Composition, structure and packing
Tablets are white or nearly white, ploskotsilindricheskie, with beveled and risks.
1 tab. amlodipine (in the form bezilata) 5 mg.
Excipients: lactose, microcrystalline cellulose, calcium stearate, croscarmellose sodium, aerosil.
Clinico-pharmacological group: Calcium channel blockers.
Pharmacological action
Blocker of slow calcium channel II generation dihydropyridine derivative. Has antihypertensive and antianginal. 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).
Has a long dose-dependent hypotensive effect. Hypotensive effect 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. Antianginal due to increased coronary and peripheral arteries and arterioles: angina reduces the severity of myocardial ischemia, increasing peripheral arterioles, reduces TPVR, reduces preload 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. In diabetic nephropathy does not increase the severity of microalbuminuria. 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 administration of amlodipine slowly absorbed from the gastrointestinal tract. The average absolute bioavailability was 64%, Cmax plasma levels observed after 6-9 hours Css achieved after 7 days of therapy.
Food does not affect the absorption of amlodipine.
Distribution
Vd is 21 L / kg body weight, which indicates that most of the drug is in the tissues, and relatively smaller - in the blood. Most of the drug located in the blood (95%), binds to plasma proteins. Penetrates through the BBB.
Metabolism
Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites. It has the effect of "first pass" through the liver. The metabolites have no 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, and 20-25 % - with feces, as well as through breast milk. 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 increases to 60 h). Renal failure has no significant effect on the kinetics of amlodipine. When hemodialysis is not removed.
Statement
hypertension (as monotherapy or in combination therapy with other antihypertensive drugs);
angina;
vasospastic angina (Prinzmetal angina).
Dosage regimen
Assign inside. In the treatment of hypertension and angina, the initial dose is 5 mg 1 time / day. Maximum dose may be increased to 10 mg 1 time / day. When hypertension maintenance dose may be 2.5-5 mg / day. If angina and vasospastic angina - 5-10 mg 1 time per day. For prevention of angina attacks - 10 mg / day.
Patients with underweight, patients with low growth, as well as elderly patients, patients with impaired liver function as an antihypertensive drug amlodipine administered in an initial dose of 2.5 mg, as an antianginal medications - 5 mg. 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.
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, very rarely - 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 very rarely - ataxia, apathy, agitation, amnesia.
On the part of the digestive system: nausea, vomiting, epigastric pain, rarely - increased activity of hepatic transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gingival hyperplasia, constipation or diarrhea, very rare - gastritis, increased appetite.
From the urinary system: rarely - thamuria, tenesmus, nocturia, very rarely - dysuria, polyuria.
On the part of the reproductive system: rarely - violation of sexual function (including reduction of potency), gynecomastia.
On the part of the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia (with prolonged use), very rarely - myasthenia gravis.
On the part of metabolism: rarely - poliurikemiya, increase / decrease in body weight, hyperglycemia, increased sweating, thirst.
From the sensory organs: rarely - blurred vision, diplopia, conjunctivitis, eye pain, ringing in the ears is very rare - a violation of tastes, breach of accommodation, xerophthalmia, parosmiya.
On the part of the hemopoietic system: rarely - thrombocytopenia, leukopenia.
Dermatological reactions: very rare - dermatoxerasia, alopecia, dermatitis, purpura, skin discoloration.
Allergic reactions: itching, rash (including erythematous, maculopapular rash, urticaria), angioedema.
Other: rarely - back pain, dyspnea, epistaxis, very rarely - a cold clammy sweat, cough, rhinitis.
Contraindications
marked arterial hypotension;
collapse;
cardiogenic shock;
Pregnancy
lactation;
the age of 18 years (effectiveness and safety have not been established);
Hypersensitivity to amlodipine and other derivatives of dihydropyridine.
Precautions used drug in violation of the liver, SSS (pronounced bradycardia, tachycardia), decompensated congestive heart failure, with mild or moderate hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after ), diabetes mellitus, lipid profile, in elderly patients.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation (breastfeeding).
Application for violations of liver function
Precautions used drug in violation of liver function. Patients with liver failure is expected lengthening T1 / 2, and prolonged accumulation of the drug in the appointment of an organism is higher (T 1 / 2 to 60 h).
Application for violations of renal function
Renal failure has no significant effect on the kinetics of amlodipine.
Cautions
In the period of treatment necessary to control body weight and sodium intake, applying the proper diet. Necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).
Dosing regimens for the elderly 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 vehicles and management mechanisms
There were no reports on the effect of amlodipine on the drive or operate machinery. Nevertheless, some patients mainly at the beginning of treatment may occur drowsiness and dizziness.
When they occur, the patient must observe special precautionary measures while driving and using machinery.
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 and 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 the blood plasma (increasing the risk of side effects), and inducers of microsomal liver enzymes decrease the concentration of amlodipine.
The hypotensive effect is reduced by simultaneous application of the drug with NSAIDs, especially indomethacin (sodium retention and the blockade of prostaglandin synthesis by the kidneys), with alpha-adrenomimetics, estrogens (sodium retention), with sympathomimetics.
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.
Amlodipine did not affect 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. The drug should be stored out of reach of children, dry, dark place at a temperature not exceeding 25 ° C.
Shelf life - 3 years.
Tablets are white or nearly white, ploskotsilindricheskie, with beveled and risks.
1 tab. amlodipine (in the form bezilata) 5 mg.
Excipients: lactose, microcrystalline cellulose, calcium stearate, croscarmellose sodium, aerosil.
Clinico-pharmacological group: Calcium channel blockers.
Pharmacological action
Blocker of slow calcium channel II generation dihydropyridine derivative. Has antihypertensive and antianginal. 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).
Has a long dose-dependent hypotensive effect. Hypotensive effect 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. Antianginal due to increased coronary and peripheral arteries and arterioles: angina reduces the severity of myocardial ischemia, increasing peripheral arterioles, reduces TPVR, reduces preload 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. In diabetic nephropathy does not increase the severity of microalbuminuria. 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 administration of amlodipine slowly absorbed from the gastrointestinal tract. The average absolute bioavailability was 64%, Cmax plasma levels observed after 6-9 hours Css achieved after 7 days of therapy.
Food does not affect the absorption of amlodipine.
Distribution
Vd is 21 L / kg body weight, which indicates that most of the drug is in the tissues, and relatively smaller - in the blood. Most of the drug located in the blood (95%), binds to plasma proteins. Penetrates through the BBB.
Metabolism
Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites. It has the effect of "first pass" through the liver. The metabolites have no 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, and 20-25 % - with feces, as well as through breast milk. 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 increases to 60 h). Renal failure has no significant effect on the kinetics of amlodipine. When hemodialysis is not removed.
Statement
hypertension (as monotherapy or in combination therapy with other antihypertensive drugs);
angina;
vasospastic angina (Prinzmetal angina).
Dosage regimen
Assign inside. In the treatment of hypertension and angina, the initial dose is 5 mg 1 time / day. Maximum dose may be increased to 10 mg 1 time / day. When hypertension maintenance dose may be 2.5-5 mg / day. If angina and vasospastic angina - 5-10 mg 1 time per day. For prevention of angina attacks - 10 mg / day.
Patients with underweight, patients with low growth, as well as elderly patients, patients with impaired liver function as an antihypertensive drug amlodipine administered in an initial dose of 2.5 mg, as an antianginal medications - 5 mg. 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.
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, very rarely - 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 very rarely - ataxia, apathy, agitation, amnesia.
On the part of the digestive system: nausea, vomiting, epigastric pain, rarely - increased activity of hepatic transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gingival hyperplasia, constipation or diarrhea, very rare - gastritis, increased appetite.
From the urinary system: rarely - thamuria, tenesmus, nocturia, very rarely - dysuria, polyuria.
On the part of the reproductive system: rarely - violation of sexual function (including reduction of potency), gynecomastia.
On the part of the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia (with prolonged use), very rarely - myasthenia gravis.
On the part of metabolism: rarely - poliurikemiya, increase / decrease in body weight, hyperglycemia, increased sweating, thirst.
From the sensory organs: rarely - blurred vision, diplopia, conjunctivitis, eye pain, ringing in the ears is very rare - a violation of tastes, breach of accommodation, xerophthalmia, parosmiya.
On the part of the hemopoietic system: rarely - thrombocytopenia, leukopenia.
Dermatological reactions: very rare - dermatoxerasia, alopecia, dermatitis, purpura, skin discoloration.
Allergic reactions: itching, rash (including erythematous, maculopapular rash, urticaria), angioedema.
Other: rarely - back pain, dyspnea, epistaxis, very rarely - a cold clammy sweat, cough, rhinitis.
Contraindications
marked arterial hypotension;
collapse;
cardiogenic shock;
Pregnancy
lactation;
the age of 18 years (effectiveness and safety have not been established);
Hypersensitivity to amlodipine and other derivatives of dihydropyridine.
Precautions used drug in violation of the liver, SSS (pronounced bradycardia, tachycardia), decompensated congestive heart failure, with mild or moderate hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after ), diabetes mellitus, lipid profile, in elderly patients.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation (breastfeeding).
Application for violations of liver function
Precautions used drug in violation of liver function. Patients with liver failure is expected lengthening T1 / 2, and prolonged accumulation of the drug in the appointment of an organism is higher (T 1 / 2 to 60 h).
Application for violations of renal function
Renal failure has no significant effect on the kinetics of amlodipine.
Cautions
In the period of treatment necessary to control body weight and sodium intake, applying the proper diet. Necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gingival hyperplasia).
Dosing regimens for the elderly 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 vehicles and management mechanisms
There were no reports on the effect of amlodipine on the drive or operate machinery. Nevertheless, some patients mainly at the beginning of treatment may occur drowsiness and dizziness.
When they occur, the patient must observe special precautionary measures while driving and using machinery.
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 and 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 the blood plasma (increasing the risk of side effects), and inducers of microsomal liver enzymes decrease the concentration of amlodipine.
The hypotensive effect is reduced by simultaneous application of the drug with NSAIDs, especially indomethacin (sodium retention and the blockade of prostaglandin synthesis by the kidneys), with alpha-adrenomimetics, estrogens (sodium retention), with sympathomimetics.
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.
Amlodipine did not affect 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. The drug should be stored out of reach of children, dry, dark place at a temperature not exceeding 25 ° C.
Shelf life - 3 years.
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