(i) ROUTE OF ADMINISTRATION

Oral

DOSAGE AND ADMINISTRATION

The tablets must be swallowed whole with a glass of water and not chewed or crushed.

Adults
4 or 8 mg tablets twice daily.

Children (3-12 years)
4 mg twice daily.

(ii) THERAPEUTIC / DIAGNOSTIC CLAIMS

Health 2000 Salbutamol 4mg SA tablet is indicated for the relief of bronchospasm in asthma, chronic bronchitis and emphysema, and other conditions associated with airways obstruction. It is also indicated to prevent symptoms in circumstances recognized by the patient to precipitate an asthma attack (e.g. before exercise, unavoidable allergic exposure).

(iii) DESCRIPTION OF DOSAGE FORM

Salbutamol is a beta-adrenergic stimulant which has a highly selective action on the beta2- receptors in bronchial muscle resulting in bronchodilation, and in therapeutic doses little or no action on the b1- cardiac receptors. Health 2000 Salbutamol 4mg SA tablet contains salbutamol in a sustained-release formulation for oral administration which allows a 12 hour dosing interval.

(iv) CONTRAINDICATIONS

Pre-existing cardiac tachyarrhythmia and in patients with known hypersensitivity to Salbutamol.
Although intravenous Salbutamol and occasionally Salbutamol tablets are used in the management of premature labour, ante-partum haemorrhage or toxemia of pregnancy are contraindications.

WARNINGS AND PRECAUTIONS

DRUG INTERACTIONS
Beta-blockers: Salbutamol oral preparations and non-selective beta-blocking drugs such as propranolol should not usually be prescribed together.
Steroids, diuretics etc: Potentially serious hypokalaemia may result from beta2-agonist therapy. Particular caution is advised in acute, severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids, diuretics, and by hypoxia. It is recommended that serum potassium levels are monitored in such situations.

PREGNANCY
Salbutamol has been in widespread use for many years in human beings without apparent ill consequence. However, as with the majority of drugs, there is little published evidence of its safety in the early stages of human pregnancy.

NURSING MOTHERS
Salbutamol probably enters breast milk and is not recommended unless the expected benefits outweigh any potential risk.

OTHERS
Health 2000 Salbutamol 4mg SA tablet should be used with caution in patients with diabetes mellitus, serious cardiovascular disorders, hypertension or hyperthyroidism.

(v) SIDE EFFECTS

The likely side effects that may be attributed to Salbutamol are gastrointestinal disturbances such as nausea, vomiting, burning substernal or epigastric pain and diarrhoea.
Other side effects such as palpitation, fine tremors of the skeletal muscle (particularly the hand) and muscle cramps may occur especially due to Salbutamol.
Reduction in the dosage generally results in the control of these side effects.

Over dosage
The preferred antidote for over dosage is a cardio-selective beta-blocking agent, but beta-blocking drugs should be used with caution in patients with a history of bronchospasm.

(vi) TOXIC EFFECT:

Mutagenecity, Teratogenecity and Carcinogenecity:

Administration of medicines during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
During worldwide marketing experience, rare cases of various congenital anomalies, including cleft palate and limb defects have been reported in the offspring of patients being treated with Salbutamol. Some of the mothers were taking multiple medications during their pregnancies. In common with other potent selective ß2 receptor agonists, Salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of foetuses were found to have cleft palate, at 2.5mg/kg, 4 times the maximum human oral dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50mg/kg/day orally throughout pregnancy resulted in no significant foetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care. A reproductive study in rabbits revealed cranial malformations in 37% of foetuses at 50mg/kg/day, 78 times the maximum human oral dose.

Salbutamol sulphate has been found to cause a dose-related increase in the incidence of benign leiomyomas of the mesovarium in the rat at oral doses corresponding to 3, 16 and 78 times the maximum oral dose for a 50 kg human. The relevance of these findings to humans is not known. A study in mice, and a lifetime oral study in hamsters, showed no evidence of an oncogenic potential.

In-vitro studies have shown no evidence of mutagenicity.