propranolol HCl 20 MG Oral Tablet
Generic Name: PROPRANOLOL HYDROCHLORIDE
Brand Name: Propranolol Hydrochloride
- Substance Name(s):
- PROPRANOLOL HYDROCHLORIDE
WARNINGS
Angina Pectoris 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 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 ).
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.
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 The necessity or desirability of withdrawal of beta-blocking therapy prior to major surgery is controversial.
It should be noted, however, that the impaired ability of the heart to respond to reflex adrenergic stimuli in propranololtreated patients 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 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 T4 and reverse T3 and decreasing T3.
Wolff-Parkinson-White Syndrome 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.
Pheochromocytoma 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.
DRUG INTERACTIONS
Drug Interactions Caution should be exercised when propranolol is administered with drugs that have an effect on CYP2D6, 1A2, or 2C19 metabolic pathways.
Coadministration of such drugs with propranolol may lead to clinically relevant drug interactions and changes on its efficacy and/or toxicity (see Drug Interactions in PHARMACOKINETICS AND DRUG METABOLISM ).
Cardiovascular Drugs Antiarrhythmics Propafenone has negative inotropic and beta-blocking properties that can be additive to those of propranolol.
Quinidine increases the concentration of propranolol and produces greater degrees of clinical beta-blockade and may cause postural hypotension.
Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with β-blockers such as propranolol.
The clearance of lidocaine is reduced with administration of propranolol.
Lidocaine toxicity has been reported following co-administration with propranolol.
Caution should be exercised when administering propranolol 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 heartrate.
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 betablockers.
Propranolol 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 T3 concentration when used concomitantly with propranolol.
Alcohol Alcohol, when used concomitantly with propranolol, may increase plasma levels of propranolol.
OVERDOSAGE
Propranolol is not significantly dialyzable.
In the event of overdosage or exaggerated response, the following measures should be employed: General: If ingestion is or may have been recent, evacuate gastric contents, taking care to prevent pulmonary aspiration.
Supportive Therapy: Hypotension and bradycardia have been reported following propranolol overdose and should be treated appropriately.
Glucagon can exert potent inotropic and chronotropic effects and may be particularly useful for the treatment of hypotension or depressed myocardial function after a propranolol overdose.
Glucagon should be administered as 50-150 mcg/kg intravenously followed by continuous drip of 1-5 mg/hour for positive chronotropic effect.
Isoproterenol, dopamine or phosphodiesterase inhibitors may also be useful.
Epinephrine, however, may provoke uncontrolled hypertension.
Bradycardia can be treated with atropine or isoproterenol.
Serious bradycardia may require temporary cardiac pacing.
The electrocardiogram, pulse, blood pressure, neurobehavioral status and intake and output balance must be monitored.
Isoproterenol and aminophylline may be used for bronchospasm.
DESCRIPTION
Propranolol hydrochloride is a synthetic beta-adrenergic receptor blocking agent chemically described as (±)-1-(Isopropylamino)-3-(1-naphthyloxy)-2- propanol hydrochloride.
Its structural formula is: C16H21NO2 • HCl M.W.
295.80 Propranolol hydrochloride is a stable, white crystalline solid which is readily soluble in water and ethanol.
Propranolol hydrochloride is available as 10 mg, 20 mg, 40 mg and 80 mg tablets for oral administration.
Propranolol Hydrochloride Tablets USP 10 mg, 20 mg, 40 mg, and 80 mg contain the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, D&C Yellow No.
10, magnesium stearate, microcrystalline cellulose and stearic acid.
Propranolol Hydrochloride Tablets USP 10 mg and 80 mg also contain FD&C Yellow No.
6.
Propranolol Hydrochloride Tablets USP 20 mg and 40 mg also contain FD&C Blue No.
1.
HOW SUPPLIED
Propranolol Hydrochloride Tablets USP 10 mg are 9/32″, scored, round, orange tablets imprinted DAN 5554 and 10 .
Propranolol Hydrochloride Tablets USP 20 mg are 9/32″, scored, round, blue tablets imprinted DAN 5555 and 20.
Propranolol Hydrochloride Tablets USP 40 mg are 11/32″, scored, round, green tablets imprinted DAN 5556 and 40 .
Propranolol Hydrochloride Tablets USP 80 mg are 12/32″, scored, round, yellow tablets imprinted DAN 5557 and 80 .
They are supplied by State of Florida DOH Central Pharmacy as follows: NDC Strength Quantity/Form Color Source Prod.
Code 53808-0771-1 20 mg 30 Tablets in a Blister Pack blue 0591-5555 53808-0772-1 40 mg 30 Tablets in a Blister Pack green 0591-5556 Dispense in a well-closed, light-resistant container with child-resistant closure.
Store at 20°-25°C (68°-77°F).
[See USP controlled room temperature.] Protect from light.
Manufactured By: Watson Pharma Private Limited Verna, Salcette Goa 403 722 INDIA Distributed By: Watson Pharma, Inc.
Corona, CA 92880 USA This Product was Repackaged By: State of Florida DOH Central Pharmacy 104-2 Hamilton Park Drive Tallahassee, FL 32304 United States
GERIATRIC USE
Geriatric Use Clinical studies of propranolol 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.
MECHANISM OF ACTION
Mechanism of Action The mechanism of the antihypertensive effect of propranolol has not been established.
Factors that may contribute 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 betaadrenergic 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 antimigraine effect of propranolol has not been established.
Beta-adrenergic receptors have been demonstrated in the pial vessels of the brain.
The specific mechanism of propranolol’s antitremor effects has not been established, but beta-2 (noncardiac) receptors may be involved.
A central effect is also possible.
Clinical studies have demonstrated that propranolol is of benefit in exaggerated physiological and essential (familial) tremor.
INDICATIONS AND USAGE
Hypertension Propranolol hydrochloride tablets are indicated in the management of hypertension.
It may be used alone or used in combination with other antihypertensive agents, particularly a thiazide diuretic.
Propranolol hydrochloride is not indicated in the management of hypertensive emergencies.
Angina Pectoris Due to Coronary Atherosclerosis Propranolol hydrochloride tablets are indicated to decrease angina frequency and increase exercise tolerance in patients with angina pectoris.
Atrial Fibrillation Propranolol hydrochloride tablets are indicated to control ventricular rate in patients with atrial fibrillation and a rapid ventricular response.
Myocardial Infarction Propranolol is indicated to reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.
Migraine Propranolol is indicated for the prophylaxis of common migraine headache.
The efficacy of propranolol in the treatment of a migraine attack that has started has not been established, and propranolol is not indicated for such use.
Essential Tremor Propranolol is indicated in the management of familial or hereditary essential tremor.
Familial or essential tremor consists of involuntary, rhythmic, oscillatory movements, usually limited to the upper limbs.
It is absent at rest but occurs when the limb is held in a fixed posture or position against gravity and during active movement.
Propranolol causes a reduction in the tremor amplitude but not in the tremor frequency.
Propranolol is not indicated for the treatment of tremor associated with Parkinsonism.
Hypertrophic Subaortic Stenosis Propranolol improves NYHA functional class in symptomatic patients with hypertrophic subaortic stenosis.
Pheochromocytoma Propranolol is indicated as an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine-secreting tumors.
PEDIATRIC USE
Pediatric Use 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.
PREGNANCY
Pregnancy: Pregnancy Category C 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.
NUSRING MOTHERS
Nursing Mothers Propranolol is excreted in human milk.
Caution should be exercised when propranolol is administered to a nursing woman.
DOSAGE AND ADMINISTRATION
General Because of the variable bioavailability of propranolol, the dose should be individualized based on response.
Hypertension 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 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.
Angina Pectoris 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 t.i.d., with titration after 1 month to 60 mg to 80 mg t.i.d.
as tolerated.
The recommended daily dosage is 180 mg to 240 mg propranolol hydrochloride per day in divided doses.
Although a t.i.d.
regimen was used in BHAT and a q.i.d.
regimen in the Norwegian Multicenter Trial, there is a reasonable basis for the use of either a t.i.d.
or b.i.d.
regimen (see PHARMACOKINETICS AND DRUG METABOLISM ).
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 (see above).
Migraine 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.
Essential Tremor 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.
Pheochromocytoma 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.