Bidop^®Cor (Tablets) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Plc. (Hungary)

Manufactured By

Gedeon Richter-Rus, JSC (Russia)

Quality Control Release

GEDEON RICHTER-RUS, JSC (Russia)

Contact Information

GEDEON RICHTER Plc. (Hungary)

ATC Code

C07AB07 (Bisoprolol)

Active Substance

Bisoprolol (Rec.INN WHO registered)

Dosage Form

Bidop®Cor

Tablets 2.5 mg: 28 or 56 pcs.

Dosage Form, Packaging, and Composition

Tablets are white, oblong, with a score on both sides and the marking “BI” to the left of the score and the number “2.5” to the right of the score on one side. The tablet can be divided into equal doses.

Excipients: lactose monohydrate, microcrystalline cellulose, magnesium stearate, crospovidone.

14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Beta-adrenergic blockers; selective beta-adrenergic blockers

Pharmacological Action

Bisoprolol is a selective beta₁-adrenergic blocker without intrinsic sympathomimetic activity and does not have membrane-stabilizing action. In therapeutic doses, Bisoprolol has little affinity for the β₂-adrenoceptors of internal organs (pancreas, skeletal muscles, smooth muscle of peripheral arteries, bronchi, and uterus), as well as for the β₂-adrenoceptors involved in the regulation of metabolism.

Consequently, Bisoprolol (unlike non-selective beta-blockers) generally does not affect airway resistance, has a less pronounced effect on organs containing β₂-adrenoceptors and on carbohydrate metabolism, and does not cause sodium ion retention in the body. The severity of the atherogenic effect of bisoprolol does not differ from that of propranolol.

In therapeutic doses, Bisoprolol blocks cardiac β₁-adrenoceptors, reduces the catecholamine-stimulated formation of cAMP from ATP. It reduces the intracellular flow of calcium ions, and has negative chronotropic, dromotropic, bathmotropic, and a not clearly pronounced inotropic effect. Bisoprolol reduces heart rate at rest and during exercise, slows AV conduction, and reduces myocardial excitability. It reduces cardiac output and, to a small extent, stroke volume. It reduces myocardial oxygen demand and reduces plasma renin activity.

At the beginning of treatment, within the first 24 hours after taking bisoprolol, the total peripheral vascular resistance increases slightly (due to a reciprocal increase in α-adrenoceptor activity). After 1-3 days, the total peripheral vascular resistance returns to the initial level. With long-term therapy, the initially increased total peripheral vascular resistance decreases.

The maximum hemodynamic effect is achieved 3-4 hours after oral administration. When used once a day, the therapeutic effect of Bisoprolol persists for 24 hours due to its 10-12 hour plasma T_1/2.

Bisoprolol has the same electrophysiological effects as other beta-blockers. In electrophysiological studies, Bisoprolol slowed the heart rate, increased the conduction time and refractory periods of the sinoatrial and atrioventricular nodes. There is a prolongation of the RR and PQ intervals, as well as the corrected QT interval (QT_c) on the ECG (within normal limits).

Bisoprolol has antihypertensive, antiarrhythmic, and antianginal effects.

Pharmacokinetics

Absorption

Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. The bioavailability due to insignificant first-pass metabolism through the liver (approximately 10%) is about 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol demonstrates linear kinetics, and its plasma concentrations are proportional to the dose taken in the dose range from 5 to 20 mg.

C_max in plasma is reached 2-3 hours after oral administration.

Distribution

Bisoprolol is distributed quite widely. The V_d is 3.5 l/kg. Plasma protein binding reaches approximately 30%.

Metabolism

Bisoprolol is metabolized via the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites found in plasma and urine do not exhibit pharmacological activity.

Data obtained from experiments with human liver microsomes in vitro show that Bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), while the CYP2D6 isoenzyme plays only a minor role.

Excretion

The clearance of bisoprolol is determined by the balance between renal excretion unchanged (about 50%) and metabolism in the liver (about 50%) to metabolites, which are then also excreted by the kidneys. The total clearance is 15 l/h. The T_1/2 is 10-12 hours.

Pharmacokinetics in special patient groups

Renal impairment. In a study of patients with renal failure (mean creatinine clearance 28 ml/min), it was shown that a decrease in creatinine clearance is accompanied by an increase in the C_max, AUC, and T_1/2 of bisoprolol. Since the clearance of bisoprolol is equally carried out by the kidneys and liver, no significant accumulation of bisoprolol is noted in patients with mild to moderate renal impairment. In case of severe renal impairment (creatinine clearance <20 ml/min), accumulation may occur, and the drug dose should not exceed 10 mg/day.

Hepatic impairment. In patients with liver cirrhosis, high variability and a significant slowdown in elimination compared to healthy people are noted (the T_1/2 of bisoprolol ranges from 8.3 to 21.7 hours). Clinically significant differences in pharmacokinetics between patients with normal and impaired liver function were not identified. In case of severe hepatic impairment, accumulation may occur, and the drug dose should not exceed 10 mg/day.

Chronic heart failure. In patients with chronic heart failure (CHF) of functional class III according to the NYHA classification, higher plasma levels of bisoprolol and an increased T_1/2 were noted compared to healthy volunteers. The C_max of bisoprolol in plasma at steady state is 64±21 ng/ml at a daily dose of 10 mg; the T_1/2 is 17±5 hours. The pharmacokinetics of bisoprolol in patients with CHF and concomitant hepatic or renal impairment has not been studied.

Elderly age. In elderly patients, a slight increase in some pharmacokinetic parameters ( T_1/2, AUC, C_max) of bisoprolol is noted compared to young patients, presumably due to age-related decrease in renal clearance. However, these differences are not clinically significant and do not require correction of the bisoprolol dose.

Indications

For use in adults from 18 years of age

• Treatment of chronic heart failure.

ICD codes

Dosage Regimen

Bidop^®Cor should be taken orally once a day with a small amount of liquid in the morning before breakfast, during or after it. The tablets should not be chewed or crushed into powder.

The standard treatment regimen for CHF includes the use of ACE inhibitors or angiotensin II receptor antagonists (in case of intolerance to ACE inhibitors), beta-blockers, diuretics and, optionally, cardiac glycosides. Initiating treatment of CHF with Bidop^®Cor requires mandatory implementation of a special titration phase and regular medical supervision.

A prerequisite for treatment with Bidop^®Cor is stable CHF without signs of exacerbation.

Treatment of CHF with Bidop^®Cor is initiated according to the following titration scheme. In this case, individual adaptation may be required depending on how well the patient tolerates the prescribed dose, i.e., the dose can only be increased if the previous dose was well tolerated.

The recommended starting dose is 1.25 mg (0.5 tab. of 2.5 mg) once a day. Depending on individual tolerance, the dose should be gradually increased to 2.5 mg, 3.75 mg (1.5 tab. of 2.5 mg), 5 mg, 7.5 mg (3 tab. of 2.5 mg or 1.5 tab. of bisoprolol 5 mg with a score) and 10 mg (2 tab. of bisoprolol 5 mg or 1 tab. of bisoprolol 10 mg) once a day. To ensure the specified dosing regimen, the drug Bidop^® can be used. Each subsequent dose increase should be made no less than 2 weeks apart.

If the dose increase is poorly tolerated by the patient, a dose reduction is possible.

The maximum recommended dose for CHF is 10 mg of Bidop^®Cor once a day.

During titration, regular monitoring of blood pressure, heart rate, and the severity of CHF symptoms is recommended. Worsening of CHF symptoms is possible from the first day of drug use.

If the patient does not tolerate the maximum recommended dose of the drug well, a gradual dose reduction is possible.

During the titration phase or after it, temporary worsening of CHF, arterial hypotension, or bradycardia may occur. In this case, it is recommended first of all to adjust the doses of concomitant therapy drugs. It may also be necessary to temporarily reduce the dose of Bidop^®Cor or discontinue it.

After the patient’s condition stabilizes, dose re-titration should be performed or treatment should be continued.

Duration of treatment

Treatment with Bidop^®Cor is usually long-term therapy.

Renal or hepatic impairment

In case of mild or moderate hepatic or renal impairment, dose adjustment is usually not required.

In case of severe renal impairment (creatinine clearance less than 20 ml/min) and in patients with severe liver disease, the maximum daily dose is 10 mg.

Dose increase in such patients should be carried out with extreme caution.

Elderly patients

No dose adjustment is required.

Children

It is not recommended to prescribe Bidop^®Cor to children under 18 years of age, due to the lack of clinical experience with the drug in children.

To date, there is insufficient data regarding the use of bisoprolol in patients with CHF combined with type 1 diabetes mellitus, severe renal and/or hepatic impairment, restrictive cardiomyopathy, congenital heart defects, or heart valve disease with significant hemodynamic disorders. Also, sufficient data have not yet been obtained regarding patients with CHF with myocardial infarction within the last 3 months.

Adverse Reactions

The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000).

Nervous system disorders common – dizziness, headache; rare – loss of consciousness.

Psychiatric disorders uncommon – depression, insomnia; rare – hallucinations, nightmares.

Eye disorders: rare – reduced lacrimation (should be considered when wearing contact lenses); very rare – conjunctivitis.

Ear and labyrinth disorders rare – hearing impairment.

Cardiac and vascular disorders very common – bradycardia; common – worsening of CHF symptoms, feeling of coldness or numbness in the extremities, pronounced decrease in blood pressure; uncommon – AV conduction disturbance, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders uncommon – bronchospasm in patients with a history of bronchial asthma or airway obstruction; rare – allergic rhinitis.

Gastrointestinal disorders common – nausea, vomiting, diarrhea, constipation; rare – hepatitis.

Musculoskeletal and connective tissue disorders uncommon – muscle weakness, muscle cramps.

Skin and subcutaneous tissue disorders rare – hypersensitivity reactions such as pruritus, rash, skin hyperemia, angioedema; very rare – alopecia. Beta-blockers may exacerbate psoriasis symptoms or cause psoriasis-like rash.

Reproductive system and breast disorders rare – erectile dysfunction.

General disorders: common – asthenia, increased fatigue.

Investigations: rare – hypertriglyceridemia, increased activity of liver transaminases (ALT, AST).

Contraindications

• Hypersensitivity to bisoprolol or to any of the excipients included in the drug;
• Acute heart failure, chronic heart failure in the stage of decompensation, requiring inotropic therapy;
• Cardiogenic shock;
• Second- and third-degree AV block in patients without a pacemaker;
• Sick sinus syndrome;
• Sinoatrial block;
• Severe bradycardia (heart rate less than 60 beats/min) before the start of therapy;
• Severe arterial hypotension (systolic blood pressure less than 100 mm Hg);
• Severe forms of bronchial asthma;
• Severe peripheral arterial circulatory disorders or Raynaud’s syndrome;
• Pheochromocytoma (without simultaneous use of alpha-blockers);
• Metabolic acidosis;
• Age under 18 years (lack of clinical experience in children);
• Lactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

With caution

Desensitizing therapy, Prinzmetal’s angina, hyperthyroidism, type 1 diabetes mellitus and diabetes mellitus with significant fluctuations in blood glucose concentration, first-degree AV block, severe renal failure (creatinine clearance less than 20 ml/min), severe hepatic impairment, psoriasis, restrictive cardiomyopathy, congenital heart defects or heart valve disease with significant hemodynamic disorders, CHF with myocardial infarction within the last 3 months, mild and moderate peripheral arterial circulatory disorders, severe forms of COPD, non-severe forms of bronchial asthma, bronchospasm (in history), allergic reactions (in history), extensive surgical interventions and general anesthesia, pregnancy, strict diet.

Use in Pregnancy and Lactation

Pregnancy

The pharmacological effects of bisoprolol may adversely affect the course of pregnancy and the fetus/newborn. In general, beta-blockers reduce placental blood flow, which can lead to fetal growth retardation, intrauterine fetal death, or premature birth. Adverse events (such as hypoglycemia and bradycardia) may develop in the fetus and newborn.

If treatment with beta-blockers is necessary, selective beta₁-blockers should be preferred.

During pregnancy, Bisoprolol should be used only in case of absolute necessity, if the expected benefit to the mother outweighs the possible risk of side effects to the fetus and/or newborn. Placental and uterine blood flow should be monitored, and the growth and development of the unborn child should be observed. If adverse events occur in relation to pregnancy and/or the fetus, alternative methods of therapy are recommended.

The newborn should be carefully examined after delivery. Symptoms of bradycardia and hypoglycemia may occur during the first three days of life.

Breastfeeding period

According to preclinical studies, Bisoprolol and/or its metabolites are excreted in the milk of lactating rats. There are no data on the excretion of bisoprolol into breast milk. Therefore, the use of bisoprolol is not recommended for women during breastfeeding. If the use of bisoprolol during lactation is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

The drug should be used with caution in severe hepatic impairment.

Use in Renal Impairment

The drug should be used with caution in severe renal failure (creatinine clearance less than 20 ml/min).

Pediatric Use

It is not recommended to prescribe the drug to patients under 18 years of age, due to the lack of clinical experience with the drug in children.

Geriatric Use

No dose adjustment is required in elderly patients.

Special Precautions

Discontinuation of therapy and withdrawal syndrome

Treatment with bisoprolol should not be abruptly interrupted or the recommended dose changed without prior consultation with a doctor, as this may lead to a temporary deterioration in cardiac activity. Treatment should not be interrupted suddenly, especially in patients with coronary artery disease (worsening of angina attacks, development of myocardial infarction, and occurrence of ventricular arrhythmias have been observed in patients with coronary artery disease upon sudden discontinuation of beta-blockers). If discontinuation of treatment is necessary, the dose should be reduced gradually. In case of significant worsening of angina or development of acute coronary syndrome, bisoprolol should be temporarily resumed.

Diseases requiring cautious use of the drug

Bisoprolol should be used with caution in the following cases

• severe forms of COPD and non-severe forms of bronchial asthma;

• diabetes mellitus with significant fluctuations in blood glucose concentration: Bisoprolol may mask the symptoms of hypoglycemia (pronounced decrease in blood glucose concentration), such as tachycardia, palpitations, or increased sweating;

• strict diet;

• desensitizing therapy;

• first-degree AV block;

• vasospastic angina (Prinzmetal’s angina); cases of coronary spasm have been observed. Despite high beta₁-selectivity, angina attacks cannot be completely excluded when taking bisoprolol in patients with Prinzmetal’s angina, the drug should be taken with particular caution;

• mild and moderate peripheral arterial circulatory disorders (symptoms may increase at the beginning of therapy);

• psoriasis (including in history).

Cardiovascular system diseases

Beta-adrenoblockers should not be used in decompensated chronic heart failure until the patient’s condition has stabilized.

During the initial stages of bisoprolol use, patients require constant monitoring.

Beta-adrenoblockers can cause bradycardia. If the resting heart rate falls below 50-55 beats/min, the dose of bisoprolol should be reduced or its administration discontinued.

Like other beta-adrenoblockers, Bisoprolol can cause prolongation of the PQ interval on the ECG. Bisoprolol should be used with caution in patients with first-degree AV block.

Nonselective beta-adrenoblockers may increase the frequency and duration of anginal attacks in patients with vasospastic angina (Prinzmetal’s angina) due to alpha-receptor-mediated coronary artery vasoconstriction. Cardioselective beta₁-adrenoblockers (including Bisoprolol) should be used with caution in vasospastic angina.

To date, there is insufficient data regarding the use of bisoprolol in patients with CHF in combination with type 1 diabetes mellitus, severe impairment of renal and/or hepatic function, restrictive cardiomyopathy, congenital heart defects, or heart valve disease with significant hemodynamic disturbances. Also, sufficient data have not yet been obtained regarding patients with CHF with a myocardial infarction within the last 3 months.

Respiratory System

Although selective beta-adrenoblockers affect respiratory function less than nonselective beta-adrenoblockers, Bisoprolol should be prescribed to patients with COPD and mild forms of bronchial asthma with particular caution and only if the potential benefits of its use outweigh the potential risk. In bronchial asthma or COPD, the simultaneous use of bronchodilators is indicated.

In patients with bronchial asthma, an increase in airway resistance is possible, which requires a higher dose of beta₂-adrenomimetics.

In patients with COPD, Bisoprolol, prescribed as part of combination therapy for the treatment of heart failure, should be started at the lowest possible dose, and patients should be carefully monitored for the appearance of new symptoms (e.g., shortness of breath, exercise intolerance, cough).

Major Surgical Interventions and General Anesthesia

If surgical intervention is necessary, the anesthesiologist should be informed that the patient is taking beta-adrenoblockers (risk of drug interaction with the development of severe bradyarrhythmias, decreased reflex tachycardia, and arterial hypotension). It is recommended not to discontinue bisoprolol in the perioperative period without clear necessity (since beta-adrenoreceptor blockade reduces the risk of arrhythmias and myocardial ischemia during induction of anesthesia and tracheal intubation). If it is necessary to interrupt treatment with bisoprolol before surgery, the drug should be discontinued at least 48 hours before the operation.

Pheochromocytoma

In patients with pheochromocytoma, Bisoprolol may be prescribed only against the background of alpha-adrenoblockers.

Thyrotoxicosis

In hyperfunction of the thyroid gland, beta-adrenoblockers (including Bisoprolol) can mask tachycardia and reduce the severity of symptoms of thyrotoxicosis. Abrupt withdrawal of the drug can cause an exacerbation of disease symptoms and the development of a thyrotoxic crisis.

Hypersensitivity Reactions

Beta-adrenoblockers, including Bisoprolol, can increase sensitivity to allergens and the severity of anaphylactic reactions/hypersensitivity reactions due to the weakening of adrenergic compensatory regulation under the influence of beta-adrenoblockers. The use of conventional therapeutic doses of epinephrine (adrenaline) against the background of beta-adrenoblocker use does not always lead to the desired clinical effect. Caution is necessary when prescribing bisoprolol to patients with a history of severe hypersensitivity reactions or those undergoing a course of desensitization.

Psoriasis

When deciding on the use of bisoprolol in patients with psoriasis, the expected benefit from the use of the drug and the possible risk of exacerbation of psoriasis should be carefully weighed.

Contact Lenses

Patients using contact lenses should take into account that against the background of beta-adrenoblocker use, a decrease in the production of tear fluid is possible.

Effect on Ability to Drive Vehicles and Operate Machinery

Bisoprolol does not affect the ability to drive vehicles according to a study in patients with coronary artery disease. However, due to individual reactions, the ability to drive vehicles and operate machinery may be impaired. Particular attention should be paid to this at the beginning of treatment, after changing the dose, and also when consuming alcohol simultaneously.

Overdose

Symptoms

The most frequent symptoms of overdose: AV block, severe bradycardia, pronounced decrease in BP, bronchospasm, acute heart failure, and hypoglycemia.

Sensitivity to a single high dose of bisoprolol varies greatly among individual patients, and patients with CHF are likely to have high sensitivity.

Treatment

In case of overdose, it is first necessary to discontinue the drug and initiate supportive symptomatic therapy.

For severe bradycardia: IV administration of atropine. If the effect is insufficient, a medication with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be required.

For a pronounced decrease in BP: IV administration of plasma-substituting solutions and vasopressor drugs. IV administration of glucagon may be appropriate.

For AV block: patients should be under constant observation and receive treatment with beta-adrenomimetics such as epinephrine. If necessary, placement of an artificial pacemaker.

For exacerbation of CHF: IV administration of diuretics, drugs with a positive inotropic effect, and vasodilators.

For bronchospasm: use of bronchodilators, including beta₂-adrenomimetics and/or aminophylline.

For hypoglycemia: IV administration of dextrose (glucose).

Drug Interactions

Not Recommended Combinations

Class I antiarrhythmic drugs (e.g., quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) when used concomitantly with bisoprolol may reduce AV conduction and myocardial contractility.

Slow calcium channel blockers (CCBs) of the verapamil type and, to a lesser extent, diltiazem, when used concomitantly with bisoprolol, can lead to a decrease in myocardial contractility and impairment of AV conduction. In particular, IV administration of verapamil to patients taking beta-adrenoblockers can lead to severe arterial hypotension and AV block.

Centrally acting antihypertensive agents (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to a decrease in heart rate and cardiac output, as well as vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before discontinuation of beta-adrenoblockers, may increase the risk of developing “rebound” arterial hypertension.

Fingolimod may enhance the negative chronotropic effect of beta-adrenoblockers and lead to severe bradycardia. Concomitant use of fingolimod and metoprolol is not recommended. If concomitant use of fingolimod and the drug Bidop^®Cor is necessary, careful monitoring of the patient’s condition is required. It is recommended to initiate combination therapy in a hospital setting and carry out appropriate monitoring (prolonged heart rate control is indicated, at least until the morning of the next day after the first simultaneous intake of fingolimod and the drug Bidop^®Cor).

Combinations Requiring Special Caution

CCBs, dihydropyridine derivatives (e.g., nifedipine, felodipine, amlodipine) when used concomitantly with bisoprolol may increase the risk of developing arterial hypotension. In patients with CHF, the risk of subsequent worsening of cardiac contractile function cannot be excluded.

Class III antiarrhythmic drugs (e.g., amiodarone) may enhance the impairment of AV conduction.

The effect of topical beta-adrenoblockers (e.g., eye drops for glaucoma treatment) may enhance the systemic effects of bisoprolol (decreased BP, decreased heart rate).

Parasympathomimetics when used concomitantly with bisoprolol may enhance the impairment of AV conduction and increase the risk of developing bradycardia.

The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced. Signs of hypoglycemia, in particular tachycardia, may be masked or suppressed. Such interaction is more likely with the use of nonselective beta-adrenoblockers.

Agents for general anesthesia may increase the risk of cardiodepressive action, leading to arterial hypotension (see the “Special Instructions” section).

Cardiac glycosides when used concomitantly with bisoprolol may lead to an increase in impulse conduction time and, thus, to the development of bradycardia.

NSAIDs may reduce the antihypertensive effect of bisoprolol.

Concomitant use of the drug Bidop^®Cor with beta-adrenomimetics (e.g., isoprenaline, dobutamine) may lead to a reduction in the effect of both drugs.

The combination of bisoprolol with adrenomimetics affecting beta- and alpha-adrenoreceptors (e.g., norepinephrine, epinephrine) may enhance the vasoconstrictor effects of these drugs, mediated by alpha-adrenoreceptors, leading to an increase in BP. Such interaction is more likely with the use of nonselective beta-adrenoblockers.

Antihypertensive agents, as well as other agents with a possible antihypertensive effect (e.g., tricyclic antidepressants, barbiturates, phenothiazines), may enhance the antihypertensive effect of bisoprolol.

Mefloquine when used concomitantly with bisoprolol may increase the risk of developing bradycardia.

MAO inhibitors (except for MAO-B inhibitors) may enhance the antihypertensive effect of beta-adrenoblockers. Concomitant use may also lead to the development of a hypertensive crisis.

Combinations to be Considered

Ergot Alkaloids

Non-hydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders. Ergotamine increases the risk of developing peripheral circulatory disorders.

Pharmacokinetic Interaction

Pharmacokinetic studies have not revealed an interaction of bisoprolol with thiazide diuretics, such as hydrochlorothiazide, and cimetidine.

Bisoprolol did not affect the pharmacokinetics of theophylline.

Rifampicin increases the metabolic clearance and shortens the T_1/2 of bisoprolol, but no dose adjustment of the drug is required.

Bisoprolol does not affect prothrombin time in patients receiving a stable dose of warfarin.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date stated on the packaging.

Dispensing Status

The drug is dispensed by prescription.

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.