EVOPRANOL

Propranolol is a racemic mixture of 2 enantiomers where the S(-)-enantiomer has approximately 100 times the binding affinity for beta adrenergic receptors.

Propranolol is used to treat a number of conditions but most commonly is used for hypertension. 8, 9, 10 Propranolol was granted FDA approval on 13 November 1967.

Propranolol is indicated to treat hypertension. 10, 9 Propranolol is also indicated to treat angina pectoris due to coronary atherosclerosis, atrial fibrillation, myocardial infarction, migraine, essential tremor, hypertrophic subaortic stenosis, pheochromocytoma, and proliferating infantile hemangioma. 9,

Propranolol is a beta-adrenergic receptor antagonist used to treat hypertension. 9, 10 Propranolol has a long duration of action as it is given once or twice daily depending on the indication. 8, 9, 10 When patients abruptly stop taking propranolol, they may experience exacerbations of angina and myocardial infarctions.

Patients taking doses of 40 mg, 80 mg, 160 mg, and 320 mg daily experienced C max values of 18±15ng/mL, 52±51ng/mL, 121±98ng/mL, and 245±110ng/mL respectively.

Propranolol has a

T max of approximately 2 hours, though this can range from 1-4 hours in fasting patients.

Taking propranolol with food does not increase T max but does increase bioavailability.

The volume of distribution of propranolol is approximately 4 L/kg 8, 9 or 320 L.

Propranolol undergoes side chain oxidation to α-naphthoxylactic acid, ring oxidation to 4'-hydroxypropranolol, or glucuronidation to propranolol glucuronide.

It can also be N-desisopropylated to become N-desisopropyl propranolol. 1 17% of a dose undergoes glucuronidation and 42% undergoes ring oxidation.

Hover over products below to view reaction partners Propranolol N-desisopropylpropranolol 4'-hydroxypropanolol Propranolol Glucuronide α-Naphthoxylactic Acid.

91% of an oral dose of propranolol is recovered as 12 metabolites in the urine.

The elimination half-life of propranolol is approximately 8 hours.

The plasma half-life of propranolol is 3-6 hours. 8, 9.

The clearance of propranolol is 2.7±0.03 L/h/kg in infants 90 days.

Propranolol clearance increases linearly with hepatic blood flow.

Propranolol has a clearance in hypertensive adults of 810 mL/min.

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Symptoms of overdose include hypotension, hypoglycemic seizure, restlessness, euphoria, insomnia.

Patients with asthma may develop bronchospasm.

In case of overdose, monitor vital signs, mental status, and blood glucose.

Treat hypotension with intravenous fluids, bradycardia with atropine, and isoproterenol and aminophylline for bronchospasm.

If patients do not respond to intravenous fluids, follow up with glucagon 50-150 µg/kg Intravenous, then 1-5 mg/hour, followed by catecholamines. 8, 9, 10 Dialysis will not be useful as propranolol is highly protein bound. 8, 9, 10.

There have been reports of exacerbation of angina and, in some cases, myocardial infarction, following abrupt discontinuance of propranolol therapy.

Therefore, when discontinuance of propranolol is planned, the dosage should be gradually reduced over at least a few weeks and the patient should be cautioned against interruption or cessation of therapy without the physician’s advice.

If propranolol therapy is interrupted and exacerbation of angina occurs, it usually is advisable to reinstitute propranolol therapy and take other measures appropriate for the management of angina pectoris.

Since coronary artery disease may be unrecognized, it may be prudent to follow the above advice in patients considered at risk of having occult atherosclerotic heart disease who are given propranolol for other indications.

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.

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.

In Patients without a History of Heart Failure, Continued use of beta blockers can, in some cases, lead to cardiac failure.

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.

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.

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.

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 and reverse T and decreasing T 3.

Beta-adrenergic blockade in patients with Wolf-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.

Blocking only the peripheral dilator (beta) action of epinephrine with propranolol leaves its constrictor (alpha) action unopposed.

In the event of hemorrhage or shock, there is a disadvantage in having both beta and alpha blockade since the combination prevents the increase in heart rate and peripheral vasoconstriction needed to maintain blood pressure.

Propranolol is contraindicated in 1) cardiogenic shock; 2) sinus bradycardia and greater than first degree block; 3) bronchial asthma; and 4) in patients with known hypersensitivity to propranolol hydrochloride.

Because of the variable bioavailability of propranolol, the dose should be individualized based on response.

The usual initial dosage is 40 mg propranolol hydrochloride twice daily, whether used alone or added to a diuretic.

Dosage may be increased gradually until adequate blood pressure control is achieved.

The usual maintenance dosage is 120 mg/day to 240 mg per day. In some instances a dosage of 640 mg a day may be required.

The time needed for full antihypertensive response to a given dosage is variable and may range from a few days to several weeks.

While twice-daily dosing is effective and can maintain a reduction in blood pressure throughout the day, some patients, especially when lower doses are used, may experience a modest rise in blood pressure toward the end of the 12-hour dosing interval.

This can be evaluated by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. If control is not adequate, a larger dose, or 3-times-daily therapy may achieve better control.

Total daily doses of 80 mg to 320 mg propranolol hydrochloride, when administered orally, twice a day, three times a day, or four times a day, have been shown to increase exercise tolerance and to reduce ischemic changes in the ECG.

If treatment is to be discontinued, reduce dosage gradually over a period of several weeks. See WARNINGS. Atrial Fibrillation The recommended dose is 10 mg to 30 mg propranolol hydrochloride three or four times daily before meals and at bedtime.

Myocardial Infarction In the Beta-Blocker Heart Attack Trial (BHAT), the initial dose was 40 mg three times a day, with titration after 1 month to 60 mg to 80 mg three times a day as tolerated.

The recommended daily dosage is 180 mg to 240 mg propranolol hydrochloride per day in divided doses.

Although a three times a day regimen was used in the BHAT and a four times a day regimen in the Norwegian Multicenter Trial, there is a reasonable basis for the use of either a three times a day or twice daily regimen See PHARMACODYNAMICS AND CLINICAL EFFECTS.

The effectiveness and safety of daily dosages greater than 240 mg for prevention of cardiac mortality have not been established.

However, higher dosages may be needed to effectively treat coexisting diseases such as angina or hypertension.

The initial dose is 80 mg propranolol hydrochloride daily in divided doses.

The usual effective dose range is 160 mg to 240 mg per day. The dosage may be increased gradually to achieve optimum migraine prophylaxis.

If a satisfactory response is not obtained within four to six weeks after reaching the maximum dose, propranolol therapy should be discontinued.

It may be advisable to withdraw the drug gradually over a period of several weeks.

The initial dosage is 40 mg propranolol hydrochloride twice daily.

Optimum reduction of essential tremor is usually achieved with a dose of 120 mg per day. Occasionally, it may be necessary to administer 240 mg to 320 mg per day. Hypertrophic Subaortic Stenosis The usual dosage is 20 mg to 40 mg propranolol hydrochloride three or four times daily before meals and at bedtime.

The usual dosage is 60 mg propranolol hydrochloride daily in divided doses for three days prior to surgery as adjunctive therapy to alpha-adrenergic blockade.

For the management of inoperable tumors, the usual dosage is 30 mg daily in divided doses as adjunctive therapy to alpha-adrenergic blockade.

Tablets, USP 10 mg – Orange, round, convex, debossed tablets on one side with PLIVA and scored on the other side.

They are available as follows

Blistercards of 30: NDC 0615-8417-39 20 mg – Blue, round, convex, debossed tablets on one side with PLIVA and scored on the other side. 40 mg – Green, round, convex, debossed tablets on one side with PLIVA and scored on the other side.

Blistercards of 30: NDC 0615-8413-39 60 mg – Pink, round, convex, debossed tablets on one side with PLIVA and scored on the other side. 80 mg – Yellow, round, convex, debossed tablets on one side with PLIVA and scored on the other side.

Store at 20° to 25°C (68° to 77°F) .

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

This product’s label may have been revised after this insert was used in production.

For further product information and current package insert, please visit or call at 1-877-835-5472.

In a series of reproductive and developmental toxicology studies, propranolol hydrochloride 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 hydrochloride 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 abnormalities have been reported in neonates whose mothers received propranolol during pregnancy.

Neonates whose mothers received propranolol at parturition have exhibited bradycardia, hypoglycemia, and/or respiratory depression.

Adequate facilities for monitoring such infants at birth should be available.

Propranolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Propranolol is excreted in human milk.

Caution should be exercised when propranolol is administered to a nursing woman.

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

Bronchospasm and congestive heart failure have been reported coincident with the administration of propranolol therapy in pediatric patients.