This combination tablet is used for the treatment of hypertension as substitution therapy in patients who are already well controlled with the individual components given together at the same dose, but as separate tablets.

Amlodipine is a dihydropyridine calcium channel blocker that inhibits the influx of calcium ions into vascular smooth muscle and cardiac muscle. Since contraction of these muscles depends on calcium entry into cells, amlodipine reduces calcium movement across cell membranes, with a greater effect on vascular smooth muscle than on cardiac muscle. This results in vasodilation, decreased peripheral vascular resistance, and lowering of blood pressure.

Bisoprolol Fumarate is a synthetic, cardioselective beta₁-adrenergic receptor blocker without significant intrinsic sympathomimetic or membrane-stabilizing activity. It has minimal affinity for beta₂ receptors in bronchial and vascular smooth muscles as well as those involved in metabolic regulation. Therefore, bisoprolol is unlikely to affect airway resistance or beta₂-mediated metabolic processes. Its beta₁ selectivity is maintained even at higher therapeutic doses.

One tablet once daily in patients whose blood pressure is adequately controlled with separately administered monocomponent products of the same doses as the recommended fixed-dose combination.

Combinations not recommended: Concomitant use with calcium channel blockers such as verapamil and diltiazem, as well as centrally acting antihypertensive agents, is not advised.

Combinations to be used with caution: Caution is required when used with strong or moderate CYP3A4 inhibitors or inducers, simvastatin, tacrolimus, cyclosporine, class I and class III antiarrhythmic agents, parasympathomimetic drugs, topical beta-blockers (e.g., eye drops), insulin and oral antidiabetic drugs, anesthetic agents, digitalis glycosides, NSAIDs, sympathomimetic agents, antihypertensive drugs, and other blood pressure–lowering medications.

Combinations to be considered: Mefloquine, rifampicin, ergotamine derivatives, and monoamine oxidase (MAO) inhibitors (except MAO-B inhibitors).

This combination should not be used in patients with acute heart failure or episodes of decompensated heart failure, obstruction of left ventricular outflow (e.g., severe aortic stenosis), cardiogenic shock, second or third-degree AV block, sick sinus syndrome, sinoatrial block, symptomatic bradycardia or hypotension, severe bronchial asthma, advanced peripheral arterial occlusive disease, severe Raynaud’s syndrome, untreated pheochromocytoma, metabolic acidosis, or hypersensitivity to bisoprolol, amlodipine, dihydropyridine derivatives, or any excipients.

Common: Dizziness, headache, drowsiness, palpitations, flushing, coldness or numbness in extremities, gastrointestinal disturbances (nausea, vomiting, diarrhea, constipation, abdominal pain), edema (e.g., ankle swelling), fatigue.

Uncommon: Insomnia, mood changes (including anxiety), depression, sleep disorders, hypoesthesia, paresthesia, taste disturbances, tremor, visual disturbances (including diplopia), tinnitus, AV conduction disturbances, worsening heart failure, bradycardia, hypotension, syncope, dyspnea, bronchospasm (especially in patients with asthma), rhinitis, dyspepsia, dry mouth, alopecia, purpura, skin discoloration, pruritus, rash, joint pain, muscle pain, muscle weakness, cramps, back pain, urinary disorders, nocturia, increased urination, sexual dysfunction, gynecomastia, weakness, chest pain, malaise, weight gain or loss.

Rare: Allergic skin reactions, nightmares, hallucinations, confusion, reduced tear secretion, hearing disturbances, allergic rhinitis, hepatitis, increased triglycerides, elevated liver enzymes (ALAT, ASAT).

Use during pregnancy and lactation is not recommended.

Patients with heart failure should be treated cautiously, as further deterioration of ventricular function may occur. Sudden discontinuation of bisoprolol may worsen clinical condition, especially in ischemic heart disease; therefore, withdrawal should be gradual. Caution is required in patients with hepatic impairment. Beta-blockers should generally be avoided in obstructive airway diseases unless necessary. Use with caution in conditions such as bronchial asthma (with possible bronchodilator therapy), diabetes with fluctuating glucose levels (hypoglycemia symptoms may be masked), strict fasting, desensitization therapy, first-degree AV block, Prinzmetal’s angina, peripheral arterial disease, and psoriasis. Symptoms of thyrotoxicosis may be masked. During general anesthesia, the anesthetist should be informed about beta-blocker therapy. If discontinuation is required before surgery, it should be done gradually and completed about 48 hours prior.

Geriatric use: Standard doses may be used in elderly patients; however, caution is advised when increasing the dose.

Pediatric use: The safety and effectiveness of bisoprolol fumarate/amlodipine in children and adolescents under 18 years have not been established, and no sufficient data are available.

Patients with liver disease: In hepatic impairment, the elimination of amlodipine may be prolonged. Specific dosing guidelines are not well defined; therefore, the drug should be used cautiously. In severe hepatic impairment, the daily dose of bisoprolol should not exceed 10 mg.

Patients with kidney disease: No dose adjustment is generally required in mild to moderate renal impairment. Amlodipine is not removed by dialysis, and caution is advised in patients undergoing dialysis. In severe renal impairment (creatinine clearance <20 ml/min), the daily dose of bisoprolol should not exceed 10 mg.

Overdose of beta-blockers commonly presents with bradycardia, hypotension, bronchospasm, acute cardiac failure, and hypoglycemia. Excessive intake of amlodipine may lead to pronounced peripheral vasodilation and reflex tachycardia. Severe and prolonged hypotension, including shock with fatal outcomes, has been reported. If overdose occurs, discontinuation of the drug along with supportive and symptomatic management is recommended.

Anti-hypertensive

Store in a dry place below 30°C. Protect from light. Keep out of reach of children.