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Interactions with Substrates, Inhibitors or Inducers of Cytochrome P450 Enzymes

Because propranolol's metabolism involves multiple pathways in the cytochrome P450 system (CYP2D6, 1A2, 2C19), administration of Propranolol Hydrochloride (InnoPran-XL) capsules 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.

Plasma propranolol levels may increase with acute alcohol consumption and decrease upon chronic use.

Substrates or Inhibitors of CYP2D6

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

Substrates or Inhibitors of CYP2C19

Blood levels and/or toxicity of propranolol may be increased by administration of InnoPran-XL (Propranolol) capsules with substrates or inhibitors of CYP2C19, such as fluconazole, fluoxetine, cimetidine, fluvoxamine, teniposide, and tolbutamide. No interaction was observed with omeprazole.

Inducers of Hepatic Drug Metabolism

Blood levels of propranolol may be decreased by administration of InnoPran-XL (Propranolol HCl) with inducers such as rifampin. Cigarette smoking also induces hepatic metabolism and has been shown to increase up to 100% the clearance of propranolol, resulting in decreased plasma concentrations.

Cardiovascular Drugs


The concomitant administration of InnoPran-XL (Propranolol HCl) capsules and propafenone increased propranolol average steady-state plasma concentrations (213%), AUC (113%), Cmax (83%), Tmax (55%), and T (30%), and significantly decreased plasma levels of 4hydroxy-propranolol. Co-administration of propranolol and propafenone did not produce any significant change in propafenone pharmacokinetics. While the therapeutic range for propranolol is wide, a reduction in dosage may be necessary during concomitant administration with propafenone.

The metabolism of propranolol is reduced by co-administration of quinidine, leading to a 2- to 3fold increase in blood concentrations and greater degrees of clinical beta-blockade.

Concomitant administration of InnoPran-XL (Propranolol Hydrochloride) with lidocaine, bupivacaine or mepivacaine has been reported to decrease the clearance of these amide anesthetics significantly, resulting in higher serum concentrations of the anesthetic.

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 coadministration of InnoPran-XL (Propranolol Hydrochloride) capsules.

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

Non-Cardiovascular Drugs

Anti-Ulcer Drugs

Co-administration of propranolol with cimetidine, a non-specific CYP450 inhibitor, increased propranolol concentrations by about 40%. Co-administration with aluminum hydroxide gel (1.2 g) resulted in a 50% decrease in propranolol concentrations.

Co-administration of metoclopramide with Propranolol (InnoPran-XL) did not have a significant effect on propranolol's pharmacokinetics.


Propranolol (InnoPran-XL) capsules 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.

Lipid Lowering Drugs

Co-administration of cholesteramine or colestipol with Propranolol HCl (InnoPran-XL) resulted in up to a 50% decrease in propranolol concentrations.

Co-administration of this medication with lovastatin or pravastatin decreased 20% to 25% the AUC of both, but did not alter their pharmacodynamics. Propranolol did not have an effect on the pharmacokinetics of fluvastatin.

Migraine Drugs

Administration of zolmitriptan or rizatriptan with Propranolol HCl (InnoPran-XL) capsules 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).

Neuroleptic Drugs

Co-administration of Propranolol Hydrochloride (InnoPran-XL) at doses greater than or equal to 160 mg/day resulted in increased thioridazine plasma concentrations ranging from 50% to 370% and increased thioridazine metabolites concentrations ranging from 33% to 210%.

Co-administration of chlorpromazine with propranolol resulted in increased plasma levels of both drugs (70% increase in propranolol concentrations).


Co-administration of theophylline with Propranolol Hydrochloride (InnoPran-XL) capsules decreases theophylline oral clearance by 33% to 52%.


Concomitant administration of InnoPran-XL and warfarin has been shown to increase warfarin bioavailability and increase prothrombin time.

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