Co-Trimoxazole

Pronunciation
U.S. Brand Names
Generic Available
Canadian Brand Names
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Pregnancy/Breast-Feeding
Implications
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Stability
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Dietary Considerations
Test Interactions
Mental Health: Effects on Mental
Status
Mental Health: Effects on Psychiatric
Treatment
Dental Health: Local
Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental
Treatment
Patient Information
Nursing Implications
Dosage Forms
References

Pronunciation

U.S. Brand Names

Bactrim; Bactrim DS; Cotrim; Cotrim DS; Septra; Septra DS; Sulfatrim

Generic Available

Yes

Canadian Brand Names

Apo-Sulfatrim; Novo-Trimel; Nu-Cotrimox; Pro-Trin; Roubac; Trisulfa; Trisulfa-
S

Synonyms
SMZ-TMP; Sulfamethoxazole and Trimethoprim; TMP-SMZ; Trimethoprim and
Sulfamethoxazole

Pharmacological Index

Antibiotic, Sulfonamide Derivative

Use
Oral treatment of urinary tract infections due to E. coli, Klebsiella and Enterobacter sp,
M. morganii, P. mirabilis and P. vulgaris; acute otitis media in children and acute
exacerbations of chronic bronchitis in adults due to susceptible strains of H. influenzae or
S. pneumoniae; prophylaxis of Pneumocystis carinii pneumonitis (PCP), traveler's
diarrhea due to enterotoxigenic E. coli or Cyclospora

I.V. treatment or severe or complicated infections when oral therapy is not feasible, for
documented PCP, empiric treatment of PCP in immune compromised patients; treatment
of documented or suspected shigellosis, typhoid fever, Nocardia asteroides infection, or
other infections caused by susceptible bacteria

Unlabeled use: Cholera and salmonella-type infections and nocardiosis; chronic

prostatitis; as prophylaxis in neutropenic patients with P. carinii infections, in leukemics,
and in patients following renal transplantation, to decrease incidence of gram-negative
rod infections

Pregnancy Risk Factor

C; D (if used near term, per expert analysis)

Pregnancy/Breast-Feeding Implications

Do not use at term to avoid kernicterus in the newborn and use during pregnancy only if
risks outweigh the benefits since folic acid metabolism may be affected

Contraindications

Hypersensitivity to any sulfa drug or any component; porphyria; megaloblastic anemia

due to folate deficiency; infants <2 months of age; marked hepatic damage

Warnings/Precautions

Use with caution in patients with G-6-PD deficiency, impaired renal or hepatic function;
maintain adequate hydration to prevent crystalluria; adjust dosage in patients with renal
impairment. Injection vehicle contains benzyl alcohol and sodium metabisulfite. Fatalities
associated with severe reactions including Stevens-Johnson syndrome, toxic epidermal
necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias;
discontinue use at first sign of rash. Elderly patients appear at greater risk for more severe
adverse reactions. May cause hypoglycemia, particularly in malnourished, or patients
with renal or hepatic impairment. Use with caution in patients with porphyria or thyroid
dysfunction. Slow acetylators may be more prone to adverse reactions.

Adverse Reactions
>10%:

Dermatologic: Allergic skin reactions including rashes and urticaria, photosensitivity

Gastrointestinal: Nausea, vomiting, anorexia

1% to 10%:

Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis (rare)

Hematologic: Blood dyscrasias

Hepatic: Hepatitis

<1%: Confusion, depression, hallucinations, seizures, fever, ataxia, kernicterus in

neonates, erythema multiforme, stomatitis, diarrhea, pseudomembranous colitis,
pancytopenia, pancreatitis, rhabdomyolysis, thrombocytopenia, megaloblastic anemia,
granulocytopenia, aplastic anemia, hemolysis (with G-6-PD deficiency), cholestatic
jaundice, interstitial nephritis, serum sickness

Overdosage/Toxicology
Symptoms of acute overdose include nausea, vomiting, GI distress, hematuria,
crystalluria

Following GI decontamination, treatment is supportive; adequate fluid intake is essential;

peritoneal dialysis is not effective and hemodialysis only moderately effective in
removing co-trimoxazole

Drug Interactions
CYP2C9 enzyme inhibitor

Increased effect/toxicity: Phenytoin, cyclosporines (nephrotoxicity), methotrexate

(displaced from binding sites), dapsone, sulfonylureas, and oral anticoagulants; may
compete for renal secretion of methotrexate; digoxin concentrations increased

Stability
Do not refrigerate injection; is less soluble in more alkaline pH; protect from light; do not
use NS as a diluent; injection vehicle contains benzyl alcohol and sodium metabisulfite

5 mL/125 mL D5W = 6 hours

5 mL/100 mL D5W = 4 hours

5 mL/75 mL D5W = 2 hours

Mechanism of Action

Sulfamethoxazole interferes with bacterial folic acid synthesis and growth via inhibition
of dihydrofolic acid formation from para-aminobenzoic acid; trimethoprim inhibits
dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of
enzymes of the folic acid pathway

Pharmacodynamics/Kinetics
Absorption: Oral: 90% to 100%

Distribution: Crosses the placenta; distributes widely into body tissues, breast milk, and
fluids including middle ear fluid, prostatic fluid, bile, aqueous humor, and CSF

Protein binding: SMX: 68%; TMP: 68%

Metabolism: SMX is N-acetylated and glucuronidated; TMP is metabolized to oxide and

hydroxylated metabolites
Half-life: SMX: 9 hours; TMP: 6-17 hours, both are prolonged in renal failure

Time to peak serum concentration: Within 1-4 hours

Elimination: In urine as metabolites and unchanged drug

Usual Dosage
Dosage recommendations are based on the trimethoprim component

Mild to moderate infections: Oral, I.V.: 8 mg TMP/kg/day in divided doses every 12

hours

Serious infection/ Pneumocystis: I.V.: 20 mg TMP/kg/day in divided doses every 6 hours

Urinary tract infection prophylaxis: Oral: 2 mg TMP/kg/dose daily

Prophylaxis of Pneumocystis: Oral, I.V.: 10 mg TMP/kg/day or 150 mg TMP/m2/day in

divided doses every 12 hours for 3 days/week; dose should not exceed 320 mg
trimethoprim and 1600 mg sulfamethoxazole 3 days/week

Adults:

Urinary tract infection/chronic bronchitis: Oral: 1 double strength tablet every 12 hours
for 10-14 days

Sepsis: I.V.: 20 TMP/kg/day divided every 6 hours

Pneumocystis carinii:

Prophylaxis: Oral: 1 double strength tablet daily or 3 times/week

Treatment: Oral, I.V.: 15-20 mg TMP/kg/day in 3-4 divided doses

Dosing adjustment in renal impairment: Adults:

I.V.:

Clcr 15-30 mL/minute: Administer 2.5-5 mg/kg every 12 hours

Clcr <15 mL/minute: Administer 2.5-5 mg/kg every 24 hours

Oral:

Clcr 15-30 mL/minute: Administer 1 double strength tablet every 24 hours or 1 single
strength tablet every 12 hours

Clcr <15 mL/minute: Not recommended

Dietary Considerations

Should be administered with a glass of water on empty stomach

Test Interactions

creatinine (Jaff alkaline picrate reaction); increased serum methotrexate by

dihydrofolate reductase method
Mental Health: Effects on Mental Status

Rarely may cause depression, hallucination, or confusion; sulfonamides may cause

euphoria, restlessness, irritability, disorientation, panic, and delusions

Mental Health: Effects on Psychiatric Treatment

May rarely cause granulocytopenia; use caution with clozapine and carbamazepine

Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health: Effects on Dental Treatment

No effects or complications reported

Patient Information

Take oral medication with 8 oz of water on an empty stomach (1 hour before or 2 hours
after meals) for best absorption. Finish all medication; do not skip doses. You may
experience increased sensitivity to sunlight; use sunblock, wear protective clothing and
dark glasses, or avoid direct exposure to sunlight. Small frequent meals, frequent mouth
care, sucking lozenges, or chewing gum may reduce nausea or vomiting. Report skin
rash, sore throat, blackened stool, or unusual bruising or bleeding immediately.
Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Nursing Implications
Maintain adequate fluid intake to prevent crystalluria; infuse I.V. co-trimoxazole over 60-
90 minutes; must be further diluted 1:25 (5 mL drug to 125 mL diluent, ie, D5W); in
patients who require fluid restriction, a 1:15 dilution (5 mL drug to 75 mL diluent, ie,
D5W) or a 1:10 dilution (5 mL drug to 50 mL diluent, ie, D5W) can be administered

Monitor CBC, renal function test, liver function test, urinalysis

Dosage Forms
The 5:1 ratio (SMX to TMP) remains constant in all dosage forms:

Suspension, oral: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (20 mL,

100 mL, 150 mL, 200 mL, 480 mL)

Tablet: Sulfamethoxazole 400 mg and trimethoprim 80 mg

Tablet, double strength: Sulfamethoxazole 800 mg and trimethoprim 160 mg

References
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Infected With Human Immunodeficiency Virus. USPHS/IDSA Prevention of
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Bissuel F, Cotte L, Crapanne JB, et al, "Trimethoprim-Sulphamethoxazole Rechallenge in

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Domingo P, Ferrer S, Cruz J, et al, "Trimethoprim-Sulfamethoxazole-Induced Renal

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Fischl MA, Dickinson GM, and La Voie L, "Safety and Efficacy of Sulfamethoxazole and
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Hennessy S, Strom BL, Berlin JA, et al, "Predicting Cutaneous Hypersensitivity

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