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Logo ‘DIBENYLINE’Capsules

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

‘DIBENYLINE’Capsules

COMPOSITION:
Each ‘Dibenyline’capsule contains 10 mg
phenoxybenzamine hydrochloride.

PHARMACOLOGICAL CLASSIFICATION:
A.5.2 Adrenolytics (Sympathicolytics)

PHARMACOLOGICAL ACTION:
‘Dibenyline’ (phenoxybenzamine hydrochloride) is a long-acting adrenergic a-receptor blocking agent. It increases blood flow to the skin, mucosa and abdominal viscera under certain conditions and lowers both supine and erect blood pressures. The effect of ‘Dibenyline’lasts up to one week, depending on the dosage used. The serum half-life is 24 hours.

INDICATIONS:
It is indicated in the management of hypertensive episodes associated with phaeochromocytoma.

CONTRA-INDICATIONS:
Pregnancy
Conditions where a fall in blood pressure may be undesirable such as cerebrovascular incidents and in the recovery period following acute myocardial infarction.

DOSAGE AND DIRECTIONS FOR USE:
Adults:
In phaeochromocytoma - the dosage generally required to achieve blood pressure control is 1 - 2 mg/kg body mass daily.
Small initial doses should be slowly increased until the desired effect is obtained or the adverse reactions from blockade become troublesome. The patient’s response should be the guide after each increase, the patient should be observed at that level for at least four days before instituting another increase. Dosage range is usually 20 to 60 mg daily in two doses. Concomitant beta-adrenergic blockade is required to control tachycardia and arrhythmias when phaeochromocytomas are excreting an appreciable amount of adrenaline as well as noradrenaline.

Children:
There is little experience in children, but doses of 1 - 1,5 mg/kg body mass per day in phaeochromocytoma have been used in divided dosages. Dosages may be titrated according to the clinical effect.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Sedation, fatigue, nasal congestion, miosis, postural hypotension with dizziness and compensatory tachycardia, inhibition of ejaculation may occur. These side-effects are actually evidence of adrenergic blockade and vary to the degree of blockade. Furthermore, they tend to decrease as therapy is continued. Gastro-intestinal irritation has also been reported, especially if taken on an empty stomach.
‘Dibenyline’should be administered with caution in patients with marked cerebral or coronary arteriosclerosis or renal damage and in patients where tachycardia or hypotension would be undesirable. Adrenergic blocking effect may aggravate symptoms of respiratory infections.
The adrenergic blocking effects may be enhanced by the concurrent administration of opiates.

Mutagenicity and Carcinogenicity:
Phenoxybenzamine has shown in vitro mutagenic activity in the bacterial Ames Test and in the mouse-lymphoma assay; in vivo it has not shown mutagenic activity in the micronucleus test in mice. In rats and mice, repeated intraperitoneal administration of phenoxybenzamine in very high doses resulted in peritoneal sarcomas. Recent studies done in rats with high doses given by gavage have resulted in the development of squamous cell carcinoma of the rat forestomach. The clinical significance of such test results is not established. Nevertheless, these results should be considered in determining the benefit - risk ratio as it applies to the individual patient. There have been no reports of carcinoma in humans, due to the administration of phenoxybenzamine hydrochloride, since the drug was introduced in 1956. Even though phenoxybenzamine hydrochloride has been used in patients for many years, information about its mutagenic and carcinogenic effects in recent experiments preclude its long term use. The physician should carefully weigh the benefit to risk ratio before prescribing this drug.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms are largely the result of blockade of the sympathetic nervous system and of the circulating epinephrine. They may include postural hypotension resulting in dizziness or fainting; tachycardia, particularly postural; vomiting; lethargy; shock.
Treatment of circulatory failure, if present, is a prime consideration. In cases of mild overdosage, recumbent position with legs elevated usually restores cerebral circulation. In the more severe cases, the usual measures to combat shock should be instituted. Usual pressor agents are not effective. Epinephrine is contra-indicated because it stimulates both alpha and beta receptors. The patient may have to be kept flat for 24 hours or more in the case of overdose, as the effect is prolonged. Leg bandages and an abdominal binder may shorten the period of disability.

IDENTIFICATION:
Hard gelatin capsules consisting of a white opaque body and clear red cap, containing a white powder and bearing a grey SKF monogram.

PRESENTATION:
10 mg capsules in packs of 100.

STORAGE INSTRUCTIONS:
Store in a cool dry place below 25°C and dispense in moisture-proof containers.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
K/5.2/229

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Ltd.
6 Carey Street Wynberg, Ext. 6,
Johannesburg 2090

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
13.5.1987

        PO186

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