eported following co-administration with propranolol. caution should be exercised when administering inderal la with drugs that slow a-v nodal conduction, e.g., lidocaine and calcium channel blockers. digitalis glycosides both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. concomitant use can increase the risk of bradycardia. calcium channel blockers caution should be exercised when patients receiving a beta-blocker are administered a calcium-channel-blocking drug with negative inotropic and/or chronotropic effects. both agents may depress myocardial contractility or atrioventricular conduction. there have been reports of significant bradycardia, heart failure, and cardiovascular collapse with concurrent use of verapamil and beta-blockers. co-administration of propranolol and diltiazem in patients with cardiac disease has been associated with bradycardia, hypotension, high degree heart block, and heart failure. ace inhibitors when combined with beta-blockers, ace inhibitors can cause hypotension, particularly in the setting of acute myocardial infarction. the antihypertensive effects of clonidine may be antagonized by beta-blockers. inderal la should be administered cautiously to patients withdrawing from clonidine. alpha blockers prazosin has been associated with prolongation of first dose hypotension in the presence of beta-blockers. postural hypotension has been reported in patients taking both beta-blockers and terazosin or doxazosin. reserpine patients receiving catecholamine-depleting drugs, such as reserpine should be closely observed for excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension. inotropic agents patients on long-term therapy with propranolol may experience uncontrolled hypertension if administered epinephrine as a consequence of unopposed alpha-receptor stimulation. epinephrine is therefore not indicated in the treatment of propranolol overdose (see overdosage ). isoproterenol and dobutamine 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. also, propranolol may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia. non-cardiovascular drugs nonsteroidal anti-inflammatory drugs nonsteroidal anti-inflammatory drugs (nsaids) have been reported to blunt the antihypertensive effect of beta-adrenoreceptor blocking agents. administration of indomethacin with propranolol may reduce the efficacy of propranolol in reducing blood pressure and heart rate. antidepressants the hypotensive effects of mao inhibitors or tricyclic antidepressants may be exacerbated when administered with beta-blockers by interfering with the beta blocking activity of propranolol. anesthetic agents methoxyflurane and trichloroethylene may depress myocardial contractility when administered with propranolol. warfarin propranolol when administered with warfarin increases the concentration of warfarin. prothrombin time, therefore, should be monitored. neuroleptic drugs hypotension and cardiac arrest have been reported with the concomitant use of propranolol and haloperidol. thyroxine thyroxine may result in a lower than expected t 3 concentration when used concomitantly with propranolol.

ration 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 ). 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 diuretics as needed. beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle. in patients without a history of heart failure, continued use of beta blockers can, in some cases, lead to cardiac failure. 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 provoke a bronchial asthmatic attack by blocking 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. diabetes and hypoglycemia beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and 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 when given to infants and children, diabetic or not, has been associated with hypoglycemia especially during fasting as in preparation for surgery. hypoglycemia has been reported in patients taking propranolol 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 t 4 and reverse t 3 , and decreasing t 3 . wolff-parkinson-white syndrome beta-adrenergic blockade in patients with wolff-parkinson-white syndrome and tachycardia has been associated with severe bradycardia requiring treatment with a pacemaker. in one case, this result was reported after an initial dose of 5 mg propranolol.

al weeks. angina pectoris starting with 80 mg inderal la once daily, dosage should be gradually increased at three- to seven-day intervals until optimal response is obtained. although individual patients may respond at any dosage level, the average optimal dosage appears to be 160 mg once daily. in angina pectoris, the value and safety of dosage exceeding 320 mg per day have not been established. if treatment is to be discontinued, reduce dosage gradually over a period of a few weeks (see " warnings " ). migraine the initial oral dose is 80 mg inderal la once daily. the usual effective dose range is 160 to 240 mg once daily. the dosage may be increased gradually to achieve optimal migraine prophylaxis. if a satisfactory response is not obtained within four to six weeks after reaching the maximal dose, inderal la therapy should be discontinued. it may be advisable to withdraw the drug gradually over a period of several weeks depending on the patient's age, comorbidity, and dose of inderal la. hypertrophic subaortic stenosis the usual dosage is 80 to 160 mg inderal la once daily.

hylactoid reactions; pharyngitis and agranulocytosis; erythematous rash; fever combined with aching and sore throat; laryngospasm; respiratory distress. respiratory: bronchospasm. hematologic: agranulocytosis, nonthrombocytopenic purpura, and thrombocytopenic purpura. autoimmune: systemic lupus erythematosus (sle). skin and mucous membranes: stevens-johnson syndrome, toxic epidermal necrolysis, dry eyes, exfoliative dermatitis, erythema multiforme, urticaria, alopecia, sle-like reactions, and psoriasisiform rashes. oculomucocutaneous syndrome involving the skin, serous membranes, and conjunctivae reported for a beta-blocker (practolol) have not been associated with propranolol. genitourinary: male impotence; peyronie's disease.

eported following co-administration with propranolol. caution should be exercised when administering inderal la with drugs that slow a-v nodal conduction, e.g., lidocaine and calcium channel blockers. digitalis glycosides both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. concomitant use can increase the risk of bradycardia. calcium channel blockers caution should be exercised when patients receiving a beta-blocker are administered a calcium-channel-blocking drug with negative inotropic and/or chronotropic effects. both agents may depress myocardial contractility or atrioventricular conduction. there have been reports of significant bradycardia, heart failure, and cardiovascular collapse with concurrent use of verapamil and beta-blockers. co-administration of propranolol and diltiazem in patients with cardiac disease has been associated with bradycardia, hypotension, high degree heart block, and heart failure. ace inhibitors when combined with beta-blockers, ace inhibitors can cause hypotension, particularly in the setting of acute myocardial infarction. the antihypertensive effects of clonidine may be antagonized by beta-blockers. inderal la should be administered cautiously to patients withdrawing from clonidine. alpha blockers prazosin has been associated with prolongation of first dose hypotension in the presence of beta-blockers. postural hypotension has been reported in patients taking both beta-blockers and terazosin or doxazosin. reserpine patients receiving catecholamine-depleting drugs, such as reserpine should be closely observed for excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension. inotropic agents patients on long-term therapy with propranolol may experience uncontrolled hypertension if administered epinephrine as a consequence of unopposed alpha-receptor stimulation. epinephrine is therefore not indicated in the treatment of propranolol overdose (see overdosage ). isoproterenol and dobutamine 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. also, propranolol may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia. non-cardiovascular drugs nonsteroidal anti-inflammatory drugs nonsteroidal anti-inflammatory drugs (nsaids) have been reported to blunt the antihypertensive effect of beta-adrenoreceptor blocking agents. administration of indomethacin with propranolol may reduce the efficacy of propranolol in reducing blood pressure and heart rate. antidepressants the hypotensive effects of mao inhibitors or tricyclic antidepressants may be exacerbated when administered with beta-blockers by interfering with the beta blocking activity of propranolol. anesthetic agents methoxyflurane and trichloroethylene may depress myocardial contractility when administered with propranolol. warfarin propranolol when administered with warfarin increases the concentration of warfarin. prothrombin time, therefore, should be monitored. neuroleptic drugs hypotension and cardiac arrest have been reported with the concomitant use of propranolol and haloperidol. thyroxine thyroxine may result in a lower than expected t 3 concentration when used concomitantly with propranolol.

ia, hypoglycemia and/or respiratory depression. adequate facilities for monitoring such infants at birth should be available. inderal la should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

lol, a possible need for retitration upwards should be considered, especially to maintain effectiveness at the end of the dosing interval. in most clinical settings, however, such as hypertension or angina where there is little correlation between plasma levels and clinical effect, inderal la has been therapeutically equivalent to the same mg dose of conventional inderal as assessed by 24-hour effects on blood pressure and on 24-hour exercise responses of heart rate, systolic pressure, and rate pressure product. mechanism of action the mechanism of the antihypertensive effect of propranolol has not been established. among the factors that may be involved in contributing to the antihypertensive action include: (1) decreased cardiac output, (2) inhibition of renin release by the kidneys, and (3) diminution of tonic sympathetic nerve outflow from vasomotor centers in the brain. although total peripheral resistance may increase initially, it readjusts to or below the pretreatment level with chronic use of propranolol. effects of propranolol on plasma volume appear to be minor and somewhat variable. in angina pectoris, propranolol generally reduces the oxygen requirement of the heart at any given level of effort by blocking the catecholamine-induced increases in the heart rate, systolic blood pressure, and the velocity and extent of myocardial contraction. propranolol may increase oxygen requirements by increasing left ventricular fiber length, end diastolic pressure, and systolic ejection period. the net physiologic effect of beta-adrenergic blockade is usually advantageous and is manifested during exercise by delayed onset of pain and increased work capacity. propranolol exerts its antiarrhythmic effects in concentrations associated with beta-adrenergic blockade, and this appears to be its principal antiarrhythmic mechanism of action. in dosages greater than required for beta blockade, propranolol also exerts a quinidine-like or anesthetic-like membrane action which affects the cardiac action potential. the significance of the membrane action in the treatment of arrhythmias is uncertain. the mechanism of the anti-migraine effect of propranolol has not been established. beta-adrenergic receptors have been demonstrated in the pial vessels of the brain.

isture, freezing, and excessive heat. dispense in a tight, light-resistant container as defined in the usp. for medical inquires, contact ani pharmaceuticals, inc. at 1-800-308-6755. manufactured by: pfizer ireland pharmaceuticals little connell, newbridge, co. kildare, ireland distributed by: ani pharmaceuticals, inc. baudette, mn 56623 n4624 rev 08/19 ani.jpg