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 drugs).
Angina pectoris, vasospastic angina (Prinzmetal’s angina).

Pharmacological effect

Pharmacotherapeutic group: BMCC (blocker of “slow” calcium channels).

ATX code: C08CA01

Pharmacological properties

Pharmacodynamics

The dihydropyridine derivative is a second-generation blocker of “slow” calcium channels, has an antianginal and hypotensive effect. By binding to dihydropyridine receptors, it blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (more into vascular smooth muscle cells than into cardiomyocytes). The antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: in case of angina pectoris, it reduces the severity of myocardial ischemia; by expanding peripheral arterioles, it reduces total peripheral vascular resistance, reduces preload on the heart, and reduces myocardial oxygen demand. By expanding the main coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, it increases the supply of oxygen to the myocardium (especially with vasospastic angina); prevents the development of constriction of the coronary arteries (including those caused by smoking). In patients with angina pectoris, a single daily dose increases the time of physical activity, slows down the development of angina and “ischemic” depression of the ST segment, reduces the frequency of angina attacks and nitroglycerin consumption.

It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on vascular smooth muscle. For arterial hypertension, a single dose provides a clinically significant decrease in blood pressure (BP) over 24 hours (in the patient’s “lying” and “standing” positions). Does not cause a sharp decrease in blood pressure, exercise tolerance, or left ventricular ejection fraction. Reduces the degree of left ventricular myocardial hypertrophy, has an antiatherosclerotic and cardioprotective effect in coronary heart disease (CHD). It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate (HR), inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. Does not have adverse effects on metabolism and blood plasma lipids. The onset of the effect is 2-4 hours, the duration of the effect is 24 hours.

Pharmacokinetics

After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. The average absolute bioavailability is
64%, maximum concentration in blood serum is observed after 6-9 hours. A stable equilibrium concentration is achieved after 7 days of therapy. Food does not affect the absorption of amlodipine. The mean volume of distribution is 21 L/kg body weight, indicating that most of the drug is in the tissues and a relatively smaller portion is in the blood. Most of the drug in the blood (95%) binds to blood plasma proteins.

Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites and has a “first pass” effect through the liver. Metabolites do not have significant pharmacological activity.

After a single oral dose, the half-life (T1/2) varies from 31 to 48 hours; with repeated administration, T1/2 is approximately 45 hours. About 60% of the dose taken orally is excreted in the urine, mainly in the form of metabolites, 10% unchanged, and 20-25% in feces and breast milk. The 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 of age), the elimination of amlodipine is slowed

(T1/2 65 hours) compared with young patients, but this difference is not clinically significant. In patients with liver failure, a prolongation of T1/2 is expected, and with long-term administration, the accumulation of the drug in the body will be higher (T1/2 up to 60 hours). Renal failure does not significantly affect the kinetics of amlodipine. The drug penetrates the blood-brain barrier. It is not removed by hemodialysis.

Special instructions

During the treatment period, it is necessary to monitor body weight and sodium intake, and prescribe an appropriate diet.

It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gum hyperplasia).
The dosage regimen for the elderly is the same as for patients of other age groups. When increasing the dose, careful monitoring of elderly patients is necessary.

Despite the absence of withdrawal syndrome with slow calcium channel blockers, a gradual dose reduction is recommended before stopping treatment.

Amlodipine does not affect plasma concentrations of K+, glucose, triglycerides, total cholesterol, LDL, uric acid, creatinine and uric acid nitrogen.

Impact on the ability to drive a car and operate machinery

There have been no reports of the effect of amlodipine on driving or using machinery. However, some patients may experience drowsiness and dizziness, primarily at the beginning of treatment. If they occur, the patient must take special precautions when driving and operating machinery.

Active ingredient

Amlodipine

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).

Contraindications

hypersensitivity to amlodipine and other dihydropyridine derivatives;
severe arterial hypotension;
collapse, cardiogenic shock;
unstable angina (with the exception of Prinzmetal’s angina);
pregnancy and lactation;
age under 18 years (efficacy and safety have not been established).

With caution: impaired liver function, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure in the stage of decompensation, mild or moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), diabetes mellitus, lipid profile disorders, old age.

Side Effects

From the cardiovascular system: palpitations, shortness of breath, marked decrease in blood pressure, fainting, vasculitis, edema (swelling of the ankles and feet), flushing of the face, rarely – rhythm disturbances (bradycardia, ventricular tachycardia, atrial flutter), chest pain, orthostatic hypotension, very rarely – development or worsening of heart failure, extrasystole, migraine.

From the central nervous system: headache, dizziness, fatigue, drowsiness, mood changes, convulsions, rarely – loss of consciousness, hypoesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams, very rarely – ataxia, apathy, agitation, amnesia.

From the digestive system: nausea, vomiting, epigastric pain, rarely – increased levels of liver transaminases and jaundice (caused by cholestasis), pancreatitis, dry mouth, flatulence, gum hyperplasia, constipation or diarrhea, very rarely – gastritis, increased appetite, anorexia, hyperbilirubinemia.

From the genitourinary system: rarely – pollakiuria, painful urge to urinate, nocturia, sexual dysfunction (including decreased potency); very rarely – dysuria, polyuria.

From the skin: very rarely – xeroderma, alopecia, dermatitis, purpura, skin discoloration.

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

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

Other: rarely – gynecomastia, hyperuricemia, weight gain/loss, thrombocytopenia, leukopenia, hyperglycemia, blurred vision, diplopia, conjunctivitis, eye pain, tinnitus, back pain, dyspnea, nosebleeds, increased sweating, thirst; very rarely – cold sticky sweat, cough, rhinitis, parosmia, impaired taste, impaired accommodation, xerophthalmia.

Interaction

Inhibitors of microsomal oxidation increase the concentration of amlodipine in the blood plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes reduce it.

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

Thiazide and loop diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates enhance the antianginal and hypotensive effects.

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

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

When used together with lithium drugs, it is possible to increase the manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Calcium supplements may reduce the effect of slow calcium channel blockers.

Procainamide, quinidine, and other drugs known to prolong the QT interval enhance the negative inotropic effect and may increase the risk of significant QT prolongation.

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

Overdose

Symptoms:

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

Treatment:

gastric lavage, administration of activated charcoal, maintaining the function of the cardiovascular system, monitoring indicators of heart and lung function, monitoring the volume of circulating blood and diuresis, giving the patient a horizontal position with raised legs. To restore vascular tone, use vasoconstrictor drugs (in the absence of contraindications to their use); to eliminate the consequences of blockade of calcium channels – intravenous administration of calcium gluconate. Hemodialysis is not effective.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25°C.

Shelf life

3 years.

Manufacturer

Vertex, Russia