Amlodipine - instructions for use, dose, side effects, contraindications

The dihydropyridine derivative blocking the "slow" calcium channels of the second generation, has an antianginal and hypotensive effect. Linking with dihydropyridine receptors, blocks calcium channels, reduces transmembrane transition of calcium ions into the cell (mostly in smooth muscle cells of blood vessels, than in cardiomyocytes). Antianginal effect is due to the expansion of coronary and peripheral arteries and arterioles: with angina decreases the severity of myocardial ischemia; expanding peripheral arterioles, reduces the overall peripheral vascular resistance, reduces preload on the heart, reduces the need for myocardium in oxygen. Expanding the main coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic angina); prevents the development of constriction of the coronary arteries (including caused by smoking). In patients with angina, a single daily dose increases the time of exercise, slows the development of angina pectoris and the "ischemic" depression of the segment ST, reduces the incidence of angina attacks and consumption of nitroglycerin. Has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on smooth muscle vessels.With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure (BP) for 24 hours (in the patient's position "lying" and "standing"). Does not cause a sharp decrease in blood pressure, a decrease in exercise tolerance, a fraction of the ejection of the left ventricle. Reduces the degree of myocardial hypertrophy of the left ventricle, has antiatherosclerotic and cardioprotective action in ischemic heart disease (CHD). Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in the heart rate (HR), inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. Does not have adverse effects on the metabolism and lipids of blood plasma. The time of 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%, the maximum serum concentration is observed after 6-9 hours.The equilibrium concentration is achieved after 7 days of therapy. Food does not affect the 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 in the blood (95%), binds to blood plasma proteins. Amlodipine is subjected to a slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites, has the effect of a "first pass" through the liver. Metabolites do not have significant pharmacological activity.

After a single oral intake, the elimination half-life (T_1/2) varies from 31 to 48 hours, with a reappointment of T_1/2 is approximately 45 hours. About 60% of the ingested dose is excreted urine mainly in the form of metabolites, 10% unchanged, and 20-25% with feces, as well as with 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 excretion of amlodipine is slowed down (T_1/2 65 h) compared with young patients, but this difference is not of clinical significance.

In patients with hepatic insufficiency, an extension of T_1/2, and with long-term administration, cumulation of the drug in the body will be higher (T_1/2 up to 60 hours).

Renal failure does not significantly affect the kinetics of amlodipine. The drug penetrates the blood-brain barrier. When hemodialysis is not removed.

Indications:

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

- Stenocardia of tension, vasospastic angina (Prinzmetal angina)

Contraindications:

- Pincreased sensitivity to amlodipine and other dihydropyridine derivatives;

- severe arterial hypotension;

- collapse, cardiogenic shock;

- unstable angina (with the exception of Prinzmetal angina)

- pregnancy and lactation;

- age to 18 years (efficacy and safety not established).

Carefully:

Hliver function disorder, sinus node weakness syndrome (severe bradycardia, tachycardia), chronic heart failure in decompensation stage, mild or moderate degree of arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and.within 1 month after), diabetes mellitus, lipid profile disorder, elderly age.

Pregnancy and lactation:Contraindicated.

Dosing and Administration:

Inside, the initial dose for the treatment of hypertension and angina is 5 mg once a day. The maximum dose can be increased to 10 mg once a day. With hypertension, the maintenance dose can be 5 mg per day.

With angina pectoris stress (vasospastic angina) - 5 - 10 mg per day, once.

There is no need for dose changes with simultaneous administration with thiazide diuretics, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors.

Do not require dose changes in patients with renal insufficiency.

Side effects:

From the cardiovascular system: palpitations, dyspnea, marked decrease in blood pressure, fainting, vasculitis, swelling (swelling of the ankles and feet), "tides" of blood to the face, rarely - rhythm disturbances (bradycardia, ventricular tachycardia, atrial flutter), chest pain, orthostatic hypotension, very rarely - the development or aggravation of heart failure, extrasystole, migraine.

From the central nervous system: headache, dizziness, fatigue, drowsiness, mood changes, cramps, 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, gingival hyperplasia, constipation or diarrhea, very rarely gastritis, increased appetite.

From the genitourinary system: rarely - pollakiuria, painful urge to urinate, nocturia, violation of sexual function (including a decrease in potency); very rarely - dysuria, polyuria.

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

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

From the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia (with prolonged use); very rarely - myasthenia gravis.

Other: rarely - gynecomastia, hyperuricemia, increase / decrease in body weight, thrombocytopenia, leukopenia, hyperglycemia, impaired vision, diplopia, conjunctivitis, eye pain, ringing in the ears, back pain, dyspnoea, epistaxis, increased sweating, thirst; very rarely - cold sticky sweat, cough, rhinitis, parosmia, taste disorders, accommodation disorder, xerophthalmia.

Overdose:

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

Treatment: gastric lavage, the appointment of activated charcoal, maintenance of cardiovascular function, monitoring of heart and lung function, elevated limb position, control of circulating blood volume and diuresis. To restore the vascular tone - the use of vasoconstrictive drugs (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is not effective.

Interaction:

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

Hypotensive effect weakens non-steroidal anti-inflammatory drugs, especially indomethacin (sodium retention and blockade of prostaglandin synthesis by the kidneys), alpha-adrenostimulants, estrogens (sodium retention), sympathomimetics.

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

Amiodarone, quinidine, alpha 1-adrenoblockers, antipsychotic drugs (neuroleptics) and blockers of "slow" calcium channels can enhance hypotensive action.

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

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

Calcium preparations can reduce the effect of blockers of "slow" calcium channels.

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

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

Special instructions:

During the period of treatment, it is necessary to control the body weight and sodium intake, the appropriate diet. It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).

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 lack of "slow" calcium channels of the syndrome of "cancellation" in blockers, a gradual decrease in doses is recommended before cessation of treatment.

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

Effect on the ability to drive transp. cf. and fur:

There were no reports of the effects of amlodipine on driving or working with machinery. However, some patients may experience drowsiness and dizziness at the beginning of treatment.When they occur, the patient should refrain from driving and working with machinery.

Form release / dosage:

Tablets of 5 and 10 mg.

Packaging:

By 10, 14 tablets in a planar cell pack of film polyvinyl chloride and aluminum foil lacquered.

According to 1, 2, 3 contour cell packs of 10 tablets, 1, 2 contour cell pack of 14 tablets together with the instructions for use are placed in a pack of cardboard.

For 50 or 100 tablets in a jar for packaging medicines from polypropylene or in a jar of high-density polyethylene or low-density polyethylene, sealed with a lid of polypropylene or polyethylene. Each bank along with the instruction for use is placed in a pack for consumer tare subgroups chrome or chrome-ersatz.

Storage conditions:

List B. Store in a dry place, protected from light and out of reach of children, at a temperature of no higher than 25 ° C.

Shelf life:

2 years. Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004932/07

Date of registration:17.12.2007 / 07.10.2015

Expiration Date:Unlimited

The owner of the registration certificate:ZIO-HEALTH, JSC ZIO-HEALTH, JSC Russia

Manufacturer: & nbsp

ZIO-HEALTH, JSC Russia

Information update date: & nbsp10.08.2017

Illustrated instructions

Instructions

Amlodipine (Amlodipine)