Amlodipine-Vertex, tablets 10 mg 30 pcs

Pharmacotherapeutic group: BMCC (slow calcium channel blocker).

ATC code: C08CA01

Pharmacological properties

Pharmacodynamics

Dihydropyridine derivative is a “slow” calcium channel blocker of II generation, has antianginal and hypotensive effects. It binds to dihydropyridine receptors, blocks calcium channels, decreases transmembrane transition of calcium ions into cells (more in vascular smooth muscle cells than in cardiomyocytes). Antianginal action is due to the dilation of coronary and peripheral arteries and arterioles: in angina pectoris it reduces the severity of myocardial ischemia; by dilation of peripheral arterioles, it reduces total peripheral vascular resistance, reduces the preload on the heart, reduces myocardial oxygen demand. By dilating the main coronary arteries and arterioles in the unchanged and ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina); prevents the development of coronary artery constriction (including that caused by smoking). In patients with angina a single daily dose increases exercise time, delays the development of angina and “coronary” ST-segment depression, reduces the frequency of angina attacks and nitroglycerin consumption.

Has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to direct vasodilating effect on the vascular smooth muscles. In arterial hypertension a single dose provides clinically significant reduction of arterial pressure (BP) for 24 hours (in “lying” and “standing” position of the patient). It does not cause a sharp decrease in BP, decreases exercise tolerance and left ventricular ejection fraction. It reduces the degree of myocardial hypertrophy of the left ventricle, has anti-atherosclerotic and cardioprotective effect in coronary heart disease (CHD). It does not affect myocardial contractility and conduction, does not cause reflex increase in heart rate (HR), inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria. It does not have adverse effects on metabolism and blood plasma lipids. Time of effect – 2-4 hours, duration of effect – 24 hours.

Pharmacokinetics

After oral administration amlodipine is slowly absorbed from the gastrointestinal tract. The average absolute bioavailability is
64%, the maximum concentration in blood serum is observed after 6-9 hours. Stable equilibrium concentration is reached after 7 days of therapy. Food has no effect on absorption of amlodipine. The average volume of distribution is 21 l/kg body weight, indicating that most of the drug is in the tissues and relatively less in the blood. Most of the drug that is in the blood (95%) is bound to plasma proteins.

Amlodipine undergoes slow but extensive metabolism (90%) in liver with formation of inactive metabolites, has “first pass” effect through liver. Metabolites have no significant pharmacological activity.

After single oral administration, the elimination half-life (T1/2) varies from 31 to 48 hours, with a repeat administration T1/2 of approximately 45 hours. About 60% of oral dose is excreted with urine mainly as metabolites, 10% unchanged, and 20-25% with feces, as well as with breast milk. Total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg).
In elderly patients (over 65 years) the excretion of amlodipine is slower

(T1/2 65 h) compared to younger patients, but this difference has no clinical significance. In patients with hepatic insufficiency, a prolonged T1/2 is expected, and the drug cumulation in the body will be higher with long-term administration (T1/2 up to 60 h). Renal insufficiency has no significant effect on amlodipine kinetics. The drug penetrates through the blood-brain barrier. It is not eliminated by hemodialysis.

Indications

Arterial hypertension (monotherapy or in combination with other antihypertensive agents).
Stress angina pectoris, vasospastic angina pectoris (Prinzmetal’s angina pectoris).

Active ingredient

Composition

one tablet contains the active substance amlodipine besylate in terms of amlodipine – 5 mg or 10 mg;

excipients:

microcrystalline cellulose,

lactose (milk sugar),

croscarmellose sodium (primellose),

calcium stearate (calcium octadecanoate).

How to take, the dosage

In the oral route, the initial dose for the treatment of arterial hypertension and angina pectoris is 5 mg of the drug once daily. The dose may be maximally increased to 10 mg once daily. For arterial hypertension, the maintenance dose may be 5 mg per day.

In angina of tension and vasospastic angina 5-10 mg/day once daily; for prevention of angina attacks – 10 mg/day.
Dosage adjustment is not required if concomitantly administered with thiazide diuretics, beta-adrenoblockers and angiotensin-converting enzyme inhibitors (ACE). No dose modification is required in patients with renal insufficiency.

Interaction

Microsomal oxidation inhibitors increase the plasma concentration of amlodipine, increasing the risk of side effects, and inducers of microsomal liver enzymes decrease.

Hypotensive effect is weakened by nonsteroidal anti-inflammatory drugs, especially indomethacin (sodium retention and blockade of prostaglandin synthesis by kidneys), alpha-adrenergic stimulants, estrogens (sodium retention), sympathomimetics.

Thiazide and “loop” diuretics, beta-adrenoblockers, verapamil, ACE inhibitors and nitrates increase antianginal and hypotensive effects.

Amiodarone, quinidine, alpha1-adrenoblockers, antipsychotic drugs (neuroleptics) and slow calcium channel blockers may increase the hypotensive effect.

Does not affect the pharmacokinetic parameters of digoxin and warfarin.
Cimetidine does not affect the pharmacokinetics of amlodipine.

When combined with lithium preparations there may be increased manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Calcium preparations may decrease the effect of “slow” calcium channel blockers.

Procainamide, quinidine and other drugs that cause QT interval prolongation increase the negative inotropic effect and may increase the risk of significant QT interval prolongation.

Grapefruit juice may decrease the plasma concentration of amlodipine, but this decrease is so small that it does not significantly alter the effect of amlodipine.

Special Instructions

Body weight and sodium intake should be monitored and an appropriate diet prescribed during treatment.

It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and hyperplasia of the gums).
The dosing regimen for the elderly is the same as for patients in other age groups. Careful monitoring of elderly patients is necessary when increasing the dose.

Although slow calcium channel blockers have no withdrawal syndrome, a gradual reduction in doses is recommended before discontinuing treatment.

Amlodipine has no effect on plasma concentrations of K+, glucose, triglycerides, total cholesterol, LDL, uric acid, creatinine and uric acid nitrogen.

Influence on driving and operating machinery

There have been no reports about the effect of amlodipine on driving or operating machinery. However, drowsiness and dizziness may occur in some patients mainly at the beginning of treatment. If they occur, the patient should take special precautions when driving and working with mechanisms.

Contraindications

Side effects

Cardiovascular system disorders: palpitation, shortness of breath, marked decrease in blood pressure, fainting, vasculitis, edema (swelling of ankles and feet), “flushes” of blood to the face, rarely – rhythm disturbances (bradycardia, ventricular tachycardia, atrial flutter), chest pain, orthostatic hypotension, very rarely – development or aggravation of heart failure, extrasystole, migraine.

Central nervous system: headache, dizziness, fatigue, somnolence, mood changes, seizures, rarely – loss of consciousness, hypoesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams, very rarely – ataxia, apathy, agitation, amnesia.

Digestive system disorders: nausea, vomiting, epigastric pain, rarely – increased liver transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gum hyperplasia, constipation or diarrhea, very rarely – gastritis, increased appetite, anorexia, hyperbilirubinemia.

Urinary system disorders: rarely – pollakiuria, painful urge to urinate, nycturia, sexual dysfunction (including decreased potency); very rarely – dysuria, polyuria.

Skin disorders: very rarely xeroderma, alopecia, dermatitis, purpura, changes in skin color.

Allergic reactions: skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema.

Musculoskeletal system: rarely – arthralgia, arthrosis, myalgia (with long-term use); very rarely – myasthenia.

Other: rare – gynecomastia, hyperuricemia, weight gain/decrease, thrombocytopenia, leukopenia, hyperglycemia, visual disturbances, diplopia, conjunctivitis, eye pain, tinnitus, back pain, dyspnea, nosebleed, increased sweating, thirst; very rare – cold sticky sweat, cough, rhinitis, parosmia, taste disturbances, accommodation disturbances, xeroftalmia.

Overdose

Symptoms:

pronounced decrease in blood pressure, tachycardia, excessive peripheral vasodilation.

Treatment:

Gastric lavage, administration of activated charcoal, maintenance of cardiovascular function, control of cardiac and pulmonary function parameters, control of circulating blood volume and diuresis, putting the patient in a horizontal position with elevated legs. To restore vascular tone – use vasoconstrictors (if there are no contraindications for their use); to eliminate the effects of calcium channel blockade – intravenous injection of calcium gluconate. Hemodialysis is not effective.

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