Verapamil hydrochloride tablet extended release drug interactions: Difference between revisions
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==Drug interactions== | |||
<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> | ===HMG-CoA reductase inhibitors=== | ||
The use of [[statins|HMG-CoA reductase inhibitors]] that are [[CYP3A4 ]]substrates in combination with verapamil has been associated with reports of myopathy/[[rhabdomyolysis]]. | |||
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. | |||
===Beta-blockers=== | |||
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. | |||
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. | |||
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. | |||
===Digitalis=== | |||
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. | |||
===Antihypertensive agents=== | |||
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]]. | |||
===Antiarrhythmic agents=== | |||
====Disopyramide==== | |||
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. | |||
====Flecainide==== | |||
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. | |||
====Quinidine==== | |||
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. | |||
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. | |||
===Other agents=== | |||
====Alcohol==== | |||
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]]). | |||
====Nitrates==== | |||
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. | |||
====Cimetidine==== | |||
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. | |||
====Lithium==== | |||
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. | |||
====Carbamazepine==== | |||
Verapamil therapy may increase [[carbamazepine ]]concentrations during combined therapy. This may produce [[carbamazepine ]]side effects such as [[diplopia]], [[headache]], [[ataxia]], or [[dizziness]]. | |||
====Rifampin==== | |||
Therapy with [[rifampin ]]may markedly reduce oral verapamil bioavailability. | |||
====Phenobarbital==== | |||
[[Phenobarbital ]]therapy may increase verapamil clearance. | |||
====Cyclosporin==== | |||
Verapamil therapy may increase serum levels of [[cyclosporin]]. | |||
===Theophylline==== | |||
Verapamil may inhibit the clearance and increase the plasma levels of [[theophylline]]. | |||
====Inhalation anesthetics==== | |||
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. | |||
====Neuromuscular blocking agents==== | |||
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. | |||
====Telithromycin==== | |||
Hypotension and bradyarrhythmias have been observed in patients receiving concurrent [[telithromycin]], an antibiotic in the ketolide class. | |||
====Clonidine==== | |||
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> | |||
Revision as of 20:47, 4 March 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
Drug interactions
HMG-CoA reductase inhibitors
The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis.
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.
Beta-blockers
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.
Asymptomaticbradycardia (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.
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.
Digitalis
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 withhepatic 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.
Antihypertensive agents
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.
Antiarrhythmic agents
Disopyramide
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.
Flecainide
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.
Quinidine
In a small number of patients withhypertrophic 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.
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.
Other agents
Alcohol
Verapamil has been found to inhibit ethanol elimination significantly, resulting in elevated blood ethanol concentrations that may prolong the intoxicating effects of alcohol (see CLINICAL PHARMACOLOGY, Pharmacokinetics and metabolism).
Nitrates
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.
Cimetidine
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.
Lithium
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.
Carbamazepine
Verapamil therapy may increase carbamazepine concentrations during combined therapy. This may produce carbamazepine side effects such as diplopia, headache, ataxia, or dizziness.
Rifampin
Therapy with rifampin may markedly reduce oral verapamil bioavailability.
Phenobarbital
Phenobarbital therapy may increase verapamil clearance.
Cyclosporin
Verapamil therapy may increase serum levels of cyclosporin.
Theophylline=
Verapamil may inhibit the clearance and increase the plasma levels of theophylline.
Inhalation anesthetics
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.
Neuromuscular blocking agents
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.
Telithromycin
Hypotension and bradyarrhythmias have been observed in patients receiving concurrent telithromycin, an antibiotic in the ketolide class.
Clonidine
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.[1]