Hemangiol

- Angina pectoris.

- Hypertension.

- Long-term prophylaxis against myocardial reinfarction after recovery from acute myocardial infarction

- Hypertrophic obstructive cardiomyopathy.

- Essential tremor.

- Supraventricular cardiac arrhythmia.

- Ventricular cardiac arrythmias.

- Hyperthyroidism and thyrotoxicosis

- Phaeochromocytoma (with an alpha-blocker).

- Migraine.

- Prophylaxis of upper gastrointestinal bleeding in patients with portal hypertension and oesophageal varices.

Hypertension

Hemangiol is indicated in the management of hypertension. It may be used alone or used in combination with other antihypertensive agents, particularly a thiazide diuretic. Hemangiol is not indicated in the management of hypertensive emergencies.

Angina Pectoris Due to Coronary Atherosclerosis

Hemangiol is indicated to decrease angina frequency and increase exercise tolerance in patients with angina pectoris.

Atrial Fibrillation

Hemangiol is indicated to control ventricular rate in patients with atrial fibrillation and a rapid ventricular response.

Myocardial Infarction

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

Migraine

Hemangiol 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

Hemangiol 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. Hemangiol causes a reduction in the tremor amplitude, but not in the tremor frequency. Hemangiol is not indicated for the treatment of tremor associated with Parkinsonism.

Hypertrophic Subaortic Stenosis

Hemangiol improves NYHA functional class in symptomatic patients with hypertrophic subaortic stenosis.

Pheochromocytoma

Hemangiol is indicated as an adjunct to alpha-adrenergic blockade to control blood pressure and reduce symptoms of catecholamine-secreting tumors.

Hypertension

Hemangiol is indicated in the management of hypertension. It may be used alone or used in combination with other antihypertensive agents, particularly a thiazide diuretic. Hemangiol is not indicated in the management of hypertensive emergencies.

Angina Pectoris Due To Coronary Atherosclerosis

Hemangiol is indicated to decrease angina frequency and increase exercise tolerance in patients with angina pectoris.

Migraine

Hemangiol 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.

Hypertrophic Subaortic Stenosis

Hemangiol improves NYHA functional class in symptomatic patients with hypertrophic subaortic stenosis.

Cardiac Arrhythmias

Intravenous administration is usually reserved for life-threatening arrhythmias or those occurring under anesthesia.

1. Supraventricular arrhythmias

Intravenous propranolol is indicated for the short-term treatment of supraventricular tachycardia, including Wolff-Parkinson-White syndrome and thyrotoxicosis, to decrease ventricular rate. Use in patients with atrial flutter or atrial fibrillation should be reserved for arrythmias unresponsive to standard therapy or when more prolonged control is required. Reversion to normal sinus rhythm has occasionally been observed, predominantly in patients with sinus or atrial tachycardia.

2. Ventricular tachycardias

With the exception of those 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 intravenously in low dosage and very slowly, as the failing heart requires some sympathetic drive for maintenance of myocardial tone. (See DOSAGE AND ADMINISTRATION). Some patients may respond with complete reversion to normal sinus rhythm, but reduction in ventricular rate is more likely. Ventricular arrhythmias do not respond to propranolol as predictably as do the supraventricular arrhythmias.

Intravenous propranolol is indicated for the treatment of persistent premature ventricular extrasystoles that impair the well-being of the patient and do not respond to conventional measures.

3. Tachyarrhythmias of digitalis intoxication

Intravenous propranolol is indicated to control ventricular rate in life-threatening digitalis-induced arrhythmias. Severe bradycardia may occur. (See OVERDOSAGE).

4. Resistant tachyarrhythmias due to excessive catecholamine action during anesthesia

Intravenous propranolol is indicated to abolish tachyarrhythmias due to excessive catecholamine action during anesthesia when other measures fail. These arrhythmias may arise because of release of endogenous catecholamines or administration of catecholamines. 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, usually with constant monitoring of the ECG and central venous pressure. (See WARNINGS).

Adults:

Hypertension

Initially 40 mg two or three times daily, which may be increased by 80 mg per day at weekly intervals according to response. The usual dose range is 160 to 320 mg per day. With concurrent diuretic or other antihypertensive drugs a further reduction of blood pressure is obtained.

Angina, migraine and essential tremor

The starting dose is 40 mg two to three times daily, increasing by the same amount at weekly intervals according to the patient response. An adequate response in migraine is usually seen in the range 80 to 160 mg/day and in angina and essential tremor in the range 120 to 240 mg/day.

Arrhythmias, hypertrophic obstructive cardiomyopathy and thyrotoxicosis

A dosage range of 10 to 40 mg three or four times a day usually achieves the required response.

Post myocardial infarction

Treatment should start between days 5 and 21 after myocardial infarction, with an initial dose of 40mg four times a day for two or three days. In order to improve compliance, the total daily dosage may thereafter be given as 80mg twice a day.

Hyperthyroidism

The dose is adjusted according to clinical response.

Portal Hypertension

Dosage should be titrated to achieve approximately 25% reduction in heart rate at rest. Dosing should begin with 40mg twice daily, increasing to 80mg twice daily depending on heart rate response. If necessary, the dose may be increased incrementally to a maximum of 160mg twice daily.

Phaeochromocytoma

(Used only with an alpha-receptor blocking drug).

Pre-operative: 60 mg daily for 3 days is recommended. Non-operable malignant cases: 30 mg daily.

Hepatic impairment:

The bioavailability of Hemangiol may be increased in patients with hepatic impairment and dose adjustments may be required. In patients with severe liver disease (e.g. cirrhosis) a low initial dose is recommended (not exceeding 20mg three times a day) with close monitoring of the response to treatment (such as the effect on heart rate).

Renal impairment:

Concentrations of Hemangiol may increase in patients with significant renal impairment and haemodialysis. Caution should be exercised when starting treatment and selecting the initial dose.

As with other beta-adrenoceptor blocking agents, treatment should not be discontinued abruptly. The dosage should be withdrawn gradually over a period of 7 to 14 days. Either the equivalent dosage of another beta-adrenoceptor blocker may be substituted or the withdrawal of Hemangiol should be gradual. Patients should be followed during withdrawal especially those with ischaemic heart disease. The risk/benefit of stopping beta blockade should be made for each patient.

Elderly:

Evidence concerning the relationship between blood level and age is conflicting. Hemangiol should be used to treat older people with caution. It is suggested that treatment should start with the lowest dose. The optimum dose should be individually determined according to clinical response.

Paediatric population

Arrhythmias

Dosage should be determined according to the cardiac status of the patient and the circumstances necessitating treatment. The dose should be adjusted individually and the following is a guide: Children and adolescents: 0.25-0.5 mg / kg 3-4 times daily, adjusted according to clinical response.

Migraine

Oral: Under the age of 12: 20 mg two or three times daily. Over the age of 12: The adult dose.

Method of administration

For oral 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 Hemangiol 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 Hemangiol, 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 Hemangiol 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 Hemangiol per day in divided doses. Although a t.i.d. regimen was used in the 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 bid. 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 (see above).

Migraine

The initial dose is 80 mg Hemangiol 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, Hemangiol 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 Hemangiol 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 Hemangiol three or four times daily before meals and at bedtime.

Pheochromocytoma

The usual dosage is 60 mg Hemangiol 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.

General

Inderal^® LA provides propranolol hydrochloride in a sustained-release capsule for administration once daily. If patients are switched from Inderal Tablets to Hemangiol Capsules, care should be taken to assure that the desired therapeutic effect is maintained. Hemangiol should not be considered a simple mg-for-mg substitute for Inderal. Hemangiol has 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 Hemangiol 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 Hemangiol 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 Hemangiol 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, Inderal LA 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 Hemangiol.

Hypertrophic Subaortic Stenosis

The usual dosage is 80 to 160 mg Hemangiol once daily.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The usual dose is 1 to 3 mg administered under careful monitoring, such as electrocardiography and central venous pressure. The rate of administration should not exceed 1 mg (1 mL) per minute to diminish the possibility of lowering blood pressure and causing cardiac standstill.

Sufficient time should be allowed for the drug to reach the site of action even when a slow circulation is present. If necessary, a second dose may be given after two minutes. Thereafter, additional drug should not be given in less than four hours. Additional Hemangiol should not be given when the desired alteration in rate or rhythm is achieved.

Transfer to oral therapy as soon as possible.

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.

- Cardiac decompensation which is not adequately treated.

- Sick sinus syndrome/SA-block.

- History of bronchospasm or bronchial asthma, chronic obstructive pulmonary disease.

- Metabolic acidosis.

- Second and third-degree heart block.

- Patients prone to hypoglycaemia, e.g. due to prolonged fasting or restricted counter regulatory reserve.

- Cardiogenic shock.

- Untreated phaeochromocytoma.

- Severe bradycardia.

- Severe hypotension

- Severe peripheral arterial disturbances

- Prinzmetal's angina

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.

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

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 Hemangiol.