Nebivolol-Nanolek (Tablets) Instructions for Use

Marketing Authorization Holder

NANOLEK LLC (Russia)

Manufactured By

NANOLEK LLC (Russia)

ATC Code

C07AB12 (Nebivolol)

Active Substance

Nebivolol (Rec.INN registered by WHO)

Dosage Form

Nebivolol-Nanolek

Tablets 5 mg: 10, 20, 30, 60, or 90 pcs.

Dosage Form, Packaging, and Composition

Tablets white color, round, flat, with a score on one side.

Auxiliary substances : lactose monohydrate – 92.28 mg, corn starch – 45 mg, croscarmellose sodium – 10 mg, microcrystalline cellulose – 23.67 mg, magnesium stearate – 1 mg, colloidal silicon dioxide – 0.6 mg, povidone – 2 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.

Clinical-Pharmacological Group

Third-generation beta₁-adrenoblocker with vasodilating properties

Pharmacotherapeutic Group

Selective beta1-adrenergic blocker

Indications

• Essential hypertension: Nebivolol-Nanolek is indicated for the treatment of high blood pressure. It can be used as monotherapy or in combination with other antihypertensive agents.
• Chronic heart failure: The drug is used in the treatment of stable chronic heart failure of mild to moderate severity, as an adjunct to standard therapy, in patients aged 70 years and older. Treatment should be initiated and titrated by a physician experienced in the management of chronic heart failure.

The therapeutic effect in hypertension is primarily due to a reduction in peripheral vascular resistance, while maintaining cardiac output. In heart failure, nebivolol improves left ventricular function and reduces the risk of hospitalization for cardiovascular causes.

Contraindications

• Hypersensitivity to nebivolol or any of the excipients listed in the composition.
• Acute heart failure, cardiogenic shock, or decompensated chronic heart failure requiring intravenous inotropic therapy.
• Sick sinus syndrome, including sinoatrial block.
• Second or third-degree atrioventricular (AV) block, without a functioning pacemaker.
• Severe bradycardia (heart rate less than 60 beats per minute before initiation of therapy).
• Hypotension (systolic blood pressure below 90 mm Hg).
• Severe hepatic impairment (Child-Pugh class C).
• Severe peripheral arterial circulatory disorders and Raynaud’s syndrome.
• Metabolic acidosis.
• Concomitant use with floctafenine or sultopride.
• Pheochromocytoma (unless treated with alpha-blockers).

Patients with bronchospastic diseases (e.g., bronchial asthma, chronic obstructive pulmonary disease) should generally not receive beta-blockers. However, if use is deemed necessary, nebivolol may be used with extreme caution under close medical supervision due to its relative beta1-selectivity.

Dosage Regimen

For essential hypertension: The recommended starting dose is 5 mg once daily, preferably taken at the same time each day. The antihypertensive effect is usually seen within 1-2 weeks. If the desired therapeutic response is not achieved, the dose may be increased to 10 mg once daily. The maximum recommended daily dose is 10 mg. In elderly patients and those with renal impairment, no initial dose adjustment is typically required. For patients with moderate hepatic impairment, the recommended initial dose is 2.5 mg once daily; dose escalation should be performed with caution.

For chronic heart failure: Treatment must be initiated with a strict titration phase. The starting dose is 1.25 mg once daily. The dose should be increased gradually, at 1-2 week intervals, if the previous dose is well tolerated. The recommended titration steps are: 1.25 mg → 2.5 mg → 5 mg → 10 mg once daily. The maximum recommended dose is 10 mg once daily. During titration, the patient’s blood pressure, heart rate, and signs of worsening heart failure should be closely monitored. If a side effect occurs, temporary dose reduction or interruption of therapy may be necessary.

Tablets can be divided into equal doses. The drug can be taken with or without food.

Adverse Reactions

Adverse reactions are listed below by system organ class and frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Nervous system disorders: Very common – headache, dizziness. Common – paresthesia, insomnia. Uncommon – depression, nightmares.

Cardiac disorders: Common – bradycardia, heart failure (in patients with chronic heart failure), AV block (first degree), edema of the lower extremities. Uncommon – severe bradycardia, postural hypotension.

Vascular disorders: Common – hypotension. Uncommon – cold extremities, Raynaud’s phenomenon.

Gastrointestinal disorders: Common – diarrhea, constipation, nausea, dyspepsia, flatulence.

General disorders and administration site conditions: Common – asthenia, fatigue. Uncommon – visual disturbances.

Investigations: Common – increased triglyceride levels.

As with other beta-blockers, adverse reactions such as bronchospasm, sexual dysfunction, and masking of hypoglycemia symptoms in patients with diabetes mellitus may occur, although these are less common with nebivolol due to its beta1-selectivity and vasodilatory properties.

Drug Interactions

Concomitant use with other antihypertensive agents (e.g., diuretics, ACE inhibitors, calcium channel blockers) may lead to an additive hypotensive effect. Close monitoring of blood pressure is recommended, especially at the beginning of combination therapy.

Class I antiarrhythmic drugs (e.g., disopyramide, quinidine) and amiodarone may enhance the negative inotropic and chronotropic effects of nebivolol, increasing the risk of bradycardia and AV block. Calcium channel blockers of the verapamil and diltiazem type should be used with great caution due to similar risks; intravenous administration of calcium channel blockers to patients receiving beta-blockers is contraindicated.

Central alpha2-agonists (e.g., clonidine, methyldopa) may enhance the reduction in heart rate and cardiac output. Abrupt withdrawal of clonidine during treatment with a beta-blocker can lead to a sharp rise in blood pressure.

Digitalis glycosides (e.g., digoxin) in combination with nebivolol may increase the risk of bradycardia.

Insulin and oral antidiabetic drugs: Beta-blockers may potentiate the hypoglycemic effect and mask tachycardia as a warning sign of hypoglycemia. Blood glucose monitoring should be intensified.

NSAIDs (non-steroidal anti-inflammatory drugs) may reduce the antihypertensive effect of nebivolol.

CYP2D6 inhibitors: Nebivolol is metabolized by the cytochrome P450 2D6 isoenzyme. Concomitant use with potent inhibitors of CYP2D6 (e.g., fluoxetine, paroxetine, quinidine, propafenone) may lead to increased plasma concentrations of nebivolol. In such cases, a dose reduction of nebivolol should be considered.

Overdose

Symptoms of overdose are primarily related to excessive pharmacodynamic effects and may include severe bradycardia, hypotension, acute cardiac insufficiency, bronchospasm, and hypoglycemia. In severe cases, cardiac arrest may occur.

There is no specific antidote for nebivolol overdose. Treatment should be symptomatic and supportive. Gastric lavage and administration of activated charcoal can be considered if ingestion was recent. Bradycardia should be treated initially with intravenous atropine. If the response to atropine is inadequate, isoprenaline or a cardiac pacemaker may be used. For hypotension, intravenous fluids and vasopressors (e.g., dopamine, dobutamine, norepinephrine) should be administered. Bronchospasm can be treated with inhaled beta2-adrenergic agonists (e.g., salbutamol) and/or aminophylline. Blood glucose levels should be monitored and corrected if necessary. The patient should be under continuous monitoring of ECG and vital signs until stable.

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.