Simultaneous use of verapamil and beta-blockers, antiarrhythmic drugs, funds for inhalation anesthesia can lead to increased cardiotoxic effect (increased risk of atrioventricular blockade, a sharp decrease in frequency
cardiac contractions, the development of heart failure, a sharp fall in blood pressure). The administration of verapamil and beta-blockers should be performed at intervals of several hours. Verapamil enhances AUC (the area under the plasma concentration / time curve) and FROMmax (maximum plasma concentrations) of metoprolol and propranolol in patients with angina.
Simultaneous use with antihypertensive agents and diuretics can lead to an increase in the hypotensive effect of verapamil.
Verapamil increases the concentration of digoxin in the blood plasma due to the deterioration of its excretion by the kidneys (so it is necessary to monitor the level of digoxin in the blood plasma in order to determine its optimal dosage and prevent intoxication). Verapamil increases the concentration of cardiac glycosides (requires careful monitoring and reduction of the dose of glycosides).
With simultaneous application with quinidine, the level of concentration of quinidine in the blood plasma increases and the risk of side effects increases. Patients with hypertrophic cardiomyopathy may develop severe arterial hypotension.
Verapamil potentiates the effect of depolarizing and curare-like muscle relaxants.
Verapamil increases AUC, FROMmax and Css (constant plasma concentrations with repeated use), cyclosporine.
Increases the concentration of theophylline (due to lower clearance), ethanol (lengthens its effect).
Raises the FROMmax prazosin and terazosin and AUC terazosin.
Verapamil increases AUC carbamazepine in patients with persistent partial epilepsy (risk of side effects such as diplopia, headache, ataxia and dizziness).
When used simultaneously with lithium carbonate, the risk of neurotoxic effects increases.
With the simultaneous use of verapamil with acetylsalicylic acid, the possibility of bleeding increases.
As verapamil is a substrate of isoenzyme CYP3A4, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, amiodarone, midazolam, cyclosporine, theophylline, it is possible to increase the concentration of these drugs in blood plasma while simultaneously using them. Increases significantly AUC and FROMmax simvastatin.
Verapamil increases the plasma concentration of colchicine (a substrate for CYP3A and p-glycoprotein).
Verapaml increases the concentration of sirolimus and tacrolimus.
Such inhibitors of isoenzyme CYP3A4, as antifungal agents (clotrimazole, ketoconazole), protease inhibitors (ritonavir, indinavir), macrolides (erythromycin, clarithromycin), cimetidine slow the hepatic metabolism of verapamil, as a result of which, its plasma concentrations increase. With the simultaneous use of verapamil with herbal preparations containing St. John's Wort (Hypericum perforatum) increases its concentration in the blood plasma. Phenobarbital, rifampicin accelerate the metabolism of verapamil and reduce its concentration in the blood, resulting in a decrease in its therapeutic effect.
When ingestion significantly increases AUC and FROMmax doxorubicin; IV injection of verapamil in patients with progressive neoplasms does not affect the pharmacokinetics of doxorubicin.
With the simultaneous use of verapamil with:
imipramine and other tricyclic antidepressants, their plasma concentrations increase; Slightly increases AUC imipramine; does not affect the concentration of the active metabolite, desipramine.
- grapefruit juice increases the concentration of verapamil in blood plasma;
antipsychotic drugs (antipsychotics) - increases the hypotensive effect of verapamil;
- almotriptan and hl and storm house - raises AUC and FROMmax.
- anxiolytics and hypnotics - the metabolism of midazolam is inhibited (plasma concentration increases with an increase in the sedative effect);
Nicotine, accelerating metabolism in the liver, leads to a decrease in the concentration of verapamil in the blood, reduces the severity of antianginal, hypotensive and antiarrhythmic action.
Procainamide, quinidine and other drugs that cause lengthening of the interval Q-T, increase the risk of its more significant lengthening when combined with verapamil.
Nonsteroidal anti-inflammatory drugs reduce the hypotensive effect of verapamil due to suppression of prostaglandin synthesis, delay Na+ and fluid in the body.
Sympathomimetics reduce the hypotensive effect of verapamil.
Dysopyramide and flecainide should not be administered within 48 hours before or 24 hours after the use of verapamil (summation of negative inotropic effect, up to a fatal outcome).
Estrogens reduce the hypotensive effect due to fluid retention in the body.
It is possible to increase plasma concentrations of drugs characterized by a high degree of binding to proteins (including coumarin and indanedione derivatives, NSAIDs, quinine, salicylates, sulfinpyrazone).