Normodipin tablets 10mg №10×3

Name:
Normodipin tabl 10mg in bl. in pack. No. 10×3 Main active ingredient Amlodipine Form of release tablets Composition Each tablet contains: Active ingredients: 5 mg of amlodipine (in the form of 6.944 mg of amlodipine besylate) or 10 mg of amlodipine (in the form of 13.889 mg of amlodipine besylate) in each tablet. Excipients: magnesium stearate, sodium carboxymethyl starch (type A), anhydrous calcium hydrogen phosphate, microcrystalline cellulose.
Description:
5 mg tablets: White or almost white, biconvex, oblong-round tablets debossed with “5” on one side; 10 mg tablets: White or almost white, biconvex, oblong-round tablets debossed with “10” on one side and a notch on the other. Dosage 5 mg and 10 mg Pharmacological properties Pharmacodynamics Being a derivative of dihydropyridine, amlodipine inhibits the transmembrane transition of calcium ions (a blocker of “slow” calcium channels, or an antagonist of calcium ions), and also blocks the transmembrane current of calcium ions into smooth muscle cells of the myocardium and blood vessels. The mechanism of the hypotensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The exact mechanism of action of amlodipine in angina pectoris has not been fully established, however, the anti-ischemic effect of amlodipine occurs in the following two ways: Amlodipine dilates peripheral arterioles and, thus, reduces the total peripheral vascular resistance (afterload), which is overcome by the work of the heart. Since the heart rate does not change, reducing the load on the heart reduces energy consumption and myocardial oxygen demand. The mechanism of action of amlodipine probably also involves the expansion of the main coronary arteries and coronary arterioles in both normal and ischemic areas of the myocardium, thereby increasing the supply of oxygen to the myocardium in patients with coronary artery spasm (Prinzmetal’s angina or variant angina pectoris). In patients with arterial hypertension, a single daily dose of amlodipine provides a clinically significant reduction in blood pressure over 24 hours, both in the supine and standing positions. Due to the gradual action of amlodipine, acute orthostatic hypotension is rare. In patients with angina pectoris, a single daily dose of amlodipine increases the time of exercise, delays the development of an angina attack and ST segment depression (1 mm below the isoline) during exercise, reduces the frequency of angina attacks and the consumption of nitroglycerin tablets. Amlodipine does not adversely affect the metabolism and lipid profile of blood plasma, so it can be used to treat patients with bronchial asthma, diabetes mellitus and gout. Use in patients with coronary heart disease (CHD) The efficacy of amlodipine in the prevention of clinical events in patients with coronary heart disease (CHD) was studied in an independent, multicenter, randomized, double-blind, placebo-controlled study CAMELOT (Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis – Comparison of amlodipine with enalapril in relation to the prevention of thrombosis), which included 1997 patients. In this study, 663 patients received amlodipine 5–10 mg for 2 years, 673 patients received enalapril 10–20 mg, and 655 patients received placebo in combination with standard therapy, which included statins, beta-blockers, diuretics, and aspirin. The main efficacy results are presented in Table 1. The results of the study indicate that treatment with amlodipine was accompanied by a decrease in the frequency of hospitalizations due to angina pectoris and a decrease in the number of revascularization procedures in patients with coronary artery disease. Table 1. Frequency of significant clinical outcomes in the CAMELOT study Cardiovascular complications, number, (%) Amlodipine vs. Placebo Clinical outcome Amlodipine Placebo Enalapril Hazard ratio (95% CI) P-value Primary endpoint Adverse cardiovascular events 110(16.6) 151(23.1) 136(20.2) 0.69(0.54-0) .88) 0.003 Individual components Coronary artery revascularization 78(11.8) 103 (15.7) 95(14.1) 0.73 (0.54-0.98) 0.03 Hospitalization due to angina pectoris 51 (7 .7) 84 (12.8) 86(12.8) 0.58 (0.41-0.82) 0.002 Non-fatal MI 14(2.1) 19 (2.9) 11(1.6) 0.73 (0.37-1.46) 0.37 Stroke or TIA 6 (0.9) 12(1.8) 8(1.2) 0.50 (0.19-1.32) 0, 15 Death due to cardiovascular disease 5 (0.8) 2 (0.3) 5 (0.7) 2.46 (0.48-12.7) 0.27 Hospitalization due to CHF 3 (0, 5) 5 (0.8) 4 (0.6) 0.59 (0.14-2.47) 0.46 Resuscitation after cardiac arrest 0 4 (0.6) 1 (0.1) NA 0.04 Newly diagnosed peripheral vascular disease 5 (0.8) 2 (0.3) 8(1.2) 2.6 (0.50-13.4) 0.24 Abbreviations: CHF – congestive heart failure, CI – confidence interval, MI – myocardial infarction, TIA – transient ischemic attack. Use in patients with heart failure Hemodynamic studies and controlled clinical studies using exercise testing have shown that amlodipine does not cause deterioration in patients with chronic heart failure (NYHA functional class II-IV), as evidenced by the degree of exercise tolerance, left ventricular ejection fraction and clinical symptoms. In a placebo-controlled study (PRAISE) in patients with NYHA functional class III-IV heart failure treated with digoxin, diuretics, and ACE inhibitors, amlodipine did not increase the risk of death or the overall risk of mortality and complications associated with heart failure . In an additional placebo-controlled study (PRAISE-2) in patients with chronic heart failure (NYHA functional class III-IV) without clinical or objective signs of coronary artery disease, who constantly received ACE inhibitors, digitalis and diuretics, amlodipine had no effect on general and cardiovascular mortality. In the same patients, the use of amlodipine was accompanied by an increase in the incidence of pulmonary edema. The Antihypertensive and Lipid-lowering Treatment for the Prevention of Myocardial Infarction Trial (ALLHAT) A randomized, double-blind study of morbidity and mortality called the Anti-hypertensive and lipid-lowering treatment for the prevention of myocardial infarction (ALLHAT) study was conducted to compare the effects of more modern drugs such as amlodipine in 2.5–10 mg/day (calcium channel blocker) or lisinopril 10–40 mg/day (ACE inhibitor) as first-line agents with the thiazide diuretic chlorthalidone 12.5–25 mg/day for treatment mild and moderate arterial hypertension. A total of 33,357 hypertensive patients aged 55 years and older were randomized and followed up for a mean of 4.9 years. Patients had at least one additional risk factor for CHD (coronary heart disease), including previous myocardial infarction or stroke (> 6 months prior to enrollment in the study); documented other cardiovascular disease of atherosclerotic origin (51.5% in total); type 2 diabetes mellitus (36.1%); HDL-C <35 mg/dL (11.6%); left ventricular hypertrophy diagnosed by ECG or echocardiography (20.9%); smoking (21.9%). The primary end point was a composite combination of fatal CHD or non-fatal myocardial infarction. There was no significant difference in the frequency of the main endpoint between amlodipine and chlorthalidone therapy: RR 0.98 95% CI 0.90-1.07 p = 0.65. Among the secondary endpoints, heart failure (a component of a composite cardiovascular endpoint) was significantly higher in the amlodipine group than in the chlorthalidone group (10.2% vs. 7.7%, RR 1.38, 95 % CI 1.25-1.52 p < 0.001). However, there was no significant difference in all-cause mortality between amlodipine and chlorthalidone therapy: RR 0.96 95% CI 0.89-1.02 p = 0.20. Pediatric patients (children and adolescents 6 years of age and older) In a study involving 268 children aged 6 to 17 years, predominantly suffering from secondary arterial hypertension, amlodipine at doses of 2.5 mg and 5 mg was compared with placebo. The study demonstrated that both doses of the drug reduced systolic blood pressure to a significantly greater extent compared to placebo. The difference between the two doses was not statistically significant. The long-term effects of amlodipine on growth, puberty and overall development have not been studied. The long-term effect of amlodipine therapy in childhood on the reduction of cardiovascular morbidity and mortality in adulthood has also not been established. Pharmacokinetics Absorption, distribution and binding to plasma proteins Amlodipine is well absorbed after oral administration at therapeutic doses. The maximum concentration of the drug in the blood is observed after 6-12 hours. Absolute bioavailability is approximately 64-80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins. Eating does not affect the bioavailability of amlodipine. Biotransformation/elimination The terminal half-life is approximately 35-50 hours, which allows the drug to be administered once a day. Amlodipine is extensively metabolized in the liver to inactive metabolites, the drug is excreted in the urine in the form of the parent substance (10%) and metabolites (60%). Impaired liver function There are limited clinical data on the use of amlodipine in patients with impaired liver function. Patients with liver failure; have a reduced clearance of amlodipine, resulting in an increase in AUC of approximately 40-60% and a prolongation of the half-life. Elderly patients The time to reach the maximum plasma concentration of amlodipine in young and elderly patients is the same. However, in elderly patients, the clearance of amlodipine is reduced, which leads to an increase in AUC and half-life in the elderly. An increase in AUC and half-life is also observed in patients with congestive heart failure. Children and adolescents A pharmacokinetic study was conducted in 74 children and adolescents aged 12 months to 17 years with arterial hypertension (34 patients aged 6 to 12 years, 28 patients aged 13 to 17 years). Patients received amlodipine in doses of 1.25 to 20 mg once or twice daily. In children aged 6-12 years and adolescents aged 13-17 years, the apparent clearance (CL / F) after oral administration was 22.5 and 27.4 l / h, respectively, in boys, and 16.4 and 21, 3 l / h, respectively - in girls. Large interindividual variability was observed. Data for children under 6 years of age is limited. Indications for use Arterial hypertension. Chronic stable angina. Vasospastic angina (Prinzmetal's angina). Contraindications Normodipin is contraindicated in patients with the following conditions: hypersensitivity to amlodipine, dihydropyridine derivatives or any other components of the drug listed in the "Composition" section; severe arterial hypotension; shock (including cardiogenic shock); obstruction of the outflow tract of the left ventricle (for example, severe aortic stenosis); hemodynamically unstable heart failure after acute myocardial infarction. Use during pregnancy and lactation Pregnancy The safety of amlodipine for the treatment of pregnant women has not been established. Studies conducted on animals indicate that in high doses the drug has a toxic effect on reproductive function. Use during pregnancy is recommended only if there is no safer alternative, or if the disease of the mother poses a greater risk to the mother and fetus than treatment. Breastfeeding period It is not known whether amlodipine passes into breast milk. The decision to continue/stop breastfeeding or continue/stop treatment with amlodipine should be made taking into account the benefits of breastfeeding for the baby and the benefits to the mother from treatment. Fertility Reversible biochemical changes in the heads of spermatozoa have been reported in some patients receiving calcium channel blockers. Clinical data regarding the possible effect of amlodipine on fertility is not enough. In one study in rats, the drug was found to affect male fertility. Dosing and Administration Doses Adults For both hypertension and angina pectoris, the usual starting dose is 5 mg once daily. Depending on the patient's individual response to treatment, this dose may be increased up to a maximum dose of 10 mg per day. In patients with arterial hypertension, Normodipin is used in combination with a thiazide diuretic, an alpha-blocker, a beta-blocker, or an angiotensin-converting enzyme inhibitor. In patients with angina who do not respond to treatment with nitrates and / or adequate doses of beta-blockers, Normodipine can be used both as monotherapy and in combination with other antianginal agents. With the simultaneous appointment of the drug Normodipin with thiazide diuretics, beta-blockers and inhibitors, dose adjustment is not required. Special groups of patients Elderly When used in similar doses, Normodipin is equally well tolerated by both young and elderly patients. Elderly patients are recommended the usual treatment regimen, however, dose increases should be carried out with caution (see sections "With caution" and "Pharmacokinetics"). Impaired liver function Recommended doses for patients with mild or moderate hepatic impairment have not been established. Dose selection should be carried out with caution, treatment should be started with the lowest recommended dose (see sections "With caution" and "Pharmacokinetics"). The pharmacokinetics of amlodipine in subjects with severe hepatic impairment has not been studied. Treatment of patients with severe hepatic impairment should begin with a minimum dose of amlodipine, dose titration should be carried out gradually. Impaired renal function Changes in the concentration of amlodipine in blood plasma do not correlate with the degree of impaired renal function, so these patients are recommended to use the usual doses. Amlodipine is not excreted by hemodialysis. Pediatric patients Children and adolescents aged 6 to 17 years with hypertension The recommended starting dose for the treatment of hypertension in patients aged 6 to 17 years is 2.5 mg daily; if after 4 weeks of using the drug it was not possible to achieve control over blood pressure, the dose may be increased to 5 mg per day. The use of doses exceeding 5 mg per day for the treatment of pediatric patients has not been studied (see sections "Pharmacodynamics" and "Pharmacokinetics"). This drug is not manufactured in the 2.5 mg dosage. Children under 6 years No data available. How to use Tablets for oral administration. Side effectsA brief overview of the safety profile The most frequently observed adverse reactions during the treatment period were the following: drowsiness, dizziness, headache, palpitations, hot flashes, abdominal pain, nausea, swelling of the ankles, edema and fatigue. Tabular list of adverse reactions During treatment with amlodipine, the following adverse reactions were noted, their frequency is determined using the following designations: very often (? 1/10); often (? 1/100 and < 1/10); infrequently (? 1/1000 and < 1/100); rarely (? 1/10000 and < 1/1000); very rarely (< 1/10000). Within each organ system class, adverse reactions are presented in descending order of severity. Class of organ systems Frequency Adverse reactions Blood and lymphatic system disorders Very rare Leukocytopenia, thrombocytopenia Immune system disorders Very rare Allergic reactions Metabolic and nutritional disorders Very rare Hyperglycemia Psychiatric disorders Uncommon Depression, mood changes (including anxiety), insomnia Rare Confusion Nervous system disorders Common Drowsiness, dizziness, headache (especially at the beginning of treatment) Uncommon Tremor, dysgeusia, syncope, hypesthesia, paresthesia Very rare Increased muscle tone, peripheral neuropathy Visual disturbances Uncommon Visual disturbances (including diplopia ) Ear and labyrinth disorders Uncommon Tinnitus Heart problems Common Palpitations Uncommon Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) Very rare Myocardial infarction Vascular disorders Common Flushing Uncommon Hypotension Very rare Vasculitis Respiratory, chest and mediastinal disorders Common Dyspnea Uncommon Cough, rhinitis Gastrointestinal disorders Common Abdominal pain, nausea, dyspepsia, change in bowel habits (including diarrhea and constipation) Uncommon Vomiting, dry mouth Very rare Pancreatitis, gastritis, gingival hyperplasia Liver and biliary tract disorders Very rare Hepatitis, jaundice, elevated liver transaminases* Skin and subcutaneous tissue disorders Uncommon Alopecia, purpura, discoloration of the skin, hyperhidrosis , pruritus, rash, exanthema, urticaria Very rare Angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema, photosensitivity Musculoskeletal and connective tissue disorders Common Ankle edema, muscle cramps Uncommon Arthralgia, myalgia, back pain Kidney and urinary disorders tract disorders Uncommon Urination disorders, nocturia, frequent urination Genital and breast disorders Uncommon Impotence, gynecomastia General disorders and injection site disorders Very common Edema Common Malaise, weakness Uncommon Chest pain, pain, malaise Influence on laboratory and instrumental results studies Uncommon Weight gain, weight loss *usually accompanied by cholestasis Isolated cases of extrapyramidal syndrome have been reported. Overdose Experience in the treatment of intentional drug overdose in humans is limited. Symptoms Available data suggest that a significant overdose can lead to excessive peripheral vasodilation with the possible development of reflex tachycardia. Cases of severe and persistent arterial hypotension, including those with the development of shock and death, have been described. Treatment In case of clinically significant arterial hypotension caused by an overdose of amlodipine, active measures are required to maintain the function of the cardiovascular system, including bringing the lower extremities to an elevated position, monitoring heart and lung function, monitoring blood volume and diuresis. To restore vascular tone and normalize blood pressure, in the absence of contraindications, it is possible to use vasoconstrictor drugs. To eliminate the effects of calcium channel blockade, calcium gluconate is administered intravenously. In some cases, gastric lavage may be effective. The appointment of activated charcoal to healthy volunteers immediately or within 2 hours after taking amlodipine at a dose of 10 mg led to a significant decrease in the absorption of the drug. Since amlodipine is largely bound to serum proteins, hemodialysis is ineffective. Interactions with other drugs Effects of other drugs on amlodipine CYP3A4 inhibitors Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine, which may increase the risk of hypotension. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this regard, monitoring of the clinical condition and dose adjustment may be required. Clarithromycin is a CYP3A4 inhibitor. There is an increased risk of hypotension in patients taking clarithromycin and amlodipine. Close monitoring of patients receiving amlodipine concomitantly with clarithromycin is recommended. CYP3A4 inducers There are no data on the effects of CYP3A4 inducers on amlodipine. Simultaneous use of inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. Caution should be exercised when prescribing amlodipine and CYP3A4 inducers at the same time. The simultaneous use of amlodipine and the use of grapefruit or grapefruit juice is not recommended, as this may lead to an increase in the bioavailability of amlodipine in some patients, which, in turn, may enhance the hypotensive effect. Dantrolene (infusion): Cases of ventricular fibrillation and cardiovascular insufficiency accompanied by hyperkalemia have been reported in laboratory animals, with a fatal outcome and collapse during the use of verapamil and intravenous administration of dantrolene. Due to the risk of developing hyperkalemia, the simultaneous use of dantrolene and slow calcium channel blockers, including amlodipine, should be avoided in patients susceptible to malignant hyperthermia, as well as in the treatment of malignant hyperthermia. Effects of amlodipine on other medicinal products Amlodipine enhances the hypotensive effect of other antihypertensive drugs used to lower blood pressure. Tacrolimus Co-administration of tacrolimus and amlodipine may result in increased blood levels of tacrolimus; The mechanism of this interaction is not fully understood. In order to avoid the toxic effects of tacrolimus, the concentration of tacrolimus in the blood should be monitored during therapy with amlodipine and, if necessary, adjust the dose of tacrolimus. Cyclosporine No interaction studies have been conducted to date with cyclosporine and amlodipine in healthy volunteers or other populations, with the exception of kidney transplant recipients who have experienced increases in blood ciclosporin concentrations (mean 0%-40%). In this regard, in such patients, the concentration of cyclosporine in the blood should be monitored during therapy with amlodipine and, if necessary, the dose of cyclosporine should be reduced. Simvastatin Co-administration of multiple doses of amlodipine 10 mg with simvastatin 80 mg resulted in a 77% increase in simvastatin concentrations compared with simvastatin alone. For this reason, it is recommended to limit the dose of simvastatin in patients taking amlodipine to 20 mg per day. In clinical drug interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin, or cyclosporine. Precautions The safety and efficacy of amlodipine in hypertensive crisis has not been established. Heart failure In long-term, placebo-controlled clinical trials in patients with heart failure (NYHA functional class III-IV), it was found that the incidence of pulmonary edema increased in the amlodipine group compared to the placebo group, but this was not associated with worsening heart failure (see section "Pharmacodynamics"). Blockers of "slow" calcium channels, including amlodipine, should be used with caution in the treatment of patients with congestive heart failure, as they increase the risk of cardiovascular complications and the percentage of deaths. Impaired liver function In patients with impaired liver function, the half-life of amlodipine and AUC values increase, recommended doses for such patients have not been established. Treatment with amlodipine should be started with minimal doses. Caution should be exercised when starting treatment and when increasing the dose. In patients with severe hepatic impairment, dose titration should be carried out under close medical supervision. Elderly patients Increasing the dose in elderly patients should be carried out with caution (see sections "Method of application and doses" and "Pharmacokinetics"). Impaired renal function In this group of patients, amlodipine can be used at normal doses. Changes in the concentration of amlodipine in plasma do not correlate with the degree of impaired renal function. Amlodipine is not excreted by hemodialysis. Storage conditions Store at a temperature not exceeding 30 ° C in the original packaging to protect from light. Keep out of the reach of children. Buy Normodipin tablets 10mg No. 10x3 Price for Normodipin tablets 10mg No. 10x3