Diltiazem, 30 pcs., 90 mg, extended-release tablets

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, 30 pcs., 90 mg, extended-release tablets

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.

Pharmacological properties of the drug Diltiazem

Antagonist of calcium ions of the group of benzothiazepine derivatives. Reduces the flow of calcium ions through selective voltage-dependent (slow) membrane calcium channels into cardiomyocytes and smooth muscle cells. By reducing the concentration of calcium ions inside the smooth muscle cells of blood vessels, it expands coronary and peripheral arteries and arterioles, providing a hypotensive and antianginal effect. By inhibiting the transmembrane flow of calcium into cardiomyocytes, cells of the sinus and AV node, it reduces myocardial contractility, slows down AV conduction and has a therapeutic effect in supraventricular tachycardia. The mechanism of antianginal action in angina pectoris, in addition to dilation of the coronary vessels, is also due to a decrease in afterload on the myocardium and heart function. Used mainly for the treatment of stable and vasospastic angina. Diltiazem has a hypotensive effect, reducing both systolic and diastolic blood pressure. Does not affect normal blood pressure levels. Unlike most drugs that have a peripheral vasodilating effect, diltiazem does not lead to the development of reflex tachycardia. Despite the moderate negative inotropic effect of diltiazem, its use does not reduce cardiac stroke volume and left ventricular ejection fraction. With long-term systematic use, diltiazem can cause regression of left ventricular hypertrophy. Does not have a negative effect on the lipid spectrum of blood serum. After oral administration, almost 90% of diltiazem is absorbed. Bioavailability is about 40% due to first pass metabolism through the liver. 70–80% of diltiazem is bound to plasma proteins, of which 35–40% is bound to albumin. Maximum plasma concentrations are achieved 2–3 hours after oral administration of diltiazem in tablet form. The onset of action is 30–60 minutes after ingestion of the tablets, the maximum effect develops after 3 hours (with systematic use, the maximum antihypertensive effect develops after 2–4 weeks). Duration of action when taken orally is 4-8 hours, when using retard forms - 6-14 hours. Metabolized in the liver with the participation of the cytochrome P450 oxidase system. The main metabolite is desacetyldilthiazem, the coronary lytic activity of which is 1/2–1/4 of the parent compound. The half-life when taken orally is biphasic: the duration of the first phase is 20–30 minutes, the final phase is about 3.5 hours (5–8 hours). It is excreted in the form of inactive metabolites with bile (60%) and urine (40%). About 2–4% of diltiazem is excreted unchanged.

Drug interactions Diltiazem

When used simultaneously with β-adrenergic receptor blockers, progression of bradycardia and AV conduction disturbances may be observed. Diltiazem may increase serum digoxin concentrations by 20–60%. Potentiates the hypotensive effect of diuretics and other antihypertensive drugs; enhances the negative impact of fluorotane on cardiac activity. Reduces the concentration of diazepam in the blood when used simultaneously; H2 receptor blockers (cimetidine) may cause an increase in serum concentrations of diltiazem.

List of pharmacies where you can buy Diltiazem:

• Moscow
• Saint Petersburg