Verapamil hydrochloride (coated tablets 0.04 g and 0.08 g)
Tabulettae Verapamili hydrochloridi 0.04 et 0.08 obductae
International Non-proprietary Name
Verapamil.
Verapamil.
Pharmacotherapeutic group
Cardiovascular agents. Calcium channel blockers.
Composition
1 tablet contains 40 or 80 mg of verapamil hydrochloride.
Pharmacological action
Pharmacodynamics
Verapamil exhibits anti-anginal, antihypertensive, antiarrhythmic action.
Blocks calcium channels (acts from the inner side of the membrane) and decreases transmembrane calcium flow. Decreases contractility, frequency cardiac pacer and conduction velocity in AV node, sinoatrial and AV conductance, causes relaxation of smooth muscles (of arterioles in greater extent compared to veins), causes peripheral vasodilatation, decreases peripheral resistance, decreases afterload. Increases perfusion of myocardium, decreases disproportion between the requirement and oxygen supply of the heart, promotes regression of left ventricle hypertrophy, decreases blood pressure. Prevents the development and obviates coronary artery spasm during variant angina pectoris. In patients with uncomplicated hypertrophic cardiomyopathy it increases outflow from cardiac ventricles. Decreases the frequency and intensity of the headaches of vascular genesis.
Following oral administration the onset of the action is seen in 1 - 2 h, the duration of the action is 8 - 10 hours.
Pharmacokinetics
Following oral administration more 90% of the administered dosage is absorbed, bioavailability is 20 - 35% due to first-pass metabolism in liver. Maximum concentration in blood plasma is achieved within 1 - 2 h. Plasma protein binding is 90%. Metabolized in liver. Eliminated predominantly by kidneys, partially with faeces (16%). Penetrates in breast milk, crosses placenta. In severe impairment of liver function clearance from plasma decreases by 70%, elimination half-life is 14 - 16 h.
Indications
Verapamil is used for paroxysmal supraventricular tachycardia (except for WPW-syndrome), sinus tachycardia, auricular extrasystole, atrial flutter fibrillation, angina pectoris (including Prinzmetal angina, exertional angina, postinfarction angina), arterial hypertension, hypertrophic cardiomyopathy.
Administration and dosing regimen
Verapamil is administered orally during or immediately after food, with sufficient quantity of liquid. The recommended dosages are as follows:
angina pectoris: 80 - 120 mg 3 times a day, in liver function impairment, elderly patients - 40 mg 3 times a day;
arrhythmias: in chronic atrial fibrillation with concomitant therapy with cardiac glycosides - 240 - 320 mg daily in 2-3 divided dosages; prevention of paroxysmal supraventricular tachycardia - 240 - 480 mg daily in 2-3 divided dosages;
hypertension: 80 mg 3 times a day, if required daily dose can be increased up to 360 mg; from elderly patients or patients with small body weight the recommended dose is 40 mg 3 times a day.
For children up to 6 years the recommended dose is 40 - 60 mg of verapamil daily, 6 - 14 years of age - 80 - 360 mg daily. The daily dose should be divided in to 3 - 4 intakes.
Special indications
During treatment alcohol consumption should be avoided.
Side effects
During verapamil treatment hypotension, bradycardia (sinus), AV blockade, heart failure can occur; headache, dizziness, nervousness, lethargy, drowsiness, weakness, fatigability, paresthesia; nausea, dyspeptic events, constipation, rarely - gingival hyperplasia, increase of hepatic transaminases activity, alkaline phosphatase; allergic reactions - skin rash, hives, skin pruritus; rarely - angioedema, Steven-Johnson Syndrome; face flushing, peripheral oedema, very rarely -gynecomastia, in isolated cases - prolactin hypersecretion.
Contraindications
Contraindications are: increased individual sensitivity to verapamil, marked hypotension, cardiogenic shock, AV blockade of II and III degree, myocardial infarction (acute or recent and complicated by brachycardia, hypotension, left ventricular failure), chronic cardiac insufficiency of III degree, WPW-syndrome and sick sinus syndrome (if there is no pacemaker implanted), sinoatrial blockade, Morgagni-Adams-Stokes syndrome, intoxication with digitalis, severe aortic entrance stenosis, pregnancy, breast-feeding (breast-feeding should be avoided during treatment).
Restrictions: AV blockade of I degree, chronic cardiac insufficiency of I and II degree, marked bradycardia (less than 50 bpm), mild or moderate hypotension, pronounced myopathy (Duchenne syndrome), impairment of hepatic and/or renal functions.
Precautions
Caution should be exercised when administering in patients with hypertrophic cardiomyopathy, complicated left ventricle obstruction, high pulmonary capillary wedge pressure, paroxysmal nocturnal dyspnea or orthopnea, impairment of sinoatrial node function. When administering in patients with pronounces impairment of hepatic function and neuromuscular transmission (Duchenne myopathy) close medical monitoring should be established and the dose should be reduced if necessary.
Drivers and individuals requiring increased reaction rate and concentration should use the product with caution (reaction rate can be decreased).
Drug interactions
Verapamil increases digoxin, cyclosporin, theophylline, carbamazepine, and decreases lithium plasma levels. It suppresses antibacterial activity of rifampicin, effect of phenobarbital, decreases metoprolol and propranolol clearance, increases activity of muscle relaxants. Rifampicin, sulfinpyrazone, phenobarbital, calcium salts, vitamin D decrease verapamil activity. Hypotensive effect is increased when co-administered with antihypertensive preparations (diuretics, vasodilators), tricyclic and tetracyclic antidepressants and neuroleptics, antianginal effect - with nitrates. Beta-adrenergic blocking agents, antiarrhythmic drug of Iа class, cardiac glycosides, inhalation anesthetics, radiopaque agents potentiate (when co-administered) depressant action on automatism of sinoatrial node, AV conductance and contractility of myocardium. When used in combination with acetylsalicylic acid existing hemorrhage can be enhanced. Cimetidine increases verapamil levels in plasma.
Overdosage
Symptoms: arterial hypotension, bradycardia, AV blockade, cardiogenic shock, come, asystole.
Treatment: calcium gluconate (10 - 20 mL of 10% solution i/v) can be used as specific antidote; during brachycardia and AV blockade atropine, isoprenaline or orciprenaline should administered; during hypotension — plasma-substituting solutions, dopamine, norepinephrine; during the manifestation of heart failure signs - dobutamine.
Presentation
Tablets 40 mg. 10 tablets are packed in blisters, 50 and 100 tablets in a jar.
Tablets 80 mg. 10 tablets are packed in blisters, 50 and 100 tablets in a jar.
