Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.

25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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Bisoprolol Fumarate and d) Each film-coated tablet contains:

Bisoprolol fumarate USP 5mg
Hydrochlorthiazide Tablets Hydrochlorothiazide USP 12.5mg
USP 2.5mg/6.25mg, Excipients: q.s.
Colours: Yellow Oxide of Iron and Titanium
5mg/6.25mg, 10mg/6.25mg, Dioxide
5mg/12.5mg
For the full list of excipients, see section 6.1.
1. Name of the medicinal 3. Pharmaceutical form
product
Film-coated tablet.
Bisoprolol Fumarate and Hydrochlorthiazide
Tablets USP 2.5mg/6.25mg Taj Pharma 4. Clinical particulars
Bisoprolol Fumarate and Hydrochlorthiazide
Tablets USP 5mg/6.25mg Taj Pharma Therapeutic indications

Bisoprolol Fumarate and Hydrochlorthiazide Treatment of essential hypertension.

Tablets USP 10mg/6.25mg Taj Pharma
The fixed dose combinations are indicated
Bisoprolol Fumarate and Hydrochlorthiazide in patients whose blood pressure is not
Tablets USP 5mg/12.5mg Taj Pharma
adequately controlled on bisoprololfumarate
2. Qualitative and quantitative or hydrochlorothiazide alone.
composition 4.2 Posology and method of
administration
a) Each film-coated tablet contains:
Bisoprolol fumarate USP 2.5mg The fixed dose combination
Hydrochlorothiazide (bisoprololfumarate 5
USP 6.25mg
mg/hydrochlorothiazide 12.5 mg) may be
Excipients: q.s.
Colours: Yellow Oxide of Iron and Titanium administered in patients whose blood
Dioxide pressure is not adequately controlled by
bisoprololfumarate5 mgor
b) Each film-coated tablet contains: hydrochlorothiazide 12.5 mg. When
Bisoprolol fumarate USP 5mg clinically appropriate, direct change from
Hydrochlorothiazide USP 6.25mg
Excipients: q.s.
monotherapy to the fixed combination may
Colours: Yellow Oxide of Iron and Titanium be considered.
Dioxide
Posology
c) Each film-coated tablet contains:
Bisoprolol fumarate USP 10mg The usual starting dose is 5 mg
Hydrochlorothiazide USP 6.25mg bisoprolol/12.5 mg hydrochlorothiazide per
Excipients: q.s. day.
Colours: Yellow Oxide of Iron and Titanium
Dioxide
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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Individual dose titration with the The film-coated tablets are to be swallowed
components is recommended. whole with some liquid at breakfast.
The dose may be increased to 5 4.3 Contraindications
mgbisoprolol/ 12.5 mghydrochlorothiazide
• Hypersensitivity to the active substances,
per day, if necessary.
other thiazides, sulphonamides or to any
Elderly of the excipients listed in section 6.1.
• Acute heart failure or during episodes of
No dosage adjustment is normally required. heart failure decompensation requiring
It is recommended to start with the lowest IV inotropic therapy.
possible dose. • Cardiogenic shock.
• AV block of the 2nd or 3rd degree.
Renal or hepatic insufficiency • Sick sinus syndrome.
In patients with mild to moderate renal • Sinoatrial block.
insufficiency (creatinine clearance > 30 • Bradycardia with less than 60 beats/min
prior to the treatment.
ml/min) or mild to moderate hepatic
• Late stages of peripheral arterial
insufficiency preference may have to be
occlusive disease and Raynaud’s
given to the lower dosage
syndrome.
form (5 mg bisoprolol/12.5 mg • Severe bronchial asthma or severe
hydrochlorothiazide). However, in patients chronic obstructive pulmonary disease.
with mild to moderate impairment of the • Metabolic acidosis.
liver function monitoring is recommended • Refractory hypokalaemia.
(see section 4.4). • Severe hyponatraemia.
• Hypercalcaemia.
In co-existing impairment of kidney and • Severe renal insufficiency with oliguria
liver function the elimination of the or anuria (creatinine clearance < 30
hydrochlorothiazide component of the ml/min and/or serum creatinine > 1.8
bisoprololfumarate/hydrochlorothiazide is mg/100 ml).
reduced, so that preference may have to be • Acute glomerulonephritis.
given to the lower dose (see section 4.4). • Severe hepatic insufficiency including
hepatic precoma and coma.
Paediatric population • Untreated phaeochromocytoma (see
section 4.4).
There is no paediatric experience with • Lactation (see section 4.6)
bisoprololfumarate/hydrochlorothiazide, • Concomitant administration of
therefore its use cannot be recommended for floctafenine and sultopride (see section
children. 4.5).
• Gout.
Method of administration
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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4.4 Special warnings and precautions for Patients with psoriasis or with a history of
use psoriasis should only be given β-blockers
(e.g.
The cessation of therapy with β-blockers
(e.g. bisoprolol) should not be done abruptly bisoprolol) after carefully balancing the
unless clearly indicated. After long-term benefits against the risks.
therapy - particularly in the presence of
ischaemic heart disease - Under treatment with β-blockers (e.g.
bisoprololfumarate/hydrochlorothiazide bisoprolol) the symptoms of a
should be discontinued gradually (dividing thyrotoxicosis may be masked.
in half the dose over 7-10 days), since an
abrupt withdrawal may lead to an acute In patients with phaeochromocytoma β-
deterioration of the patient’s condition. blockers (e.g. bisoprolol) must not be
administered until after alpha-receptor
Patients with any of the following should be blockade.
monitored closely:
In patients undergoing general anaesthesia:
• Heart failure (in patients with
The anaesthetist must be aware of beta-
concomitant stable chronic heart failure
blockade. If it is thought necessary to
the treatment has to be initiated with the
withdraw beta-blocker therapy before
monopreparation of bisoprololfumarate
surgery, this should be done gradually and
using a special titration phase).
completed about 48 hours before
• Diabetes mellitus showing large anaesthesia. Patients undergoing
fluctuations in blood glucose values; concomitant treatment with inhalation
symptoms of glycaemia can be masked. anaesthetics should be monitored closely.
• Strict fasting.
• AV block of 1st degree. In bronchial asthma or other chronic
obstructive lung diseases, which may cause
• Prinzmetal’s angina. symptoms, bronchodilating therapy should
• Peripheral arterial occlusive disease be given concomitantly. Occasionally an
(intensification of the complaints might increase of the airway resistance may occur
happen especially during start of in patients with asthma; therefore the dose
therapy). of β2-stimulants may have to be increased.
• Hypovolaemia. Patients with bronchospasms (bronchial
• Reduced liver function. asthma, obstructive airway diseases) should
As with other beta-blockers, bisoprolol may be monitored closely.
increase both the sensitivity towards
If photosensitivity reactions occur, it is
allergens and the severity of anaphylactic
reactions. This also applies to recommended to protect exposed areas to
desensitisation therapy. Adrenaline the sun or to artificial UVA light. In severe
treatment may not always give the expected cases it may be necessary to stop the
therapeutic effect. treatment.
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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Due to the hydrochlorothiazide component (BCC) and squamous cell carcinoma (SCC)]
the long-term, continuous administration of with increasing cumulative dose of
bisoprololfumarate/hydrochlorothiazide hydrochlorothiazide (HCTZ) exposure has
may lead to disturbance of the fluid and been observed in two epidemiological
electrolyte balance, especially to studies based on the Danish National Cancer
hypokalaemia and hyponatraemia, further to Registry. Photosensitising actions of HCTZ
hypomagnesaemia and hypochloraemia, as could act as a possible mechanism for
well as hypercalcaemia. NMSC.

Hypokalaemia facilitates the development Patients taking HCTZ should be informed of

of severe arrhythmias, particularly torsades the risk of NMSC and advised to regularly
de points, which may be fatal. check their skin for any new lesions and
promptly report any suspicious skin lesions.
During long term-therapy with Possible preventive measures such as
bisoprololfumarate/hydrochlorothiazide, the limited exposure to sunlight and UV rays
serum electrolytes (especially potassium, and, in case of exposure, adequate
sodium, and calcium), creatinine and urea, protection should be advised to the patients
the serum lipids (cholesterol and in order to minimize the risk of skin cancer.
triglycerides), uric acid as well as blood Suspicious skin lesions should be promptly
glucose should be monitored regularly. examined potentially including histological
examinations of biopsies. The use of HCTZ
During treatment with bisoprololfumarate/ may also need to be reconsidered in patients
hydrochlorothiazide patients should ensure who have experienced previous NMSC (see
an adequate supply of fluid and food rich in also section 4.8).
potassium (e.g. bananas, vegetables, nuts) to
compensate for the increased loss of
potassium. The potassium losses may be 4.5 Interaction with other medicinal
reduced or prevented by concomitant products and other forms of interaction
therapy with potassium-sparing diuretics.
General information
In patients with hyperuricaemia the risk for
It should be considered that due to serum
attacks of gout may be increased.
potassium disturbances certain medicinal
Metabolic alkalosis may worsen due to products may be affected.
disturbance of fluid and electrolyte
haemostasis. Contraindicated combinations

In patients with cholelithiasis acute Floctafenine: Bisoprolol may inhibit

cholecystitis has been reported. compensatory cardiovascular reactions to
floctafenine-induced hypotonia or shock.
Non-melanoma skin cancer
An increased risk of non-melanoma skin
cancer (NMSC) [basal cell carcinoma
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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Sultopride: concomitant administration with IV erythromycin, halofantrine, pentamidine,

bisoprolol may lead to an increased risk for sparfloxacin, terfenadine, vincamine.
ventricular arrhythmia. Hypokalaemia may facilitate the occurrence
of torsades de pointes. In case of
Combinations not recommended hypokalaemia use medicinal products that
do not produce torsades de pointes.
Lithium:
Bisoprololfumarate/hydrochlorothiazide Combinations to be used with caution
may intensify the cardiotoxic and neurotoxic
Calcium antagonists such as
effect of lithium through a reduction of dihydropyridine derivatives (e.g.
lithium excretion. nifedipine): Concomitant use may increase
the risk of hypotension, and an increase in
Calcium antagonists such as the verapamil
the risk of a further deterioration of the
type and the diltiazem type: Negative
ventricular pump function in patients with
influence on contractility and atrio-
heart failure cannot be excluded.
ventricular conduction. Intravenous
administration of verapamil in patients on β- Concomitant use with other
blocker treatment may lead to profound antihypertensive agents or with other
hypotension and atrioventricular block. medicinal products with blood pressure
Centrally-acting antihypertensive agents lowering potential may increase the risk of
(e.g. reserpine, alpha-methyldopa, hypotension.
guanfacine, clonidine): Concomitant use of
centrally-acting antihypertensive agents may ACE inhibitors (e.g. enalapril, captopril),
lead to a further reduction in heart rate and Angiotensin II antagonists (e.g. losartan):
cardiac output and to vasodilatation. Abrupt Risk of significant fall in blood pressure
withdrawal may increase the risk of and/or acute renal failure during initiation of
'rebound hypertension'. These must not be ACE inhibitor therapy in patients with pre-
discontinued unless the use of existing sodium depletion (particularly in
bisoprololfumarate/ hydrochlorothiazide patients with renal artery stenosis).
was stopped some days before. This may be
then followed by the step-wise withdrawal If prior diuretic therapy has produced
of the centrally-acting antihypertensive sodium depletion, either stop the diuretic 3
agent. days before starting ACE inhibitor therapy,
or initiate ACE inhibitor therapy at a low
Monoamine oxidase inhibitors (except
dose.
MAO-B inhibitors): Enhanced hypotensive
effect of β-blockers but also risk of Class-I antiarrhythmic agents (e.g.
hypertensive crisis. disopyramide, quinidine): Effect on atrio-
ventricular conduction time may be
Non-antiarrhythmic medicinal products that potentiated and negative inotropic effect
may induce torsades de pointes: astemizole, increased.
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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Class-III antiarrhythmic agents (e.g. show increased sensitivity to cardiac

amiodarone): Effect on atrio- ventricular glycosides, thus leading to a potentiation of
conduction time may be potentiated. their effects and adverse effects of the
glycosides.
Antiarrhythmic medicinal products that may
produce torsades de pointes: Class IA
medicinal products (quinidine, Prostaglandin synthetase inhibiting
disopyramide), amiodarone, sotalol. Prevent medicinal products: Decreased hypotensive
and, if necessary, correct hypokalaemia. effects. In high-dose salicylate
Monitor QT interval. In case of torsades de administration the toxic effect of salicylates
pointes do not administer antiarrhythmics on the central nervous system may be
(electrical pacing). potentiated.
Parasympathomimetic medicinal products Non-steroidal anti-inflammatory drugs
(including tacrine): Atrio-ventricular (NSAIDs): NSAIDs may reduce the
conduction time and the risk of bradycardia hypotensive effect.
may be increased.
In patients developing hypovolaemia the
Topical β-blockers, including eye drops, concomitant administration of non-steroidal
may add to the systemic effects of anti-inflammatory medicinal products
bisoprolol. (NSAIDs) can trigger acute renal failure.
Insulin and oral antidiabetic agents: Beta-sympathomimetics: Combination with
Intensification of blood sugar lowering bisoprolol may reduce the effect of both
effect. Blockade of β-adrenoceptors may agents.
mask symptoms of hypoglycaemia.
Sympathomimetic medicinal products:
Anaesthetic agents: Attenuation of the reflex Combination with bisoprolol may reduce the
tachycardia and increase of the risk of effect of both medicinal products. Higher
hypotension. Continuation of β-blockade doses of epinephrine may be necessary for
reduces the risk of arrhythmia during treatment of allergic reactions.
induction and intubation. The
Sympathomimetics that activate both beta-
anaesthesiologist should be informed when
and alpha-adrenoceptors: Combination with
the patient is receiving a β-blocker (e.g.
bisoprolol may lead to blood pressure
bisoprolol) (see section 4.4).
increase. Such interactions are considered to
Digitalis glycosides: Prolongation of atrio- be more likely with nonselective beta-
ventricular conduction time, reduction in blockers.
heart rate. In hypokalaemia and/or
hypomagnesaemia developing during The concurrent use of
treatment with bisoprololfumarate/ bisoprololfumarate/hydrochlorothiazide and
hydrochlorothiazide the myocardium may potassium-wasting agents (e.g.
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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glucocorticoids, ACTH, carbenoxolone, Other concomitant treatment that should be

amphotericin B, furosemide or laxatives) used with caution: oral anticoagulants (the
may result in increased potassium losses. antithrombotic effect can be reduced by the
use of thiazides) and probenecid (diminished
Methyldopa: haemolysis due to the diuretic action).
formation of antibodies to
hydrochlorothiazide has been described in Combinations to be considered
isolated cases. Mefloquine: increased risk of bradycardia.
The effect of uric-acid-lowering medicinal Corticosteroids: Reduced antihypertensive
products may be attenuated in concomitant effect.
administration of
4.6 Fertility, pregnancy and lactation
bisoprololfumarate/hydrochlorothiazide.
Pregnancy
Cholestyramine, colestipol: reduces the
absorption of the hydrochlorothiazide There is limited experience with
component of hydrochlorothiazide or bisoprolol during
bisoprololfumarate/hydrochlorothiazide. pregnancy, especially during the first
trimester. Animal studies are insufficient for
Ergotamine derivatives: Exacerbation of hydrochlorothiazide and do not indicate any
peripheral circulatory disturbances. teratogenic effect with bisoprolol.

Tricyclic antidepressants, barbiturates, Bisoprolol, β-adrenoceptor blocking agents

phenothiazines: Increased blood pressure reduce placental perfusion, which has been
associated with growth retardation,
lowering effect.
intrauterine death, abortion or early labour.
Rifampicin: Slight reduction of the half -life Adverse reactions (e.g. hypoglycaemia,
of bisoprolol possible due to the induction of bradycardia) may occur in the foetus and
newborn infant. If treatment with β-
hepatic medicinal product-metabolising
adrenoceptor blocking agents is necessary,
enzymes. Normally a dosage adjustment is
those with better established safety profile
not necessary.
should be considered. The uteroplacental
The effect of curare-type muscle relaxants blood flow and foetal growth shouldbe
monitored. The newborn infant must be
may be potentiated or prolonged by
closely monitored. Symptoms of
bisoprololfumarate/hydrochlorothiazide. hypoglycaemia and bradycardia are
generally to be expected within the first 5
Cytostatics (e.g. cyclophosphamide,
days.
fluorouracil, methotrexate): increased bone
marrow toxicity is to be expected. Hydrochlorothiazide crosses the placenta.
Based on the pharmacological mechanism of
action of hydrochlorothiazide its use during
the second and third trimester may
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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compromise foeto-placental perfusion and Bisoprololfumarate/hydrochlorothiazide has

may cause foetal and neonatal effects like no or negligible influence on the ability to
icterus, disturbance of electrolyte balance drive and use machines.
and thrombocytopenia.
However, due to individual variations in
Hydrochlorothiazide should not be used for reactions to the medicinal product, the
gestational oedema, gestational hypertension ability to drive a vehicle or to operate
or preeclampsia due to the risk of decreased machinery may be impaired. This should be
plasma volume and placental hypoperfusion, considered particularly at start of therapy
without a beneficial effect on the course of and upon change of medication as well as in
the disease. conjunction with alcohol.

Hydrochlorothiazide should not be used for 4.8 Undesirable effects

essential hypertension in pregnant women
except in rare situations where no other The reported undesirable effects of this
treatment could be used. medicinal product are generally attributable
to its pharmacological effects.
Breast-feeding
These symptoms specially occur at the
Hydrochlorothiazide is excreted in human beginning of the therapy. They are generally
milk. So far it is not known whether mild and often disappear within 1-2 weeks.
bisoprolol is excreted in human milk.
Therefore this medicine must not be used Description of selected adverse reactions
during breast-feeding. Alternative treatments Non-melanoma skin cancer
with better established safety profiles during
breast-feeding are preferable, especially Based on available data from
while nursing a newborn or preterm infant. epidemiological studies, cumulative dose-
Hydrochlorothiazide can inhibit the milk dependent association between HCTZ and
production. NMSC has been observed (see also sections
4.4 and 5.1).
Fertility
Special notes
There are no nonclinical data with
hydrochlorothiazide and bisoprolol. Clinical signs of hypokalaemia: tiredness,
fatigue, muscular weakness, paraesthesia,
As with some other drugs used in the paresis, apathy, adynamia of smooth
treatment of hypertension, clinical reports
muscles with constipation, meteorism or
have suggested that hydrochlorothiazide and cardiac arrhythmia, paralytic ileus,
bisoprolol may occasionally induce
disturbances of consciousness, coma and
impotence in males. ECG alterations.
4.7 Effects on ability to drive and use
The therapy should be discontinued in:
machines
• Refractory disturbances of the electrolyte
balance.
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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• Orthostatic regulatory disturbances. Management

• Hypersensitivity reactions.
In general, if overdose occurs,
• Pronounced gastrointestinal complaints.
discontinuation of
• Central nervous disorder.
bisoprololfumarate/hydrochlorothiazide and
• Pancreatitis.
supportive and symptomatic treatment is
• Changes in blood count (anaemia, recommended.
leukopenia, thrombocytopenia).
• Acute cholecystitis. Bradycardia arising from an overdose is
• Occurrence of vasculitis. treated with atropine (1 mg to 2 mg
• Deterioration of existing myopia. intravenous), isoprenaline or temporarily
• Serum creatinine concentrations more with a pacemaker. The decrease of blood
than 1.8 mg/100 ml or creatinine pressure is treated with intravenous liquids
clearance ≤ 30 ml/min. and, if necessary, vasopressors such as
catecholamines.
Reporting of suspected adverse reactions
Bronchospasms can be treated with
theophylline, theophylline derivatives or -
Reporting suspected adverse reactions after
mimetic medicinal products.
authorisation of the medicinal product is
important. It allows continued monitoring of If a short time (0-2h) has passed from the
the benefit/risk balance of the medicinal overdose, active charcoal is given to the
product. patient and gastric lavage may be
4.9 Overdose considered. Heart rate, blood pressure,
electrolyte- and glucose balance has to be
Symptoms monitored. Haemodialysis does not
significantly increase the elimination of
The most common symptoms expected with bisoprolol. The degree to which
overdose of a beta-blocker include hydrochlorothiazide is removed by
bradycardia, hypotension, bronchospasm, haemodialysis has not been established.
acute cardiac insufficiency, hypoglycaemia
and conduction disorders on ECG. There is a 5.PHARMACOLOGICAL
wide inter -individual variation in sensitivity
to one single high dose of bisoprolol and PROPERTIES
patients with heart failure are probably very
sensitive. 5.1 Pharmacodynamic properties

The clinical picture in acute or chronic Pharmacotherapeutic group: Beta blocking

overdose of hydrochlorothiazide is agents, selective and thiazides
characterised by the extent of fluid and
Bisoprolol
electrolyte loss. Most common signs are
dizziness, nausea, somnolence, Bisoprolol is a beta-blocker which occupies
hypovolaemia, hypotension, hypokalaemia. an intermediate position with regard to
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lipophilia/ hydrophilia. Bisoprolol is highly The glomerular filtration rate is initially

β1-selective (“cardioselective”) without any diminished to a slight extent. During long-
intrinsic sympathomimetic activity (ISA) term therapy with hydrochlorothiazide, the
and without any clinically relevant calcium excretion via the kidneys is reduced
membrane-stabilising effect. Through so that hypercalcaemia may result.
blockade of cardiac β-receptors bisoprolol
depresses the response to Hydrochlorothiazide reduces the peripheral
sympathoadrenergic activity. This causes a resistance by relaxing smooth muscles of the
decrease in heart rate and in contractility and blood vessels.
thus a reduction of myocardial oxygen
consumption.
In patients with chronic renal insufficiency
Hydrochlorothiazide (creatinine clearance less than 30 ml/min
and/or serum creatinine above 1.8 mg/100
Hydrochlorothiazide is a benzothiadiazine ml) hydrochlorothiazide is practically
derivative which primarily increases ineffective. In patients with renal and ADH-
electrolyte excretion and secondarily sensitive diabetes insipidus,
enhances urinary flow by osmotically bound hydrochlorothiazide has an antidiuretic
water. effect.

The sodium transport from the renal tubule Non-melanoma skin cancer
to the blood is inhibited. This hinders
sodium reabsorption. The natriuretic effect Based on available data from
is accompanied by an increased potassium epidemiological studies, cumulative dose-
and magnesium excretion. dependent association between HCTZ and
NMSC has been observed. One study
Hydrochlorothiazide inhibits predominantly included a population comprised of 71,533
sodium absorption in the distal tubule, so cases of BCC and of 8,629 cases of SCC
that maximally about 15 % of the sodium matched to 1,430,833 and 172,462
undergoing glomerular filtration can be population controls, respectively. High
excreted. The extent of chloride excretion HCTZ use (≥ 50,000 mg cumulative) was
roughly corresponds to that of sodium associated with an adjusted OR of 1.29 (95
excretion. % CI: 1.23-1.35) for BCC and 3.98 (95 %
CI: 3.68- 4.31) for SCC. A clear cumulative
Hydrochlorothiazide also causes an increase dose response relationship was observed for
in potassium excretion which is essentially both BCC and SCC. Another study showed
determined by the potassium secretion in the a possible association between lip cancer
distal tubule and in the collecting tube (SCC) and exposure to HCTZ: 633 cases of
(increased exchange between sodium and lip-cancer were matched with 63,067
potassium ions). The saluretic or diuretic population controls, using a risk -set
effect of hydrochlorothiazide is not sampling strategy. A cumulative dose-
influenced to any appreciable extent by response relationship was demonstrated
acidosis or alkalosis. with an adjusted OR 2.1 (95 % CI: 1.7-2.6)
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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increasing to OR 3.9 (3.0-4.9) for high use Hydrochlorothiazide

(~25,000 mg) and OR 7.7 (5.7-10.5) for the
highest cumulative dose (~100,000 mg) (see After oral administration about 80 % of
also section 4.4). hydrochlorothiazide is absorbed from the
gastrointestinal tract. The systemic
5.2 Pharmacokinetic properties
availability is 71 ± 15 %.
Bisoprolol
The plasma protein binding of
The bioavailability of bisoprolol from the hydrochlorothiazide is 64 %; the relative
film coated tablets is about 90 %. Bisoprolol volume of distribution is 0.5-1.1 l/kg.
is absorbed almost completely (> 90 %)
from the gastrointestinal tract. Together In healthy humans more than 95 % of
with the very small first pass effect in the hydrochlorothiazide is excreted via the
liver (< 10 %) this results in an absolute kidneys as unchanged substance.
bioavailability of 88 %. Bisoprolol can be
taken on an empty stomach or with With normal kidney function the elimination
breakfast, without any change in the half-life is 9-13 hours. Peak plasma
absorption or bioavailability. The plasma concentrations are usually measured after 2-
protein binding of bisoprolol is about 30 %. 5 hours. This period increases in the
Pathophysiological changes in plasma presence of impaired kidney function and is
proteins like a1 glycoproteins, do not have about 20 hours in patients with terminal
an effect on the pharmacokinetics of
renal insufficiency.
bisoprolol. Peak plasma concentrations are
usually measured after 1-3 hours after The diuretic effect sets in within 1-2 hours
administration. Bisoprolol is only and lasts for 10-12 hours depending on the
moderately lipophilic, and therefore it binds
dose; the antihypertensive effect lasts for up
only weakly to plasma proteins, its
distribution volume being 226 ± 11 l (x ± to 24 hours.
SEM). 5.3 Preclinical safety data
Bisoprolol is removed from the organism via Bisoprolol or hydrochlorothiazide has not
two equally effective clearance routes: half been found to be hazardous to humans
of it is transformed into inactive metabolites according to the standard preclinical toxicity
in the liver with excretion of the metabolites tests (long term toxicity, mutagenicity,
via the genotoxicity and carcinogenicity tests). Like
other beta-blockers, bisoprolol at high doses
kidneys, and half are excreted as unchanged has been found in animal experiments to
substance via the kidneys. The plasma cause toxic effects to the mother (decreased
elimination half-life is 10-12 hours. The food intake and body weight gain) and to the
Cmax and AUC-values of bisoprolol in the embryo/foetus (increased late resorptions,
steady state are bioequivalent in the fixed reduced birth weight of the offspring,
combination with hydrochlorothiazide and retardation of the physical development up
in the monodrug preparation.
 Bisopr olol Fumarate and Hydr ochlorothia zide Tablets USP 2.5 mg/6. 25 mg, 5mg/ 6.25 mg, 10 mg/6. 25mg, 5mg/ 12.5 mg Tablets Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, Bisopr olol Fumarate and Hydr ochlorothia zide Dosage & Rx Info | Bisoprolol Fumarate and Hydrochlor othiazide Uses, Side E ffe cts – Constipati on, Bi sopr olol Fumarate and Hydr ochlorothia zide : Indications, Side E ffe cts, War nings, Bisoprolol Fumarate and Hy drochlorothia zide - Drug Infor mation – Taj P harma, Bisoprolol Fumarate and Hy drochlorot hiazide dose Taj pharma ceuti cals Bis oprol ol Fumarate a nd Hydrochl orothiazide i nteractions, Taj Phar maceutical Bi sopr olol Fumarate and Hydr ochlorothia zide contraindications, Bis oprol ol Fumarate a nd Hydrochl orothiazi de price , Bis oprol ol F umarate and Hydrochlor othiazide Taj Phar ma ACE inhi bitors Bis opr olol Fumarate and Hydr ochl orothiazi de Tablets P IL - Taj Phar ma. Stay conne cted to all updated on Bis oprol ol Fumarate and Hydrochl orothiazide
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to the end of lactation). However, bisoprolol Maharashtra chambers of Commerce Lane,

as well as hydrochlorothiazide were not Fort, Mumbai - 400001
teratogenic. There was no increase in at:Gujarat, INDIA.
toxicity when both components were given Customer Service and Product Inquiries:
in combination. 1-800-TRY-FIRST (1-800-222-434 & 1-
800-222-825)
6. PHARMACEUTICAL Monday through Saturday 9:00 a.m. to 7:00
p.m. EST
PARTICULARS E-mail: tajgroup@tajpharma.com
6.1 List of excipients

Tablet core
Microcrystalline cellulose, calcium
hydrogen phosphate, pregelatinised maize
starch, colloidal anhydrous silica,
magnesium stearate
Tablet coating
Hypromellose, dimeticone ,macrogol,
titanium dioxide, iron oxide red.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in the original package

Do not store above 30 °C

6.5 Special precautions for disposal and
other handling
No special requirements.
7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,