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

Excipients: lactose monohydrate (sugar milk) 128 mg; povidone (polyvinylpyrrolidone) 6 mg; calcium carbonate 40 mg; potato starch 10 mg; calcium stearate 2 mg.

Description:

Tablets are white or white with a creamy hue of a flat-cylindrical shape with a bevel.

Pharmacotherapeutic group:blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Amlodipine is a dihydropyridine derivative. Linking with dihydropyridine receptors, blocks "slow" calcium channels, inhibits the transmembrane transition of calcium into the cells of the smooth muscle of the heart and vessels (mostly in the smooth muscle cells of the vessels, rather than in cardiomyocytes).Has hypotensive and antianginal effect.

The mechanism of hypotensive action of amlodipine is due to a direct relaxing effect on the smooth muscles of the vessels.

Amlodipine reduces myocardial ischemia in the following two ways:

- Expands the peripheral arterioles and, thus, reduces the overall peripheral resistance (afterload), with the heart rate practically unchanged, which leads to a reduction in energy consumption and myocardial oxygen demand.

- Expands coronary and peripheral arteries and arterioles both in normal and ischemic zones of the myocardium, which increases oxygen supply to the myocardium in patients with vasospastic angina (Prinzmetal angina) and prevents the development of coronarospasm caused by smoking.

In patients with arterial hypertension, a single daily dose of the drug provides a reduction in blood pressure (BP) for 24 hours (both in the "lying" and "standing"). Due to the slow start of action amlodipine does not cause a sharp drop in blood pressure.

In patients with angina, a single daily dose of the drug increases the time of physicalload, delays the development of another attack of angina and depression of the segment ST (by 1 mm) against the background of physical activity, reduces the frequency of angina attacks and the consumption of nitroglycerin.

The use in patients with coronary heart disease (CHD)

In patients with cardiovascular diseases (including coronary atherosclerosis with single vessel damage and up to stenosis of 3 or more arteries and carotid artery atherosclerosis) who underwent myocardial infarction, percutaneous transluminal angioplasty of coronary arteries (TPL) or with angina, the use of the drug prevents development thickening of the intima-media of carotid arteries, significantly reduces the mortality from cardiovascular causes, myocardial infarction, stroke, pulmonary tuberculosis, coronary artery bypass grafting, leads to a decrease in the number of gepp tion of for unstable angina and progression of chronic heart failure (CHF), reduces the frequency of interventions aimed at restoring coronary blood flow.

Use in patients with heart failure

The drug does not increase the risk of death or the development of complications and fatalities in patients with chronic heart failure (CHF) III-IV functional class (according to the classification NYHA) on the background of therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF III-IV functional class by classification NYHA non-ischemic etiology when using the drug there is a chance of developing pulmonary edema.

The drug does not have any adverse effect on the metabolism and concentration of plasma lipids.

Pharmacokinetics:

Suction. After oral administration at therapeutic doses amlodipine is well absorbed, reaching a maximum concentration in the blood plasma 6-12 hours after admission. Absolute bioavailability is 64-80%. The volume of distribution is approximately 21 l / kg. The connection with plasma proteins is approximately 97.5%. The intake of food does not affect the absorption of amlodipine, amlodipine penetrates the blood-brain barrier.

Biotransformation / excretion. The half-life period (T1 / 2) from the blood plasma is about 35-50 hours, which corresponds to the prescription of the drug once a day. The total ground clearance is 0.43 l / h / kg. Stable equilibrium concentration in the blood plasma is achieved after 7-8 days of constant reception of amlodipine, it is metabolized in the liver with the formation of inactive metabolites; 10% of the original drug and 60% of metabolites is excreted by the kidneys. Excretion with breast milk is unknown.During hemodialysis is not removed.

Use in patients with hepatic and CHF: In patients with hepatic and severe CHF insufficiency T1 / 2, increases to 56-60 hours.

Use in patients with renal insufficiency. T1 / 2 from blood plasma in patients with renal insufficiency increases to 60 hours. The change in the concentration of amlodipine in the blood plasma does not correlate with the degree of impaired renal function.

Application in the elderly. In the elderly, the time required to reach the maximum concentration of amlodipine in the blood plasma, and its magnitude, practically do not differ from those of younger people. In elderly people suffering from CHF, there is a tendency to decrease the clearance of amlodipine, which leads to an increase in the area under the concentration-time curve and T1 / 2 up to 65 hours.

Indications:

- arterial hypertension (both in monotherapy, and in combination with other antihypertensive drugs).

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

Contraindications:

increased sensitivity to amlodipine and other dihydropyridine derivatives, as well as to the auxiliary substances that make up the drug;

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

aortic stenosis;

mitral stenosis;

hypertrophic obstructive cardiomyopathy with obstruction of the outflow tract of the left ventricle;

hemodynamically unstable heart failure after myocardial infarction;

lactose intolerance, lactase deficiency and glucose-galactose malabsorption;

Carefully:

Carefully prescribe to patients with hepatic insufficiency, CHF of non-ischemic etiology III-IV class, unstable angina, acute myocardial infarction (and within 1 month after it), with simultaneous intake of inhibitors and inducers of isoenzyme CYP3A4, under the age of 18 years (efficiency and safety are not precisely established).

As with the appointment of other BCCC, caution should be used against the background of amlodipine administration in patients with sinus node weakness syndrome, arterial hypotension.

Pregnancy and lactation:

The safety of the drug during pregnancy and breastfeeding has not been established, so use during pregnancy is only possible if the benefit to the mother exceeds the risk to the fetus and newborn.For the period of breastfeeding it is recommended to stop either taking the medication or breast-feeding (there is no data on the excretion of amlodipine with breast milk).

Dosing and Administration:

Inside, once a day, washing down with the necessary amount of water (100 ml).

With arterial hypertension and angina, the usual initial dose is 5 mg, depending on the individual reaction of the patient it can be increased to a maximum daily dose of -10 mg.

Application in the elderly. It is recommended to use in usual doses, a change in the dose of the drug is not required.

Use in patients with impaired liver function. Despite the fact that T1 / 2 of the drug, like all BCCCs, increases in patients with this pathology, no changes in the dosage of the drug in patients with impaired liver function are usually required (see section "Special instructions").

Application in renal failure. It is recommended to use in usual doses, but it is necessary to take into account a possible slight increase in T1 / 2.

A change in the dosage regimen of the drug with simultaneous use of thiazide diuretics, beta-blockers or ACE inhibitors is not required.

Side effects:

Further under the frequency of adverse reactions is understood: frequent (> 1%), infrequent (<1%), rare (0.1%), very rare (0.01%).

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

From the musculoskeletal system: infrequently - arthralgia, muscle cramps, myalgia, back pain, arthrosis, rarely - myasthenia gravis.

Central and peripheral nervous system: often a feeling of heat and "tides" of blood to the skin of the face, increased fatigue, dizziness, headache, drowsiness, infrequent malaise, fainting, asthenia, hypesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, nervousness, depression, anxiety; rarely - cramps, apathy, agitation; very rarely - ataxia, amnesia.

The digestive tract: pain in the abdominal cavity, nausea, infrequent vomiting, changes in the bowel movement (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 of "hepatic" transaminases, hepatitis.

The system of hematopoiesis: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

Metabolic disorders: very rarely - hyperglycemia.

Respiratory system: infrequently - shortness of breath, rhinitis, very rarely - cough.

Genitourinary system: infrequent - frequent urination, painful urination, nocturia, impotence, very rarely - dysuria, polyuria.

Allergic reactions: infrequently - itchy skin, rash, very rarely - angioedema, erythema multiforme, urticaria.

Other: infrequently - alopecia, ringing in the ears, gynecomastia, increase / decrease in body weight, visual impairment, diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, taste distortion, chills, epistaxis, increased sweating, rarely dermatitis; very rarely - parosmia, xeroderma, "cold" sweat, a violation of skin pigmentation.

Overdose:

Symptoms: marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (there is a possibility of a pronounced and persistent arterial hypotension, including with the development of shock and death).

Treatment: The purpose of activated carbon (especially in the first 2 hours after an overdose), gastric lavage (in some cases), elevating the lower extremities with a low head, active maintenance of the cardiovascular system, monitoring heart and lung function, monitoring the volume of circulating blood and diuresis.

To restore the tone of blood vessels and blood pressure, if there are no contraindications, it may be useful to use vasoconstrictors. Intravenous administration of calcium gluconate is used. Because the amlodipine is largely associated with blood serum proteins - hemodialysis is not effective.

Interaction:

It can be expected that inhibitors of microsomal oxidation will increase the concentration of amlodipine in plasma, increasing the risk of side effects, and inductors of microsomal liver enzymes - reduce.

Cimetidine: while the simultaneous use of amlodipine with cimetidine, the pharmacokinetics of amlodipine does not change.

Grapefruit juice: simultaneous single intake of 240 ml of grapefruit juice and 10 mg of amlodipine inside is not accompanied by a significant change in the pharmacokinetics of amlodipine.

Unlike other BCCI, the clinically significant drug interaction Amlodipine (The third generation of BCCI) was not detected when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), especially indomethacin.

Erythromycin when combined, increases the maximum concentration (C_m_Oh) of amlodipine in young patients by 22%, and in the elderly by 50%.

It is possible to enhance the anti-anginal and antihypertensive effect of BCCC when combined with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-adrenoblockers and nitrates, as well as increase their hypotensive effect when combined with alpha1-adrenoblockers, neuroleptics.

With the simultaneous use of amlodipine and simvastatin there is an increase AUC and the maximum concentration of simvastatin in blood plasma at 1.3 and 1.4 times, respectively, without changing the hypolipidemic effect of simvastatin.With the simultaneous use of amlodipine and simvastatin in a dose of 80 mg, there is a slightly increased risk of myopathy.

Isoflurane can lead to a marked decrease in blood pressure when used in patients treated with calcium channel antagonists, especially dihydropyridine derivatives.

Although no negative inotropic effects were usually observed in the study of amlodipine, nevertheless, some BCCCs can increase the severity of the negative inotropic effect of antiarrhythmic agents that cause lengthening of the interval QT (e.g. amiodarone and quinidine).

Antiviral drugs (ritonavir) increases plasma concentrations of blockers of "slow" calcium channels (BCCC), including amlodipine.

Calcium preparations can reduce the effect of slow calcium channel blockers (BCCI).

In the joint application of BCCI with lithium preparations it is possible to increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Amlodipine does not affect in vitro on the degree of binding to blood plasma proteins digoxin, phenytoin, warfarin and indomethacin.

Aluminum / Magnesium containing antacids: their single administration does not significantly affect the pharmacokinetics of amlodipine.

Sildenafil: a single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine. Atorvastatin: repeated use of amlodipine in a dose of 10 mg and atorvastatin 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Digoxin: with the simultaneous use of amlodipine with digoxin in healthy volunteers, serum concentrations and renal clearance of digoxin do not change. Ethanol (alcoholic beverages): with a single and repeated application in a dose of 10 mg amlodipine has no significant effect on the pharmacokinetics of ethanol. Warfarin: amlodipine does not affect the changes in prothrombin time caused by warfarin.

Cyclosporine: amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

Special instructions:

In the treatment of hypertension Amlodipine can be used in combination with thiazide diuretics, alpha and beta adrenoblockers, ACE inhibitors,nitrates of prolonged action, sublingual nitroglycerin, NSAIDs, antibiotics and hypoglycemic agents for oral administration.

For the treatment of angina pectoris Amlodipine can be prescribed as a means of monotherapy or in combination with other antianginal agents, including in patients refractory to treatment with nitrates and / or beta-adrenoblockers in adequate doses.

In patients with chronic heart failure III-IV functional class by classification NYHA, Amlodipine was associated with an increased incidence of pulmonary edema.

Amlodipine does not have any adverse effect on the metabolism and lipids of blood plasma and can be used in the treatment of patients with bronchial asthma, diabetes and gout.

Amlodipine can be used also in those cases when the patient is predisposed to vasospasm / vasoconstriction.

Patients with low body weight, low growth patients and patients with severe liver dysfunction may need a lower dosage.

During treatment, it is necessary to control body weight and monitor the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Efficacy and safety of the drug Amlodipine with hypertensive crisis not established.

Despite the absence of the "cancellation" syndrome in BCC, the discontinuation of drug treatment Amlodipine preferably carried out, gradually reducing the dose of the drug.

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

Although amlodipine treatment did not have any negative impact on the ability to drive vehicles and work with mechanisms, however, due to the possible excessive decrease in blood pressure, development of dizziness, drowsiness and other side effects, one should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when the dosage regimen is changed.

Form release / dosage:

Tablets 10 mg.

Packaging:

10 tablets per contour cell pack.

By 20, 30, 50 or 100 tablets in cans of polymeric.

Each jar or 1, 2, 3, 5, 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002239

Date of registration:20.09.2013

The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia

Manufacturer: & nbsp

MEDISORB, CJSC Russia

Information update date: & nbsp20.09.2013

Illustrated instructions

Instructions

Amlodipine (Amlodipine)