Amlorus
A dihydropyridine derivative, II generation BMCC, has antianginal and hypotensive effects. By binding to the S6 segment of the III and IV domains of the alpha1 subunit of the L-type calcium channel, it blocks calcium channels and reduces the transmembrane transition of Ca2+ into the cell (more into vascular smooth muscle cells than into cardiomyocytes). It has a hypotensive and antianginal effect.
The mechanism of the hypotensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle.
A decrease in myocardial ischemia occurs due to the expansion of coronary and peripheral arteries and arterioles in unchanged and ischemic areas of the myocardium, a decrease in peripheral resistance, a decrease in afterload, and myocardial oxygen demand.
Increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal's angina); prevents the development of coronary spasm caused by smoking. In patients with angina pectoris, a single daily dose increases the time it takes to perform physical activity, delays the development of the next attack of angina and ST segment depression (by 1 mm) during physical activity, reduces the frequency of angina attacks and nitroglycerin consumption.
It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to a direct vasodilating effect on vascular smooth muscle. For arterial hypertension, a single daily dose provides a clinically significant reduction in blood pressure over 24 hours (in the patient’s “lying” and “standing” position).
In patients with CCC disease (including single-vessel coronary atherosclerosis to 3-vessel stenosis, carotid atherosclerosis), post-myocardial infarction, percutaneous transluminal coronary angioplasty, or patients with angina, the use of amlodipine prevents carotid intima-media thickening. , reduces mortality from MI, stroke, transluminal angioplasty, coronary artery bypass grafting; leads to a decrease in the number of hospitalizations for unstable angina and progression of CHF; reduces the frequency of interventions aimed at restoring coronary blood flow.
Does not increase the risk of death or the development of complications and deaths in patients with CHF (NYHA class III-IV) during therapy with digoxin, diuretics and ACE inhibitors. In patients with CHF (NYHA class III-IV) of non-ischemic etiology, when using amlodipine, there is a possibility of pulmonary edema.
Does not cause a sharp decrease in blood pressure, a decrease in exercise tolerance, or LV ejection fraction. Reduces the degree of LV myocardial hypertrophy.
It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. Does not have adverse effects on metabolism and plasma lipids.
The onset of effect is 2-4 hours; duration - 24 hours.
Amlovas®
Amlodipine can be safely used for the treatment of arterial hypertension together with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors. In patients with stable angina, amlodipine can be combined with other antianginal agents, for example, long- or short-acting nitrates, beta-blockers.
Unlike other BMCCs, no clinically significant interaction of amlodipine (III generation BMCCs) was found when used together with non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin. It is possible to enhance the antianginal and hypotensive effect of BMCC when used together with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as enhance their hypotensive effect when used together with alpha1-blockers, antipsychotics.
Although negative inotropic effects have generally not been observed in amlodipine studies, some CBMCs may enhance the negative inotropic effects of antiarrhythmic drugs that prolong the QT interval (eg, amiodarone and quinidine).
Amlodipine can also be safely used concomitantly with antibiotics and oral hypoglycemic agents.
A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Simvastatin: simultaneous repeated use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in simvastatin exposure by 77%. In such cases, the dose of simvastatin should be limited to 20 mg.
Ethanol (drinks containing alcohol): amlodipine with single and repeated use in a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Antiviral agents (ritonavir): increases plasma concentrations of BMCC, including amlodipine.
Neuroleptics and isoflurane: enhancing the hypotensive effect of dihydropyridine derivatives.
Calcium supplements can reduce the effect of BMCC.
When BMCC is used together with lithium preparations (no data are available for amlodipine), it is possible that their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus) may increase.
Studies of the simultaneous use of amlodipine and cyclosporine in healthy volunteers and all groups of patients, with the exception of patients after kidney transplantation, have not been conducted. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporine to varying degrees, up to 40%. These data should be taken into account and cyclosporine concentrations should be monitored in this group of patients when cyclosporine and amlodipine are co-administered.
Does not affect the serum concentration of digoxin and its renal clearance.
Does not significantly affect the effect of warfarin (prothrombin time).
Cimetidine does not affect the pharmacokinetics of amlodipine.
in vitro studies
amlodipine does not affect the binding of digoxin, phenytoin, warfarin and indomethacin to plasma proteins.
Grapefruit juice: simultaneous single administration of 240 mg of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine. However, it is not recommended to use grapefruit juice and amlodipine at the same time, since genetic polymorphism of the CYP3A4 isoenzyme may increase the bioavailability of amlodipine and, as a result, increase the hypotensive effect.
Aluminum- or magnesium-containing antacids: their single dose does not have a significant effect on the pharmacokinetics of amlodipine.
Inhibitors of the CYP3A4 isoenzyme: with simultaneous use of diltiazem at a dose of 180 mg and amlodipine at a dose of 5 mg in patients from 69 to 87 years of age with arterial hypertension, there is an increase in systemic exposure of amlodipine by 57%. Concomitant use of amlodipine and erythromycin in healthy volunteers (18 to 43 years of age) does not lead to significant changes in amlodipine exposure (increase in area under the concentration-time curve (AUC) by 22%). Although the clinical significance of these effects is unclear, they may be more pronounced in older patients.
Potent inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole) may increase the plasma concentration of amlodipine to a greater extent than diltiazem. Amlodpine and inhibitors of the CYP3A4 isoenzyme should be used with caution.
Clarithromycin: CYP3A4 inhibitor. Patients taking clarithromycin and amlodipine at the same time have an increased risk of low blood pressure. Patients taking this combination are advised to be under close medical supervision.
Inducers of the CYP3A4 isoenzyme: there is no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored during concomitant use of amlodipine and inducers of the CYP3A4 isoenzyme.
Tacrolimus: When used concomitantly with amlodipine, there is a risk of increasing the concentration of tacrolimus in the blood plasma. To avoid toxicity of tacrolimus when used concomitantly with amlodipine, the concentration of tacrolimus in the blood plasma of patients should be monitored and the dose of tacrolimus should be adjusted if necessary.
Mammalian target of rapamycin (mTOR) inhibitors: mTOR inhibitors such as sirolimus, temsirolimus and everolimus are substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of the CYP3A isoenzyme. When used concomitantly with mTOR inhibitors, amlodipine may increase their exposure.
Amlorus tablet 10 mg pack cont cell/pack card x30
ATX code: C08CA01 (Amlodipine) Active substance: amlodipine (amlodipine) Rec.INN registered by WHO Dosage form AMLORUS® tab. 10 mg: 30 pcs. reg. No.: LS-001556 dated 01.08.11 - Validity period of the reg. beat not limited Release form, composition and packaging White or almost white tablets, flat-cylindrical, chamfered, marbling is allowed.
1 tab. amlodipine (as besylate) 10 mg
Excipients: lactose monohydrate - 88.34 mg, microcrystalline cellulose - 87.8 mg, crospovidone - 2 mg, colloidal silicon dioxide (aerosil) - 1 mg, talc - 5 mg, calcium stearate - 2 mg.
10 pieces. — cellular contour packages (3) — cardboard packs.
Clinical and pharmacological group: Calcium channel blocker Pharmaco-therapeutic group: BMKK Pharmacological action Dihydropyridine derivative – blocker of slow calcium channels. Has antihypertensive and antianginal effects. Blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent into vascular smooth muscle cells than into cardiomyocytes).
The antihypertensive effect is due to a direct vasodilating effect on vascular smooth muscle. It has a long-term dose-dependent antihypertensive effect.
Amlodipine reduces myocardial ischemia (has an antianginal effect) in two ways:
1) dilates peripheral arterioles and thus reduces peripheral vascular resistance, reduces afterload on the heart, while heart rate remains virtually unchanged, which leads to a decrease in energy consumption and myocardial oxygen demand,
2) expands coronary and peripheral arteries and arterioles in unchanged and ischemic areas of the myocardium, which increases the supply of oxygen to the myocardium (especially with vasospastic angina), reduces the severity of myocardial ischemia and prevents the development of spasm of the coronary arteries (including those caused by smoking).
For arterial hypertension, a single dose provides a clinically significant reduction in blood pressure over 24 hours (in the patient’s “lying” and “standing” position). Due to its slow onset of action, amlodipine does not cause a sharp decrease in blood pressure. Does not reduce exercise capacity and left ventricular ejection fraction.
In patients with angina pectoris, a single daily dose of amlodipine increases the time of physical activity, slows down the development of angina and ischemic depression of the ST segment (by 1 mm), reduces the frequency of angina attacks and the consumption of nitroglycerin and other nitrates.
Reduces the degree of left ventricular myocardial hypertrophy, has an antiatherosclerotic and cardioprotective effect in ischemic heart disease.
In patients with coronary artery disease (including coronary atherosclerosis with damage to one vessel and up to stenosis of three or more arteries and atherosclerosis of the carotid arteries), who have had myocardial infarction, percutaneous transluminal angioplasty of the coronary arteries (PTCA) or suffering from angina, the use of amlodipine prevents the development of carotid intima-media thickening arteries, significantly reduces mortality from cardiovascular causes, myocardial infarction, stroke, PTAP, coronary artery bypass surgery, leads to a decrease in the number of hospitalizations for unstable angina and progression of chronic heart failure, reduces the frequency of interventions aimed at restoring coronary blood flow.
Amlodipine does not increase the risk of death or complications leading to death in patients with chronic heart failure (III-IV functional class according to the New York Heart Association (NYHA) classification) during therapy with digoxin, diuretics and ACE inhibitors.
In patients with chronic heart failure (III-IV functional class according to the NYHA classification) of non-ischemic etiology, when using amlodipine, there is a possibility of pulmonary edema.
It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases the glomerular filtration rate, and has a weak natriuretic effect. In diabetic nephropathy, it does not increase the severity of microalbuminuria. It has no adverse effects on metabolism and the concentration of lipids in the blood plasma and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout.
The onset of the effect of the drug is 2-4 hours, the duration of the effect is 24 hours. With long-term therapy, the maximum decrease in blood pressure occurs 6-12 hours after taking amlodipine orally. If amlodipine is discontinued after long-term treatment, the effective reduction in blood pressure persists for 48 hours after the last dose. Then blood pressure levels gradually return to the original level over 5-6 days.
Pharmacokinetics Absorption
Absorption is slow, independent of food intake, and is about 90%. Bioavailability is 60-90%, Cmax in blood serum is observed 6-12 hours after administration.
Distribution
Vd is approximately 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 (95-97%) binds to blood plasma proteins. Amlodipine penetrates the BBB. It is not removed by hemodialysis. Css of amlodipine in blood plasma is achieved after 7-8 days of continuous use of the drug.
Metabolism
Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites and has a “first pass” effect through the liver. Metabolites do not have significant pharmacological activity.
Removal
After a single oral dose, T1/2 varies from 31 to 48 hours; with repeated administration, T1/2 is approximately 45 hours (which corresponds to the administration of the drug 1 time per day). The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg).
About 60% of the dose taken orally is excreted by the kidneys mainly in the form of metabolites, 10% unchanged, with bile and through the intestines - 20-25% in the form of metabolites.
Pharmacokinetics in special clinical situations
In elderly patients over 65 years of age, the elimination of amlodipine is slowed (T1/2 increases to 65 hours) compared to young patients. In elderly and young patients, the time required to achieve Cmax of amlodipine in blood plasma is almost the same.
In patients with liver failure and severe chronic heart failure, T1/2 increases to 56-60 hours.
T1/2 from blood plasma in patients with renal failure increases to 60 hours. Changes in the concentration of amlodipine in blood plasma do not correlate with the degree of renal dysfunction.
Indications: arterial hypertension (monotherapy or in combination with other antihypertensive drugs),
- stable angina pectoris, vasospastic angina (Prinzmetal angina) (monotherapy or in combination with other antianginal drugs).
ICD-10 codes ICD-10 code Indication I10 Essential [primary] hypertension I20 Angina pectoris I20.1 Angina pectoris with documented spasm (Prinzmetal's angina, variant angina)
Dosage regimen The tablets are taken orally once, with the required volume of water (up to 100 ml).
For the treatment of arterial hypertension and angina pectoris, the initial dose is 5 mg 1 time / day. Depending on the individual response of the patient, if necessary, the dose can be increased to a maximum of 10 mg 1 time / day.
For arterial hypertension, the maintenance dose can be 5 mg/day. For vasospastic angina (Prinzmetal's angina) - 5-10 mg/day, dose taken 1 time/day.
No dose change is required when administered concomitantly with thiazide diuretics, beta-blockers and ACE inhibitors.
In patients with hepatic insufficiency and elderly patients, a dose change may be required; the initial dose for arterial hypertension may be 2.5 mg.
When prescribing the drug to patients with renal failure, no change in dosage regimen is required.
Side effects The frequency of adverse reactions means: very often (≥1/10), often (≥1/100, From the cardiovascular system: often - peripheral edema (ankles and feet), palpitations, sensations of heat and “hot flashes” blood to the skin of the face, infrequently - excessive decrease in blood pressure, orthostatic hypotension, vasculitis, rarely - development or worsening of chronic heart failure, very rarely - heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain .
From the side of the central nervous system: often - increased fatigue, dizziness, headache, drowsiness, migraine, infrequently - general malaise, fainting, increased sweating, asthenia, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, nervousness, depression , anxiety, rarely - convulsions, apathy, agitation, very rarely - ataxia, amnesia.
From the senses: infrequently - ringing in the ears, visual disturbances, eye pain, diplopia, xerophthalmia, conjunctivitis, disturbance of accommodation, perversion of taste, very rarely - parosmia.
From the digestive system: often - abdominal pain, nausea, infrequently - vomiting, constipation, flatulence, dyspepsia, diarrhea, anorexia, dry oral mucosa, thirst, rarely - gingival hyperplasia, increased appetite, very rarely - gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of liver transaminases, hepatitis.
From the urinary system: infrequently - frequent urination, painful urination, nocturia, impotence, very rarely - dysuria, polyuria.
From the respiratory system: infrequently - shortness of breath, rhinitis, nosebleeds, very rarely - cough.
From the musculoskeletal system: infrequently - arthralgia, muscle cramps, myalgia, back pain, arthrosis, rarely - myasthenia gravis.
From the skin: infrequently - alopecia, rarely - dermatitis, very rarely - impaired skin pigmentation, xeroderma.
From the hematopoietic organs: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.
Metabolism: very rarely - hyperglycemia.
Allergic reactions: infrequently - skin itching, rash, very rarely - angioedema, erythema multiforme, urticaria.
Other: infrequently - gynecomastia, weight gain/loss, chills, very rarely - cold sweat.
Contraindications for use: severe arterial hypotension (systolic blood pressure less than 90 mm Hg),
- cardiogenic shock,
- acute myocardial infarction during the first 28 days,
- unstable angina (with the exception of vasospastic/Prinzmetal angina),
- left ventricular outflow tract obstruction (including clinically significant aortic stenosis),
- age up to 18 years,
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption,
- hypersensitivity to amlodipine, other dihydropyridine derivatives and other components of the drug.
With caution: impaired liver function, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology of functional class III-IV according to the NYHA classification, arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, old age.
Use during pregnancy and breastfeeding The safety of amlodipine during pregnancy has not been established, therefore use during pregnancy is possible only if the benefit to the mother outweighs the potential risk to the fetus.
There is no data indicating the excretion of amlodipine in breast milk. However, other slow calcium channel blockers, dihydropyridine derivatives, are known to be excreted in breast milk. In this connection, if it is necessary to prescribe the drug Amlorus® during lactation, the issue of stopping breastfeeding should be decided.
Women of childbearing age should use reliable methods of contraception.
Use for impaired liver function In patients with liver failure, a dose change may be required; the initial dose for arterial hypertension may be 2.5 mg.
Use for impaired renal function When prescribing the drug to patients with renal failure, no change in dosage regimen is required. Use in children The drug is contraindicated for use in children and adolescents under 18 years of age (efficacy and safety have not been established). Use in elderly patients In elderly patients, dose adjustment may be required; the initial dose for arterial hypertension may be 2.5 mg. Special instructions When treating arterial hypertension, Amlorus® can be used in combination with thiazide diuretics, alpha-blockers, beta-blockers and ACE inhibitors.
For the treatment of angina pectoris, Amlorus® can be combined with other antianginal drugs, for example, long-acting or short-acting nitrates, beta-blockers.
Amlorus® can also be used in cases where the patient is predisposed to vascular spasm (vasoconstriction).
Amlorus® does not affect plasma concentrations of potassium ions, glucose, triglycerides, total cholesterol, low-density lipoproteins, uric acid, creatinine and urea nitrogen and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout.
For patients with low body weight, patients of short stature and patients with severe liver dysfunction, Amlorus® is prescribed as an antihypertensive agent at an initial dose of 2.5 mg, and as an antianginal agent - 5 mg.
During treatment, it is necessary to monitor body weight and sodium intake, prescribing an appropriate diet, and observation by a dentist (to prevent pain, bleeding and gum hyperplasia).
Despite the absence of withdrawal symptoms from the drug, a gradual dose reduction is recommended before stopping treatment.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, care should be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Overdose Symptoms: pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (there is a possibility of severe and persistent arterial hypotension, including the development of shock and death).
Treatment: gastric lavage, administration of activated charcoal, maintaining the function of the cardiovascular system, monitoring indicators of heart and lung function, elevated position of the lower extremities, monitoring the volume of circulating blood and diuresis. To restore vascular tone - use vasoconstrictor drugs (in the absence of contraindications to their use), to eliminate the consequences of blockade of calcium channels - intravenous administration of calcium gluconate. Since amlodipine is highly bound to serum proteins, 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 reduce it.
Amlodipine has no effect on the pharmacokinetic parameters of digoxin and warfarin, and does not affect changes in prothrombin time caused by warfarin.
Cimetidine does not affect the pharmacokinetics of amlodipine.
Calcium supplements may reduce the effect of slow calcium channel blockers (including amlodipine).
Unlike other slow calcium channel blockers, no significant interaction was found when used together with NSAIDs (including indomethacin).
Thiazide and loop diuretics, beta-blockers, verapamil, ACE inhibitors and nitrates enhance the antianginal and antihypertensive effects of amlodipine.
Alpha1-blockers, antipsychotics, amiodarone and quinidine may enhance the antihypertensive effect of amlodipine when used together.
Blockers of slow calcium channels (including amlodipine) can enhance the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (amiodarone, quinidine, procainamide).
When used together with lithium drugs, it is possible to increase the manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
A single dose of sildenafil in a dose of 100 mg in patients with essential hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Antiviral drugs (ritonavir) increase plasma concentrations of slow calcium channel blockers (including amlodipine).
A single dose of aluminum and magnesium-containing antacids does not have a significant effect on the pharmacokinetics of amlodipine.
Grapefruit juice can reduce the concentration of amlodipine in the blood plasma, however, a simultaneous single dose of 240 mg of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine.
Conditions for dispensing from pharmacies The drug is dispensed with a prescription. Conditions and periods of storage The drug should be stored out of the reach of children, in a dry place, protected from light at a temperature not exceeding 25°C. Shelf life: 3 years.
