sp;
Propranolol is not significantly dialyzable.
Hepatic Impairment: The pharmacokinetics of propranolol after administration of INNOPRAN XL have not been eva luated in patients with hepatic impairment. However, propranolol is extensively metabolized by the liver. In a study conducted in 7 patients with cirrhosis and 9 healthy subjects receiving 80 mg oral propranolol every 8 hours for 7 doses, the steady-state unbound propranolol concentration in patients with cirrhosis was 3-fold that of controls. In cirrhosis, the half-life increased to 11 hours compared to 4 hours.
12.7 Drug-Drug Interactions
Impact of Propranolol on Other Drugs
The effect of propranolol on exposure to other drugs is shown in Table 2.
Table 2 Impact of propranolol on other drugs
Other drug Effect on their exposure
Amide anesthetics (lidocaine, bupivacaine, mepivicaine) Increased
Warfarin Increased
Propafenone Increased >200%
Nifedipine Increased 80%
Verapamil None
Pravastatin, lovastatin Decreased 20%
Fluvastatin None
Zolmitriptan Increased 60%
Rizatriptan Increased 80%
Thioridazine Increased 370%
Diazepam Increased
Oxazepam, triazolam, lorazepam, alprazolam None
Theophylline Increased 70%
Impact of Other Drugs on Propranolol
The effect of propranolol on exposure to other drugs is shown in Table 3.
Table 3 Impact of other drugs on exposure to propranolol
Other drug Effect on propranolol exposure
Inhibitors of CYP2D6, CYP1A2, or CYP2C19 Increased
Inducers of CYP1A2 or CYP2C19 Decreased
Quinidine Increased >200%
Nisoldipine Increased 50%
Nicardipine Increased 80%
Chlorpromazine Increased 70%
Cimetidine Increased 50%
Cholestyramine, colestipol Decreased 50%
Alcohol Increased
Diazepam None
Verapamil None
Metochlopramide None
Ranitidine None
Lansoprazole None
Omeprazole None
Alcohol Increase acutely or decrease chronically
Propafenone Increased 200%
Quinidine Increased 200%
Cimetidine Increased 40%
Aluminum hydroxide Decreased 50%
Diazepam None
Nisoldipine, nicardipine, nifedipine Increased 50-80%CLOSE
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In dietary administration studies in which mice and rats were treated with propranolol HCl for up to 18 months at doses of up to 150 mg/kg/day, there was no evidence of drug-related tumorigenesis. On a body surface area basis, this dose in the mouse and rat is, respectively, about equal to and about twice the MRHD of 640 mg propranolol HCl. In a study in which both male and female rats were exposed to propranolol HCl in their diets at concentrations of up to 0.05% (about 50 mg/kg body weight and less than the MRHD), from 60 days prior to mating and throughout pregnancy and lactation for 2 generations, there were no effects on fertility. Based on differing results from Ames tests performed by d |
