CONCOMITANT THERAPY WITH BETA-ADRENERGIC BLOCKERS AND VERAPAMIL MAY RESULT IN ADDITIVE NEGATIVE EFFECTS ON HEART RATE, ATRIOVENTRICULAR CONDUCTION AND/OR CARDIAC CONTRACTILITY.
VERAPAMIL IN DIGITALIZED PATIENTS HAS SHOWN THE COMBINATION TO BE WELL TOLERATED IF DIGOXIN DOSES ARE PROPERLY ADJUSTED. HOWEVER, CHRONIC VERAPAMIL TREATMENT CAN INCREASE SERUM DIGOXIN LEVELS BY 50% TO 75% DURING THE FIRST WEEK OF THERAPY. CONCOMITANT THERAPY WITH FLECAINIDE AND VERAPAMIL MAY RESULT IN ADDITIVE NEGATIVE INOTROPIC EFFECT AND PROLONGATION OF ATRIOVENTRICULAR CONDUCTION. CONCOMITANT USE OF VERAPAMIL AND QUINIDINE RESULTED IN SIGNIFICANT HYPOTENSION. VERAPAMIL HAS BEEN GIVEN CONCOMITANTLY WITH SHORT- AND LONG-ACTING
NITRATES WITHOUT ANY UNDESIRABLE DRUG INTERACTIONS. PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTIONS BETWEEN ORAL VERAPAMIL AND LITHIUM HAVE BEEN REPORTED. THE FORMER MAY RESULT IN A LOWERING OF SERUM LITHIUM LEVELS IN PATIENTS RECEIVING CHRONIC STABLE ORAL LITHIUM THERAPY. THE LATTER MAY RESULT IN AN INCREASED SENSITIVITY TO THE EFFECTS OF LITHIUM. CARBAMAZEPINE CONCENTRATIONS IS INCREASED DURING COMBINED THERAPY. RIFAMPIN MAY MARKEDLY REDUCE ORAL VERAPAMIL BIOAVAILABILITY. PHENOBARBITAL THERAPY MAY INCREASE VERAPAMIL CLEARANCE. VERAPAMIL THERAPY MAY INCREASE SERUM LEVELS OF CYCLOSPORIN. VERAPAMIL MAY POTENTIATE THE ACTIVITY OF NEUROMUSCULAR BLOCKING AGENTS (CURARE-LIKE AND DEPOLARIZING). IT MAY BE NECESSARY TO DECREASE THE DOSE OF VERAPAMIL AND/OR THE DOSE OF THE NEUROMUSCULAR BLOCKING AGENT WHEN THE DRUGS ARE USED CONCOMITANTLY.
DRUG INTERACTIONS OF CALCIUM CHANNEL BLOCKERS IN GENERAL : SEVERE HYPOTENSION AND/OR INCREASED FLUID VOLUME REQUIREMENTS HAVE BEEN REPORTED IN PATIENTS RECEIVING NIFEDIPINE TOGETHER WITH A BETA BLOCKING AGENT WHO UNDERWENT CORONARY ARTERY BYPASS SURGERY USING HIGH DOSE FENTANYL ANESTHESIA. IT MAY ELEVATE SERUM CONC. OF DIGOXIN SO CARE SHOULD BE TAKEN FOR DIGOXIN TOXICITY. MAY EFFECT GLUCOSE LEVELS IN DIABETICS. PLASMA CONCENTRATION OF THEOPHYLLINE. RANITIDINE AND CIMETIDINE INCREASES BIOAVAILABILITY OF NIFEDIPINE AND ITS EFFECT. CALCIUM CHANNEL BLOCKERS AND BETA BLOCKING AGENTS IS USUALLY WELL TOLERATED, BUT OCCASIONAL LITERATURE REPORTS SUGGEST THAT THE COMBINATION MAY INCREASE THE LIKELIHOOD OF CONGESTIVE HEART FAILURE, SEVERE HYPOTENSION OR EXACERBATION OF ANGINA. CO-ADMINISTRATION OF NIFEDIPINE WITH GRAPEFRUIT JUICE RESULTS IN UP TO A 2-FOLD INCREASE IN AUC AND C MAX , DUE TO INHIBITION OF CYP3A4 RELATED FIRST-PASS METABOLISM. EFFECTS OF CALCIUM CHANNEL BLOCKERS IS REDUCED BY PHENYTOIN, CARBAMAZEPINE & PHENOBARBITONES. ITRACONAZOLE, FLUCONAZOLE, CYCLOSPORIN REDUCE ITS METABOLISM. CONCURRENT USE WITH MAGNESIUM SALTS MAY CAUSE PROFOUND HYPOTENSION OR NEUROMUSCULAR BLOCK. ALPRAZOLAM'S CLEARANCE IS EFFECTED SO ITS DOSE SHOULD BE REDUCED TO 1/3. THE DEPRESSION OF CARDIAC CONTRACTILITY, CONDUCTIVITY, AND AUTOMATICITY, AS WELL AS THE VASCULAR DILATION ASSOCIATED WITH ANESTHETICS, MAY BE POTENTIATED BY CALCIUM CHANNEL BLOCKERS. WHEN USED CONCOMITANTLY, ANESTHETICS AND CALCIUM BLOCKERS SHOULD BE TITRATED CAREFULLY . CONCURRENT USED WITH OTHER CARDIAC DEPRESSANTS SUCH AS AMIODARONE, BETA BLOCKERS, DIGOXIN, AND MEFLOQUINE THERE MAY BE RISK OF BRADYCARDIA AND ATRIOVENTRICULAR BLOCK.