Diltiazem Lannacher film-coated tablets with prolonged release 90 mg No. 20

Diltiazem

Dantrolene (iv)

Fatal atrial fibrillation has been observed in animals with simultaneous intravenous administration of dantrolene and verapamil. For this reason, simultaneous intravenous administration of dantrolene and diltiazem should be avoided (see section "Contraindications").

Lithium

Risk of increased lithium-induced neurotoxicity.

Diltiazem hydrochloride may enhance the effects of blood pressure-lowering medications when used concomitantly.

When diltiazem is used concomitantly with drugs that reduce myocardial contractility, heart rate and/or suppress impulses (AV conduction) (for example, beta blockers, antiarrhythmic drugs or cardiac glycosides), an enhanced effect, for example, a higher degree of AV blockade, may occur. a decrease in heart rate, a significant decrease in blood pressure and the possible occurrence of heart failure.

For these reasons, careful monitoring of patients is necessary when diltiazem hydrochloride is used concomitantly with this type of drug. When treating with diltiazem hydrochloride, concomitant intravenous beta-blockers should be avoided (see section "Contraindications").

Diltiazem hydrochloride may inhibit the metabolism of drugs that are metabolized by certain P-450 enzymes, especially cytochrome-3A. These include HMG-CoA reductase inhibitors metabolized via CYP3A4, such as simvastatin, lovastatin or atorvastatin. This may result in increased and/or prolonged effectiveness of these medications, including their side effects (eg, rhabdomyolysis, myositis, or hepatitis). If concomitant use with diltiazem is necessary, use a statin that is not metabolized by CYP3A4 or require close monitoring for signs and symptoms of possible statin toxicity.

mTOR (mammalian target of rapamycin) inhibitors

With simultaneous oral administration of 10 mg sirolimus solution and 120 mg diltiazem, the Cmax and AUC of sirolimus (CYP3A4 substrate) increased by 1.4 and 1.6 times, respectively. Diltiazem may increase blood concentrations of everolimus by inhibiting its metabolism by CYP3A4 or by releasing everolimus from intestinal cells via P-glycoprotein.

A dose reduction of mTOR inducers such as sirolimus, temsirolimus or everolimus may be necessary when coadministered with diltiazem.

When used simultaneously with diltiazem hydrochloride, it is possible to increase the concentrations of carbamazepine, alfentanil, theophylline, cyclosporine, as well as the concentrations of digoxin and digitoxin in the blood plasma. For these reasons, you need to pay attention to the symptoms of overdose with these drugs, ultimately, determine the concentration of the drug in the plasma and, if necessary, reduce the dose of the active substance (see section “Special instructions”).

Diltiazem significantly increases plasma concentrations of midazolam and triazolam and prolongs their half-life. Particular attention should be paid when prescribing short-acting benzodiazepines metabolized through CYP3A4 in patients receiving diltiazem (see section "Special Instructions").

Rifampicin

There is a risk of decreased plasma concentrations of diltiazem after starting rifampicin. Patients who initiate or discontinue treatment with rifampicin in addition to their diltiazem treatment should be closely monitored.

Nitrate derivatives

Combination therapy may lead to increased hypotensive effect and syncope (additive vasodilator effect). If the patient is receiving treatment with calcium antagonists, then when prescribing nitrate derivatives, their dose must be increased gradually.

Concomitant use with alpha antagonists may cause or worsen hypotension. The combination of diltiazem with alpha antagonists should only be considered when monitoring blood pressure.

When taking diltiazem hydrochloride and midazolam or alfentanil simultaneously, the postoperative period after extubation of the tracheal tube may be prolonged.

When taking diltiazem hydrochloride and cimetidine or ranitidine concomitantly, plasma concentrations of diltiazem hydrochloride may increase. Patients who initiate or discontinue treatment with H2-receptor antagonists in addition to their diltiazem treatment should be closely monitored. In such cases, it may be necessary to adjust the daily dose of diltiazem.

Hypotension or bradycardia may occur in rare cases when diltiazem hydrochloride is taken concomitantly with inhalational anesthetics.

Diltiazem hydrochloride reduces the clearance of nifedipine. In the case of concomitant therapy, careful monitoring of patients and possibly a reduction in the dose of nifedipine are indicated.

Concomitant use with diazepam may result in decreased plasma concentrations of diltiazem hydrochloride, possibly to reduce resorption.

Concomitant use with ivabradine is contraindicated due to the additive effect of diltiazem on reducing heart rate (see section "Contraindications").

Therefore, diltiazem should not be used simultaneously with the above substances without the clear advice of a doctor.

Note:

Particular attention should be paid to post-transplant patients.

Concomitant use with diltiazem may lead to an increase in plasma concentrations of cyclosporine A. With long-term use of cyclosporine A and diltiazem hydrochloride (orally), the dose of cyclosporine A should be reduced due to the maintenance of constant plasma levels of cyclosporine A. The dose is individually reduced, under the control of the concentration of cyclosporine A using special methods (for example, using monoclonal antibodies).

General information to be taken into account

Because of the potential for additive effects, patients taking diltiazem with other drugs known to affect cardiac contractility and/or impulse conduction should receive special attention and careful dosage titration.

Diltiazem is metabolized by CYP3A4. Increased plasma concentrations may be seen when coadministered with a stronger CYP3A4 inhibitor.

Cases of significant increases (less than 2 times) in the concentration of diltiazem in blood plasma have been reported. Diltiazem is also an inhibitor of CYP3A4 isoforms. Coadministration with other CYP3A4 substrates may result in increased plasma concentrations of the two drugs administered. Coadministration of CYP3A4 inducers may result in decreased plasma concentrations of diltiazem.

Glucocorticoids (methylprednisolone): inhibition of methylprednisolone metabolism (CYP3A4) and inhibition of P-glycoprotein. Patients taking methylprednisolone should be appropriately monitored. It may be necessary to adjust the dose of methylprednisolone.

Diltiazem retard

Pharmacodynamic

With simultaneous use of diltiazem with antihypertensive drugs, an increase in the hypotensive effect is observed.

When taking diltiazem and digoxin simultaneously, it is possible to increase the concentration of digoxin in the blood.

When taken simultaneously with antiarrhythmic drugs, beta-blockers, cardiac glycosides, bradycardia, impaired atrioventricular conduction, and symptoms of heart failure may develop.

When used simultaneously with adenosine, the risk of developing prolonged bradycardia is increased.

Salicylates additionally inhibit the ability of platelet aggregation.

Ethanol: increased hypotensive effect.

Procainamide, quinidine, and other drugs known to prolong the QT interval increase the risk of significant QT prolongation.

Inhalation anesthesia agents (hydrocarbon derivatives), thiazide diuretics and other blood pressure-lowering agents enhance the hypotensive effect of diltiazem.

Phenytoin reduces the effect of diltiazem.

Antipsychotics (neuroleptics) enhance the hypotensive effect. Simultaneous administration of nitrates (including prolonged forms) is possible. Lithium preparations may enhance the neurotoxic effects of diltiazem (nausea, vomiting, diarrhea, ataxia, tremors and/or tinnitus).

Indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroids and estrogens, as well as symptomatic drugs reduce the hypotensive effect.

Pharmacokinetic

Concomitant use with cimetidine leads to a significant increase in plasma concentrations of diltiazem, which in turn can lead to its toxic effect on the cardiovascular system.

Diltiazem increases the concentration of theophylline and carbamazepine in the blood plasma (40-70%) and increases the risk of adverse reactions, incl. ataxia, nystagmus, diplopia, headache, vomiting, confusion, and also increases the concentrations of cyclosporine, digoxin (up to 50%), imipramine, lithium and midazolam.

Strengthening the effect of hypoglycemic agents for oral administration (for example, chlorpropamide and glipizide).

With the simultaneous use of diltiazem and cyclosporine in patients with a kidney transplant, the development of intoxication and paresthesia is possible. Therefore, it is necessary to monitor plasma concentrations of cyclosporine in this group of patients. Eating food increases the absorption and bioavailability of diltiazem by up to 20-30%. May increase the bioavailability of propranolol. Increases the concentration of moracizine in blood plasma.

Phenobarbital, diazepam, rifampicin reduce the concentration of diltiazem in the blood plasma. Increases blood concentrations of quinidine and valproic acid (dose reduction may be required).

Antivirals: Ritonavir may increase plasma concentrations of BMCC.

Anxiolytics and hypnotics: diltiazem inhibits the metabolism of midazolam (increases plasma concentration with increased sedative effect).

BMCC: the elimination of nifedipine is reduced by diltiazem (plasma concentration increases).

Diltiazem significantly increases the plasma concentration of lovastatin. It also enhances the effect of simvastatin, therefore, when used simultaneously, the dose of simvastatin must be reduced. When diltiazem is used concomitantly with lovastatin and simvastatin, patient monitoring is necessary due to the possibility of developing myositis or rhabdomyolysis.

Diltiazem Lannacher film-coated tablets with prolonged release 90 mg No. 20

Directions for use and doses

Pharmacodynamics
When diltiazem is taken concomitantly with antihypertensive drugs, an increase in antihypertensive effect is observed.

When taking diltiazem and digoxin simultaneously, it is possible to increase the concentration of digoxin in the blood.

When taking diltiazem simultaneously with antiarrhythmic drugs, beta-blockers, cardiac glycosides, bradycardia, impaired atrioventricular conduction, and symptoms of heart failure may develop.

When used simultaneously with adenosine, the risk of developing prolonged bradycardia is increased.

Salicylates additionally inhibit the ability of platelet aggregation.

Ethanol: enhanced antihypertensive effect.

Procainamide, quinidine, and other drugs known to prolong the QT interval increase the risk of significant QT prolongation.

Inhalation anesthesia agents (hydrocarbon derivatives), thiazide diuretics and other drugs that lower blood pressure enhance the hypotensive effect of diltiazem.

Phenytoin reduces the effect of diltiazem.

Antipsychotic drugs (neuroleptics) enhance the antihypertensive effect of diltiazem.

Simultaneous administration of nitrates (including prolonged forms) is possible.

Lithium preparations may enhance the neurotoxic effects of diltiazem (nausea, vomiting, diarrhea, ataxia, tremors and/or tinnitus).

Indomethacin and other non-steroidal anti-inflammatory drugs, glucocorticosteroids and estrogens, as well as sympathetic drugs reduce the hypotensive effect.

Strengthens the cardiodepressive effect of general anesthetics.

Pharmacokinetic

Cimetidine weakens the process of biotransformation of diltiazem in the liver, slows down its elimination, increasing the duration of action of diltiazem.

Diltiazem increases the concentration of theophylline and carmazepine in the blood plasma (40-70%) and increases the risk of adverse reactions, incl. ataxia, nystagmus, diplopia, headache, vomiting, confusion, and also increases the concentrations of cyclosporine, digoxin (up to 50%), imipramine, lithium and midazolam.

Enhances the effect of oral hypoglycemic agents (for example, chlorpropamide and glipizide).

With the simultaneous use of diltiazem and cyclosporine in patients with a kidney transplant, the development of intoxication with the latter and paresthesia is possible. Therefore, it is necessary to closely monitor the level of plasma concentrations of cyclosporine in this group of patients.

Eating increases the absorption and bioavailability of diltiazem by 20-30%.

May increase the bioavailability of propranolol. Increases the concentration of moracizine in blood plasma.

Phenobarbital, diazepam, rifampicin reduce the concentration of diltiazem in the blood plasma.

Increases blood concentrations of quinidine and valproic acid (dose reduction may be required).

Antivirals: Ritonavir may increase plasma concentrations of BMCC.

Anxiolytics and hypnotics: diltiazem inhibits the metabolism of midazolam (plasma concentration increases with increased sedative effect.

BMCC: the elimination of nifedipine is reduced by diltiazem (plasma concentration increases).

Diltiazem significantly increases the plasma concentration of lovastatin. It also enhances the effect of simvastatin, therefore, when used simultaneously, the dose of simvastatin must be reduced. When diltiazem is used concomitantly with lovastatin and simvastatin, patient monitoring is necessary due to the possibility of developing myositis or rhabdomyolysis.