Verapamil

α-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-isopropylphenylacetonitrile hydrochloride

1 Cytotoxic drugs such as cyclophosphamide, vincristine, procarbazine, prednisone, vinblastine, doxorubicin, and cisplatin reduce the absorption of verapamil. 2 Phenobarbital increases the clearance of verapamil. 3 Ramifen significantly reduces the bioavailability of oral verapamil. 4 Cimetidine may increase the bioavailability of verapamil. 5 Verapamil inhibits the elimination of ethanol, leading to increased ethanol concentration in the blood, which may prolong the toxic effects of alcohol. 6 Combined with beta-receptor blockers, it may enhance the inhibitory effect on atrioventricular conduction, heart rate, and/or cardiac contraction. 7 Long-term use of verapamil increases the blood concentration of digoxin by 50-75%. Verapamil significantly affects the pharmacokinetics of digoxin in patients with cirrhosis, reducing the total clearance and extrarenal clearance of digoxin by 27% and 29%, respectively. Therefore, when taking verapamil, the doses of digoxin and digitalis must be reduced. 8 When used in combination with antihypertensive drugs such as vasodilators, angiotensin-converting enzyme inhibitors, and diuretics, the antihypertensive effects are additive, and patients receiving combined antihypertensive therapy should be appropriately monitored. 9 Combination with amiodarone may increase cardiac toxicity. 10 When verapamil is used in combination with flecainide, negative inotropic effects can be additive and atrioventricular conduction can be prolonged. 11 Verapamil can increase the blood concentrations of carbamazepine, cyclosporine, and theophylline. 12 There are reports that verapamil increases patients' sensitivity to lithium (neurotoxicity). 13 Animal experiments suggest that when inhaled anesthetics are used simultaneously with verapamil, the doses of both drugs need to be carefully adjusted to avoid excessive cardiac suppression. 14 Do not take disopyramide within 48 hours before or 24 hours after taking verapamil.

Chemical name: α-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-isopropylphenylacetonitrile hydrochloride Chemical structure: Molecular formula: C27H38N2O4•HCl Molecular weight: 491.07

Attention must be paid to the interactions between this product and the following drugs: antiarrhythmic drugs; beta-blockers; inhaled anesthetics: they can enhance the effects on the cardiovascular system (severe atrioventricular block, severe heart rate slowing, inducing heart failure, and enhancing the hypotensive effect). Antihypertensive drugs; diuretics; vasodilators: they can enhance the antihypertensive effect. Digoxin: this product can reduce renal excretion, thereby increasing the plasma concentration of digoxin (pay attention to monitor the symptoms of digoxin overdose, reduce the dose of cardiac glycosides when necessary, and adjust the plasma concentration of digoxin to an appropriate level). Quinidine: it may promote the reduction of blood pressure, and may also cause pulmonary edema in patients with hypertrophic obstructive cardiomyopathy and increase the plasma concentration of quinidine. Carbamazepine: it can enhance the effects of carbamazepine and increase its neurotoxicity. Lithium preparations: they weaken the drug effects of lithium and increase the neurotoxicity of lithium. Muscle relaxants: this product may enhance the effects of these drugs. Aspirin: it can increase the tendency to bleed. Disopyramide: Do not take disopyramide within 48 hours before or 24 hours after taking verapamil. Carbamazepine: Increases the effect of carbamazepine and increases its neurotoxicity. Neuromuscular blockers: Verapamil can enhance the activity of neuromuscular blockers. The dose of verapamil and/or neuromuscular blockers should be reduced when used in combination. Cytotoxic drugs: Cyclophosphamide, vincristine, procarbazine, prednisone, vinblastine, doxorubicin, cisplatin, etc. can reduce the absorption of verapamil. Alcohol: Slows down the degradation of alcohol and increases the plasma concentration of alcohol, thereby enhancing the effect of alcohol. During treatment with this product, intravenous administration of beta-blockers should be avoided (unless under intensive care conditions). Interactions caused by cytochrome P450 isoenzyme 3A4: This product is first metabolized in the liver by cytochrome P450 isoenzyme 3A4 and inhibits this enzyme. Therefore, the following interactions should be noted: Other cytochrome P450 isoenzyme 3A4 inhibitors such as azole antifungal agents (such as clotrimazole and ketoconazole), protease inhibitors (such as ritonavir and indinavir), macrolide preparations (such as erythromycin and clarithromycin) and cimetidine: due to the influence on drug metabolism, the plasma concentration of this product and/or the above drugs will be increased. Drugs that induce cytochrome P450 isoenzyme 3A4 such as phenytoin, rifampicin, phenobarbital and carbamazepine: reduce the concentration of this product in plasma and weaken its effect. Cytochrome P450 isoenzyme 3A4 substrates such as antiarrhythmic drugs (such as amiodarone and quinidine), CSE inhibitors (such as lovastatin, simvastatin and atorvastatin), midazolam, cyclosporine, theophylline, prazosin: increase the plasma concentration of these drugs. Note: Patients taking this drug should avoid food and drinks containing grapefruit juice, which may increase the concentration of verapamil in plasma.