Description of the drug DILTIAZEM LANNACHER
When used simultaneously with beta-blockers (including propranolol, atenolol, metoprolol, pindolol, sotalol), an additive cardiodepressive effect is possible along with an increase in the antianginal effect in most patients. Patients with pre-existing left ventricular dysfunction or conduction disturbances are at increased risk of developing severe and life-threatening bradycardia.
Diltiazem inhibits the metabolism of propranolol, metoprolol, but not atenolol.
When used simultaneously with amiodarone, the negative inotropic effect, bradycardia, conduction disturbances, and AV block are enhanced.
Since diltiazem inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, drug interactions due to increased plasma concentrations of statins are theoretically possible. Cases of rhabdomyolysis have been described.
When used simultaneously with buspirone, the concentration of buspirone in the blood plasma increases, its therapeutic and side effects increase.
When used simultaneously with vecuronium chloride, the duration of neuromuscular blockade may be increased.
When used simultaneously with digoxin and digitoxin, it is possible to increase the concentrations of digoxin and digitoxin in the blood plasma.
When used simultaneously with imipramine, the concentration of imipramine in the blood plasma increases and there is a risk of developing undesirable changes on the ECG.
Cases of increased plasma concentrations of trimipramine and nortriptyline when used simultaneously with diltiazem have been described.
Diltiazem increases the bioavailability of imipramine by reducing its clearance. Changes in the ECG are due to an increase in the concentration of imipramine in the blood plasma and the additive inhibitory effect of diltiazem and imipramine on AV conduction. Diltiazem is believed to interact in the same way with trimipramine and nortriptyline.
When used simultaneously with insulin, a case of decreased insulin effectiveness has been described.
Due to the inhibition of the metabolism of anticonvulsants in the liver under the influence of diltiazem and a decrease in their clearance from the body, it is possible to increase the concentrations of carbamazepine and phenytoin in the blood plasma with the risk of developing toxic effects.
When used simultaneously with lithium carbonate, cases of the development of acute parkinsonism syndrome and psychosis have been described.
When used simultaneously with midazolam, triazolam, the concentration of midazolam and triazolam in the blood plasma increases and their effects are enhanced due to the inhibition of the CYP3A4 isoenzyme under the influence of diltiazem, with the participation of which the metabolism of these benzodiazepines is carried out.
When used simultaneously with sodium amidotrizoate, the antihypertensive effect of diltiazem may be enhanced.
When used simultaneously with sodium nitroprusside, a significant increase in effectiveness in controlled arterial hypotension is possible.
When used simultaneously with nifedipine, the antihypertensive effect is enhanced.
Rifampicin induces liver enzyme activity, accelerating the metabolism of diltiazem, which leads to a decrease in its effectiveness.
When used simultaneously with theophylline, a slight decrease in the metabolism of theophylline in the liver is possible, apparently due to inhibition of the CYP1A2 isoenzyme under the influence of diltiazem.
When used concomitantly with cisapride, a case of impaired consciousness has been described, apparently due to a pronounced prolongation of the QT interval. It is believed that diltiazem inhibits the activity of the CYP3A4 isoenzyme, which leads to increased plasma concentrations of cisapride and possibly increased cardiotoxicity.
With simultaneous use, diltiazem inhibits the metabolism of cyclosporine in the liver, which leads to a decrease in its elimination and an increase in plasma concentrations. At the same time, a decrease in the manifestations of nephrotoxicity and an increase in the immunosuppressive effect were noted.
When used simultaneously with cimetidine, the concentration of diltiazem in the blood plasma increases due to inhibition of its oxidative metabolism in the liver under the influence of cimetidine. The effects of diltiazem may be enhanced.
When used simultaneously with enflurane, cases of impaired AV conduction of the myocardium have been reported.
Diltiazem Lannacher retard tablets p/o 90 mg No. 10x2
Name
Diltiazem Lannacher tablet ret.p/film.vol.90mg in blisters in pack No. 10x2
Description
White, film-coated tablets, round and biconvex, without a break mark.
Main active ingredient
Diltiazem
Release form
Pills
Dosage
90 mg
Pharmacological properties
Pharmacodynamics
Diltiazem belongs to the pharmacotherapeutic group of calcium antagonists (calcium channel blockers). The mode 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. It has virtually no effect on the formation of the sinus node impulse. In the case of sinus node dysfunction, cessation of sinus node activity or sinoauricular block may occur. The potential for significant negative inotropic effects is usually offset by decreased afterload, decreased myocardial oxygen consumption, and through reflex sympathetic activation over the therapeutic dosing range, including in patients with relatively normal myocardial function. Additive effects have been reported when diltiazem is used in combination with nitrates in patients with 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 nonlinear kinetics such that its bioavailability increases with dose in a highly disproportionate manner. Distribution Diltiazem is approximately 70-80% bound to plasma proteins (approximately 35-40% bound to albumin). Metabolism Diltiazem is metabolized in the liver by multifunctional cytochrome P450 oxidases. Only 2-4% enters the urine unchanged. Two metabolites, desacetyl-diltiazem and N-dimethyl-diltiazem, have reduced pharmacological effects. Excretion Diltiazem and its metabolites are excreted through the intestines with bile and kidneys. The half-life is approximately 4-10 hours. Kinetics in special groups of patients In patients with impaired hepatic function, bioavailability may be increased and elimination may be delayed. In patients with impaired renal function, the pharmacokinetics of diltiazem do not differ from those in healthy individuals. Clinical studies of diltiazem did not include sufficient numbers of subjects aged 65 years or older to determine differences in pharmacokinetics compared with younger patients. Other clinical trials have shown no differences between older and younger patients. In general, dosing in the elderly should be done cautiously, starting at the lower end of the dosage range due to the greater incidence of decreased liver, renal, or cardiac function and concomitant diseases or other drug therapy. Preclinical Safety Data No significant risks to humans were observed in repeated dose toxicity, mutagenicity and carcinogenicity studies. 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, dispersible polyacrylate 30%, copolymer of methacrylic acid and ethyl acrylate, ammonium methacrylate copolymer (type B), hypromellose, magnesium stearate, macrogol 6000, titanium dioxide (E 171), talc.
Indications for use
long-term treatment of coronary heart disease, including chronic stable angina, vasospathic angina (Prinzmetal's angina) and angina after myocardial infarction; long-term treatment of arterial hypertension.
Directions for use 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 can be increased to a maximum of 2 film-coated tablets twice a day. For long-term treatment, after achieving a constant therapeutic effect with a higher dose, the possibility of reducing the dosage should be considered. Patients with coronary artery 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 can 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). Renal impairment Patients with mild to moderate renal impairment can be given the usual dose. If necessary, the dose should be adjusted depending on individual tolerance (see Special instructions and precautions). Hepatic impairment Patients with mild or moderate hepatic impairment may 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 available regarding the use of diltiazem in children. For this reason, children should not take Diltiazem Lannacher (see Warnings and Precautions). The tablets should be taken with liquid during meals. 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 has been detected in animal studies (see Preclinical Safety Data). The use of the drug Diltiazem Lannacher during pregnancy and in women of childbearing potential who do not use 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).
Precautionary measures
Diltiazem should be used with caution in patients with asymptomatic and mild heart failure (NYHA I-II), as well as first-degree SA 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 stopped abruptly 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 case of long-term treatment, monitoring of liver function is necessary, especially in predisposed patients. There are no data regarding the use of diltiazem in children. For this reason, children should not take Diltiazem Lannacher. Diltiazem Lannacher contains 40 mg of lactose monohydrate in each 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 drugs
Drugs with which co-administration is contraindicated: Dantrolene IV In animal studies, lethal atrial fibrillation was observed during combined IV administration of verapamil and dantrolene. Myocardial depression and cardiogenic shock have been observed with concomitant intravenous administration of diltiazem and dantrolene to humans. For this reason, concomitant IV administration of diltiazem and dantrolene should be avoided. Medicines that require caution when used together: Lithium Risk of increased lithium-induced neurotoxicity. Nitrate derivatives Increase the hypotensive effect and feeling of weakness (have an additive vasodilatory effect). In all patients treated with potassium antagonists, other nitrate derivatives should be prescribed only in gradually increasing doses. Theophylline Increases circulating levels of theophylline. Anesthetics Inhibition of cardiac contractility, conduction and automaticity, as well as vasodilation associated with the action of anesthetics can be enhanced by calcium channel blockers. When using anesthetics and calcium channel blockers simultaneously, their doses should be carefully selected. Alpha antagonists Increase the hypotensive effect. Concomitant treatment with alpha antagonists may cause or worsen symptomatic hypotension. The combination of diltiazem and alpha antagonists should be weighed in advance and should be prescribed only with strict blood pressure control. Amiodarone, digoxin Increase the risk of bradycardia. Caution is recommended when combined with diltiazem, 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 conduction disturbances and cardiac arrest (have a synergistic effect). This combination of drugs should only be taken with clinical and ECG monitoring, especially at the beginning of treatment. Other antiarrhythmic drugs Diltiazem is also an antiarrhythmic drug, and its use together with other antiarrhythmic drugs is not recommended (due to the risk of an additive increase in adverse effects on the heart). This combination of drugs should only be used under clinical and ECG monitoring. Carbamazepine Increases circulating levels of carbamazepine. It is recommended to determine plasma concentrations of carbamazepine so that the dose can be adjusted if necessary. Rifampicin When treated with rifampicin, there is a risk of decreased plasma levels of diltiazem. Patients should be carefully monitored when starting and ending treatment with rifampicin. H2 receptor antagonists (cimetidine, ranitidine) Increased plasma concentrations of diltiazem. Patients who start or stop taking anti-H2 agents in addition to their diltiazem treatment should be closely monitored. In such cases, it may be necessary to adjust the daily dose of diltiazem. Cyclosporine Increases circulating levels of cyclosporine. During combination therapy and after its completion, it is recommended to reduce the dose of cyclosporine, monitor renal function and adjust the level of cyclosporine so that the dose of diltiazem can be determined. Antihypertensive drugs, tri- and tetracyclic antidepressants, antipsychotic drugs The hypotensive effect is enhanced. Muscle relaxants such as curare Diltiazem may enhance neuromuscular blockade. Calcium salts, vitamin D Elevated serum calcium levels may reduce the effects of diltiazem. Drugs that require special attention during co-administration: Due to the potential for additive effects, careful dosage adjustment is necessary in patients taking diltiazem with other drugs that affect heart rate and/or intraventricular conduction. Diltiazem is metabolized by cytochrome CYP3 A4. On average, there was a (less than double) increase in plasma concentrations of diltiazem when administered concomitantly with a strong CYP3 inhibitor A4. Diltiazem is an isomorphic inhibitor of cytochrome CYP3 A4. Concomitant use with other cytochrome CYP3 A4 substrates may result in increased plasma concentrations of the drug taken together. Concomitant use of diltiazem with an inducer of cytochrome CYP3 A4 may result in a decrease in the plasma concentration of diltiazem. Buspirone In nine healthy volunteers, diltiazem significantly increased the mean AUC for buspirone and Cmax by 4.1-fold 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 dosage adjustments may be necessary when drugs are used together and should be based on clinical judgment. Benzodiazepines (midazolam, triazolam) Diltiazem significantly increases 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 the metabolism of methylprednisolone (CYP3 A4) and suppression of P-glycoprotein. Patients who initiate treatment with methylprednisolone should be monitored. It may be necessary to reduce the dose of methylprednisolone. Statins Diltiazem, as an inhibitor of cytochrome CYP3 A4, significantly increases the AUC of some statins. When taking diltiazem concomitantly with statins that are metabolized by cytochrome CYP3 A4, the risk of myopathy and rhabdomyolysis may increase. If possible, concomitant use of diltiazem and statins metabolized by 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 pulmonary congestion, radiologically confirmed; moderate or severe heart failure (NYHA III and IV); severe conduction disturbances (sick sinus syndrome, sinoauricular block and atrioventricular block 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 less than 50 beats/min); childhood (lack of relevant clinical data); pregnancy; lactation; severe dysfunction of the liver and kidneys. Caution should be exercised in case of mild heart failure (NYHA I, II) sinoauricular block and first degree atrioventricular block. There is insufficient clinical data for use in children.
Compound
Diltiazem hydrochloride………………………………………..90 mg For a complete list of excipients, see the section List of excipients.
Overdose
The toxic dose for humans is not known. The drug is metabolized quite quickly in the body and the blood level of diltiazem after taking a standard dose can vary tenfold. In case of diltiazem overdose, hypotension, bradycardia, heart block and heart failure may occur. Treatment for overdose depends on the type and severity of symptoms. In addition to gastric lavage and treatment with adsorbents (activated carbon), the following measures may be required: Low blood pressure Correct positioning of the patient, volume replacement therapy, dopamine or norepinephrine, if necessary. Bradycardia, second or third degree atrioventricular block Atropine, isoprenaline, orciprenaline, pacemaker if necessary. 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 relieved by intravenous administration of 10-20 ml of 10% calcium gluconate solution, if necessary. Removal of the active substance by hemodialysis is impossible due to its high protein binding ability (approximately 80%).
Storage conditions
Store in a place protected from light. Store at a temperature not exceeding 25°C. Keep out of the reach of children.
Diltiazem tablets - reviews
Alla Valentinovna
https://pharm-market.ru/catalog/diltiazem.aspx
Previously, my blood pressure often increased, and as a result, arrhythmia could begin. The condition was very bad then. But recently my GP prescribed me Diltiazem Regard. I use it according to the instructions, 2 tablets 3 times a day and am very pleased with its effect. My condition has stabilized, I feel much better now, calmer and my mood has improved.
Kaleria
https://pharm-market.ru/catalog/diltiazem.aspx
Oh, and for us, thank God, everything worked out somehow without any side effects. My husband developed a terrible arrhythmia and our doctor advised him to take diltiazem. My husband took it three times a day as directed. Now his condition has stabilized. We can conclude that the drug is very effective.
valentine
Mild dizziness sometimes occurs after taking diltiazem. But this drug works effectively. It lowers blood pressure gradually. This is precisely its advantage.
Alexandra Batistova
https://www.piluli.ru/product/Diltiazem/review
She took Diltiazem as part of a complex treatment for arrhythmia. I noticed that my blood pressure began to rise a little, I was tempted to take another drug, but the doctor said that this was a side effect. I had to cancel because with my diagnosis I can’t experience pressure surges. These pills are probably good for those who do not have problems with blood pressure.
Inessa
https://www.apreka.ru/?l=diltiazem_tabletki
I have been taking Diltiazem for about three months. At first I took 60 mg 3 times a day, but since I often forgot about taking it at lunch, I wasn’t happy with it. I switched to taking 90 mg morning and evening, it’s more convenient.
2 weeks after starting treatment, I began to notice a sharp decrease in blood pressure, the doctor advised me to reduce the dose to 60 mg 2 times a day. I stopped at this level. Since I inject insulin, the doctor warned that it might be necessary to reconsider the insulin dose, but everything turned out fine. Selecting the dose of the drug was somewhat delayed, almost a month, which brought its own concerns, but with previous medications it was even longer. I think it’s positive that when climbing stairs I don’t feel the same discomfort and shortness of breath.
What makes it a little uncomfortable is that you have to swallow the tablet whole; for me it’s like a test, but I’ve already gotten the hang of it.
The price of the drug is a little high, I thought about switching to substitutes, but my health has improved so much that I’ll probably stick with Diltiazem. The fact that there is no need to combine multiple medications is also in favor of Diltiazem. Of course, no matter how suitable the drug is, it is necessary to constantly monitor the pressure, although I increasingly listen to my perception of well-being and forget about this event.
