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

Excipients; cellulose microcrystalline - 48 mg, 96 mg or 192 mg, calcium hydrogen phosphate dihydrate 24 mg, 48 mg or 96 mg, sodium carboxymethyl starch - 7.50 mg, 15 mg or 30 mg, magnesium stearate 0.50 mg, 1 mg or 2 mg.

Description:

A white or almost white, diamond-shaped tablet with a risk on one side and labeled 2.5 mg, 5 mg, 10 mg on the other.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.01 Amlodipine

Pharmacodynamics:

The "slow" calcium channel blocker (BCCC), a dihydropyridine derivative, has an antianginal and antihypertensive effect. Linking with dihydropyridine receptors blocks calcium channels,reduces the transmembrane transition of 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: with angina decreases the severity of ischemia myocardium; 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 tablets.

In patients with diseases of the cardiovascular system, including coronary atherosclerosis with the lesion of one vessel and up to stenosis of 3 or more arteries, atherosclerosis of carotid arteries,myocardial infarct, percutaneous transluminal angioplasty (TLO) or coronary arteries of patients with angina pectoris, amlodipine prevents the development intima-media thickening of carotid arteries, reduces mortality from myocardial infarction, stroke, TLO, coronary artery bypass surgery; leads to a decrease in the number of hospitalizations for unstable angina and the progression of chronic heart failure (CHF). Reduces the frequency of interventions aimed at restoring coronary blood flow. Does not increase the risk of death or development of complications and deaths in patients with CHF (III-IV functional class by classification NYHA) on the background of therapy with digoxin, diuretics and inhibitors of angiotensin-converting enzyme (i-ACE). 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.

Has a long-term dose-dependent antihypertensive effect. Antihypertensive action is due to 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 (heart rate), inhibits platelet aggregation, enhances the glomerular filtration rate, has a weak natriuretic effect. With diabetic nephropathy, no increases 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.Equilibrium concentrations are achieved after 7 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 undergoes a slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites, has the effect of "primary passage" through the liver. Metabolites do not have significant pharmacological activity.

After a single oral intake, the half-life period (T_1/2) varies from 31 to 48 hours, with a reappointment T_1/2is approximately 45 hours. About 60% of the dose taken internally excreted by the kidneys mainly in the form of metabolites, 10% in unchanged form, and 20-25% through the intestine, 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 (T_1/2 65 h) compared with young patients, but this difference has no clinical significance.In patients with hepatic insufficiency, an extension 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 pharmacokinetics of amlodipine. Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed.

Indications:

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

Stenocardia of tension is stable, vasospastic angina (Prinzmetal angina) (monotherapy or in combination with other antianginal drugs).

Contraindications:

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

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

- acute myocardial infarction (within the first 28 days);

- clinically significant aortic stenosis;

- collapse, cardiogenic shock;

- unstable angina (with the exception of Prinzmetal angina)

- pregnancy and the period of breastfeeding;

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

Carefully:

Violation of the liver function, syndrome of weakness of the sinus node (pronounced bradycardia, tachycardia), arterial hypotension, chronic heart failure of nonischemic etiology (III-IV 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:

The drug is contraindicated for use during pregnancy and during breastfeeding.

In experimental studies, the fetotoxic and embryotoxic effects of the drug have not been established, so use in pregnancy is only possible if the benefit to the mother exceeds the potential risk to the fetus.

There is no evidence that amlodipine is excreted in breast milk. However, it is known that other BCCC - dihydropyridine derivatives are secreted into breast milk. In this regard, if you need to prescribe the drug during breastfeeding, you should decide whether to stop breastfeeding.

Dosing and Administration:

Inside, washing down with the necessary amount of water (100 ml).Initial dose for treatment arterial hypertension and angina pectoris is 5 mg of the drug 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.

When angina pectoris and vasospastic angina pectoris - 5-10 mg per day, once.

Patients with a violation of liver function as an antihypertensive agent are prescribed in an initial dose of 2.5 mg; as an antianginal agent - 5 mg.

There is no need for dose adjustment with simultaneous administration with thiazide diuretics, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, as well as in patients with renal insufficiency.

Side effects:

The frequency of side effects is distributed in the following order; very often (more than 10% of cases), often (in 1-10% of cases); infrequently (in 0.1-1% of cases); rarely (in 0.01-1.1% of cases); very rarely (less than 0.01% of cases), including individual reports.

From the cardiovascular system: often - a feeling of palpitation, a marked decrease in blood pressure, fainting, vasculitis, peripheral edema (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 nervous system: often - headache, dizziness, fatigue, drowsiness, mood lability, convulsions; 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: often - nausea, epigastric pain; infrequent - vomiting, flatulence, constipation or diarrhea, dyspepsia, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - increased activity of "liver" transaminases and jaundice (due to cholestasis), pancreatitis, gastritis, hyperbilirubinemia, hepatitis.

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

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

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

From the skin: very rarely - xeroderma, alopecia, dermatitis, purpura, discoloration, increased sweating, cold sticky sweat.

From the sense organs: infrequent - ringing in the ears, impaired vision, diplopia, disruption of accommodation, xerophthalmia, conjunctivitis, pain in the eyes; very rarely - parosmia, a violation of taste.

From the side of metabolism: very rarely - hyperglycemia.

Allergic reactions: infrequently - skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema.

Other: rarely - gynecomastia, increase / decrease in body weight, nosebleed.

Overdose:

Symptoms: excessive peripheral vasodilation with prolonged and possiblya long decrease in blood pressure and the possible development of reflex tachycardia, including - with the development of shock and death.

Treatment: gastric lavage, the appointment of activated charcoal (especially in the first 2 hours after an overdose). In the case of a marked decrease in blood pressure - taking measures to maintain the function of the cardiovascular system: monitoring indicators of heart and lung function, elevated limb position, control of the volume of circulating blood 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:

Amlodipine can be safely used for the therapy of arterial hypertension along with thiazide diuretics, alpha-adrenoblockers or ACE inhibitors. In patients with stable angina pectoris amlodipine can be combined with other antianginal agents, for example, with long-acting or short-acting nitrates.

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. Antihypertensive effect weaken 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 antihypertensive effects.

Amiodarone, quinidine, alpha1-adrenergic blockers, antipsychotic drugs (antipsychotics) and BCCC can enhance antihypertensive 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 BCCC.

Procainamide, quinidine and other drugs that elongate the QT interval, enhance the negative inotropic effect and may increase the risk of a significant prolongation of the QT interval.

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 plasma concentrations of slow calcium channel blockers, including amlodipine.

Neuroleptics and isoflurane: increased antihypertensive effects of dihydropyridine derivatives.

Erythromycin, when combined, can increase the maximum equilibrium concentration of amlodipine.

Dantrolene (infusion) - cases of ventricular fibrillation with a lethal outcome were observed in experiments on animals after the administration of verapamil and dantrolene (intravenously).You should avoid the simultaneous use of verapamil and dantrolene.

Aluminum - and magnesium-containing antacids: their single administration does not have a significant effect on the pharmacokinetics of amlodipine.

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 pharmacokinetics and effects of amlodipine.

Special instructions:

During the period of treatment, control over body weight and sodium intake (cooking

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

When using the drug in patients with chronic heart failure III and IV functional class by classification NYHA possibly the development of pulmonary edema. In acute myocardial infarction, the drug is prescribed after stabilization of hemodynamic parameters (see the section "Contraindications").

Patients with hepatic insufficiency, if necessary taking Karmagip®, should be under the supervision of a physician

In elderly patients, half-life may increase T1 / 2 and decrease the clearance of the drug.Dose changes are not required, but more careful monitoring of patients of this category is necessary.

In patients with impaired renal function, monitoring of the condition is necessary.

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

Efficacy and safety of the drug with hypertensive crisis not established Karmagip® does not affect the potassium (K +) and plasma concentrations of glucose, triglycerides, total cholesterol, LDL (low density lipoproteins), uric acid, creatinine and blood urea nitrogen.

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

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

There were no reports of the effects of Karmagip® on the ability to drive vehicles or work with machinery. However, some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. If they occur, the patient must observe special precautions when dealing with potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 2.5; 5 and 10 mg.

Packaging:7 tablets per blister made of polyvinylidene chloride film and foil laminated aluminum. For 1, 2 or 4 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

In dry, the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001951

Date of registration:25.12.2012

Expiration Date:25.12.2017

The owner of the registration certificate:Suzhou Dunrais Pharmaceutical Co., Ltd. Ltd.Suzhou Dunrais Pharmaceutical Co., Ltd. Ltd. China

Manufacturer: & nbsp

SUZHOU DAWNRAYS PHARMACEUTICALS, Co.Ltd. China

Information update date: & nbsp13.12.2017

Illustrated instructions

Instructions

Karmagip® (Karmagip®)