Cardiac Failure

Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta-blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, some have been shown to be highly beneficial when used with close follow-up in patients with a history of failure who are well compensated and are receiving additional therapies, including diuretics as needed. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle.

Hypersensitivity and Skin Reactions

Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been associated with the administration of propranolol (see ADVERSE REACTIONS).

Cutaneous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, and urticaria, have been reported with use of propranolol (see ADVERSE REACTIONS).

Nonallergic Bronchospasm (e.g., Chronic Bronchitis, Emphysema)

In general, patients with bronchospastic lung disease should not receive beta-blockers. Propranolol should be administered with caution in this setting since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta-receptors.

Major Surgery

Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Propranolol is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension.

Diabetes and Hypoglycemia

Beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and blood pressure changes) of acute hypoglycemia, especially in labile insulin-dependent diabetics. In these patients, it may be more difficult to adjust the dosage of insulin.

Propranolol therapy, particularly in infants and children, diabetic or not, has been associated with hypoglycemia especially during fasting, as in preparation for surgery. Hypoglycemia has been reported with propranolol use after prolonged physical exertion and in patients with renal insufficiency.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism. Therefore, abrupt withdrawal of propranolol may be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. Propranolol may change thyroid-function tests, increasing T₄ and reversing T₃, and decreasing T₃.

Wolff-Parkinson-White Syndrome

Beta-adrenergic blockade in patients with Wolf-Parkinson-White syndrome and tachycardia have been associated with severe bradycardia requiring treatment with a pacemaker. In one case, this resulted after an initial dose of 5-mg propranolol.

General

Propranolol should be used with caution in patients with impaired hepatic or renal function. Innopran XL (propranolol hydrochloride) is not indicated for the treatment of hypertensive emergencies.

Beta-adrenergic receptor blockade can cause reduction of intraocular pressure. Patients should be told that Innopran XL (propranolol hydrochloride) may interfere with the glaucoma screening test. Withdrawal may lead to a return of intraocular pressure.

Myopathy

Caution should be exercised when administering propranolol to patients with underlying skeletal muscle disease. Isolated cases of exacerbation of myopathy and myotonia have been reported.

Risk of Anaphylactic Reaction

While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Clinical Laboratory Tests

In patients with hypertension, use of propranolol has been associated with elevated levels of serum potassium, and serum transaminases and alkaline phosphatase. In severe heart failure, the use of propranolol has been associated with increases in blood urea nitrogen.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In dietary administration studies in which mice and rats were treated with propranolol HC1 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 maximum recommended human oral daily dose (MRHD) of 640 mg propranolol HC1. In a study in which both male and female rats were exposed to propranolol HC1 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 different laboratories, there is equivocal evidence for a genotoxic effect of propranolol HC1 in bacteria (S. typhimurium strain TA 1538).

Pregnancy

Pregnancy Category C: In a series of reproductive and developmental toxicology studies, propranolol was given to rats by gavage or in the diet throughout pregnancy and lactation. At doses of 150 mg/kg/day, but not at doses of 80 mg/kg/day (equivalent to the MRHD on a body surface area basis), treatment was associated with embryotoxicity (reduced litter size and increased resorption rates) as well as neonatal toxicity (deaths). Propranolol HC1 also was administered (in the feed) to rabbits (throughout pregnancy and lactation) at doses as high as 150 mg/kg/day (about 5 times the maximum recommended human oral daily dose). No evidence of embryo or neonatal toxicity was noted.

There are no adequate and well controlled studies in pregnant women. Intrauterine growth retardation, small placentas, and congenital anomalies have been reported for neonates whose mothers received propranolol during pregnancy. Neonates whose mothers received propranolol HC1 at parturition have exhibited bradycardia, hypoglycemia, and/or respiratory depression. Adequate facilities for monitoring such infants at birth should be available. Innopran XL (propranolol hydrochloride) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Propranolol is excreted in human milk. Caution should be exercised when Innopran XL (propranolol hydrochloride) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of propranolol in pediatric patients have not been established.

Geriatric Use

Clinical studies of Innopran XL (propranolol hydrochloride) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 2/3/2011
This monograph has been modified to include the generic and brand name in many instances.