propranolol HCl 120 MG 24HR Extended Release Oral Capsule
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 unstable 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 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.
DRUG INTERACTIONS
Drug Interactions Caution should be exercised when Propranolol Hydrochloride Extended-Release Capsules, USP, are administered with drugs that have an affect on CYP2D6, 1A2, or 2C19 metabolic pathways.
Co-administration 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 ).
Alcohol when used concomitantly with propranolol, may increase plasma levels of propranolol.
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 Hydrochloride Extended-Release Capsules, USP, 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.
Propranolol Hydrochloride Extended-Release Capsules, USP, 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.
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 2-Propanol, 1-[(1-methylethyl)amino]-3-(1-naphthalenyloxy)-, hydrochloride,(±)-.
It’s molecular and structural formulae are: C 16 H 21 NO 2 ∙ HCl Propranolol hydrochloride is a stable, white, crystalline solid which is readily soluble in water and ethanol.
Its molecular weight is 295.80.
Propranolol Hydrochloride Extended-Release Capsules, USP, are formulated to provide a sustained release of propranolol hydrochloride.
Propranolol Hydrochloride Extended-Release Capsules, USP, are available as 60 mg, 80 mg, 120 mg, and 160 mg capsules for oral administration.
Each capsule for oral administration contains sugar spheres, ethylcellulose, hypromellose phthalate, povidone, diethyl phthalate, polyethylene glycol, titanium dioxide, ammonium hydroxide, potassium hydroxide, black iron oxide, and gelatin.
The 80 mg, 120 mg, and 160 mg capsules contain red and yellow iron oxide.
In addition, the 160 mg capsules contain FD&C Blue No.
2.
These capsules comply with USP Dissolution Test 1.
Chemical Structure
HOW SUPPLIED
Propranolol Hydrochloride Extended-Release Capsules, USP.
Each white/opaque capsule, imprinted with “60”on cap and “RD203” on body contains 60 mg of propranolol hydrochloride in bottles of 100 (NDC 51991-817-01) and 500 (NDC 51991-817-05).
Each capsule with white/opaque body and orange/opaque cap, imprinted with “80”on cap and “RD203” on body contains 80 mg of propranolol hydrochloride in bottles of 100 (NDC 51991-818-01) and 500 (NDC 51991-818-05).
Each orange/opaque capsule, imprinted with “120”on cap and “RD203” on body contains 120 mg of propranolol hydrochloride in bottles of 100 (NDC 51991-819-01) and 500 (NDC 51991-819-05).
Each light brown/opaque capsule, imprinted with “160”on cap and “RD203” on body contains 160 mg of propranolol hydrochloride in bottles of 100 (NDC 51991-820-01) and 500 (NDC 51991-820-05).
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Protect from light, moisture, freezing, and excessive heat.
Dispense in a tight, light-resistant container as defined in the USP.
GERIATRIC USE
Geriatric Use Clinical studies of Propranolol Hydrochloride Extended-Release Capsules, USP, 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 the 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.
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.
INDICATIONS AND USAGE
Hypertension Propranolol Hydrochloride Extended-Release Capsules, USP, are indicated in the management of hypertension.
They may be used alone or used in combination with other antihypertensive agents, particularly a thiazide diuretic.
Propranolol Hydrochloride Extended-Release Capsules, USP, are not indicated in the management of hypertensive emergencies.
Angina Pectoris Due to Coronary Atherosclerosis Propranolol Hydrochloride Extended-Release Capsules, USP, are indicated to decrease angina frequency and increase exercise tolerance in patients with angina pectoris.
Migraine Propranolol Hydrochloride Extended-Release Capsules, USP, are 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.
Hypertrophic Subaortic Stenosis Propranolol Hydrochloride Extended-Release Capsules, USP, improve NYHA functional class in symptomatic patients with hypertrophic subaortic stenosis.
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 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 are receiving propranolol at parturition have exhibited bradycardia, hypoglycemia and/or respiratory depression.
Adequate facilities for monitoring such infants at birth should be available.
Propranolol Hydrochloride Extended- Release Capsules, USP, 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 Hydrochloride Extended-Release Capsules, USP, are administered to a nursing woman.
DOSAGE AND ADMINISTRATION
General Propranolol Hydrochloride Extended-Release Capsules, USP, provide propranolol hydrochloride in a sustained-release capsule for administration once daily.
If patients are switched from propranolol hydrochloride tablets to Propranolol Hydrochloride Extended-Release Capsules, USP, care should be taken to assure that the desired therapeutic effect is maintained.
Propranolol Hydrochloride Extended-Release Capsules, USP, should not be considered a simple mg-for-mg substitute for propranolol hydrochloride tablets.
Propranolol Hydrochloride Extended-Release Capsules, USP, have different kinetics and produces lower blood levels.
Retitration may be necessary, especially to maintain effectiveness at the end of the 24-hour dosing interval.
Hypertension The usual initial dosage is 80 mg Propranolol Hydrochloride Extended-Release Capsules, USP, once daily, whether used alone or added to a diuretic.
The dosage may be increased to 120 mg once daily or higher until adequate blood pressure control is achieved.
The usual maintenance dosage is 120 to 160 mg once daily.
In some instances a dosage of 640 mg may be required.
The time needed for full hypertensive response to a given dosage is variable and may range from a few days to several weeks.
Angina Pectoris Starting with 80 mg Propranolol Hydrochloride Extended-Release Capsules, USP, 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 Propranolol Hydrochloride Extended-Release Capsules, USP, 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, Propranolol Hydrochloride Extended-Release Capsules, USP, 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 Propranolol Hydrochloride Extended-Release Capsules, USP.
Hypertrophic Subaortic Stenosis The usual dosage is 80 to 160 mg Propranolol Hydrochloride Extended-Release Capsules, USP, once daily.