Diltiazem Lannacher retard tablets p/o 90mg №10×2

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Diltiazem Lannacher tab. ret.p/cap.vol.90mg in blister.in pack No. 10×2
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White film-coated tablets, round and biconvex, without notch for breaking. The main active ingredient Diltiazem Release form Tablets Dosage 90 mg Pharmacological properties Pharmacodynamics Diltiazem belongs to the pharmacotherapeutic group of calcium antagonists (calcium channel blockers). The scheme of action is based on inhibition of calcium entry into myocardial cells (pacemaker system, cardiac conduction system, functioning myocardium) and into vascular smooth muscle cells. Diltiazem is effective against angina by dilating the coronary arteries and reducing myocardial oxygen consumption by reducing cardiac afterload. Diltiazem acts hypotensively through peripheral vasodilation and a decrease in systemic vascular resistance. Diltiazem also works as an antiarrhythmic drug, especially through inhibition of atrioventricular node conduction. Normal atrial and ventricular conduction of the myocardium is not affected. Practically does not influence formation of an impulse of a sinoatrial node. In the case of sinus node dysfunction, cessation of activity of the sinus node or sinoauricular blockade may occur. The potential for a marked negative inotropic effect is usually offset by decreased afterload, decreased myocardial oxygen consumption, and through reflex sympathetic activation over the therapeutic dosage range, including in patients with relatively normal myocardial function. When using diltiazem in conjunction with nitrates, additive effects have been reported in patients suffering from angina pectoris. Pharmacokinetics Absorption Diltiazem is almost completely absorbed from the gastrointestinal tract; there is evidence that bioavailability is about 40-50% due to extensive hepatic first pass metabolism. Diltiazem exhibits non-linear kinetics, so its bioavailability increases with dose in a highly disproportionate manner. Distribution Diltiazem is approximately 70-80% bound to plasma proteins (approximately 35-40% to albumin). Metabolism Diltiazem is metabolized in the liver by multifunctional cytochrome P450 oxidases. Only 2-4% enters the urine unchanged. Two metabolites, deacetyl-dilthiazem and N-dimethyl-dilthiazem, have reduced pharmacological activity. Excretion Diltiazem and its metabolites are excreted through the intestines with bile and kidneys. The half-life is about 4-10 hours. Kinetics in special groups of patients In patients with impaired hepatic function, bioavailability may be increased and excretion slowed down. In patients with impaired renal function, the pharmacokinetics of diltiazem does not differ from that in healthy individuals. In clinical studies of diltiazem, an insufficient number of subjects aged 65 years and older took part in order to determine the differences in pharmacokinetics compared with younger patients. According to other clinical trials, no differences were found between elderly and young patients. In general, dosing in the elderly should be cautious starting at the lower end of the dose range due to the greater incidence of decreased hepatic, renal, or cardiac function and comorbidities or other drug therapy. Preclinical safety data In studies of repeated dose toxicity, mutagenicity and carcinogenicity, no significant risks to humans were observed. Reproductive toxicity studies in mice, rats and rabbits have demonstrated increased embryonic and fetal mortality as well as skeletal abnormalities. In rats, perinatal mortality of offspring was increased. List of excipients Lactose monohydrate, polyacrylate dispersion 30%, copolymer of methacrylic acid and ethyl acrylate, copolymer of ammonium methacrylate (type B), hypromellose, magnesium stearate, macrogol 6000, titanium dioxide (E 171), talc. Indications for long-term treatment of coronary heart disease, including chronic stable angina, vasospatic angina (Prinzmetal’s angina) and angina after myocardial infarction; long-term treatment of arterial hypertension. Route of administration and doses The dose of Diltiazem Lannacher is prescribed individually depending on the severity of the disease. The recommended daily dose is 180-360 mg. The usual dose is one film-coated tablet twice a day; if necessary, the required dosage may be increased to a maximum of 2 film-coated tablets twice a day. With long-term treatment, after achieving a permanent therapeutic effect with a higher dose, the possibility of reducing the dosage should be considered. Patients with ischemic heart disease, especially after long-term treatment or bypass surgery, should not abruptly stop taking diltiazem – the dose should be reduced gradually (see Special Instructions and Precautions). Lannacher retard 180 mg film-coated is also available. Elderly Patients Elderly patients may be given the usual dose starting at the lower end of the dose range. If necessary, the dose should be adjusted depending on individual tolerance and the state of liver and kidney function (see Special instructions and precautions). Impaired renal function Patients with impaired renal function of mild to moderate severity can be given the usual dose. If necessary, the dose should be adjusted depending on individual tolerance (see. Special instructions and precautions). Impaired liver function Patients with mild or moderate hepatic insufficiency can be given the usual dose. If necessary, the dose should be adjusted depending on individual tolerance (see. Special instructions and precautions). Children There are no data on the use of diltiazem in children. For this reason, children should not take Diltiazem Lannacher (see Warnings and Precautions). Tablets should be taken with a liquid during a meal. The tablets must not be chewed. Use during pregnancy and lactation Pregnancy There are no or limited data on the use of diltiazem in pregnant women. Reproductive toxicity found in animal studies (see Preclinical Safety Data). The use of Diltiazem Lannacher during pregnancy and in women of childbearing potential who are not using contraception is not recommended (see Contraindications). Lactation Diltiazem passes into breast milk. In this regard, Diltiazem Lannacher should not be used during lactation (see Contraindications). Precautions Diltiazem should be used with caution in patients with asymptomatic and mild heart failure (NYHA I-II), as well as first-degree CA and AV block. Careful monitoring of blood pressure and heart rate is necessary for patients with impaired hepatic or renal function, as well as for elderly patients. If necessary, the dosage should be adjusted. For safety reasons, diltiazem should not be abruptly discontinued in patients with coronary artery disease, especially after long-term treatment or bypass surgery, to avoid recurrence of angina attacks. Instead, the dosage should be reduced gradually. In the case of long-term treatment, monitoring of liver function is necessary, especially in predisposed patients. There are no data on the use of diltiazem in children. For this reason, children should not take Diltiazem Lannacher. Diltiazem Lannacher contains 40 mg lactose monohydrate per tablet. They should not be taken by patients with rare hereditary metabolic disorders (galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption syndrome). Interaction with other drugsDrugs, the combined use of which is contraindicated: Dantrolene in / in animal studies, lethal atrial fibrillation was observed during the joint / in the introduction of verapamil and dantrolene. Concomitant intravenous administration of diltiazem and dantrolene to humans has been associated with myocardial depression and cardiogenic shock. For this reason, co-administration of intravenous diltiazem and dantrolene should be avoided. Medicinal products to be used with caution: Lithium Risk of increased lithium-induced neurotoxicity. Nitrate derivatives Increase the hypotensive effect and the feeling of weakness (have an additive vasodilatory effect). In all patients treated with potassium antagonists, other nitrate derivatives should only be given in gradually increasing doses. Theophylline Increases the level of circulating theophylline. Anesthetics Inhibition of cardiac contractility, conduction and automatism, as well as vasodilation associated with the action of anesthetics can be enhanced by calcium channel blockers. With the simultaneous use of anesthetics and calcium channel blockers, their doses should be carefully selected. Alpha antagonists Increase the hypotensive effect. Concomitant treatment with alpha-antagonists may cause or exacerbate symptomatic hypotension. The combination of diltiazem and alpha antagonists should be weighed in advance and should only be given under strict blood pressure control. Amiodarone, digoxin Increase the risk of bradycardia. When combined with diltiazem, caution is recommended, especially in elderly patients and when taking high doses of the drug. Beta-blockers May cause cardiac arrhythmias (excessive bradycardia, AV conduction disturbances), sinoauricular and atrioventricular impulse conduction disturbances, and cardiac arrest (have a synergistic effect). This drug combination should only be taken under clinical and ECG monitoring, especially at the start of treatment. Other antiarrhythmic drugs Diltiazem is also an antiarrhythmic drug, therefore it is not recommended to prescribe it together with other antiarrhythmic drugs (due to the risk of an additive increase in unwanted effects on the heart). This drug combination should only be used for clinical and ECG monitoring. Carbamazepine Increases the level of circulating carbamazepine. It is recommended to determine the plasma concentrations of carbamazepine so that the dose can be adjusted if necessary. Rifampicin During treatment with rifampicin, there is a risk of a decrease in diltiazem plasma levels. Patients should be closely monitored at the beginning and at the end of treatment with rifampicin. H2 receptor antagonists (cimetidine, ranitidine) Increased plasma concentrations of diltiazem. Patients who start or stop anti-H2 agents in addition to their diltiazem treatment should be closely monitored. In such cases, it may be necessary to establish the daily dose of diltiazem. Cyclosporine Increases the level of circulating cyclosporine. During combination therapy and after its termination, it is recommended to reduce the dose of cyclosporine, monitor renal function and establish the level of cyclosporine so that the dose of diltiazem can be determined. Antihypertensive drugs, tri- and tetracyclic antidepressants, antipsychotics There is an increase in the hypotensive effect. Muscle relaxants such as diltiazem curare may increase neuromuscular blockade. Calcium salts, vitamin D Elevated serum calcium levels may reduce the effects of diltiazem. Medicinal products requiring special attention when used together: Due to potential additive effects, careful dose adjustment is necessary in patients taking diltiazem concomitantly with other medicinal products that affect heart rate and/or intraventricular conduction. Diltiazem is metabolized by cytochrome CYP3 A4. On average, there was a (less than doubled) increase in plasma concentrations of diltiazem when administered concomitantly with a strong inhibitor of CYP3 A4. Diltiazem is an isomorphic inhibitor of CYP3 A4. Simultaneous administration together with other substrates of cytochrome CYP3 A4 may lead to an increase in plasma concentration of the drug taken together. Simultaneous administration of diltiazem with an inducer of cytochrome CYP3 A4 may lead to a decrease in plasma concentrations of diltiazem. Buspirone In nine healthy volunteers, diltiazem significantly increased the mean AUC for buspirone and Cmax by 4.1 times compared with placebo. Diltiazem had no significant effect on T1 / 2 and Tmax of buspirone. An increase in the effectiveness of buspirone is possible when used together with diltiazem. Subsequent dose adjustments may be necessary when drugs are co-administered and should be based on clinical judgement. Benzodiazepines (midazolam, triazolam) Diltiazem significantly increases the plasma concentrations of midazolam and triazolam and prolongs their half-life. Particular attention should be paid to the simultaneous administration of short-term benzodiazepines metabolized by cytochrome CYP3 A4. Corticosteroids (methylprednisolone) Suppression of methylprednisolone metabolism (CYP3 A4) and suppression of P-glycoprotein. Patients starting treatment with methylprednisolone should be monitored. It may be necessary to taper the dose of methylprednisolone. Statins Diltiazem, as an inhibitor of CYP3 A4, significantly increases the AUC of some statins. Co-administration of diltiazem with statins, which are metabolized by CYP3 A4, may increase the risk of myopathy and rhabdomyolysis. If possible, co-administration of diltiazem and statins metabolized by cytochrome CYP3 A4 should be avoided, otherwise monitoring for signs and symptoms of potential statin toxicity is recommended. Contraindications hypersensitivity to the active substance or to any of the excipients; cardiogenic shock; acute myocardial infarction with congestion in the lungs, radiographically confirmed; moderate or severe heart failure (NYHA III and IV); severe conduction disturbances (sick sinus syndrome, sinoauricular blockade and atrioventricular blockade of the second or third degree, except for patients with a functioning pacemaker); ventricular preexcitation syndrome (eg, Wolff-Parkinson-White) with atrial flutter or atrial fibrillation (risk of ventricular tachycardia); simultaneous intravenous administration of beta-blockers; combined use with dantrolene when administered intravenously; arterial hypotension (systolic pressure below 90 mm Hg); bradycardia (with a heart rate of less than 50 beats / min); children’s age (lack of relevant clinical data); pregnancy; lactation; severe violations of the liver, kidneys. Caution should be exercised in case of mild heart failure (NYHA I, II) sinoauricular block and first degree atrioventricular block. There are insufficient clinical data on use in children. Composition Diltiazem hydrochloride………………………………………..90 mg For a complete list of excipients, see the List of excipients section. Overdose The toxic dose for humans is not known. The drug is rapidly metabolized in the body and the content of diltiazem in the blood after taking a standard dose can vary tenfold. In case of an overdose of diltiazem, hypotension, bradycardia, heart block and heart failure may occur. Treatment of an overdose depends on the type and severity of the symptoms. In addition to gastric lavage and treatment with adsorbents (activated charcoal), the following measures may be required: Low blood pressure Proper positioning of the patient, volume replacement therapy, dopamine or norepinephrine as needed. Bradycardia, second or third degree atrioventricular block Atropine, isoprenaline, orciprenaline, pacemaker as needed. Heart failure Isoproterenol, dopamine, dobutamine, diuretics. Cardiac arrest Chest compressions, mechanical ventilation, ECG monitoring, follow-up emergency measures such as defibrillation or pacemaker. Symptoms of intoxication are very well stopped by intravenous administration of 10-20 ml of a 10% solution of calcium gluconate, if necessary. Removal of the active substance by hemodialysis is not possible due to the high ability to bind to proteins (approximately 80%). Storage conditionsKeep in a place protected from light. Store at a temperature not exceeding 25°C. Keep out of the reach of children. Buy Diltiazem Lannacher retard tablets p/o 90mg No. 10×2