Treatment of mild to moderate hypertention in adults.
Amlodipine is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine acts directly on vessels to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
Bisoprolol Fumarate is a synthetic, beta1-selective (cardioselective) adrenoceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilizing activity. It only shows low affinity to the beta2 receptor of the smooth muscles of bronchi and vessels as well as to the beta2-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence airway resistance and beta2-mediated metabolic effects. Its beta1-selectivity extends beyond the therapeutic dose range.
2.5 mg Bisoprolol Fumarate USP & Amlodipine Besilate BP equivalent to 5 mg Amlodipine daily
Combinations not recommended: Calcium antagonists of the verapamil and diltiazem type, centrally-acting antihypertensive drugs.
Combinations to be used with caution: Strong or moderate CYP3A4 inhibitors, CYP3A4 inducers, simvastatin, Tacrolimus, Cyclosporine, class I antiarrhythmic drugs, class III antiarrhythmic drugs, parasympathomimetic drugs, topical beta-blockers (e.g. eye drops), insulin and oral antidiabetic drugs, anesthetic agents, digitalis glycosides, non-steroidal anti-inflammatory drugs (NSAIDs), sympathomimetic agents, antihypertensive agents and other drugs with blood pressure lowering potential.
Combinations to be considered: Mefloquine, Rifampicin, Ergotamine derivatives, MAO inhibitors (except MAO-B inhibitor).
IN CONNECTION WITH AMLODIPINE: Severe hypotension Shock (including cardiogenic shock) Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis) Haemodynamically unstable heart failure after acute myocardial infarction IN CONNECTION WITH BISOPROLOL: Acute heart failure or during episodes of heart failure requiring i.v. inotropic therapy Cardiogenic shock Second or third degree AV block (without a pacemaker) Sick sinus syndrome Sinoatrial block Bradycardia (heart rate less than 60 beats/min) prior to start of therapy Hypotension (systolic blood pressure <100mmHg) Severe bronchial asthma or severe chronic obstructive pulmonary disease Severe forms of peripheral arterial occlusive disease and severe forms of Raynaud's syndrome Untreated phaeochromocytoma Metabolic acidosis
LYMPHATIC SYSTEM DISORDERS: Very Rare: Reduction in the number of white blood cells and/or platelets (leukopenia, thrombocytopenia). IMMUNE SYSTEM DISORDERS: Rare: Allergic reactions, mainly affecting the skin. METABOLISM AND NUTRITION DISORDERS: Very Rare: High blood sugar (hyperglycemia). PSYCHIATRIC DISORDERS: Uncommon: Insomnia, mood changes (including anxiety), depression, sleep disorders. Rare: Nightmares, hallucinations, confusion. NERVOUS SYSTEM DISORDERS: Common: Dizziness*, headache*, drowsiness (somnolence)*. Uncommon: Decreased stimuli of the senses (hypaesthesia), sensation of tingling (paraesthesia), distortion of the sense of taste (dysgeusia), tremor. Very Rare: Peripheral neuropathy. EYE DISORDERS: Uncommon: Visual disturbance including double vision (diplopia). Rare: Decreased tear secretion (to be considered if the patient uses contact lenses). Very Rare: Conjunctivitis. EAR AND LABYRINTH DISORDERS: Uncommon: Tinnitus. Rare: Hearing disorders. CARDIAC DISORDERS: Common: Conscious awareness of heart beating (palpitations). Uncommon: Atrioventricular-conduction disturbances, worsening of preexisting heart failure, slow heart beat (bradycardia). Very Rare: Heart attack (myocardial infarction), irregular heart beat (arrhythmia). VASCULAR DISORDERS: Common: Flushing, feeling of coldness and numbness in the extremities. Uncommon: Hypotension, fainting (syncope). Very Rare: Inflammation of blood vessels (vasculitis). RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Uncommon: Shortness of breath (dyspnea), bronchospasm in patients with bronchial asthma or a history of obstructive pulmonary disease, stuffy nose (rhinitis). Rare: Allergic rhinitis. Very Rare: Cough. GASTROINTESTINAL DISORDERS: Common: Gastrointestinal complaints such as nausea, vomiting, diarrhea, constipation, abdominal pain. Uncommon: Upset stomach (dyspepsia), dry mouth. Very Rare:Inflammation of the lining of the stomach (gastritis), increase in the size of the gums (gingivalhyperplasia), inflammation of the pancreas (pancreatitis). HEPATOBILIARY DISORDERS: Rare: Inflammation of the liver (hepatitis)**. Very Rare: Yellowish pigmentation of the skin (jaundice)**. SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Uncommon: Loss of hair (alopecia), discolorations on the skin e.g. caused by bleeding (purpura), increased perspiration (hyperhydrosis), itching (pruritus), exanthema. Very Rare: Rapid swelling of skin and mucosa (angio-edema), certain types of skin rash (urticaria, exfoliative dermatitis, psoriasis or psoriasis-like skin disorders or aggravated psoriasis), severe potentially life threatening bullous skin reactions (erythema multiforme, Stevens- Johnson syndrome), photosensitivity reactions. MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: Uncommon: Joint pain (arthralgia), muscle pain (myalgia), muscular weakness, muscle cramps, back pain. Very Rare: Muscular hypertonia. RENAL AND URINARY DISORDERS: Uncommon: Difficulties with urinating (pollakiuria, micturition disorder, nocturia). REPRODUCTIVE SYSTEM AND BREAST DISORDERS: Uncommon: Potency disorders, breast enlargement in men (gynecomastia). GENERAL DISORDERS: Common: Edema (e.g. ankle edema), fatigue*. Uncommon: Asthenia*, chest pain, pain, malaise. INVESTIGATIONS: Uncommon: Weight increase, weight decrease. Rare: Increased level of blood lipids (triglycerides), increased liver enzymes (ALAT, ASAT). *These symptoms especially occur at the beginning of the therapy. They are generally mild and often disappear within 1-2 weeks. **In most cases with cholestasis (bile cannot flow from the liver to the intestine).
PREGNANCY: Bisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the foetus/newborn. In general, b-adrenoceptor blockers reduce placental perfusion, which has been associated with growth retardation, intrauterine death, spontaneous abortion and early labour. BREAST-FEEDING: It is not known whether bisoprolol or amlodipine is excreted in human milk. Therefore, administration is not recommended during breast-feeding.
Most common signs expected with overdose of a beta-blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency, hypoglycemia. According to available data gross overdose of amlodipine could result in excessive peripheral vasodilation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported. In general, if overdose occurs, discontinuation of treatment and supportive and symptomatic treatment is recommended.
Keep in a dry place, below 30°C. Protect from light. Keep out of the reach of children.
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