2010/09/20

Amlorus

Composition, structure and packing

Tablets are white, round shape with beveled ploskotsilindricheskoy.

1 tab. amlodipine (in the form bezilata) 2.5 mg.

Excipients: lactose, potato starch, povidone, krospovidon, microcrystalline cellulose, calcium stearate, talc.

Clinico-pharmacological group: Calcium channel blockers.

Pharmacological action

Blocker of slow calcium channel II generation dihydropyridine derivative. Has antianginal and antihypertensive effects. Communicating with the dihydropyridine receptors, blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

Antianginal due to increased coronary and peripheral arteries and arterioles: angina reduces the severity of myocardial ischemia, increasing peripheral arterioles, reduces TPVR, reduces afterload on the heart, reduces the need for myocardial oxygen. Expanding the major coronary arteries and arterioles in the unaltered and ischemic myocardial zones, increases the oxygen supply to the myocardium (especially in vasospastic angina), prevents the development of constriction of the coronary arteries (including those caused by smoking). In patients with angina and single daily dose increases the run-time physical activity slows the development of angina and coronary segment depression ST, reduces the frequency of angina attacks and nitroglycerin consumption.

Has a long dose-dependent hypotensive effect. Antihypertensive effects due to the direct vasodilating effect on vascular smooth muscle. When hypertension single dose provides a clinically significant reduction in blood pressure over 24 h (in the position of a patient lying and standing). There is no sharp decline in blood pressure, reduce exercise tolerance, left ventricular ejection fraction. Reduces the degree of hypertrophy of the left ventricle, has antiateroskleroticheskoe and cardioprotective effect in ischemic heart disease. It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate, inhibits platelet aggregation, improves glomerular filtration rate, has a weak natriuretic effect.

In diabetic nephropathy does not increase the severity of microalbuminuria. It has no adverse effects on metabolism and plasma lipids. Time of onset of effect - 2-4 hours, duration of effect 24 hours

Pharmacokinetics

Absorption

After oral amlodipine slowly absorbed from the gastrointestinal tract. The average absolute bioavailability of 64-90%. Cmax plasma levels observed after 6-9 hours Css achieved after 7 days of therapy. Food does not affect the absorption of amlodipine.

Distribution

The average Vd is 21 L / kg, this indicates that most of the drug is in the tissues, and relatively less - in the blood. Linking to plasma proteins - 95%. The drug penetrates through the BBB. Provided with breast milk.

Metabolism

Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites, the effect of being "first pass" through the liver. Metabolites have no clinically significant pharmacological activity.

Withdrawal

After a single oral dose of T1 / 2 varies from 31 to 48 h, when re-appointment of T1 / 2 approximately 45 h. Approximately 60% of applied oral dose excreted in urine mainly as metabolites, 10% - unchanged, 20-25% - with the feces. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 L / h / kg).

Pharmacokinetics in special clinical situations

Elderly patients (over 65), amlodipine slowed elimination (T1 / 2 - 65 h) compared with younger patients, but this difference has no clinical significance.

Patients with liver failure is expected lengthening T1 / 2, and prolonged appointment cumulation of the drug in the body will be higher (T1 / 2 - up to 60 h). Renal failure has no significant effect on the pharmacokinetics of amlodipine. When hemodialysis is not removed.

Statement
hypertension (as monotherapy or in combination with other antihypertensive therapy: diuretics, beta-blockers, ACE inhibitors);
stable angina, vasospastic angina (Prinzmetal angina), (as monotherapy or in combination with other antianginal drugs).

Dosage regimen

The drug is prescribed inside.

In the treatment of hypertension and angina starting at 5 mg 1 time / day.

If necessary, the dose may be increased to a maximum of 10 mg 1 time / day.

When hypertension maintenance dose may be 5 mg / day.

In vasospastic angina (Prinzmetal angina) - 5-10 mg / day in 1 reception. Do not want to change the dose, while the appointment of thiazide diuretics, beta-blockers and ACE inhibitors.

Do not want to change the dose in patients with renal insufficiency. Patients with hepatic insufficiency, elderly patients the initial dose of hypertension may be 2.5 mg.

Side effect
Since the cardiovascular system: heart rate, shortness of breath, marked reduction of blood pressure, syncope, vasculitis, edema (swelling of the ankles and feet), a rush of blood to face, seldom - arrhythmias (bradycardia, ventricular tachycardia, atrial flutter), chest pain , orthostatic hypotension, in some cases - the development or exacerbation of heart failure, arrythmia, migraines.
From the side of the central nervous system and peripheral nervous system: headache, dizziness, fatigue, drowsiness, mood changes, seizures, rare - loss of consciousness, hypesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams, and in particular cases - ataxia, apathy, agitation, amnesia.
On the part of the digestive system: nausea, vomiting, epigastric pain, rarely - increase in liver transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gingival hyperplasia, constipation or diarrhea, and in some cases - gastritis, increased appetite.
From the urinary system: rarely - thamuria, tenesmus, nocturia, and in some cases - dysuria, polyuria.
On the part of the reproductive system: rarely - violation of sexual function (including reduction of potency), gynecomastia. Dermatological reactions: in some cases - dermatoxerasia, alopecia, dermatitis, purpura, skin discoloration. Allergic reactions: itching, rash (including erythematous, maculopapular rash, urticaria), angioedema.
On the part of the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia (with prolonged use), in some cases - myasthenia gravis.
On the part of metabolism: rarely - poliurikemiya, increase / decrease in body weight, hyperglycemia, increased sweating, thirst, and in some cases - a cold clammy sweat.
On the part of the hemopoietic system: rarely - thrombocytopenia, leukopenia.
From the sensory organs: rarely - blurred vision, diplopia, conjunctivitis, eye pain, ringing in the ears, parosmiya, breach of taste, breach of accommodation, xerophthalmia.
On the part of the respiratory system: rarely - dyspnea, epistaxis, cough, rhinitis. Other: rarely - a pain in the back.

Contraindications
marked arterial hypotension;
collapse;
cardiogenic shock;
unstable angina (excluding Prinzmetal angina);
Pregnancy
lactation;
the age of 18 years (effectiveness and safety have not been established);
Hypersensitivity to amlodipine and other derivatives of dihydropyridine.

With care use in patients with abnormal liver function, SSS (pronounced bradycardia, tachycardia), congestive heart failure in decompensated, with mild or moderate degree of arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (in within 1 month after it), diabetes mellitus, lipid profile, in elderly patients.

Application for violations of liver function

Patients with liver failure initial dose of hypertension may be 2.5 mg. Precautions should be applied drug prinarushenii liver function.

Cautions

During the period of treatment necessary to control body weight, sodium intake, you must assign the proper diet. Necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Dosing regimens for elderly patients is the same as for patients of other age groups. With increasing doses must be carefully monitored for elderly patients.

Despite the lack of slow calcium channel blocker withdrawal syndrome, before the cessation of treatment is recommended a gradual reduction in dose. Amlodipine did not affect the plasma concentrations of potassium, glucose, triglycerides, total cholesterol, LDL, uric acid, creatinine and urea nitrogen. Effects on ability to drive motor vehicles and management mechanisms Effect of amlodipine on ability to drive trucks or work with mechanisms of communication available.

Nevertheless, some patients, mainly at the beginning of treatment, there may be drowsiness and dizziness. When they occur, the patient must observe special precautionary measures in potentially hazardous activities.

Overdose

Symptoms: marked reduction of blood pressure, tachycardia, excessive peripheral vasodilatation.

Treatment: gastric lavage, the appointment of activated carbon, the maintenance function of the cardiovascular system, the control parameters of the heart and lungs, an elevated position of the limbs, control of BCC, diuresis.

To restore the tone of the vessels - the use of vasoconstrictive drugs (in the absence of contraindications to their use) to eliminate the effects of calcium channel blockade - in / to the introduction of calcium gluconate. Hemodialysis is ineffective.

Drug Interactions

Inhibitors of microsomal oxidation increase the concentration of amlodipine in plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes decrease. Reduction of the hypotensive effect of amlodipine cause NSAIDs, especially indomethacin (sodium retention and the blockade of prostaglandin synthesis by the kidneys), alpha-adrenostimulyatorov, estrogens (sodium retention), sympathomimetic.

Thiazide and loop "diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates increase antianginal and hypotensive effects. Amiodarone, quinidine, alpha 1-blockers, antipsychotic drugs (neuroleptics) and blockers of slow calcium channels may increase the hypotensive effect of amlodipine. No effect on the pharmacokinetic parameters of digoxin and warfarin. Cimetidine has no effect on the pharmacokinetics of amlodipine.

When combined with the use of lithium therapy may be increased manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Calcium may reduce the effect of blockers of slow calcium channels.

Procainamide, quinidine and other drugs causing prolongation of the interval QT, reinforce the negative inotropic effect and may increase the risk of significant lengthening of the interval QT. Grapefruit juice can reduce the concentration of amlodipine in plasma, but this reduction is so small that it was not significantly changed the effect of amlodipine.

Terms and Conditions of storage

List B. In preparation should be stored out of reach of children, dry, dark place at temperatures not above 25 ° C. Shelf life - 2 years.