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

Amlodipine - a derivative of dihydropyridine - blocker of "slow" calcium channels (BCCI) of the second generation, has an antianginal and hypotensive effect. Linking with dihydropyridine receptors, blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in smooth muscle cells of blood vessels, rather 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, the need for myocardium in oxygen. Expands 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 spasm of the coronary arteries (including those caused by smoking). In patients with angina, a single daily dose increases tolerance to physical activity, delays the development of another angina pectoris and "ischemic" depression of the segment ST; reduces the incidence of angina attacks and consumption of nitroglycerin.

Amlodipine has a prolonged dose-dependent hypotensive effect, which is caused by a direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single daily dose of amlodipine provides a clinically significant reduction in blood pressure (BP) for 24 hours (in the patient's position "lying" and "standing").

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, inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. It does not adversely affect the metabolism and concentration of plasma lipids. The time of onset of therapeutic effect is 2-4 hours, duration - 24 hours.

Pharmacokinetics:

After oral administration amlodipine is slowly absorbed from the gastrointestinal tract. Food intake does not affect the absorption of amlodipine. The average absolute bioavailability is 64%. The maximum concentration in serum is observed after 6-9 hours. The equilibrium concentration is achieved after 7-8 days of therapy. Communication with plasma proteins is 95%. The average volume of distribution is 21 l / kg of body weight. Amlodipine is subject to a slow but active metabolism (90-97%) in the liver in the absence of a significant "first passage" effect.Metabolites do not have significant pharmacological activity.

The half-life (T1 / 2) on average is 35 hours. T1 / 2 in patients with arterial hypertension - 48 hours, in elderly patients is increased to 65 hours, with liver failure - up to 60 hours, similar parameters of T1 / 2 increase are observed in severe chronic heart failure, with renal dysfunction - does not change.

About 60% of the dose taken internally is excreted by the kidneys mainly in the form of metabolites, 10% unchanged, 20-25% - with bile and through the intestines in the form of metabolites, as well as with breast milk.

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

Amlodipine penetrates the blood-brain barrier. When hemodialysis is not withdrawn.

Indications:

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

- stable angina of tension and angina of Prinzmetal (monotherapy or in combination with other antianginal agents).

Contraindications:

- Hypersensitivity to amlodipine, other dihydropyridine derivatives, other components of the drug;

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- collapse;

- cardiogenic shock;

- unstable angina (with the exception of Prinzmetal's stenocardia);

- severe aortic stenosis;

- age under 18 years (effectiveness and safety not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

- pregnancy;

- lactation period.

Carefully:Dysfunction of the liver, syndrome of weakness of the sinus node (pronounced bradycardia, tachycardia), chronic heart failure of non-ischemic, etiology III-1V functional class by classification NYHA, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), elderly age.

Pregnancy and lactation:

There was no evidence of teratogenicity of amlodipine in the study on animals, but there is no clinical experience of its use in pregnancy and lactation. therefore amlodipine should not be given to pregnant and lactating women, as well as to women of childbearing age, unless they use reliable methods of contraception.

Dosing and Administration:

Inside, regardless of food intake.

For the treatment of arterial hypertension and the prevention of angina attacks tension and vasospastic angina, the initial dose of amlodipine is 5 mg once a day. If necessary, the daily dose can be increased to a maximum of 10 mg (1 time per day).

Patients with impaired liver function as an antihypertensive drug Amlodipine appoint with caution, at an initial dose of 2.5 mg (1/2 tablet of 5 mg), as an antianginal agent - 5 mg.

In elderly patients, T1 / 2 may increase and creatinine clearance (CK) may decrease. Dose changes are not required, but more careful monitoring of patients is necessary.

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: often - palpitations, peripheral edema (swelling of the ankles and feet), infrequently - excessive reduction of blood pressure, orthostatic hypotension,vasculitis; rarely - development or aggravation of chronic heart failure; very rarely - rhythm disturbances (bradycardia, ventricular tachycardia, atrial fibrillation), myocardial infarction, chest pain, migraine.

From the central nervous system: often - headache, dizziness, increased fatigue; infrequently - malaise, fainting, asthenia, hypoesthesia ,. paresthesia, peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, nervousness, depression, anxiety; rarely convulsions,. apathy, agitation; very rarely - ataxia, amnesia.

From the hematopoiesis: very rarely - thrombocytopenia, leukopenia, thrombocytopenic purpura.

From the respiratory system^: infrequently - dyspnea, rhinitis; very rarely - cough.

From the digestive tract: often - nausea, abdominal pain; infrequent - vomiting, changing the mode of defecation (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; Very rarely - gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity, "hepatic" transaminases, hepatitis.

From the genitourinary system: infrequently - pollakiuria, painful urge to urinate, nocturia, impotence; very rarely - dysuria, polyuria.

Skin: rarely - increased sweating, very rarely - cold sticky sweat, xeroderma, alopecia, dermatitis, purpura, discoloration. Allergic reactions: infrequently - skin itching, rash; very rarely - angioedema, erythema multiforme, urticaria.

From the musculoskeletal system: infrequently - arthralgia, muscle cramps, arthrosis, myalgia (with prolonged use), back pain; rarely - myasthenia gravis.

Other: rare - alopecia, tinnitus, gynecomastia, increase / decrease in body weight, blurred vision, diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, eye pain, taste perversion, chills, nasal bleeding, increased sweating; rarely - dermatitis; very rarely - cold sticky sweat, parosmia, skin pigmentation disorder, hyperglycemia.

Overdose:

Symptoms: marked reduction of blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of severe and persistent hypotension, including the development of shock and death).

Treatment: gastric lavage, the appointment of activated charcoal (especially in the first 2 hours after an overdose), maintenance of cardiovascular function, monitoring of cardiac function and lung function, Trendelenburg posture, 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 can increase the concentration of amlodipine in the blood plasma, increasing the risk of side effects, and inductors of microsomal liver enzymes - can reduce this figure.

Unlike other BCCI, amlodipine has no clinically significant interaction with non-steroidal anti-inflammatory drugs, especially with indomethacin.

Thiazide and "loop" diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates increase the antianginal or antihypertensive effects of amlodipine. Amiodarone, quinidine, alpha1-adrenoblockers, antipsychotics (antipsychotics) and isoflurane can enhance the hypotensive effect of amlodipine. Calcium preparations can reduce the effect of BCCC.

With the combined use of amlodipine with lithium preparations, it is possible to intensify manifestations of neurotoxicity of the latter (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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

Antiviral drugs (ritonavir) contribute to an increase in the concentrations of BCCI (including amlodipine) in the blood plasma.

Special instructions:

During the treatment with Amlodipine, it is necessary to control the body weight of patients and the amount of sodium they consume; a suitable low-sal diet is prescribed.

It is necessary to maintain dental hygiene and regular visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).

The dosage regimen of amlodipine in elderly patients is similar to that of patients of other age groups. When increasing the dose, careful monitoring of elderly patients is necessary.

Despite the absence of the "cancellation" syndrome in BCC, before the cessation of treatment a gradual decrease in doses is recommended.

Amlodipine does not affect plasma concentrations in the blood of potassium ions, glucose, triglycerides, total cholesterol, low density lipoproteins, uric acid, creatinine and urea nitrogen.

It should be avoided abrupt discontinuation of the drug because of the risk of worsening of the course of angina pectoris. Tablets of the drug Amlodipine are not recommended for hypertensive crisis.

Patients with low body weight, low growth patients and patients with severe liver function disorders may need a smaller dose.

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

There were no reports of Amlodipine's influence on the management of motor vehicles or working with mechanisms. However, some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. When they occur, you must be careful when driving vehicles and engage in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets of 5 mg and 10 mg.

Packaging:For 10 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. According to 1, 2, 3, 6, 9 contour cell packs of 10 tablets or 1, 2, 3, 4 contour cell packs of 30 tablets together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

List B. Store in a dry, dark place at a temperature of no higher than 25^atC. Keep out of reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003196 / 01

Date of registration:20.11.2008

Expiration Date:Unlimited

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp10.08.2017

Illustrated instructions

Instructions

Amlodipine (Amlodipine)