Bisogamma^® (Tablets) Instructions for Use

Marketing Authorization Holder

Woerwag Pharma GmbH & Co. KG (Germany)

Manufactured By

Magistra C&C (Romania)

ATC Code

C07AB07 (Bisoprolol)

Active Substance

Bisoprolol (Rec.INN registered by WHO)

Dosage Forms

	Bisogamma®	Film-coated tablets, 5 mg: 30 or 50 pcs.
		Film-coated tablets, 10 mg: 30 or 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light yellow in color, round, convex on one side, with a score on the other side, the tablet surface is beveled towards the score; the tablet can be divided into equal doses.

Excipients: crospovidone – 10 mg, pregelatinized starch – 15 mg, microcrystalline cellulose – 65 mg, colloidal silicon dioxide – 3 mg, magnesium stearate – 2 mg.

Film coating composition: macrogol 6000 – 0.158 mg, titanium dioxide (E171) – 1.842 mg, talc – 1.456 mg, iron (III) oxide yellow (E172) – 0.018 mg, hypromellose (HPMC) – 0.526 mg.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Film-coated tablets from yellow to orange in color, round, convex on one side, with a score on the other side, the tablet surface is beveled towards the score; the tablet can be divided into equal doses.

Excipients: crospovidone – 10 mg, pregelatinized starch – 15 mg, microcrystalline cellulose – 66.5 mg, colloidal silicon dioxide – 3 mg, magnesium stearate – 0.5 mg.

Film coating composition: macrogol 6000 – 0.7 mg, polysorbate 20 – 0.35 mg, titanium dioxide (E171) – 0.35 mg, calcium carbonate (E170) – 0.35 mg, talc – 0.35 mg, iron (III) oxide yellow (E172) – 0.12 mg, hypromellose (HPMC 5) – 1.68 mg, hypromellose – (HPMC 50) – 0.42 mg.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Beta-adrenergic blockers; selective beta-adrenergic blockers

Pharmacological Action

Selective beta₁-adrenergic blocker without intrinsic sympathomimetic activity, does not possess membrane-stabilizing activity. It reduces plasma renin activity, decreases myocardial oxygen demand, reduces heart rate (at rest and during exercise) and cardiac output, while stroke volume does not decrease significantly. It inhibits AV conduction. It has antianginal and antihypertensive effects. In high doses (200 mg and more), it can cause blockade of beta₂-adrenergic receptors, mainly in the bronchi and vascular smooth muscles.

The antihypertensive effect is associated with a decrease in minute blood volume, sympathetic stimulation of peripheral vessels, a decrease in the activity of the renin-angiotensin system (more important for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure, and an effect on the central nervous system.

The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate and contractility, prolongation of diastole, and improvement of myocardial perfusion.

The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP levels, arterial hypertension), a decrease in the rate of spontaneous excitation of the sinus and ectopic pacemakers, and slowing of AV conduction (mainly in the antegrade and, to a lesser extent, in the retrograde directions through the AV node) and via accessory pathways.

Pharmacokinetics

Absorption – 80-90%, food intake does not affect absorption.

C_max in blood plasma is reached after 2-4 hours. Plasma protein binding – 26-33%. Bisoprolol penetrates the blood-brain barrier and placental barrier to a small extent; it is excreted in breast milk.

It is metabolized in the liver.

T_1/2 – 9-12 hours. It is excreted by the kidneys – 50% unchanged, less than 2% – with bile.

Indications

Arterial hypertension, prevention of angina attacks, chronic heart failure.

ICD codes

Dosage Regimen

Determine the dosage individually based on clinical condition and therapeutic response.

For arterial hypertension and angina pectoris, initiate therapy with 5 mg once daily.

If the clinical effect is insufficient after 1-2 weeks, increase the dose to 10 mg once daily.

For chronic heart failure (NYHA class II-III), initiate treatment under close medical supervision.

Start with an initial dose of 1.25 mg (one-quarter of a 5 mg tablet) once daily.

If tolerated, titrate the dose upward at intervals of no less than two weeks.

Follow this titration sequence: 2.5 mg, 3.75 mg, 5 mg, 7.5 mg, to a maximum of 10 mg once daily.

In patients with severe hepatic impairment or severe renal impairment (CrCl <20 ml/min), do not exceed the maximum daily dose of 10 mg.

Administer the tablet in the morning, with or without food, with a sufficient amount of liquid.

The tablet is scored and can be divided into equal halves for dose titration.

Do not abruptly discontinue therapy; gradually reduce the dose over 1-2 weeks under medical supervision.

Adverse Reactions

From the nervous system: weakness, fatigue, dizziness, headache, sleep disorders, mental disorders (depression, rarely – hallucinations), feeling of cold and paresthesia in the extremities.

From the cardiovascular system: orthostatic hypotension, bradycardia, impaired AV conduction, appearance of heart failure symptoms, exacerbation of intermittent claudication and main clinical symptoms in Raynaud’s syndrome.

From the organ of vision: decreased secretion of tear fluid, conjunctivitis.

From the digestive system: diarrhea, constipation, nausea, abdominal pain.

From the musculoskeletal system: muscle weakness, muscle cramps.

From the skin and subcutaneous tissues: skin itching; in some cases – exacerbation of psoriasis manifestations, appearance of psoriasis-like rashes.

From the respiratory system: in predisposed patients, the appearance of symptoms of bronchial obstruction is possible.

Other: sweating, hot flashes, impaired potency, decreased glucose tolerance in patients with diabetes mellitus, allergic reactions.

Contraindications

Acute heart failure, chronic heart failure in the stage of decompensation, cardiogenic shock, collapse, AV block II and III degree (without a pacemaker), sick sinus syndrome; sinoatrial block, severe bradycardia (heart rate <50 beats/min), Prinzmetal's angina, pronounced decrease in blood pressure (systolic blood pressure <90 mm Hg), severe forms of bronchial asthma and COPD in history, late stages of peripheral circulation disorders, Raynaud's disease, pheochromocytoma (without simultaneous use of alpha-adrenergic blockers), metabolic acidosis, simultaneous use of MAO inhibitors (except for MAO type B inhibitors), children and adolescents under 18 years of age, hypersensitivity to bisoprolol and other beta-adrenergic blockers.

Use in Pregnancy and Lactation

Use during pregnancy and lactation is not recommended and is possible only when the expected benefit to the mother outweighs the potential risk of side effects in the fetus and child.

In exceptional cases of use during pregnancy, Bisoprolol should be discontinued 72 hours before the expected date of delivery due to the possibility of bradycardia, arterial hypotension, hypoglycemia, and respiratory depression in the newborn. If discontinuation is not possible, then the condition of the newborn should be carefully monitored for 72 hours after delivery.

If it is necessary to use bisoprolol during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

The dose should not exceed 10 mg/day in severe liver dysfunction.

Use in Renal Impairment

The dose should not exceed 10 mg/day in renal failure (creatinine clearance less than 20 ml/min).

Pediatric Use

Use in children is not recommended.

Special Precautions

Use with caution in psoriasis and with a history of psoriasis in the family, diabetes mellitus in the decompensation phase, and a predisposition to allergic reactions. In pheochromocytoma, the use of bisoprolol is possible only after taking alpha-adrenergic blockers. Sudden withdrawal of bisoprolol should be avoided; the course of treatment should be ended slowly with a gradual dose reduction. Before surgery, the anesthesiologist should be informed about treatment with bisoprolol.

Bisoprolol in a dose of more than 10 mg/day should be used only in exceptional cases.

This dose should not be exceeded in renal failure (creatinine clearance less than 20 ml/min) and severe liver dysfunction.

During treatment, alcohol consumption should be avoided.

Effect on the ability to drive vehicles and operate machinery

Use with caution in patients whose activities are associated with the need for concentration and high speed of psychomotor reactions.

Drug Interactions

With simultaneous use of antacids and antidiarrheal agents, a decrease in the absorption of beta-adrenergic blockers is possible.

With simultaneous use of antiarrhythmic agents, a sharp decrease in blood pressure, a decrease in heart rate, the development of arrhythmia and/or heart failure is possible.

With simultaneous use of antihypertensive agents, an enhancement of the antihypertensive effect is possible.

With simultaneous use of cardiac glycosides, conduction disturbances are possible.

With simultaneous use of sympathomimetics (including those contained in cough, nasal drops, and eye drops), the effectiveness of bisoprolol is reduced.

With simultaneous use of verapamil, diltiazem, a sharp decrease in blood pressure, a decrease in heart rate, the development of arrhythmia and/or heart failure is possible.

With simultaneous use of guanfacine, severe bradycardia and conduction disturbances are possible.

With simultaneous use of insulin and oral hypoglycemic agents, the effect of insulin or other hypoglycemic agents is enhanced (regular monitoring of blood glucose levels is necessary).

With simultaneous use of clonidine, severe bradycardia, arterial hypotension, and conduction disturbances are possible.

In case of sudden withdrawal of clonidine in patients receiving Bisoprolol, a sharp increase in blood pressure is possible.

With simultaneous use of nifedipine, other calcium channel blockers, dihydropyridine derivatives, the antihypertensive effect of bisoprolol is enhanced.

With simultaneous use of reserpine, alpha-methyldopa, severe bradycardia is possible.

With simultaneous use of rifampicin, a slight decrease in the T_1/2 of bisoprolol is possible.

With simultaneous use of ergotamine derivatives (including migraine remedies containing ergotamine), symptoms of peripheral circulation disorders are enhanced.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.