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.

Pharmacodynamics And Clinical Effects

Hypertension

In a retrospective, uncontrolled study, 107 patients with diastolic blood pressure 110 to 150 mmHg received propranolol 120 mg t.i.d. for at least 6 months, in addition to diuretics and potassium, but with no other hypertensive agent. Propranolol contributed to control of diastolic blood pressure, but the magnitude of the effect of propranolol on blood pressure cannot be ascertained.

Four double-blind, randomized, crossover studies were conducted in a total of 74 patients with mild or moderately severe hypertension treated with Inderal LA 160 mg once daily or propranolol 160 mg given either once daily or in two 80 mg doses. Three of these studies were conducted over a 4-week treatment period. One study was assessed after a 24-hour period. Inderal LA was as effective as propranolol in controlling hypertension (pulse rate, systolic and diastolic blood pressure) in each of these trials.

Angina Pectoris

In a double-blind, placebo-controlled study of 32 patients of both sexes, aged 32 to 69 years, with stable angina, propranolol 100 mg t.i.d. was administered for 4 weeks and shown to be more effective than placebo in reducing the rate of angina episodes and in prolonging total exercise time.

Twelve male patients with moderately severe angina pectoris were studied in a double-blind, crossover study. Patients were randomized to either Inderal LA 160 mg daily or conventional propranolol 40 mg four times a day for 2 weeks. Nitroglycerine tablets were allowed during the study. Blood pressure, heart rate and ECG's were recorded during serial exercise treadmill testing. Inderal LA was as effective as conventional propranolol for exercise heart rate, systolic and diastolic blood pressure, duration of anginal pain and ST-segment depression before or after exercise, exercise duration, angina attack rate and nitroglycerine consumption.

In another double-blind, randomized, crossover trial, the effectiveness of propranolol LA 160 mg daily and conventional propranolol 40 mg four times a day were evaluated in 13 patients with angina. ECG's were recorded while patients exercised until angina developed. Inderal LA was as effective as conventional propranolol for amount of exercise performed, ST-segment depression, number of anginal attacks, amount of nitroglycerine consumed, systolic and diastolic blood pressures and heart rate at rest and after exercise.

Migraine

In a 34-week, placebo-controlled, 4-period, dose-finding crossover study with a double-blind randomized treatment sequence, 62 patients with migraine received propranolol 20 to 80 mg 3 or 4 times daily. The headache unit index, a composite of the number of days with headache and the associated severity of the headache, was significantly reduced for patients receiving propranolol as compared to those on placebo.

Hypertrophic Subaortic Stenosis

In an uncontrolled series of 13 patients with New York Heart Association (NYHA) class 2 or 3 symptoms and hypertrophic subaortic stenosis diagnosed at cardiac catheterization, oral propranolol 40-80 mg t.i.d. was administered and patients were followed for up to 17 months. Propranolol was associated with improved NYHA class for most patients.

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