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| __NOTOC__
| | #REDIRECT [[Verapamil#Drug Interactions]] |
| {{Verapamil}}
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| {{CMG}}; {{AE}} {{AK}}
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| ==Drug interactions==
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| ===HMG-CoA reductase inhibitors===
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| The use of [[statins|HMG-CoA reductase inhibitors]] that are [[CYP3A4 ]]substrates in combination with verapamil has been associated with reports of myopathy/[[rhabdomyolysis]].
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| Co-administration of multiple doses of 10 mg of verapamil with 80 mg [[simvastatin ]]resulted in exposure to simvastatin 2.5-fold that following [[simvastatin ]]alone. Limit the dose of simvastatin in patients on verapamil to 10 mg daily. Limit the daily dose of [[lovastatin ]]to 40 mg. Lower starting and maintenance doses of other [[CYP3A4 ]]substrates (e.g., [[atorvastatin]]) may be required as verapamil may increase the plasma concentration of these drugs.
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| ===Beta-blockers===
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| Concomitant therapy with beta-adrenergic blockers and verapamil may result in additive negative effects on heart rate, atrioventricular conduction and/or cardiac contractility. The combination of sustained-release verapamil and beta-adrenergic blocking agents has not been studied. However, there have been reports of excessive [[bradycardia ]]and [[AV block]], including complete heart block, when the combination has been used for the treatment of [[hypertension]]. For [[hypertensive ]]patients, the risks of combined therapy may outweigh the potential benefits. The combination should be used only with caution and close monitoring.
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| Asymptomatic[[ bradycardia]] (36 beats/min) with a wandering atrial pacemaker has been observed in a patient receiving concomitant [[timolol ]](a beta-adrenergic blocker) eyedrops and oral verapamil.
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| A decrease in [[metoprolol ]]and [[propranolol ]]clearance has been observed when either drug is administered concomitantly with [[verapamil]]. A variable effect has been seen when verapamil and [[atenolol ]]were given together.
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| ===Digitalis===
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| Clinical use of 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, and this can result in digitalis toxicity. In patients with[[ hepatic cirrhosis]] the influence of verapamil on [[digoxin ]]kinetics is magnified. Verapamil may reduce total body clearance and extrarenal clearance of [[digitoxin ]]by 27% and 29%, respectively. Maintenance and digitalization doses should be reduced when verapamil is administered, and the patient should be carefully monitored to avoid over- or under-digitalization. Whenever over-digitalization is suspected, the daily dose of [[digitalis ]]should be reduced or temporarily discontinued. On discontinuation of CALAN use, the patient should be reassessed to avoid under-digitalization.
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| ===Antihypertensive agents===
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| Verapamil administered concomitantly with oral antihypertensive agents (eg, [[vasodilators]], [[angiotensin-converting enzyme inhibitors]], [[diuretics]], [[beta-blockers]]) will usually have an additive effect on lowering blood pressure. Patients receiving these combinations should be appropriately monitored. Concomitant use of agents that attenuate alpha-adrenergic function with verapamil may result in a reduction in blood pressure that is excessive in some patients. Such an effect was observed in one study following the concomitant administration of verapamil and [[prazosin]]. | |
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| ===Antiarrhythmic agents===
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| ====Disopyramide====
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| Until data on possible interactions between verapamil and [[disopyramide ]]phosphate are obtained, [[disopyramide ]]should not be administered within 48 hours before or 24 hours after verapamil administration.
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| ====Flecainide====
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| A study in healthy volunteers showed that the concomitant administration of [[flecainide ]]and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. Concomitant therapy with [[flecainide ]]and verapamil may result in additive negative [[inotropic ]]effect and prolongation of atrioventricular conduction.
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| ====Quinidine====
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| In a small number of patients with[[ hypertrophic cardiomyopathy]] (IHSS), concomitant use of verapamil and [[quinidine ]]resulted in significant [[hypotension]]. Until further data are obtained, combined therapy of verapamil and quinidine in patients with [[hypertrophic cardiomyopathy ]]should probably be avoided.
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| The electrophysiologic effects of quinidine and verapamil on AV conduction were studied in 8 patients. Verapamil significantly counteracted the effects of quinidine on AV conduction. There has been a report of increased quinidine levels during verapamil therapy.
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| ===Other agents===
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| ====Alcohol====
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| Verapamil has been found to inhibit [[ethanol ]]elimination significantly, resulting in elevated blood ethanol concentrations that may prolong the intoxicating effects of [[alcohol ]](see [[Verapamil hydrochloride tablet extended release clinical pharmacology|CLINICAL PHARMACOLOGY, Pharmacokinetics and metabolism]]).
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| ====Nitrates====
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| Verapamil has been given concomitantly with short- and long-acting [[nitrates ]]without any undesirable drug interactions. The pharmacologic profile of both drugs and the clinical experience suggest beneficial interactions.
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| ====Cimetidine====
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| The interaction between [[cimetidine ]]and chronically administered verapamil has not been studied. Variable results on clearance have been obtained in acute studies of healthy volunteers; clearance of verapamil was either reduced or unchanged.
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| ====Lithium====
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| Increased sensitivity to the effects of [[lithium ]](neurotoxicity) has been reported during concomitant verapamil-lithium therapy; [[lithium ]]levels have been observed sometimes to increase, sometimes to decrease, and sometimes to be unchanged. Patients receiving both drugs must be monitored carefully.
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| ====Carbamazepine====
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| Verapamil therapy may increase [[carbamazepine ]]concentrations during combined therapy. This may produce [[carbamazepine ]]side effects such as [[diplopia]], [[headache]], [[ataxia]], or [[dizziness]].
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| ====Rifampin====
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| Therapy with [[rifampin ]]may markedly reduce oral verapamil bioavailability.
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| ====Phenobarbital====
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| [[Phenobarbital ]]therapy may increase verapamil clearance.
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| ====Cyclosporin====
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| Verapamil therapy may increase serum levels of [[cyclosporin]].
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| ===Theophylline====
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| Verapamil may inhibit the clearance and increase the plasma levels of [[theophylline]].
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| ====Inhalation anesthetics====
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| Animal experiments have shown that inhalation anesthetics depress cardiovascular activity by decreasing the inward movement of calcium ions. When used concomitantly, inhalation [[anesthetics]] and [[calcium antagonists]], such as verapamil, should each be titrated carefully to avoid excessive cardiovascular depression.
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| ====Neuromuscular blocking agents====
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| Clinical data and animal studies suggest that 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.
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| ====Telithromycin====
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| Hypotension and bradyarrhythmias have been observed in patients receiving concurrent [[telithromycin]], an antibiotic in the ketolide class.
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| ====Clonidine====
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| Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of [[clonidine ]]concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and [[clonidine]].<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = CALAN SR (VERAPAMIL HYDROCHLORIDE) TABLET, FILM COATED, EXTENDED RELEASE [G.D. SEARLE LLC DIVISION OF PFIZER INC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=acb6e57b-af44-432f-a4de-a293a2e20121#nlm34090-1 | publisher = | date = | accessdate = }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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