Inderide (Propranolol Hydrochloride / Hydrochlorothiazide) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug/Drug Interactions

Propranolol hydrochloride (Inderal^®)

Patients receiving catecholamine-depleting drugs such as reserpine should be closely observed if Inderide is administered. The added catecholamine-blocking action may produce an excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension.

Caution should be exercised when patients receiving a beta blocker are administered a calcium-channel blocking drug, especially intravenous verapamil, for both agents may depress myocardial contractility or atrioventricular conduction. On rare occasions, the concomitant intravenous use of a beta blocker and verapamil has resulted in serious adverse reactions, especially in patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported.

Hypotension and cardiac arrest have been reported with the concomitant use of propranolol and haloperidol.

Aluminum hydroxide gel greatly reduces intestinal absorption of propranolol.

Alcohol, when used concomitantly with propranolol, may increase plasma levels of propranolol.

Phenytoin, phenobarbitone, and rifampin accelerate propranolol clearance.

Chlorpromazine, when used concomitantly with propranolol, results in increased plasma levels of both drugs.

Antipyrine and lidocaine have reduced clearance when used concomitantly with propranolol.

Thyroxine may result in a lower than expected T₃ concentration when used concomitantly with propranolol.

Cimetidine decreases the hepatic metabolism of propranolol, delaying elimination and increasing blood levels.

Theophylline clearance is reduced when used concomitantly with propranolol.

OVERDOSAGE

The propranolol hydrochloride component may cause bradycardia, cardiac failure, hypotension, or bronchospasm. Propranolol is not significantly dialyzable.

The hydrochlorothiazide component can be expected to cause diuresis. Lethargy of varying degree may appear and may progress to coma within a few hours, with minimal depression of respiration and cardiovascular function, and in the absence of significant serum electrolyte changes or dehydration. The mechanism of central nervous system depression with thiazide overdosage is unknown. Gastrointestinal irritation and hypermotility can occur, temporary elevation of BUN has been reported, and serum electrolyte changes could occur, especially in patients with impairment of renal function.

The oral LD₅₀ dosages in rats and mice for propranolol, hydrochlorothiazide, and combined propranolol/hydrochlorothiazide (40/25, 80/25) are 364 to 533 mg/kg, greater than 2,750 to 5,000 mg/kg, and 538 to 845 mg/kg, respectively.

Treatment

The following measures should be employed:

General—If ingestion is, or may have been, recent, evacuate gastric contents, taking care to prevent pulmonary aspiration.

Bradycardia—Administer atropine (0.25 to 1.0 mg). If there is no response to vagal blockade, administer isoproterenol cautiously.

Cardiac Failure—Digitalization and diuretics.

Hypotension—Vasopressors, e.g., levarterenol or epinephrine.

Bronchospasm—Administer isoproterenol and aminophylline.

Stupor or Coma—Administer supportive therapy as clinically warranted.

Gastrointestinal Effects—Though usually of short duration, these may require symptomatic treatment.

Abnormalities in BUN and/or Serum Electrolytes—Monitor serum electrolyte levels and renal function; institute supportive measures as required individually to maintain hydration, electrolyte balance, respiration, and cardiovascular-renal function.

CONTRAINDICATIONS

Propranolol hydrochloride (Inderal^®)

Propranolol is contraindicated in 1) cardiogenic shock; 2) sinus bradycardia and greater than first-degree block; 3) bronchial asthma; 4) congestive heart failure (see “WARNINGS”) unless the failure is secondary to a tachyarrhythmia treatable with propranolol.

Hydrochlorothiazide

Hydrochlorothiazide is contraindicated in patients with anuria or hypersensitivity to this or other sulfonamide-derived drugs.