WARNINGS AND PRECAUTIONS
Cardiac Ischemia after Abrupt Discontinuation
Following abrupt discontinuation of therapy with beta-blockers, exacerbations of angina pectoris and myocardial infarction have occurred.
When discontinuing chronically administered INNOPRAN XL, particularly in patients with ischemic heart disease, gradually reduce the dose over a period of 1-2 weeks and monitor the patients. If angina markedly worsens or acute coronary insufficiency develops, promptly resume therapy, at least temporarily and take other measures appropriate for the management of unstable angina. Warn patients against interruption or discontinuation of therapy without physician’s advice.
Because coronary artery disease is common and may be unrecognized, avoid abrupt discontinuation of INNOPRAN XL therapy even in patients treated only for hypertension.
Cardiac Failure
Beta-blockers, like INNOPRAN XL, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. If signs or symptoms of heart failure develop, treat the patient according to recommended guidelines. It may be necessary to lower the dose of INNOPRAN XL or to discontinue it.
Maintain During Major Surgery
Chronically administered beta-blocking therapy, including INNOPRAN XL, should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and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.
Masked Signs of Hypoglycemia
Beta-blockers, like INNOPRAN XL, may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.
Thyrotoxicosis
INNOPRAN XL may mask clinical signs of hyperthyroidism, such as tachycardia. Avoid abrupt withdrawal of beta-blockade, which may precipitate a thyroid storm.
Bradycardia
Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of INNOPRAN XL. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders (including Wolff-Parkinson-White) may be at increased risk. The concomitant use of beta adrenergic blockers and non-dihydropyridine calcium channel blockers (e.g., verapamil and diltiazem), digoxin or clonidine increases the risk of significant bradycardia. Monitor heart rate and rhythm in patients receiving INNOPRAN XL. If severe bradycardia develops, reduce or stop INNOPRAN XL.
Reduced Effectiveness of Epinephrine in Treating Anaphylaxis
Beta adrenergic blocker- treated patients treated with epinephrine for a severe anaphylactic reaction may be less responsive to the typical doses of epinephrine. In these patients, consider other medications (e.g., intravenous fluids, glucagon).
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C. 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 HCl during pregnancy.
Animal Data: 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 maximum recommended human oral daily dose (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 HCl was also administered (in the feed) to rabbits (throughout pregnancy and lactation) at doses as high as 150 mg/kg/day (about 5 times the MRHD). No evidence of embryo or neonatal toxicity was noted.
Labor and Delivery
Neonates whose mothers received propranolol HCl at parturition have exhibited bradycardia, hypoglycemia, and/or respiratory depression. Adequate facilities for monitoring such infants at birth should be available.
Nursing Mothers
Propranolol is excreted in human milk.
Pediatric Use
Safety and effectiveness of propranolol in pediatric patients have not been established.
Geriatric Use
Clinical studies of INNOPRAN XL 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.
Renal Impairment
The exposure to propranolol is increased in patients with renal impairment. Initiate INNOPRAN XL therapy in patients with impaired renal function at the lowest dose (80 mg) once daily and monitor patients for marked bradycardia and hypotension [see Clinical Pharmacology (
12.6
)].
Hepatic Impairment
The exposure to propranolol is increased in patients with hepatic impairment. Initiate INNOPRAN XL therapy in patients with impaired hepatic function at the lowest dose (80 mg) once daily and monitor patients for marked bradycardia and hypotension [see Clinical Pharmacology (
12.6
)].
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