Beta-Adrenergic Receptor Blocking Agent
Action And Clinical Pharmacology: Propranolol is a non-selective beta-adrenergic receptor blocking drug. It has no other autonomic nervous system activity. Propranolol is a competitive antagonist which specifically competes with beta-adrenergic receptor stimulating agents for available beta-receptor sites. When access to beta-adrenergic receptor sites is blocked by propranolol, the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately.
Beta-adrenergic blockade is useful in some clinical conditions in which sympathetic activity is excessive or inappropriate, and therefore, detrimental to the patient. Sympathetic stimulation is however, vital in some situations (e.g. in patients with AV block or with a severely damaged heart) and should be preserved. The basic objective of beta-adrenergic blockade is to decrease adverse sympathetic stimulation but not to the degree that impairs necessary sympathetic support. Beta-blockade may result in bronchial constriction by interfering with endogenously or exogenously induced bronchodilation (see Contraindications and Warnings).
The mechanism of the antihypertensive effects of propranolol has not been established. Among the factors that may be involved are decreased cardiac output, inhibition of renin release by the kidneys, and diminution of tonic sympathetic nerve outflow from vasomotor centers in the brain. It has been suggested, but not established, that propranolol may achieve a better antihypertensive effect in patients with normal or elevated plasma renin activity (PRA) than those with low PRA.
Propranolol may reduce the oxygen requirement of the heart at any level of effort by blocking catecholamine induced increases in the heart rate, systolic blood pressure, and the velocity and extent of myocardial contraction. On the other hand, propranolol may increase oxygen requirements by increasing left ventricular fiber length, end diastolic pressure, and systolic ejection period. When the net effect is beneficial in anginal patients, it manifests itself during exercise or stress by delaying the onset of pain and reducing the incidence and severity of anginal attacks.
Propranolol exerts antiarrhythmic effects in concentrations producing beta-adrenergic blockade, which appears to be its principal antiarrhythmic mechanism of action. Beta-adrenergic blockade is of unique importance in the management of arrhythmias caused by increased levels of circulating catecholamines or enhanced sensitivity of the heart to catecholamines (arrhythmias associated with pheochromocytoma, thyrotoxicosis, exercise).
Mechanisms of the antimigraine and antitremor effects of propranolol have not been established. The antimigraine effect may be due to inhibition of vasodilatation or arteriolar spasms over the cortex. Beta-adrenergic receptors have been demonstrated in the pial vessels of the brain. The antitremor effects may be exerted through both peripheral and central sites of action. The mechanism by which propranolol reduces the incidence of cardiovascular mortality in post-myocardial infarct patients is unknown.
Propranolol from Inderal tablets is rapidly and completely absorbed from the gastrointestinal tract and undergoes extensive presystemic (or first-pass) elimination due to its high hepatic clearance. Inter-individual variations in circulating drug concentrations due to this first-pass effect have been documented and differ according to a number of factors including genetic make-up. Peak plasma concentrations of propranolol are attained 60 to 90 minutes after administration of Inderal tablets. The plasma half-life is 2 to 3 hours whereas the duration of pharmacological effect is longer.
Inderal-LA is a special formulation of propranolol hydrochloride consisting of capsules filled with spheroids of the active drug that have a sustained-release coating.
Propranolol from Inderal-LA capsules is almost completely absorbed from the gastrointestinal tract. A large part of the absorbed drug is lost from the systemic circulation due to first-pass metabolism in the liver. The first-pass metabolism is saturable. Steady-state plasma propranolol concentrations from Inderal-LA are proportional to the dose over the range of 60 to 160 mg/day although there is considerable intersubject variation. In healthy volunteers steady state was achieved after 2 or 3 days administration of Inderal-LA.
Peak blood levels following administration of Inderal-LA capsules occur at about 6 hours and the apparent plasma half-life has been reported to be between 10 and 12 hours i.e. 2 to 3 times that of the conventional tablet formulation.
When measured at steady state over a 24-hour period the areas under the propranolol plasma concentration-time curve (AUCs) for the LA-capsules are approximately 60 to 65% of the AUCs for a comparable divided daily dose of Inderal Tablets. The lower AUCs for the Inderal-LA capsules are due to greater hepatic metabolism of propranolol because of slower absorption. Over a 24-hour period, blood levels are fairly constant for about 12 hours, then decline exponentially.
Indications And Clinical Uses: Inderal: Hypertension: It is usually used in combination with other drugs, particularly a thiazide diuretic. Propranolol can, however, in certain patients, be used alone or as an initial agent in patients in whom, in the judgment of the physician, treatment should be started with a beta-blocker rather than a diuretic. The combination of propranolol with thiazide-like diuretics and/or peripheral vasodilators has been shown to be compatible and generally more effective than propranolol alone. Experience with most commonly used antihypertensive agents has not suggested evidence of incompatibility.
Propranolol by itself is not recommended for the emergency treatment of hypertensive crisis. It is, however, sometimes used as an adjunct to counteract the unwanted effect (tachycardia) of the primary agents used in these situations.
Angina Pectoris: For the prophylaxis of angina pectoris.
Cardiac Arrhythmias: Supraventricular arrhythmias: a) paroxysmal atrial tachycardias, particularly those arrhythmias induced by catecholamines or digitalis or associated with Wolff-Parkinson-White syndrome (see Warnings); b) persistent sinus tachycardia which is noncompensatory and impairs the well-being of the patient; c) tachycardias and arrhythmias due to thyrotoxicosis when causing distress or increased hazard and when immediate effect is necessary as adjunctive, short-term (2 to 4 weeks) therapy. May be used with, but not in place of, specific therapy (see Warnings); d) persistent atrial extrasystoles which impair the well-being of the patient and do not respond to conventional measures; e) atrial flutter and fibrillation when ventricular rate cannot be controlled by digitalis alone, or when digitalis is contraindicated.
Ventricular tachycardia: Ventricular arrhythmias do not respond to propranolol as predictably as do the supraventricular arrhythmias; a) with the exception of ventricular tachycardia induced by catecholamines or digitalis, propranolol is not the drug of first choice. In critical situations when cardioversion techniques or other drugs are not indicated or are not effective, propranolol may be considered. If, after consideration of the risks involved, propranolol is used, it should be given i.v. in low dosage and very slowly (see Dosage); b) persistent premature ventricular extrasystoles which do not respond to conventional measures and impair the well being of the patient.
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. Severe bradycardia may occur (see Symptoms and Treatment of Overdose).
I.V. propranolol is reserved for life-threatening arrhythmias. Temporary maintenance with oral therapy may be indicated (see Dosage).
Resistant tachyarrhythmias due to excessive catecholamine action during anesthesia.
Tachyarrhythmias due to excessive catecholamine action during anesthesia may sometimes arise because of release of endogenous catecholamines or administration of catecholamines. When usual measures fail in such arrhythmias, propranolol may be given i.v. to abolish them. All general inhalation anesthetics produce some degree of myocardial depression. Therefore, when propranolol is used to treat arrhythmias during anesthesia, it should be used with extreme caution and constant ECG and central venous pressure monitoring. In patients during anesthesia with agents that require catecholamine release for maintenance of adequate cardiac function, beta-blockade will impair the desired inotropic effect. Therefore, propranolol should be titrated carefully when administered for arrhythmias occurring during anesthesia.
Post-myocardial Infarction: For the reduction of cardiovascular mortality in patients who have survived the acute phase of a myocardial infarction and who are clinically stable. In the study which showed this benefit, treatment with propranolol began between 5 and 21 days after the acute phase. Data are not available as to whether benefit would ensue if the therapy were initiated later.
Migraine: The prophylaxis of migraine headache. It is not indicated for the treatment of acute migraine attacks.
Essential Tremor: The management of essential tremor.
Hypertrophic Subaortic Stenosis: The management of hypertrophic subaortic stenosis, especially for treatment of exertional or other stress induced angina, palpitations, and syncope. Propranolol also improves exercise performance. The effectiveness of propranolol in this disease appears to be due to a reduction of the elevated outflow pressure gradient which is exacerbated by beta-adrenergic receptor stimulation. Clinical improvement may be temporary.
Pheochromocytoma: After primary treatment with an alpha-adrenergic blocking agent has been instituted, propranolol may be useful as adjunctive therapy if the control of tachycardia becomes necessary before or during surgery.
It is hazardous to use propranolol unless alpha-adrenergic blocking drugs are already in use, since this would predispose to serious blood pressure rise. Blocking only the peripheral dilator (beta) action of epinephrine leaves its constrictor (alpha) action unopposed. In the event of hemorrhage or shock, producing both beta- and alpha-blockade is contraindicated since the combination prevents the increase in heart rate and peripheral vasoconstriction needed to maintain blood pressure.
In inoperable or metastatic pheochromocytoma, propranolol may be useful as an adjunct to the management of symptoms due to excessive beta-adrenergic receptor stimulation.
Inderal-LA: For maintenance therapy in the treatment of hypertension and prophylaxis of angina pectoris.
As for Inderal, the combination of Inderal-LA with thiazide-like diuretics and/or peripheral vasodilators has been shown to be compatible and generally more effective than Inderal-LA alone. Experience with most commonly used antihypertensive agents has not suggested evidence of incompatibility.
Treatment must always be initiated and individual titration of dosage carried out using the conventional tablets. The long-acting formulation may be used for maintenance provided the dosage requirement is suitable.
Not indicated for the emergency treatment of hypertensive crises.
Contra-Indications: Bronchospasm, including bronchial asthma; allergic rhinitis during the pollen season; sinus bradycardia and greater than first degree block; cardiogenic shock; right ventricular failure secondary to pulmonary hypertension; congestive heart failure (see Warnings) unless the failure is secondary to a tachyarrhythmia treatable with propranolol.
Manufacturers’ Warnings In Clinical States: Cardiac Failure: Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure; therefore, inhibition by means of beta-adrenergic blockade is a potential hazard as it may further depress myocardial contractility and precipitate cardiac failure. Propranolol acts selectively without completely abolishing the inotropic action of digitalis on the heart muscle (i.e., that of supporting the strength of myocardial contractions). In patients already receiving digitalis, the positive inotropic action of digitalis may be reduced by propranolol’s negative inotropic effect. The effects of propranolol and digitalis are additive in depressing AV conduction.
Patients without a History of Cardiac Failure: Continued depression of the myocardium over a period of time can, in some patients, lead to cardiac failure. In rare instances, this has been observed during propranolol therapy. Therefore, at the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or given a diuretic, and the response observed closely: a) if cardiac failure continues, despite adequate digitalization and diuretic therapy, propranolol should be withdrawn immediately; b) if tachyarrhythmia is being controlled, patients should be maintained on combined therapy and closely followed until threat of cardiac failure is over.
Abrupt Cessation of Therapy in Angina Pectoris: Severe exacerbation of angina and the occurrence of myocardial infarction have been reported in some patients with angina pectoris following abrupt discontinuation of propranolol therapy. Therefore, when discontinuation of propranolol is planned in patients with angina pectoris, the dosage should be gradually reduced over a period of about 2 weeks and the patient should be carefully observed. For patients receiving Inderal tablets, the same frequency of administration should be maintained. For patients on Inderal-LA, discontinuation can be achieved by substituting Inderal-LA 60, 80, 120 and 160 mg by the equivalent dosage of conventional Inderal tablets spread throughout the day, and then gradually reducing the dose. In situations of greater urgency, propranolol dosage should be reduced stepwise, in 4 days under close observation. If angina markedly worsens, or acute coronary insufficiency develops, it is recommended that treatment with propranolol be reinstituted promptly, at least temporarily. In addition, patients with angina pectoris should be warned against abrupt discontinuation of propranolol.
Oculomucocutaneous Syndrome: Various skin rashes and conjunctival xerosis have been reported in patients treated with beta-blockers including propranolol. A severe oculomucocutaneous syndrome, whose signs include conjunctivitis sicca and psoriasiform rashes, otitis, and sclerosing serositis has occurred with the long-term use of one beta-adrenergic blocking agent. This syndrome has not been observed with propranolol, however, physicians should be alert to the possibility of such reactions and discontinue treatment if they occur.
Patients with Thyrotoxicosis: Possible deleterious effects from long-term use of propranolol have not yet been adequately appraised. Special consideration should be given to propranolol’s potential for aggravating congestive heart failure. Propranolol may mask the clinical signs of developing or continuing hyperthyroidism or its complications, and give a false impression of improvement. Therefore, abrupt withdrawal of propranolol may be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm. This may be another instance where propranolol should be withdrawn slowly by reducing dosage. Propranolol does not distort thyroid function tests.
Patients with Wolff-Parkinson-White Syndrome: Propranolol should be used with caution since several cases have been reported in which, after propranolol treatment, the tachycardia was replaced by a severe bradycardia requiring a demand pacemaker. In one patient, this occurred after an initial dose of 5 mg of propranolol.
Patients Undergoing Elective or Emergency Surgery: The management of patients with angina, being treated with beta-blockers and undergoing elective or emergency surgery, is controversial because beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli, but abrupt discontinuation of therapy with propranolol may be followed by severe complications (see Warnings). Some patients receiving beta-adrenergic blocking agents have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported.
For these reasons, in patients with angina undergoing elective surgery, propranolol should be withdrawn gradually (see Warnings). According to available evidence, all clinical and physiologic effects of beta-blockade are no longer present 48 hours after cessation of medication.
In emergency surgery, since propranolol is a competitive inhibitor of beta-adrenergic receptor agonists, its effects may be reversed, if necessary, by sufficient doses of such agonists as isoproterenol or dobutamine.
Anesthesia with agents which maintain cardiac contractility by virtue of their effect on catecholamine release (e.g. ether) should be avoided in patients on propranolol therapy.
Patients prone to nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema, bronchiectasis): Propranolol should be administered with caution since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta-adrenergic receptors.
Patients with Diabetes and in those subject to Hypoglycemia: Because of its beta-adrenergic blocking activity, propranolol may block premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia. This is especially important to keep in mind in patients with labile diabetes. Hypoglycemic attacks may be accompanied by a precipitous elevation of blood pressure.
Pregnancy: The safe use of propranolol in pregnancy has not been established. Use of any drug in pregnancy or in women of childbearing potential requires that the possible risk to mother and/or fetus be weighed against the expected therapeutic benefit. Perinatal complications, such as small placenta and intrauterine growth retardation, have been reported in a few cases where the mother took propranolol during pregnancy. Some infants born to mothers treated with propranolol were reported to have hypoglycemia and/or bradycardia.
Children: While experience with propranolol in children under 12 is limited, the indications for which this drug is recommended occur infrequently in childhood. Although reports fail to indicate that children respond in a manner different from the adult, physicians are advised to undertake treatment with caution.
Precautions: There may be increased difficulty in treating an allergic type reaction in patients on beta-blockers. In these patients, the reaction may be more severe due to pharmacological effects of beta-blockers and problems with fluid changes. Epinephrine should be administered with caution since it may not have its usual effects in the treatment of anaphylaxis. On the one hand, larger doses of epinephrine may be needed to overcome the bronchospasm, while on the other, these doses can be associated with excessive alpha adrenergic stimulation with consequent hypertension, reflex bradycardia and heart-block and possible potentiation of bronchospasm. Alternatives to the use of large doses of epinephrine include vigorous supportive care such as fluids, and the use of beta agonists including parenteral salbutamol or isoproterenol to overcome bronchospasm, and norepinephrine to overcome hypotension.
Some slowing of heart due to unopposed vagal activity is usual in patients receiving propranolol; however, occasionally severe bradycardia occurs and may lead to vertigo, syncopal attacks or orthostatic hypotension. Patients, especially those with limited cardiac reserve should be monitored for signs of excessive bradycardia. Should the patient become symptomatic the dose of propranolol should be decreased or, if necessary, the drug should be discontinued. If it is essential to correct the bradycardia i.v. atropine or isoproterenol should be considered.
It has been reported that administration of propranolol to control cardiac arrhythmias in acute myocardial infarction has caused marked reduction in cardiac output. Therefore, the doses of propranolol should be kept to the minimum in patients with severe myocardial infarction. Caution should be exercised when administering propranolol in such situations, especially when a large portion of the myocardium has been damaged due to coronary occlusion since adequate sympathetic drive should be preserved to maintain ventricular function. Prior administration of other antiarrhythmic cardiac depressant drugs, such as procainamide or quinidine may potentiate the cardiac depressant activity of propranolol. Prior digitalization may be indicated and atropine should be at hand to control bradycardia.
The combination of propranolol with a thiazide like diuretic and/or peripheral vasodilator produces a greater fall in blood pressure than either drug alone. This occurs regardless of which drug is administered first. The same degree of blood pressure control can be achieved by lower than usual dosages of each drug. Therefore, when using such combined therapy, careful monitoring of the dosages is required until the patient is stabilized.
Patients receiving catecholamine depleting drugs such as reserpine or guanethidine should be closely observed if propranolol is administered concomitantly. The added catecholamine blocking action of this drug may produce an excessive reduction of the resting sympathetic nervous activity.
In patients on long-term treatment with propranolol, laboratory determinations should be made at regular intervals. The drug should be used with caution in patients with impaired renal and hepatic functions.
Adverse Reactions: The most serious adverse effects that may be encountered with propranolol are congestive heart failure and bronchospasm (see Contraindications, Warnings and Precautions).
Gastrointestinal disturbances: (anorexia, nausea, vomiting, diarrhea, abdominal pain) are the most common adverse effects reported. Other less frequently reported adverse effects are: (in descending order) cold extremities and exacerbation of Raynaud’s phenomenon; congestive heart failure; sleep disturbances including vivid dreams; dizziness, fatigue and bronchospasm.
Reported adverse effects, according to organ systems are recorded below.
Cardiovascular: congestive heart failure (see Warnings); secondary effects of decreased cardiac output which could include: syncope, vertigo, lightheadedness, decreased renal perfusion and rarely, postural hypotension; intensification of AV block and hypotension; severe bradycardia; claudication and cold extremities, Raynaud’s phenomenon; dyspnea; palpitations; precordial pain.
CNS: dizziness, lethargy, weakness, drowsiness, headache, insomnia, fatigue, anorexia, anxiety, mental depression, poor concentration, reversible amnesia and catatonia, vivid dreams with or without insomnia, hallucinations, paresthesia, incoordination.
Gastrointestinal: nausea, vomiting, epigastric distress, anorexia, bloating, mild diarrhea, constipation.
Respiratory: bronchospasm; laryngospasm and respiratory distress (see Contraindications and Warnings).
Dermatologic: A few cases of erythematous rashes and increase of facial acneiform lesions have been reported; urticaria; exfoliative psoriasiform eruption.
Others: reduction or loss of libido; reversible alopecia and rarely: diminution and loss of hearing; tinnitus; visual disturbances; diminished vision, conjunctivitis; thrombocytopenic purpura; pharyngitis and agranulocytosis, fever combined with aching and sore throat; flushing of the face.
Clinical Laboratory Test Findings: Elevated blood urea levels in patients with severe heart disease, elevated serum transaminase, alkaline phosphatase, and lactate dehydrogenase have been reported.
Symptoms And Treatment Of Overdose: Symptoms: Several reports in the published literature describe cases in which propranolol was used as a suicide agent. In most cases, other agents, e.g., alcohol, have also been involved. One patient who died was thought to have ingested 3 600 mg of propranolol. Survival of patients taking higher single doses has, however, also been reported. The common signs to be expected in overdosage are bradycardia, hypotension, bronchospasm, or acute cardiac failure.
Treatment: If overdosage occurs, in all cases therapy with propranolol should be discontinued and the patient observed closely. In addition the following therapeutic measures are suggested:
Bradycardia: Administer atropine incrementally in 600 µg (0.6 mg) doses. If there is no response to vagal blockade, administer isoproterenol cautiously.
Cardiac Failure: Digitalization and diuretics.
Hypotension: Vasopressors, e.g., epinephrine or levarterenol. (There is evidence that epinephrine is the drug of choice).
Bronchospasm: Administer isoproterenol and aminophylline.
Dosage And Administration: Inderal: Hypertension: Therapeutic response to a given dosage varies between patients, therefore, dosage must be individually titrated and should be carefully monitored. In the treatment of hypertension, Inderal Tablets may be started by administering the drug in 2 equal daily doses of 40 mg. This may be increased, if necessary, in one week, to 80 mg twice daily, before breakfast and at bedtime. If necessary, the drug may be increased to 160 mg twice daily. For most patients the dosage is within the range of 160 to 320 mg daily. A small number of patients may respond to 80 mg daily. Experience to date suggests that in some resistant patients increasing the dosage above 320 mg/day may have an additional effect. Doses above 320 mg/day should be given on a 3 or 4 times daily regimen.
The time course of full blood pressure response is variable. The antihypertensive effect will usually occur within 3 to 7 days after reaching the effective dose. The maximum decrease in blood pressure may occur 2 to 4 weeks after initiation of treatment.
Angina Pectoris: Dosage must be individualized. Initiate therapy with 20 to 40 mg twice daily before meals. If satisfactory response is not obtained after 1 week, dosage should be increased to 80 mg twice daily. Although individual patients may respond to any dosage level, the average optimum dosage appears to be 160 mg/day. Occasionally in resistant patients dosages as high as 320 to 400 mg/day have been administered with beneficial results. If treatment is to be discontinued, reduce dosage gradually over a period of about 2 weeks (see Warnings).
Arrhythmias: 10 to 30 mg 3 or 4 times daily, before meals and at bedtime.
Post-myocardial Infarction: Initiate therapy with a 20 mg dose. If no adverse reaction is noted, increase the dose to 40 mg three times daily. After one to two weeks increase the dose to 60 mg three time daily. If necessary, the dose may be increased to 80 mg three times daily. In a large study involving 3 837 patients, this larger dose was used in approximately 20% of patients.
Migraine: Dosage must be individualized. The initial dose is 40 mg twice daily. The dose may then be gradually increased until optimum migraine prophylaxis is achieved. The usual effective dose range is 80 to 160 mg/day.
Hypertrophic Subaortic Stenosis: 20 to 40 mg, 3 or 4 times daily, before meals and at bedtime.
Essential tremor: Dosage must be individualized. The initial dose is 80 mg daily in divided doses. The dosage may be increased to 120 to 160 mg daily for optimal effects. If a patient does not respond to the drug within this dosage range, it is unlikely that further increases in dosage will produce a therapeutic effect, although a few patients have benefited from a daily dose of 240 mg. In elderly patients, doses above 120 mg daily may increase the risk of side effects such as bradycardia, syncope and bronchospasm.
Pheochromocytoma: Preoperatively: 60 mg daily, in divided doses, for 3 days before surgery, concomitantly with an alpha-receptor blocking agent.
Malignant cases: 30 mg daily, in divided doses.
Inderal-LA: Intended for maintenance therapy in those patients requiring doses within the range of 60 to 320 mg/day. Initiation of treatment and individual titration of dosage should be carried out using the conventional tablets. Inderal-LA may be preferred for maintenance because of the convenience of once-daily dosage. Patients with angina or hypertension on a maintenance regimen within the range of 60 to 320 mg/day regular tablets taken in divided doses may be changed to the appropriate number of Inderal-LA capsules taken once daily in the morning or evening.
However, Inderal-LA should not be considered a simple mg-for-mg substitute for conventional Inderal tablets and blood levels achieved are lower than those of 2 to 4 times daily dosing with the same dose. When changing to Inderal-LA from conventional Inderal tablets, 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 shown to be therapeutically equivalent to the same mg dose of conventional propranolol as assessed by 24-hour effects on blood pressure, and on 24-hour exercise responses of heart rate, systolic pressure, and rate pressure product. Inderal-LA can provide effective beta blockade for 24-hour periods.
When propranolol is combined with another antihypertensive agent which is already being administered, therapy should be initiated with conventional Inderal tablets following usual dosage recommendations. Once adequate blood pressure control has been obtained, Inderal-LA capsules may be used for maintenance provided the dosage requirement is suitable.
In the treatment of hypertension, if required, further reduction of blood pressure may be attained by the addition of diuretic and/or peripheral vasodilator. Addition of another antihypertensive agent should, however, be gradual, beginning with 50% of the usual recommended starting dose, to avoid excessive reduction of blood pressure.
Inderal Injection: I.V. administration is reserved for life-threatening arrhythmias, or those occurring under anesthesia. The usual dose is from 1 to 3 mg, administered under careful monitoring, e.g., electrocardiograph, and central venous pressure recording. The rate of administration should not exceed 1 mg/minute to avoid extreme lowering of blood pressure and cardiac arrest. Sufficient time should be allowed for the drug to reach the site of action especially when a slow circulation is present. If necessary, a second dose may be given after 2 minutes. Thereafter, additional drug should not be given in less than 4 hours. Additional propranolol should not be given once the desired alteration in rate and/or rhythm is achieved. Changeover to oral therapy should be made as soon as possible.
The i.v. product contains no preservatives. Discard the unused portion after the second dose.
Availability And Storage: Inderal: 10 mg: Each scored, orange, round, biconvex tablet contains: propranolol HCl 10 mg. Nonmedicinal ingredients: D&C Yellow No. 10 aluminum lake, FD&C Yellow No. 6 aluminum lake, lactose, magnesium stearate, microcrystalline cellulose and stearic acid. Energy: 1.67 kJ (0.4 kcal). Alcohol-, gluten-, parabens-, sodium-, sulfites- and tartrazine-free. Bottles of 100 and 1 000.
20 mg: Each scored, light blue, hexagonal tablet contains: propranolol HCl 20 mg. Nonmedicinal ingredients: FD&C Blue No. 1 aluminum lake, lactose, magnesium stearate, microcrystalline cellulose and stearic acid. Energy: 1.67 kJ (0.4 kcal). Alcohol-, gluten-, parabens-, sodium-, sulfites- and tartrazine-free. Bottles of 100 and 1 000.
40 mg: Each scored, green, round, biconvex tablet contains: propranolol HCl 40 mg. Nonmedicinal ingredients: D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake, FD&C Yellow No. 6 aluminum lake, lactose, magnesium stearate, microcrystalline cellulose and stearic acid. Energy: 1.67 kJ (0.4 kcal). Alcohol-, gluten-, parabens-, sodium-, sulfites- and tartrazine-free. Bottles of 100 and 1 000.
80 mg: Each scored, yellow, round, biconvex tablet contains: propranolol HCl 80 mg. Nonmedicinal ingredients: D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake, FD&C Yellow No. 6 aluminum lake, lactose, magnesium stearate, microcrystalline cellulose and stearic acid. Energy: 2.51 kJ (0.6 kcal). Alcohol-, gluten-, parabens-, sodium-, sulfites- and tartrazine-free. Bottles of 100.
120 mg: Each scored, red, round, biconvex tablet contains: propranolol HCl 120 mg. Nonmedicinal ingredients: lactose, magnesium stearate, microcrystalline cellulose, red ferric oxide and stearic acid. Energy: 3.35 kJ (0.8 kcal). Alcohol-, gluten-, parabens-, sodium-, sulfites- and tartrazine-free. Bottles of 100.
Inderal-LA: 60 mg: Each white/light blue, controlled-release capsule, identified by 3 narrow bands, 1 wide band, and INDERAL-LA 60, contains: propranolol HCl 60 mg. Nonmedicinal ingredients: ethylcellulose, hydroxypropyl methylcellulose and microcrystalline cellulose; empty capsule: FD&C Blue No. 1, FD&C Red No. 3, gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide. Energy: 0.84 kJ (0.2 kcal). Alcohol-, gluten-, lactose-, sodium-, sugar-, sulfites- and tartrazine-free. Bottles of 100.
80 mg: Each light blue, controlled-release capsule, identified by 3 narrow bands, 1 wide band, and INDERAL-LA 80, contains: propranolol HCl 80 mg. Nonmedicinal ingredients: ethylcellulose, hydroxypropyl methylcellulose and microcrystalline cellulose; empty capsule: FD&C Blue No. 1, FD&C Red No. 3, gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide. Alcohol-, gluten-, lactose-, sodium-, sugar-, sulfites- and tartrazine-free. Energy: 0.84 kJ (0.2 kcal). Bottles 100 and 500.
120 mg: Each light blue/dark blue, controlled-release capsule, identified by 3 narrow bands, 1 wide band and INDERAL-LA 120, contains: propranolol HCl 120 mg. Nonmedicinal ingredients: ethylcellulose, hydroxypropyl methylcellulose and microcrystalline cellulose; empty capsule: FD&C Blue No. 1, FD&C Red No. 3, gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide. Energy: 0.84 kJ (0.2 kcal). Alcohol-, gluten-, lactose-, sodium-, sugar-, sulfites- and tartrazine-free. Bottles of 100.
160 mg: Each dark blue, controlled-release capsule, identified by 3 narrow bands, 1 wide band, and INDERAL-LA 160, contains: propranolol HCl 160 mg. Nonmedicinal ingredients: ethylcellulose, hydroxypropyl methylcellulose and microcrystalline cellulose; empty capsule: FD&C Blue No. 1, gelatin and titanium dioxide. Energy: 1.26 kJ (0.3 kcal). Alcohol-, gluten-, lactose-, sodium-, sugar-, sulfites- and tartrazine-free. Bottles of 100 and 500.
Inderal Injection: Each mL contains: propranolol HCl 1 mg in aqueous solution. Nonmedicinal ingredients: citric acid and water for injection. Does not contain alcohols, gluten, parabens, sugars, sulfites or tartrazine. Vials of 1 mL, boxes of 10. Vials of 10 mL, boxes of 5. (Shown in Product Recognition Section)
INDERAL® INDERAL®-LA Wyeth-Ayerst Propranolol HCl Beta-Adrenergic Receptor Blocking Agent