Cardiac arrhythmias; supraventricular arrhythmias: a) paroxysmal atrial tachycardias, b) persistent sinus tachycardia c) tachycardias and arrhythmias due to thyrotoxicosis d) persistent atrial extrasystoles e) atrial flutter and fibrillation

Tachyarrhythmias of digitalis intoxication: If digitalis-induced tachyarrhythmias persist following discontinuance of digitalis and correction of electrolyte abnormalities, they are usually reversible with oral Propranolol HCl.

Myocardial infarction: Propranolol HCl is indicated to reduce cardiovascular mortality in patients who have survived the acute phase of myocardial infarction and are clinically stable.

Migraine: Propranolol HCl is indicated for the prophylaxis of common migraine headache.

Essential tremor: Propranolol HCl is indicated in the management of familial or hereditary essential tremor.

Hypertrophic subaortic stenosis: Propranolol HCl is useful in the management of hypertrophic subaortic stenosis.

Pheochromocytoma: After primary treatment with an alpha-adrenergic blocking agent has been instituted, Propranolol HCl may be useful as adjunctive therapy if the control of tachycardia becomes necessary before of during surgery.

CONTRAINDICATIONS:

1) cardiogenic shock, 2) sinus bradycardia and greater than first degree block, 3) bronchial asthma, 4) congestive heart failure.

DESCRIPTION: Propranolol hydrochloride is a synthetic beta-adrenergic receptor blocking agent.

CLINICAL PHARMACOLOGY: Propranolol HCl is a nonselective beta-adrenergic receptor blocking agent possessing no other autonomic nervous system activity. When access to beta-receptor sites is blocked by Propranolol HCl, the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately.Propranolol is almost completely absorbed from the gastrointestinal tract. Peak effect occurs in one to one-and-one-half hours. The biologic half-life is approximately four hours.

The mechanism of the antihypertensive effect of Propranolol HCl;  (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.

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 exerts its antiarrhythmic effects in concentrations associated with beta-adrenergic blockade, and this appears to be its principal antiarrhythmic mechanism of action. 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. Clinical studies have demonstrated that Propranolol HCl is of benefit in exaggerated physiological and essential (familial) tremor.

Beta blockade results in bronchial constriction by interfering with adrenergic bronchodilator activity, which should be preserved in patients subject to bronchospasm.

WARNINGS:

Cardiac failure: sympathetic stimulation inhibition by beta blockade may precipitate more severe failure. In patients without a history of heart failure: Continued use of beta blockers can, in some cases, lead to cardiac failure. In patients with angina pectoris: There have been reports of exacerbation of angina and, in some cases, myocardial infarction, following abrupt discontinuance of Propranolol HCl therapy.

Diabetes and hypoglycemia: beta blockers may mask tachycardia occurring with hypoglycemia. Thyrotoxicosis: Propranolol may change thyroid-function tests, increasing T4 and reverse T3 and decreasing T3. In patients with wolf-parkinson-white syndrome: Several cases have been reported in which, after Propranolol, the tachycardia was replaced by a severe bradycardia requiring a demand pacemaker. In one case this resulted after an initial dose of 5 mg Propranolol.

PRECAUTIONS:

General: Propranolol should be used with caution in patients with impaired hepatic or renal function. Beta-adrenoreceptor blockade can cause reduction of intraocular pressure.

Clinical laboratory test: elevated blood urea levels in patients with severe heart disease, elevated serum transaminase, alkaline phosphatase, lactate dehydrogenase.

Pregnancy: Category C

Nursing Mothers: Propranolol HCl is excreted in human milk.

Drug Interactions:

Catecholamine-depleting drugs such as reserpine. Calcium-channel-blocking drug, especially intravenous verapamil. Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by Nonsteroidal anti-inflammatory drugs has been reported.

Haloperidol. Aluminum hydroxide gel. Ethanol. Phenytoin, Phenobarbitone, and Rifampin. Chlorpromazine, Antipyrine and lidocaine, Thyroxine, Cimetidine, Theophylline.

SIDE EFFECTS:

Most adverse effects have been mild and transient and have rarely required the withdrawal of therapy.

Cardiovascular:  bradycardia; congestive heart failure; intensification of AV block; hypotension; paresthesia of hands; thrombocytopenic purpura; arterial insufficiency.

Central Nervous System:  Light-headedness, mental depression manifested by insomnia, lassitude, weakness, fatigue; reversible mental depression progressing to catatonia; visual disturbances; hallucinations; vivid dreams; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics. For immediate formulations, fatigue, lethargy, and vivid dreams appear dose related.

Gastrointestinal:  nausea, vomiting, epigastric distress, abdominal cramping, diarrhea, constipation, mesenteric arterial thrombosis, and ischemic colitis.

Allergic: pharyngitis and agranulocytosis, erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Respiratory: bronchospasm.

Hematologic:  agranulocytosis, nonthrombocytopenic purpura, and thrombocytopenic purpura.

Autoimmune:  In extremely rare instances, systemic lupus erythematosus has been reported.

Miscellaneous:  alopecia, LE-like reactions, psoriasiform rashes, dry eyes, male impotence, and peyronie's disease have been reported rarely. Oculomucocutaneous reactions involving the skin, serous membranes, and conjunctivae reported for a beta blocker (practolol) have not been associated with Propranolol.

OVERDOSAGE:

Propranolol HCl is not significantly dialyzable.

General: If ingestion is or may have been recent, evacuate gastric contents, taking care to prevent pulmonary aspiration.

Bradycardia: ADMINISTER ATROPINE (0.25 mg to 1.0 mg); or ADMINISTER ISOPROTERENOL CAUTIOUSLY.

Cardiac failure: DIGITALIZATION AND DIURETICS.

Hypotension: VASOPRESSORS,

Bronchospasm: ADMINISTER ISOPROTERENOL AND AMINOPHYLLINE.

DOSAGE AND ADMINISTRATION:

The dosage range for Propranolol HCl is different for each indication.

Hypertension: dosage must be individualized. The usual initial dosage is 40 mg Propranolol HCl 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.

Angina pectoris: dosage must be individualized. Total daily doses of 80 mg to 320 mg, 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.

Arrhythmias: 10 mg to 30 mg three or four times daily, before meals and at bedtime.

Myocardial infarction: The recommended daily dosage is 180 mg to 240 mg per day in divided doses.

Migraine: dosage must be individualized. The initial oral dose is 80 mg Propranolol HCl 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 HCl therapy should be discontinued. It may be advisable to withdraw the drug gradually over a period of several weeks.

Essential tremor: dosage must be individualized. The initial dosage is 40 mg Propranolol HCl twice daily. Optimum reduction of essential tremor is usually achieved with a dose of 120 mg per day.

Hypertrophic subaortic stenosis: 20 mg to 40 mg three or four times daily, before meals and at bedtime.

Use in Children: Oral dosage for treating hypertension requires individual titration, beginning with a 1.0 mg per kg (body weight) per day dosage regimen (i.e., 0.5 mg per kg b.i.d.).

How Supplied: Each pack of Ruz-Propranolol 10 mg or 40 mg or 80 mg tablets contain 100 film coated tablets in a bottle.

Storage: Store temperature up to 30°C. Protect from light and moisture in a tight closed bottle.

For more information please refer to:

                  PDR 2000, page 3248-50

                  USPDI for Professional Health Care, 2004, Page 555-69

                  Martindale 2005, Page 989-90