DRUG TITLE

Norvasc (Amlodipine)

Pharmacological action

Slow calcium channel blocker (SCB) of II generation, dihydropyridine derivative. It has antianginal and hypotensive effects. Binding to dihydropyridine receptors, it blocks calcium channels, reduces transmembrane transition of calcium ions into the cell (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 dilating peripheral arterioles it reduces myocardial perfusion, reduces the preload on the heart, myocardial oxygen demand. Dilates 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 spasm (including that caused by smoking). In patients with angina a single daily dose increases exercise tolerance, delays the development of another angina attack and ischemic ST-segment depression, reduces the frequency of angina attacks and nitroglycerin consumption.

Amlodipine has a long-term dose-dependent hypotensive effect, which is due to a direct vasodilator effect on vascular smooth muscle. In arterial hypertension, a single daily dose of amlodipine provides clinically significant BP reduction for 24 hours (in lying and standing position).

It reduces the degree of left ventricular myocardial hypertrophy and has anti-atherosclerotic and cardioprotective effect in CHD. It does not affect myocardial contractility and conduction, inhibits platelet aggregation, increases FFR, has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria. It has no adverse effect on metabolism and blood plasma lipid concentration.

Time of therapeutic effect - 2-4 hours, duration - 24 hours.

Pharmacokinetics

Absorption .

After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. Food intake does not affect absorption of amlodipine. The average absolute bioavailability is 64%. Cmax in serum is reached after 6-9 hours.

Distribution

Css is reached after 7-8 days of therapy. Binding to plasma proteins is 95%. Mean Vd is 21 l/kg body weight. Amlodipine penetrates through the HEB.

Metabolism

Amlodipine undergoes slow but active metabolism (90 to 97%) in the liver with no significant "first pass" effect. Metabolites have no significant pharmacological activity.

Excretion

T1/2 is on average 35 hours. About 60% of the oral dose is excreted by the kidneys mainly as metabolites, 10% unchanged, 20-25% - in the bile and intestine as metabolites, as well as with the breast milk. Total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg). It is not excreted by hemodialysis.

Pharmacokinetics in special patient groups

T1/2 in patients with arterial hypertension is 48 hours, in elderly patients it is increased up to 65 hours, in liver failure - up to 60 hours. Similar parameters of increased T1/2 are observed in severe chronic heart failure, in renal dysfunction T1/2 is not changed.

Contraindications to use

• Severe arterial hypotension (systolic BP less than 90 mm Hg);
• collapse;
• cardiogenic shock;
• unstable angina (except for Prinzmetal's angina);
• severe aortic stenosis;
• Lactose intolerance, lactase deficiency, or glucose/galactose malabsorption syndrome;
• pregnancy;
• lactation;
• under 18 years of age (efficacy and safety have not been established);
• hypersensitivity to amlodipine, other components of the drug or other dihydropyridine derivatives.

Caution should be exercised when using the drug in patients with liver dysfunction, CCSU (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology of III-IV functional class according to NYHA classification, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and during 1 month after), elderly patients.

Administration during pregnancy and lactation

No teratogenicity of amlodipine has been shown in animal studies, but there is no clinical experience with its use in pregnancy and lactation. Therefore, amlodipine should not be administered to pregnant and lactating women and women of childbearing age unless they use reliable contraception.

Use in liver dysfunction

Caution should be exercised when prescribing the drug in patients with hepatic dysfunction.

Use in patients with impaired renal function

No change in dosage is required in patients with renal insufficiency.

Administration in children

It is contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

Administration in elderly patients

Caution should be exercised when prescribing the drug in elderly patients. There is no need to change the dose, but a more careful monitoring of patients is necessary.

Indications of the drug Norvasc (Amlodipine)

• Arterial hypertension (as monotherapy or in combination with other antihypertensive agents);
• stable angina pectoris and Prinzmetal angina (as monotherapy or in combination with other antianginal agents).

Dosing regimen

The drug is taken orally, regardless of meals.

For treatment of arterial hypertension and prevention of attacks of angina pectoris and vasospastic angina pectoris, the initial dose is 5 mg once daily. If necessary, the daily dose may be increased to a maximum of 10 mg (once daily).

In patients with impaired liver function as an antihypertensive agent Amlodipine is prescribed with caution, the initial dose is 2.5 mg (1/2 tablet of 5 mg), as an antianginal agent - 5 mg.

In patients with renal insufficiency there is no need to change the dose.

In elderly patients, the T1/2 may increase and the CK may decrease. No dose changes are required, but closer patient monitoring is necessary.

No dose changes are required when concomitantly administered with thiazide diuretics, beta-adrenoblockers and ACE inhibitors.