Amlodipine, tablets 10 mg 90 pcs

Pharmacodynamics

Amlodipine is a dihydropyridine derivative – “slow” calcium channels blocker (BMCC) of II generation, has antianginal and hypotensive effects.

Binding to dihydropyridine receptors it blocks calcium channels, decreases transmembrane transfer of calcium ions into cell (more in vascular smooth muscle cells than in cardiomyocytes).

The antianginal action is due to the dilation of coronary and peripheral arteries and arterioles:

– in angina reduces the severity of myocardial ischemia; by dilating the peripheral arterioles, it reduces total peripheral vascular resistance; reduces the afterload on the heart, myocardial oxygen demand;

– Expands the main coronary arteries and arterioles in 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).Also caused by smoking.)

In patients with stable 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 the consumption of nitroglycerin and other nitrates.

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 reduction of arterial pressure (BP) for 24 hours (in “lying” and “standing” positions).

Orthostatic hypotension with amlodipine is rare. Amlodipine does not cause a decrease in exercise tolerance, left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy. 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 has no adverse effect on metabolism and concentration of plasma lipids and can be used for treatment of patients with bronchial asthma, diabetes mellitus, and gout.

The time of onset of therapeutic effect is 2-4 hours, a significant decrease in BP is observed after 6-10 hours, the duration of effect is 24 hours.

In patients with cardiovascular diseases (including coronary atherosclerosis with lesions of one vessel and up to stenosis of 3 or more arteries, atherosclerosis of the carotid arteries) who have had a myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or in patients with angina pectoris, the use of amlodipine prevents the development of carotid intima-media thickening, reduces mortality from myocardial infarction, stroke, PTCA, aortocoronary bypass; leads to fewer hospitalizations for unstable angina and progression of chronic heart failure (CHF); reduces the frequency of interventions to restore coronary blood flow.

The therapy with digoxin, diuretics and angiotensin-converting enzyme inhibitors (ACEI) does not increase mortality index or complication and lethal outcome in patients with CHF (NYHA functional class III-IV).

In patients with CHF (functional class III-IV according to NYHA classification) of non-ischemic etiology, there is a possibility of pulmonary edema when using amlodipine.

Pharmacokinetics

Intake

After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. Food intake has no effect on absorption of amlodipine. The average absolute bioavailability is 64-80%. Maximum serum concentration is observed after 6-12 hours. Equilibrium concentration is reached after 7-8 days of therapy. Simultaneous intake of food has no effect on absorption of amlodipine.

Distribution

The average volume of distribution is 21 l/kg body weight, indicating that most of the drug is in the tissues and less in the blood. Most of the drug that is in the blood (97.5%) is bound to plasma proteins.

Metabolism

Amlodipine undergoes slow but active metabolism (90-97%) in the liver with no significant “first pass” effect.

Metabolites have no significant pharmacological activity.

The elimination half-life (T1/2) after single administration varies from 35 to 50 hours. When repeatedly administered, the T1/2 is approximately – 45 hours.

About 60% of a dose taken by mouth is excreted by kidneys mainly as metabolites, 10% – as unchanged, 20-25% – in bile and through intestine as metabolites.

The total clearance of amlodipine is 0.116 ml/kg (7 ml/min/kg,0.42 l/h/kg).

The use in elderly patients

The excretion of amlodipine is slower (T1/2 – 65 h) in elderly patients (over 65 years) compared to younger patients, but this difference has no clinical significance.

The use in patients with hepatic impairment

The prolongation of the T1/2 in patients with hepatic impairment suggests that with long-term use the cumulation of the drug in the body will be higher (T1/2 – up to 60 h).

The use in patients with renal impairment

Renal impairment has no significant effect on the kinetics of amlodipine. Amlodipine penetrates through the blood-brain barrier and is not eliminated by hemodialysis.

Indications

Arterial hypertension (monotherapy or in combination with other antihypertensive agents);

Stable angina and vasospastic angina (Prinzmetal or variant angina) both in monotherapy or in combination with other antianginal agents).

Active ingredient

Composition

1 tablet contains:

the active substance:

excipients:

calcium stearate 0.2 mg,

potato starch 38.86 mg,

silicon dioxide colloid 1 mg,

How to take, the dosage

Overly, once daily with the required amount of water (100 ml).

In arterial hypertension, angina pectoris, the initial dose of amlodipine is usually 5 mg once daily. Depending on the therapeutic response, the daily dose may be increased to a maximum of 10 mg (once daily).

The use in elderly patients

Amlodipine is recommended in an average therapeutic dose; no dose adjustment is required.

The use in patients with impaired hepatic function

While the T1/2 of amlodipine, like all BMKs, is increased in patients with impaired hepatic function, no dose adjustment is usually required (see section “Special Precautions”).

The use in patients with impaired renal function.

The use of amlodipine in normal doses is recommended, but a possible slight increase in the T1/2 must be considered.

There is no need to change the dose when concomitantly prescribed with thiazide diuretics, beta-adrenoblockers and angiotensin-converting enzyme (ACE) inhibitors.

Interaction

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

The hypotensive effect is weakened by nonsteroidal anti-inflammatory drugs, especially indomethacin (sodium retention and blockade of prostaglandin synthesis by the 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, alpha 1-adrenoblockers, antipsychotic drugs (neuroleptics) and “slow” calcium channel blockers may increase the hypotensive effect.

There is no effect on the pharmacokinetic parameters of digoxin and warfarin.

Cimetidine has no effect on the pharmacokinetics of amlodipine.

When co-administered 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 the treatment period.

Tooth hygiene should be maintained and frequent visits to the dentist (to prevent soreness, bleeding and gum hyperplasia). The dosing regimen for the elderly is the same as for patients in other age groups. Careful monitoring of elderly patients is necessary if the dose is increased.

While 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 on 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

WHO Classification of the incidence of side effects:

very often – ≥1/10;

often – ≥1/100 to < 1/10;

infrequent – ≥1/1000 to < 1/100;

rarely – ≥1/10000 to < 1/1000;

very rarely, < 1/10000, including individual reports;

frequency unknown – it is not possible to determine the frequency of occurrence from the available data.

Cardiovascular system side:

often – palpitations, peripheral edema (swelling of ankles and feet), flushes of blood to the skin of the face;

infrequently – excessive decrease in BP;

Very rare – syncope, dyspnea, vasculitis, orthostatic hypotension, development or worsening of chronic heart failure, heart rhythm disorders (including bradycardia, ventricular tachycardia, atrial fibrillation), myocardial infarction, chest pain.

Musculoskeletal system disorders:

seldom – arthralgia, muscle cramps, arthrosis, myalgia (with long-term use), back pain;

Rarely – myasthenia gravis.

The central nervous system:

often – headache, dizziness, increased fatigue;

infrequently – general malaise, fainting, asthenia, hypoesthesia, paresthesias,

peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, increased agitation, depression, anxiety, tinnitus, perversion of taste;

very rarely – migraine, increased sweating, apathy, agitation, ataxia, amnesia;

frequency unknown – extrapyramidal disorders.

Digestive system disorders:

frequently – nausea, abdominal pain;

infrequently – vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dry oral mucosa, thirst;

rare – gum hyperplasia, increased appetite;

very rare – gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of liver transaminases, hepatitis.

The hematopoietic organs:

very rare – thrombocytopenia, leukopenia, thrombocytopenic purpura.

Respiratory system disorders:

infrequent – shortness of breath, rhinitis, nasal bleeding;

very rare – cough.

Senses:

infrequent – diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, visual disturbances.

Urogenital system disorders:

infrequent – frequent urination, painful urination, nycturia, impaired erectile function;

very rare – dysuria, polyuria.

Skin disorders:

rarely – dermatitis;

very rarely – cold sweat, xeroderma, alopecia, impaired skin pigmentation.

Allergic reactions:

infrequent – skin itching, rash (including erythematous, maculopapular rash, urticaria);

very rare – angioedema, erythema multiforme.

Laboratory indices:

very rarely – hyperglycemia.

Other:

infrequent – chills, gynecomastia, pain of unspecified localization, alopecia; very rare – parosmia.

Overdose

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

Treatment:Gastric lavage, administration of activated charcoal, maintenance of cardiovascular function, control of heart and lung function parameters, elevation of extremities, control of circulating blood volume and diuresis. To restore vascular tone – the use of 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.

Pregnancy use

The safety of Amlodipine during pregnancy has not been established; therefore, use during pregnancy is possible only when the benefit to the mother exceeds the risk to the fetus and the newborn.

There is no evidence that amlodipine is excreted into breast milk. However, other dihydropyridine derivatives are known to be excreted in breast milk. Therefore, if Amlodipine should be used during lactation, it is necessary to consider stopping breastfeeding.

There was no effect of amlodipine on fertility in a study in rats.

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