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

Derivative of dihydropyridine - blocker of "slow" calcium channels (BCCI) of the second generation, has an antianginal and hypotensive effect. Linking to segments S6 III and IV domains of alpha1-subunit of calcium channel L-type, blocks calcium channels, reduces the transmembrane transition calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).

Antianginal action is due to the expansion of coronary and peripheral arteries and arterioles. When angina decreases the severity of myocardial ischemia; expanding peripheral arterioles, reduces the overall peripheral vascular resistance (OPSS), reduces preload on the heart, reduces the need for myocardium in oxygen. Expands 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 of amlodipine increases the time until the onset of the first ischemic episode during exercise, prevents the development of an attack of angina and "ischemic" depression segment ST (by 1 mm) on the background of physical activity, reduces the frequency of angina attacks and consumption of nitroglycerin andother nitrates.

Hypotensive effect is caused by a direct vasodilating effect on the smooth muscles of the vessels. Has a long-term dose-dependent hypotensive effect. 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"). Orthostatic hypotension with amlodipine is rare. Does not cause a decrease in exercise tolerance, a fraction of the ejection of the left ventricle. Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductivity of the myocardium, does not cause a reflex increase in the heart rate (heart rate).

In patients with ischemic heart disease (CHD) (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 the coronary arteries (PTCA), or with stenocardia, the use of amlodipine prevents the development of thickening of the intima-media of the carotid arteries, reduces the mortality from myocardial infarction, stroke, TPLP,aortocoronary shunting, leads to a reduction in the number of hospitalizations for unstable angina and the progression of chronic heart failure, reduces the frequency of interventions aimed at the restoration of coronary blood flow. Amlodipine does not increase the risk of death or development of complications leading to fatal outcomes in patients with chronic heart failure (CHF) (III-IV functional class by classification NYHA) on the background of therapy with digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors. In patients with CHF (III-IV functional class by classification NYHA) non-ischemic etiology in the use of amlodipine, there is a possibility of pulmonary edema.

Amlodipine does not have any adverse effect on the metabolism and concentration of plasma lipids. It inhibits platelet aggregation, increases the rate of glomerular filtration, and has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. 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 (GIT). The average absolute bioavailability is 64%, the maximum concentration (Cmah) in the serum is observed after 6-9 hours. Equilibrium serum concentrations (Css) are achieved after 7-8 days of therapy.

Food intake 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 subject to a slow but active metabolism in the liver in the absence significant effect of the "first passage." Metabolites do not have significant pharmacological activity.

After a single oral intake, the half-life period (T1 / 2) varies from 31 to 40 hours, with repeated application of T1 / 2 it is approximately 45 hours. About 60% of the dose taken internally is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - through the intestine, as well as 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), amlodipine withdrawal is slowed (T1 / 2 - 65 h) compared with young patients, but this difference is not clinically significant. Elongation of T1 / 2 in patients with hepatic insufficiency suggests that with prolonged use, the cumulation 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. When hemodialysis is not removed.

Indications:

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

- Stable angina and vasospastic angina pectoris (Prinzmetal angina) (monotherapy or in combination with other antianginal drugs).

Contraindications:

Hypersensitivity to amlodipine, dihydropyridine derivatives and 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);
clinically significant aortic stenosis;
pregnancy and lactation;
age under 18 years (effectiveness and safety not studied)

Carefully:With violations of the liver function, syndrome of weakness of the sinus node (pronounced bradycardia, tachycardia), chronic heart failure of non-ischemic etiology III-IV functional class by classification NYHA, arterial hypotension (systolic blood pressure more than 90 and less than 100 mm Hg), aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy (GOKMP), acute myocardial infarction (and within 1 month after myocardial infarction), in old age.

Pregnancy and lactation:

The safety of the use of amlodipine during pregnancy and during lactation has not been established, so the drug Amlodipine-Chaikafarm should not be prescribed to pregnant women and during lactation.

Dosing and Administration:

Inside, once a day, regardless of food intake, with a sufficient amount of water (100 ml).

Initial dose at arterial hypertension and angina pectoris is 5 mg once a day. The maximum dose can be increased to 10 mg once a day. It is recommended to increase the dose 7-14 days after the start of therapy (a faster increase in the dose requires careful monitoring of the patient).In elderly patients, T1 / 2 amlodipine may increase and creatinine clearance (CC) decrease. Dose changes are not required, but more careful monitoring of patients is necessary. Do not require dose changes when used simultaneously with thiazide diuretics, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. Do not require dose changes in patients with renal insufficiency.

Side effects:

Classification of the frequency of development of side effects of the World Health Organization (WHO):

very often: more than 1/10

often: more than 1/100 and less than 1/10

infrequently: more than 1/1000 and less than 1/100

rarely: more than 1/10000 and less than 1/1000

very rarely: more than 1/10000, including individual messages.

Co cardiovascular system: often - peripheral edema (ankles and feet), a feeling of palpitation, a feeling of heat and "tides" of blood to the skin of the face; infrequent - marked decrease in blood pressure, orthostatic hypotension, vasculitis; rarely - development or aggravation of the course of heart failure; very rarely - rhythm disturbances (bradycardia, ventricular tachycardia, atrial fibrillation), myocardial infarction, chest pain.

From the central and peripheral nervous system: often - headache, dizziness, fatigue, drowsiness; infrequently - asthenia, general malaise, hypoesthesia, paresthesia, peripheral neuropathy, tremor, vertigo, fainting, insomnia, mood lability, unusual dreams, increased excitability, depression, anxiety; rarely - cramps, apathy, agitation; very rarely - ataxia, amnesia.

From the digestive system: often - nausea, abdominal pain; infrequent - vomiting, constipation or diarrhea, flatulence, dyspepsia, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - pancreatitis, gastritis, jaundice (caused by cholestasis), hyperbilirubinemia, increased activity of "liver" transaminases, hepatitis.

On the part of the hematopoiesis system: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

From the genitourinary system: infrequent - frequent urination, painful urge to urinate, nocturia, impotence; very rarely - dysuria, polyuria.

From the skin: rarely - dermatitis; very rarely - xeroderma, a violation of skin pigmentation.

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

From the side of metabolism: very rarely - hyperglycemia.

From the respiratory system: infrequently - shortness of breath, rhinitis; very rarely - cough.

Allergic reactions: infrequently - itchy skin, rash (including erythematous, maculopapular rash); very rarely - hives, angioedema, erythema multiforme.

Other: infrequently - alopecia, ringing in the ears, gynecomastia, increase / decrease in body weight, visual impairment, diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain, taste perversion, chills, nosebleeds; very rarely - parosmia, "cold" sweat.

Overdose:

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

Treatment: patient is transferred to a horizontal position with raised legs above the level of the head, gastric lavage,reception of activated carbon, maintenance of cardiovascular function, control of heart and lung function, control of circulating blood volume and diuresis. To restore the vascular tone - the use of vasoconstrictor (in the absence of contraindications to their use); with the purpose of elimination of consequences of blockade of calcium channels - intravenous introduction of calcium gluconate. Hemodialysis is ineffective.

Interaction:

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

Amlodipine can be used simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs) (especially indomethacin), antibacterial agents and hypoglycemic agents for oral administration.

It is possible to strengthen the anti-anginal and hypotensive action of BCCC when combined with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as enhance their hypotensive effect when combined with alpha 1-blockers, neuroleptics, isoflurane.

Although the study of amlodipine negative inotropic action is usually not observed, nevertheless, some BCCI may increase the severity of the negative inotropic effects of antiarrhythmic agents capable of causing an elongation interval QT (eg, amiodarone and quinidine).

A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine.

The repeated use of amlodipine in a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Ethanol (drinks containing alcohol): amlodipine at a single and repeated application in a dose of 10 mg does not affect the pharmacokinetics of ethanol. Antiviral drugs (ritonavir) increases the plasma concentrations of BCCI, incl. amlodipine.

Calcium preparations can reduce the effect of BCCC.

When amlodipine is used together with lithium preparations, it is possible to intensify manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine does not change the pharmacokinetics of cyclosporine.

Does not affect the concentration of serum digoxin and its renal clearance.

Has no significant effect on the effect of warfarin (prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

In studies in vitro Amlodipine does not affect the binding to blood proteins of digoxin, phenytoin, warfarin and indomethacin.

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

Special instructions:

Amlodipine-Chaikafarma can be used to treat arterial hypertension in combination with thiazide diuretics, alpha-adrenoblockers, beta-adrenoblockers or ACE inhibitors. In patients with stable angina, the drug can be combined with other antianginal agents, for example, with prolonged or short-acting nitrates, beta-blockers.

During the period of treatment with the drug Amlodipine-Chaikafarma control body weight and sodium intake, the appointment of an appropriate diet. It is necessary to maintain oral hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Amlodipine does not affect the plasma concentrations of potassium, glucose, triglycerides, total cholesterol, low-density lipoproteins, uric acid, creatinine and uric acid and can be used in patients with bronchial asthma, diabetes and gout.

In elderly patients, T1 / 2 and the clearance of the drug may be prolonged. Dosage changes for elderly patients are not required; with increasing the dose, more careful monitoring of patients is necessary.

If the liver function is also impaired, T1 / 2 of the drug may be prolonged. Therefore, in such patients the drug Amlodipine-Chaikafarma should be administered with caution. Despite the fact that the discontinuation of the drug Amlodipine-Chaikafarm is not accompanied by the development of the "withdrawal" syndrome, it is desirable to stop the treatment, gradually reducing the dose of the drug.

The effectiveness and safety of the drug in hypertensive crisis is not established.

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

In some patients, mainly at the beginning of treatment or when changing the dosage regimen, due to a possible pronounced decrease in blood pressure, drowsiness, dizziness and other side effects may occur.When they occur, it is not recommended to drive the vehicle and work with mechanisms that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 5 mg or 10 mg.

Packaging:10 tablets per blister. For 3 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009122/10

Date of registration:31.08.2010

Expiration Date:Unlimited

The owner of the registration certificate:Chaikafarma High-quality Medicines, AO Chaikafarma High-quality Medicines, AO Bulgaria

Manufacturer: & nbsp

Chaikafarma High-quality Medicines, AO Bulgaria

Information update date: & nbsp25.07.2017

Illustrated instructions

Instructions

Amlodipine-Chaikafarma (Amlodipine-Chaikafarma)