heparin.
Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with
serotonin reuptake and gastrointestinal bleeding. 28275 29934 34940 55469
Sodium Hyaluronate, Hyaluronic Acid: (Moderate) Increased bruising or bleeding at the injection site may occur
when using hyaluronate sodium with anticoagulants, including heparin, especially if used within the 3 weeks prior to
the procedure. 45808 45809 45817 45819
Sodium Iodide: (Moderate) Anticoagulants may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1
week after administrations. 48920
Spironolactone: (Moderate) Simultaneous use of a potassium-sparing diuretic with heparin can increase the risk of
Streptokinase: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and
Sulfinpyrazone: (Major) Sulfinpyrazone should be avoided when possible with concurrent anticoagulants, thrombin
inhibitors, and thrombolytic agents due to potential for increased bleeding risk. Alternative uricosuric agents may be
considered. Sulfinpyrazone is a platelet inhibitor and exhibits antithrombotic actions in addition to its uricosuric
effects. Additive hematological effects are possible as a result of the platelet inhibitory effects of sulfinpyrazone; the
sulfide metabolite of sulfinpyrazone appears responsible for this effect. Sulfinpyrazone is also known to markedly
potentiate the effect of warfarin. Sulfinpyrazone may inhibit CYP2C9, leading to a decrease in the clearance of S-
warfarin. If concurrent therapy is warranted, significant initial dosage reductions (e.g., 50%) of warfarin may be
necessary, with further dosage adjusted based on INR values. The INR should be closely monitored during
concurrent therapy with warfarin, particularly during the initiation or termination phases of sulfinpyrazone
treatment. 23809 28549 62479
Sulindac: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Telavancin: (Severe) Concomitant use of intravenous unfractionated heparin infusions and telavancin is
contraindicated as the activated partial thromboplastin time (aPTT) test results are expected to be artificially
prolonged for 0 to 18 hours after telavancin administration. Although telavancin does not increase bleeding risk and
has no effect on platelet aggregation, it does interfere with some coagulation tests by binding to and preventing
activation of coagulation by phospholipid reagents commonly used in laboratory tests. For patients who require
aPTT monitoring while being treated with telavancin, a nonphospholipid dependent coagulation test, such as a
Factor Xa (chromogenic) assay, or an alternative anticoagulant not requiring aPTT monitoring may be considered.
36615
Tenecteplase: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and
Terfenadine: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the
Tetracyclines: (Minor) Tetracyclines may partially counteract the anticoagulant actions of heparin, according to the
product labels. However, this interaction is not likely of clinical significance in most patients since heparin therapy is
Thrombolytic Agents: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and
Ticagrelor: (Moderate) Because ticagrelor inhibits platelet aggregation, a potential additive pharmacodynamic effect
for bleeding exists if ticagrelor is given in combination with other agents that affect hemostasis such as heparin. No
significant pharmacokinetic changes were seen with ticagrelor was coadministered with heparin 100 international
units and enoxaparin 1 mg/kg, and the manufacturer states ticagrelor may be administered with unfractionated
heparin and low molecular weight heparins. 44951
Ticarcillin: (Moderate) Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the
risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The
Ticarcillin; Clavulanic Acid: (Moderate) Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may
increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively
rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an
increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the
intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR.
Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially
during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin. 28549
5182 57681 57682 6766
Ticlopidine: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists
if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. In clinical trials
of cardiac stenting, patients were treated with heparin and ticlopidine concomitantly for 12 hours. The tolerance and
long term safety of coadministered ticlopidine with these drugs has not been established. Per the manufacturer of
ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug
should be discontinued prior to the administration of ticlopidine. 5166
Tinzaparin: (Major) An additive risk of bleeding may be seen in patients receiving other anticoagulants in
combination with tinzaparin. 28478 41347
Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving anticoagulants.
In clinical trials, there have been reports of intracranial bleeding, including fatalities, in HIV infected patients
receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other
medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or
alcoholism/alcohol abuse) or were receiving concomitant medications, including anticoagulants, that may have
caused or contributed to these events. 8102
Tirofiban: (Moderate) Concomitant use of tirofiban and other agents that effect hemostasis, such as anticoagulants,
other platelet inhibitors, NSAIDs, and thrombolytic agents, may be associated with an increased risk of bleeding. In
addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. In clinical trials with tirofiban, many patients received aspirin and heparin concomitantly. In these studies,
the combination of tirofiban with heparin and aspirin has been associated with an increase in bleeding compared to
heparin and aspirin alone. While administering tirofiban and heparin, the aPTT should be checked 6 hours after the
start of the heparin infusion; heparin should be adjusted to maintain the aPTT approximately 2-times control. No
information is available about the concomitant use of tirofiban with thrombolytic agents. 5170 6891
Tolmetin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not
recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid
correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis). 35780
Topiramate: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran)
may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently
reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events,
patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. 28378
Trazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking
trazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner.
Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin
uptake by platelets; however, the absolute risk is not known. It would be prudent for clinicians to monitor the INR
and patient's clinical status closely if trazodone is added to or removed from the regimen of a patient stabilized on
anticoagulant therapy. 38831
Treprostinil: (Moderate) When used concurrently with anticoagulants, treprostinil may increase the risk of bleeding.
6960
Tretinoin, ATRA: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving
Triamcinolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and
Triamterene: (Moderate) Simultaneous use of a potassium-sparing diuretic with heparin can increase the risk of
Urokinase: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and
Valdecoxib: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination
Valsartan: (Minor) Concomitant use of valsartan with other drugs that may increase potassium concentrations, such
as heparin, may lead to increases in serum potassium. 29130
Vasopressin, ADH: (Minor) Heparin can decrease the antidiuretic response to vasopressin. 5784
Verteporfin: (Minor) Drugs that decrease clotting, such as anticoagulants, could decrease the efficacy of
photodynamic therapy. 6625 6751
Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking
vilazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner.
Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin
uptake by platelets; however, the absolute risk is not known. In addition, both vilazodone and warfarin are highly
protein bound, which may result in displacement of warfarin from protein binding sites and an increased
anticoagulant effect. It would be prudent for clinicians to monitor the INR and clinical status of the patient closely if
vilazodone is added to or removed from the regimen of a patient stabilized on warfarin. 43177 4996 5279
Vorapaxar: (Major) Avoid concomitant use of vorapaxar and warfarin or other anticoagulants. Because vorapaxar
inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with
other agents that affect hemostasis such as anticoagulants. 57151
Vorinostat: (Moderate) Concomitant use of vorinostat with anticoagulants may result in an additive risk of bleeding
due to vorinostat-induced thrombocytopenia; monitor patients closely. 32789
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion,
possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis,
hematomas, petechiae, hemorrhage) in patients receiving anticoagulants. Bleeding events related to drugs that
inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be
instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with anticoagulants
and to promptly report any bleeding events to the practitioner. Co-administration of vortioxetine and warfarin has
not been shown to significantly affect the pharmacokinetics of either agent. 56041
Warfarin: (Major) An additive risk of bleeding may be seen in patients receiving other anticoagulants in combination
with heparin. Heparin and warfarin therapies often overlap with no serious sequelae, although the risk of bleeding is
nonetheless increased. It should be noted that heparin also can prolong prothrombin time. When heparin and
warfarin are administered concomitantly, wait at least 5 hours after the last IV heparin dose or 24 hours after the
last subcutaneous heparin dose before drawing blood to obtain prothrombin time. 28549 41347 56872
Last revised: August 14, 2019
Reacciones adversas
adrenocortical insufficiency
alopecia
anaphylactic shock
anaphylactoid reactions
anemia
bleeding
bone fractures
bronchospasm
chills
elevated hepatic enzymes
epistaxis
erythema
fever
GI bleeding
headache
hematemesis
hematoma
hematuria
hyperkalemia
hyperlipidemia
hyphema
hypoaldosteronism
injection site reaction
intracranial bleeding
lacrimation
melena
myocardial infarction
nausea
ocular hemorrhage
osteoporosis
petechiae
priapism
prolonged bleeding time
pruritus
pulmonary embolism
purpura
retroperitoneal bleeding
rhinitis
skin necrosis
skin ulcer
stroke
subdural hematoma
thrombocytopenia
thromboembolism
thrombosis
urticaria
vaginal bleeding
vitamin D deficiency
vomiting
The most serious adverse reaction associated with heparin therapy is bleeding, which can occur at any site. This can
involve minor bleeding, such as bleeding from the gums or hematuria, or frank hemorrhage. Repeated flushing of a
catheter device with heparin can result in systemic effects, including anticoagulation and bleeding. Withdrawing the
drug can usually control an overly prolonged bleeding time or minor bleeding during therapy. Adverse bleeding
events include epistaxis, GI bleeding, hematoma, purpura, petechiae, unexplained bruising, heavy menstrual/vaginal
bleeding, or prolonged bleeding from cuts or wounds. Back pain, abdominal pain, anemia, hematuria, melena,
hematochezia, and hematemesis can indicate internal hemorrhage. If bleeding is serious, heparin therapy should be
discontinued, and protamine can be administered as a heparin antagonist. Retroperitoneal bleeding, intracranial
bleeding (e.g., subdural hematoma), or ovarian (corpus luteum) hemorrhage can be difficult to detect. Adrenal
hemorrhage, with resultant acute adrenocortical insufficiency, has occurred during anticoagulant therapy.
Therefore, discontinue heparin treatment in patients who develop signs and symptoms of acute adrenal hemorrhage
and insufficiency. Do not delay initiation of corrective therapy for laboratory confirmation, as any delay in treatment
during an acute situation may result in death. Although rare, massive ocular hemorrhage has been reported in
patients with pre-existing disciform macular degeneration receiving systemic anticoagulants, such as heparin.
Subconjunctival hemorrhage and spontaneous hyphema have also been reported.41675 56872
Thrombocytopenia is a well-known complication of heparin therapy. The reported incidence of thrombocytopenia

during heparin therapy is 30% or less. Some data suggest that heparin from bovine sources is associated with a
higher incidence of thrombocytopenia than is heparin from porcine origin.23542 Thrombocytopenia can present in 2
forms: an early, benign, reversible nonimmune thrombocytopenia and a late, more serious IgG-mediated immune
thrombocytopenia. Mild nonimmune thrombocytopenia generally occurs about days 2 to 4 of therapy. In
nonimmune heparin-associated thrombocytopenia, the decrease in platelet count may be mild and of no obvious
clinical significance; the platelet count may recover despite continued heparin treatment. In contrast, the immune
form of heparin-induced thrombocytopenia (HIT) is characterized by IgG-mediated platelet activation and usually
occurs after the 5th day of therapy. Although the precise frequency of immune-mediated HIT is uncertain, data in
orthopedic patients indicate a frequency of about 5% for unfractionated heparin, compared to about 1% with low-
molecular weight heparin. In patients previously unexposed to heparin, the platelet count usually begins to decline 5
to 10 days after starting heparin therapy in a patient with immune-mediated HIT. However, thrombocytopenia may
occur within 24 hours of initiation of heparin in patients who have been previously exposed to heparin therapy,
especially if heparin was administered within the previous 3 months. A platelet decrease of greater than 50% from
baseline is considered indicative of HIT. In patients with immune-mediated HIT, platelet aggregation is greatly
increased and the patient can develop thrombotic complications (white-clot syndrome). Thrombosis development
shortly after documenting thrombocytopenia is a characteristic finding in approximately half of all patients with
HIT. Thrombosis can occur while the platelet count is declining, but before the onset of overt thrombocytopenia,
which may occur a few days later. Therefore, thrombosis may be the initial manifestation of HIT and may be
accompanied by severe thromboembolic complications such as erythematous skin plaques, epidermal necrosis,
gangrene of extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke, thrombus
formation on a prosthetic cardiac valve, and possibly death. HIT-associated thrombosis occurs in about 1% of
patients who receive therapeutic doses of IV heparin for 5 days or more. An even higher frequency (2.4%) has been
reported in orthopedic patients receiving heparin prophylaxis. Venous thromboembolism is more common than
arterial (approximate ratio 4:1). Venous limb gangrene is characterized by distal tissue losses associated with
extensive venous thrombosis that involves both large veins and small venules. Bilateral adrenal hemorrhagic
necrosis can occur in patients with HIT and should be considered in any patient who complains of abdominal pain or
unexplained low blood pressure during heparin therapy. If the platelet count falls in a manner consistent with
immune-mediated HIT, all heparin therapy (including heparin flushes) should be stopped and an alternative
management strategy initiated. Avoid future heparin use in patients with a diagnosis of HIT, especially within 3 to 6
months of diagnosis and while patients test positive for antibodies. Following discontinuation of heparin, the median
time to platelet count recovery to normal is about 4 days; about 90% of patients recover by 1 week, although in rare
cases, the platelet count may not return to normal for several weeks. HIT can occur up to several weeks after the
discontinuation of heparin therapy, and patients presenting with thrombocytopenia or thrombosis after heparin
discontinuation should also be evaluated for HIT. Because the incidence of thrombosis is high even following
discontinuation of heparin, consideration should be given to using an alternate anticoagulant (e.g., danaparoid,
lepirudin).25334 41675
Generalized hypersensitivity reactions have been reported with heparin use. Fever, chills, and urticaria are the most
common manifestations; however, bronchospasm, rhinitis, lacrimation, headache, nausea, vomiting, and
anaphylactoid reactions, including anaphylactic shock, may also occur. (_WPS/RefShow.aspx?rid=56872)56872 Itching
and burning, especially on the plantar site of the feet, may occur. Histamine-like reactions have been observed at the
site of heparin injection. Also, episodes of painful, ischemic, and cyanosed limbs have been reported and attributed
to allergic vasospastic reactions; it is unclear whether these reactions are separate from or related to
thrombocytopenia-associated reactions. (_WPS/RefShow.aspx?rid=41347)41347
Heparin is known to inhibit aldosterone synthesis. Although heparin's effect on aldosterone synthesis is not usually
clinically important, there have been cases of heparin-induced hypoaldosteronism leading to hyperkalemia and
other metabolic abnormalities reported.25529 In 2 of these patients, heparin was administered for less than 6 weeks.
In a third case, the patient received heparin for 4 years and died from the consequences of hypoaldosteronism.
Osteoporosis has been reported in patients receiving long-term administration of high doses of heparin 56872 ; this is
particularly concerning during infancy, childhood, and adolescence, periods of active bone development. When
possible, the chronic use of unfractionated heparin should be avoided in pediatric patients. There have been a few
reports of heparin-induced osteoporosis in pediatric patients; however, these reports were complicated by additional
risk factors.49232 Significant reduction in bone density has been reported in about 30% of adult patients and
symptomatic bone fractures occur in 2% to 3% of adult patients receiving heparin for 1 month or more.25334 In
animal studies, unfractionated heparin has been found to stimulate bone resorption in addition to decreasing bone
formation.44702
Dermatologic reactions that may occur during heparin therapy include skin ulcer, hematoma, erythema, skin
plaques, and skin necrosis. Pruritus and burning, especially on the plantar side of the feet may occur. Delayed,
transient alopecia has been reported.41675 Although skin lesions usually occur at the sites of heparin injection (i.e.,
injection site reaction), there have been rare reports of necrosis at sites remote from heparin injection. Severe
injection site reactions are more commonly associated with intramuscular injections or deep subcutaneous
injections. Skin lesions usually develop 5 days or more following subcutaneous heparin administration. The delayed
onset is consistent with an immunologic reaction. Some patients with skin lesions have tested positive for HIT-IgG
even though they did not develop thrombocytopenia.25530 Patients who develop these delayed-onset skin lesions
may be at increased risk for serious systemic reactions or thrombotic events, accompanied by an abrupt fall in
platelet count, if they are given IV heparin.
Rebound hyperlipidemia on discontinuation of heparin therapy has been reported. Significantly elevated hepatic
enzymes (AST and ALT) have occurred in a high percentage of patients (including healthy subjects) receiving
heparin.51862 56872
Priapism has been reported with the use of heparin.25531 41675 However, it is unclear if the priapism was related to
heparin administration or to the underlying thrombotic condition.
Heparin inhibits the formation of 1,25(0H)2D by the kidneys and may lead to vitamin D deficiency. Monitoring of
vitamin D concentrations and supplementation with vitamin D may be necessary with prolonged therapy (i.e.,
greater than 1 month).63388
Last revised: July 18, 2019
Clasificaciones
Antithrombotic Agents
Blood and Blood Forming Organs
Heparins
Heparins For Flushing
Unfractionated Heparins
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Nombres del fármaco por país

Argentina
Calciparine - (Sanofi-Aventis)
Cervep - (Menarini)
Contractubex - (Andratx)
Croneparina - (Ivax)
Cycloparin - (Sidus)
Hepatriet - (Craveri)
Integrum - (Atlas)
Parinix - (Richmond)
Riveparin - (Rivero)
Serianon - (Fada)
Sobrius - (Fada)
Sodiparin - (Baxter Immuno)
Australia
Calcihep - (Aventis)
Calciparine - (Sanofi Synthelabo)
Caprin - (CSL)
Uniparin - (Aventis)
Austria
Ambenat - (Ratiopharm)
Calciparin - (Sanofi Synthelabo)
Contractubex - (Merz)
Derivon - (Wabosan)
Ichthalgan forte - (Ichthyol)
Lioton - (Menarini)
Lipohep - (CSC)
Liquemin - (Roche)
Pertrombon - (Gerot)
Sensicutan - (HWS OTC)
Thrombion - (Hofmann)
Thrombophob - (Nordmark)
Thrombophob - (Sanova)
Thrombophob-S - (Sanova)
Venoruton Heparin - (Novartis Consumer)
Vetren - (Takeda)
Viatromb - (Scan-Cargo)
Belgium
Calparine - (Sanofi-Aventis)
Liquemine - (Roche)
Thrombophob - (Knoll)
Brazil
Actparin - (Bergamo)
Alimax - (Cristalia)
Contractubex - (Biolab Sanus)
Disotron - (Ariston)
Hemofol - (Cristalia)
Hepamax - (Blau)
Heptar - (Eurofarma)
Liquemine - (Roche)
Parinorth - (Itaca)
Trombofob - (Abbott)
Venalot H - (Takeda)
Canada
Calcilean - (Organon Teknika)
Calciparine - (Anglo-French Laboratories)
Hepalean - (Merck)
Hepalean-Lok - (Schering-Plough)
China
Hepudiod - (Bausch & Lomb)
Jipailin - (Huadong)
Kai Rui - (Bausch & Lomb)
Li Mai Qing - (Zhaoke)
Mei De Xi - (Cui Sheng)
Qi Zheng - (Qilu)
Sai Bo Li - (Saibaoer)
Sai Luo Xi Ping - (Huakang)
Su Ke Nuo - (Wan Bang)
Czech Republic
Dolo-Rubriment - (Nordmark)
Hepa-Gel - (Lichtenstein)
Hepa-Salbe - (Lichtenstein)
Lioton - (Menarini)
Lipohep - (Medicom)
Sensicutan - (Harras-Curarina)
Trombex - (Leciva)
Viatromb - (Cyathus)
Finland
Hepaflex - (Baxter)
Trombosol - (Orion)
France
Cutheparine - (Biosedra)
Esberiven - (CSP)
Flector Tissugel Héparine - (Genevrier)
Liquemine - (Roche)
Percase - (Millot-Solac)
Percase-L - (Millot-Solac)
Germany
Ariven - (Beiersdorf-Lilly)
Arnica Kneipp Salbe - (Kneipp)
Arthro-Menthoneurin - (Tosse)
Arthroforte - (Azuchemie)
Calciparin - (Sanofi-Aventis)
Cur-Heparin - (Curarina)
Cycloarthrin - (Schaper & Brummer)
Depot-Thrombophob-N - (Knoll)
Dolo-Spondyril - (Dorsch)
Doloneuro-Gel plus - (Cascan)
Dolorgiet-plus - (Dolorgiet)
Enelbin-Salbe forte - (Cassella-med)
Enelbin-Venen Salbe - (Cassella-med)
Essaven 60 000 - (Cassella-med)
Etrat Sportsalbe - (Schwab)
Exhirud Heparin - (Winthrop)
Fibraflex - (Orion)
Hemeran - (Novartis Consumer)
Hepa-Gel - (Winthrop)
Hepa-Salbe - (Winthrop)
Hepaplus - (Hexal)
Heparin Plus - (Heumann)
Hepathromb - (Riemser)
Hepathrombin - (Teofarma)
Ichthalgan - (Ichthyol)
Juwoment Sport - (Serum-Werk Bernburg)
Liquemin N - (Roche)
Logomed Sport-Gel - (Logomed)
Logomed Venen-Salbe - (Logomed)
Ostochont - (Godecke)
Parin-POS - (Ursapharm)
Pentavenon - (Godecke)
Perivar Venensalbe - (Ipsen)
Phlogase - (Godecke)
Praecivenin - (Pfleger)
Rheuma-Enelbin - (Cassella-med)
Sensicutan - (Harras-Curarina)
Sportino - (Harras-Curarina)
Sportofit - (Gry)
Thrombareduct - (Sandoz)
Thrombo-Enelbin N - (Cassella-med)
Thrombo-Vetren - (Promonta)
Thrombophob - (Nordix)
Traumalitan - (3M)
Trirutin - (Strathmann)
Turgostad - (Stada)
Varicylum - (Liebermann)
Vascularin - (Boehringer Ingelheim)
Venalitan - (Meda)
Venalot - (Schaper & Brummer)
Venelbin N - (Hoechst)
Venoflexil - (Nycomed)
Venoruton Emulgel - (Novartis Consumer)
Venothromb - (Alcon-Thilo)
Vetren - (Madaus)
Zuk Hepagel, Zuk Hepasalbe - (Tosse)
Greece
Contractubex - (Pharmacare)
Croneparina - (UCB)
Hep Lok - (IFET)
Hepsal - (IFET)
Monoparin - (IFET (ΙΦΕΤ))
Multiparin - (IFET (ΙΦΕΤ))
Pump-Hep - (IFET (ΙΦΕΤ))
Hong Kong
Acme - (Unicorn)
Bruise-Ease - (Unicorn)
Eva - (Unicorn)
Heparub - (Unicorn)
Hiruderm - (Meyer)
Hurosil - (Unicorn)
Hypatin - (Meyer)
Lasopar - (Meyer)
Lioton - (Menarini)
Multiparin - (LCH)
Reparcol - (Meyer)
Sonlactubex - (Unicorn)
Tana-Bruise Cream - (Unicorn)
Vaxcel Heparin Sodium - (Kotra)
Hungary
Heparibene - (Teva)
Lioton - (Menarini)
India
Beparine - (Biological E)
Beprin - (Taj)
Bioclot - (Elfin)
Blockasol - (Shree Ganesh)
Caprin - (Samarth)
Cathflush - (Troikaa)
Contractubex - (Win-Medicare)
Declot - (Zydus)
Hep - (Gland)
Heparen - (Claris)
Hepgel - (Gland)
Heplock - (Gland)
Hexilak - (Menarini)
Ignava - (Health Biotech)
Inhep - (Sun)
Keparin - (Neon)
Line Flush - (CMG)
No-Clot - (Elfin)
Nuparin - (Troikaa)
Thrombophob - (Zydus)
Indonesia
Hico - (Ifars)
Inviclot - (Fahrenheit)
Thrombogel - (Tunggal Idaman)
Thrombophob - (Nordmark)
Ireland
Calciparine - (Sanofi)
Hep-Rinse - (Leo)
Heplok - (Leo)
Hepsal - (Technopharm)
Minihep - (Leo)
Monoparin - (CP Pharmaceuticals)
Multiparin - (Technopharm)
Pump-Hep - (Leo)
Unihep - (Leo)
Uniparin - (CP Pharmaceuticals)
Israel
Calciparin - (Choay)
Italy
Ateroclar - (Medibase)
Bioclaril - (GNR)
Calciparina - (Italfarmaco)
Calcipor - (Ibirn)
Chemyparin - (SIT)
Clarisco - (Teofarma)
Croneparina - (UCB)
Disebrin - (Tubilux)
Ecabil - (Mayne)
Ecafast - (Crinos)
Ecasolv - (SF)
Emoklar - (Savio)
Epacalcica - (Ibirn)
Eparical - (Aventis)
Eparinlider - (Scharper)
Eparinovis - (INTES)
Eparven - (Pantafarm)
Epsoclar - (Hospira)
Epsodil - (Biologici Italia)
Epsodilave - (Hospira)
Eudipar - (CT)
Facocinerin - (Difa)
Flebogamma - (IBP)
Flebs - (Pierre Fabre)
Flusolv - (Ecobi)
Hemofluss - (Fonten)
Hepacal - (Benedetti)
Isoclar - (Boniscontro & Gazzone)
Lioton - (Sanofi-Aventis)
Liquemin - (Roche)
Mica - (Epifarma)
Normoparin - (Caber)
Pharepa - (Pharmatex)
Reoflus - (SF)
Sosefluss - (SoSe)
Trombolisin - (Progen)
Veracer - (Medic)
Xantervit Eparina - (SIFI)
Zepac - (Ist. Chim. Inter.)
Malaysia Heparinol - (Ain Medicare)

Unihepa - (CCM)
Mexico
Helberina - (Galen)
Hep-Tec - (Tecnofarma)
Heparth - (20th Century)
Inhepar - (Pisa)
Proparin - (Probiomed)
Netherlands
Calparine - (Sanofi Synthelabo)
Liquemin - (Roche)
Minihep - (Leo)
Tromboliquine - (Organon Teknika)
New Zealand
Minihep - (CSL)
Monoparin - (Artex)
Multiparin - (Artex)
Norway
Hepaflex - (Baxter)
Nycoheparin - (Leo)
Philippines
Hemastat - (Karnataka)
Hepastal - (Stallion)
Heprin - (Gland)
Heptin - (Mustafa)
Kabihep - (Gland)
Lioton - (Transfarma)
Meparin - (Medchem)
Nuparin - (Troikaa)
Poland
Alcepalan - (Herbapol Poznan)
Cepan - (Unia)
Coaparin - (Polfa Warszawa)
Fortiven Activ - (Hasco-Lek)
Heparizen - (Ziaja)
Lioton - (Menarini)
Lioven Max - (PharmaSwiss)
Lipohep - (Medagro)
Tointex - (GSK)
Portugal
Calciparina - (Sanofi Synthelabo)
Russian Federation Contractubex - (Merz)

Lavenum - (Sintez)
Lioton - (Menarini)
Trombless - (Nizpharm)
South Africa
Calciparine - (Adcock Ingram)
Pularin - (Allen & Hanburys)
Thrombophob - (Hoechst Marion Roussel)
Thrombophob - (Winthrop)
Spain
Calciparina - (Sanofi Synthelabo)
Darkinal - (Llorente)
Liquemine - (Roche)
Menaven - (Menarini)
Sol Dial Perit - (Grifols)
Sweden
Noparin - (Novo Nordisk)
Switzerland
Assan - (Permamed)
Assan thermo - (Permamed)
Butaparin - (Streuli)
Demovarin - (Vifor)
Dolo-Arthrosenex - (Dermapharm)
Gelparin - (Streuli)
Gorgonium - (Drossapharm)
HepaSpray - (Spirig)
Hépabuzone - (Spirig)
Hépagel - (Spirig)
Héparinol - (Streuli)
Hépasol - (Sandoz)
Keppur - (Drossapharm)
Lioton - (Menarini)
Liquémine - (Drossapharm)
Lyman Mono - (Drossapharm)
Ruscovarin - (Alpinamed)
Sportium uno - (Lyron)
Sportusal assan thermo - (Permamed)
Swidro Rusco - (Alpinamed)
Thrombophob - (Knoll)
Venalot - (Asta Medica)
Turkey
Calciparine - (Sanofi Synthelabo)
Contractubex - (Assos)
Koparin - (Kocak)
Liparin-S - (Bilim)
Liquemine - (Roche)
Nevparin - (Nevzat)
Poliparin - (Polifarma)
Seloparin - (Haver)
Vasparin - (Defarma)
Ukraine
Heparil - (Arterium)
Lioton - (Berlin-Chemie)
Lyogel - (Phytopharm)
United Kingdom
Canusal - (Wockhardt)
Hep-Flush - (Leo)
Heplok - (Leo)
Hepsal - (Wockhardt)
Minihep - (Leo)
Monoparin - (Wockhardt)
Multiparin - (Wockhardt)
Pump-Hep - (Leo)
Unihep - (Leo)
Uniparin - (CP Pharmaceuticals)
Venezuela
Hirox - (Vargas)
Inhepar - (Pisa)
Liquemine - (Roche)
Riveparin - (Lapreven)
Copyright © 2019 Elsevier, Inc. Todos los derechos reservados.

Heparin - ClinicalKey

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Heparin - ClinicalKey

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28/10/2019 Heparin- ClinicalKey

Información proporcionada por Gold Standard

Affected cytochrome P450 isoenzymes: none

The half-life of heparin may be shorter in patients with pulmonary embolism.

Last revised: May 16, 2017

antiphospholipid antibody syndrome

arterial thromboembolism prophylaxis

coronary artery thrombosis prophylaxis

deep venous thrombosis (DVT)

deep venous thrombosis (DVT) prophylaxis

disseminated intravascular coagulation (DIC)

intravascular catheter occlusion prophylaxis

mural thrombosis prophylaxis

percutaneous coronary intervention (PCI)

prosthetic heart valves

pulmonary embolism prophylaxis

Converting to Oral Anticoagulants

Intravenous Infusion dosage (weight-based)

Children and Adolescents:

Neonates and Infants:

Intermittent intravenous dosage

Infants, Children, and Adolescents:

For thrombosis prophylaxis

for thrombosis prophylaxis, including arterial thromboembolism prophylaxis, during

for thrombosis prophylaxis, including arterial thromboembolism prophylaxis, during hemodialysis

Adolescents, Children, Infants, and Neonates:

for deep venous thrombosis (DVT) prophylaxis

5,000 units subcutaneous every 12 hours, starting 1 to 2 hours prior to surgery.25329

Female adults undergoing extensive gynecological surgery for malignancy:

5,000 units subcutaneously every 8 hours, starting 1 to 2 hours prior to surgery.25329

Adults undergoing major open urologic procedure (including high-risk):

Adults undergoing elective hip replacement surgery:

Adults undergoing hip-fracture surgery:

Adults undergoing neurosurgery:

Adults with acute myocardial infarction:

Adults with acute ischemic stroke and impaired mobility:

for deep venous thrombosis (DVT) prophylaxis in pregnant females

Surveillance and post partum anticoagulation.25402

Pregnant females with mechanical heart valves:

Intravenous or Subcutaneous dosage

for arterial thromboembolism prophylaxis in patients with prosthetic heart valves

Intravenous or Subcutaneous dosage

For intravascular catheter occlusion prophylaxis

to maintain patency of single and multiple-lumen catheters

Infants, Children, and Adolescents weighing more than 10 kg†:

Infants and Children weighing less than 10 kg†:

to maintain patency of peripheral catheters (i.e., heparin locks)

Infants, Children, and Adolescents weighing more than 10 kg†:

Infants and Children weighing less than 10 kg†:

to maintain patency of arterial lines

Infants, Children, and Adolescents†:

Use a final heparin concentration of 0.5 units/mL to run at 1 mL/hour IV.49232

to maintain line patency in patients receiving total parenteral nutrition (TPN)

TPN solution additive

Adolescents and Children†:

Neonates and Infants†:

For the treatment of disseminated intravascular coagulation (DIC)

Continuous Intravenous Infusion dosage

Children and Adolescents:

Neonates and Infants:

For the treatment of unstable angina

for patients receiving streptokinase or anistreplase (APSAC) concurrently

Subcutaneous dosage (streptokinase only)