Propranolol drug interactions

Propranolol
Inderal LA® FDA Package Insert
Indications and Usage
Dosage and Administration
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
How Supplied/Storage and Handling
Labels and Packages
Clinical Trials on Propranolol
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]

Drug Interactions

All drug interaction studies were conducted with propranolol. There are no data on drug interactions with Inderal LA capsules.

Interactions with Substrates, Inhibitors or Inducers of Cytochrome P-450 Enzymes

Because propranolol's metabolism involves multiple pathways in the Cytochrome P-450 system (CYP2D6, 1A2, 2C19), co-administration with drugs that are metabolized by, or affect the activity (induction or inhibition) of one or more of these pathways may lead to clinically relevant drug interactions (see Drug Interactions under PRECAUTIONS).

=Substrates or Inhibitors of CYP2D6

Blood levels and/or toxicity of propranolol may be increased by co-administration with substrates or inhibitors of CYP2D6, such as amiodarone, cimetidine, delavudin, fluoxetine, paroxetine, quinidine, and ritonavir. No interactions were observed with either ranitidine or lansoprazole.

Substrates or Inhibitors of CYP1A2

Blood levels and/or toxicity of propranolol may be increased by co-administration with substrates or inhibitors of CYP1A2, such as imipramine, cimetidine, ciprofloxacin, fluvoxamine, isoniazid, ritonavir, theophylline, zileuton, zolmitriptan, and rizatriptan.

Substrates or Inhibitors of CYP2C19

Blood levels and/or toxicity of propranolol may be increased by co-administration with substrates or inhibitors of CYP2C19, such as fluconazole, cimetidine, fluoxetine, fluvoxamine, tenioposide, and tolbutamide. No interaction was observed with omeprazole.

Inducers of Hepatic Drug Metabolism

Blood levels of propranolol may be decreased by co-administration with inducers such as rifampin, ethanol, phenytoin, and phenobarbital. Cigarette smoking also induces hepatic metabolism and has been shown to increase up to 77% the clearance of propranolol, resulting in decreased plasma concentrations.

Cardiovascular Drugs

Antiarrhythmics

The AUC of propafenone is increased by more than 200% by co-administration of propranolol.

The metabolism of propranolol is reduced by co-administration of quinidine, leading to a two to three fold increased blood concentration and greater degrees of clinical beta-blockade.

The metabolism of lidocaine is inhibited by co-administration of propranolol, resulting in a 25% increase in lidocaine concentrations.

Calcium Channel Blockers

The mean Cmax and AUC of propranolol are increased respectively, by 50% and 30% by co-administration of nisoldipine and by 80% and 47%, by co-administration of nicardipine.

The mean Cmax and AUC of nifedipine are increased by 64% and 79%, respectively, by co-administration of propranolol.

Propranolol does not affect the pharmacokinetics of verapamil and norverapamil. Verapamil does not affect the pharmacokinetics of propranolol.

Non-Cardiovascular Drugs

Migraine Drugs

Administration of zolmitriptan or rizatriptan with propranolol resulted in increased concentrations of zolmitriptan (AUC increased by 56% and Cmax by 37%) or rizatriptan (the AUC and Cmax were increased by 67% and 75%, respectively).

Theophylline

Co-administration of theophylline with propranolol decreases theophylline oral clearance by 30% to 52%.

Benzodiazepines

Propranolol can inhibit the metabolism of diazepam, resulting in increased concentrations of diazepam and its metabolites. Diazepam does not alter the pharmacokinetics of propranolol.

The pharmacokinetics of oxazepam, triazolam, lorazepam, and alprazolam are not affected by co-administration of propranolol.

Neuroleptic Drugs

Co-administration of long-acting propranolol at doses greater than or equal to 160 mg/day resulted in increased thioridazine plasma concentrations ranging from 55% to 369% and increased thioridazine metabolite (mesoridazine) concentrations ranging from 33% to 209%.

Co-administration of chlorpromazine with propranolol resulted in a 70% increase in propranolol plasma level.

Anti-Ulcer Drugs

Co-administration of propranolol with cimetidine, a non-specific CYP450 inhibitor, increased propranolol AUC and Cmax by 46% and 35%, respectively. Co-administration with aluminum hydroxide gel (1200 mg) may result in a decrease in propranolol concentrations.

Co-administration of metoclopramide with the long-acting propranolol did not have a significant effect on propranolol's pharmacokinetics.

Lipid Lowering Drugs

Co-administration of cholestyramine or colestipol with propranolol resulted in up to 50% decrease in propranolol concentrations.

Co-administration of propranolol with lovastatin or pravastatin, decreased 18% to 23% the AUC of both, but did not alter their pharmacodynamics. Propranolol did not have an effect on the pharmacokinetics of fluvastatin.

Warfarin

Concomitant administration of propranolol and warfarin has been shown to increase warfarin bioavailability and increase prothrombin time.

References

Adapted from the FDA Package Insert.