A small number of cases of acute angle closure glaucoma have been reported in patients treated with a combination of nebulised VENTOLIN and ipratropium bromide. A combination of nebulised VENTOLIN with nebulised anticholinergics should therefore be used cautiously. Patients should receive adequate instruction in correct administration and be warned not to let the solution or mist enter the eye. Potentially serious hypokalaernia may result from 132 agonist therapy mainly from parenteral and nebulised administration. 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. In common with other 3-adrenoceptor agonists, VENTOLIN can induce reversible metabolic changes, for example increased blood sugar levels. The diabetic patient may be unable to compensate for this and the development of ketacidosis has been reported. Concurrent administration of corticosteroids can exaggerate this effect. Lactic acidosis has been reported very rarely in association with high therapeutic doses of intravenous and nebulised short-acting beta-agonist therapy, mainly in patients being treated for an acute asthma exacerbation (see Adverse Reaction section). Increase in lactate levels may lead to dyspnoea and compensatory hyperventilation, which could be misinterpreted as a sign of asthma treatment failure and lead to inappropriate intensification of short-acting beta-agonist treatinent. It is therefore recommended that patients are monitored for the development of elevated serum lactate and consequent metabolic acidosis in this setting.
VENTOLIN and non-selective 3-blocking drugs, such as propranolol, should not usually be prescribed together. VENTOLIN is not contraindicated in patients under treatment with monoamine oxidase inhibitors.
Pregnancy and Lactation
Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus. During world-wide 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. Because no consistent pattern of defects can be discerned, and baseline rate for congenital anomalies is 2-3%, a relationship with salbutamol use cannot be established. As salbutamol is probably secreted in breast milk its use in nursing mothers is not recommended unless the expected benefits outweigh any potential risk. It is not known whether salbutamol in breast milk has a harmful effect on the neonate.
Effects on Ability to Drive and Use Machines None reported. Adverse Reactions Adverse events are listed below by system organ class and frequency. Frequencies are defined as very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1000 and <1/100), rare (>1/10,000 and <1/1000) and very rare (<1/10,000) including isolated reports. Very common and common events were generally determined from clinical trial data Rare and very rare events were generally determined from spontaneous data. Immune system disorders Very rare. Hypersensitivity reactions including angioedema, urticaria, bronchospasm, hypotension and collapse. Metabolism and nutrition disorders Rare: Hypokalaemia. Potentially serious hypokalaemia may result from beta, agonist therapy. Very rare: Lactic acidosis Lactic acidosis has been reported very rarely in patients receiving intravenous and nebulised salbutamol therapy for the treatment of acute asthma exacerbation.
Nervous system disorders
Common: Truing, ileauache.
Very rare: Hyperactivity.
Very rare: Cardiac arrhythmias including atrial fibrillation, supraventricular tachycardia and extrasystoles. Vascular disorders Rare. Peripheral vasodilatation.
Respiratory, thoracic and mediastinal disorders
Very rare: Paradoxical bronchospasm.
As with other inhalation therapy, paradoxical bronchospasm may occur with en immediate increase in wheezing after dosing. This should be treated immediately with an alternative presentation or a different fast-acting inhaled bronchodilator. VENTOLIN Respirator Solution should be discontinued immediately, the patient assessed, and, if necessary, alternative therapy instituted. Gastrointestinal disorders Uncommon, Mouth and throat irritation. Musculoskeletal and connective tissue disorders Uncommon: Muscle cramps. The most common signs and symptoms of overdose with VENTOLIN are transient beta agonist pharmacologically mediated PVIVS (see Warnings and Precautions and Adverse Reactions).
Beta-blocking drugs should be used with caution in patients with a history of bronchospasm. During continuous administration of VENTOLIN Respirator Solution, any signs of overdosage can usually be counteracted by withdrawal of the drug.
Pharmacodynamics Salbutamol is a selective a2 adrenoce pto r agonist. At therapeutic doses it acts on the a, adrenoceptors of bronchial muscle, with little or no action on the 5-1 adrenoceptors of cardiac muscle. Pharmacokinetics Salbutamol administered intravenously has a half-life of 4 to 6 hours and is cleared partly renally and partly by metabolism to the inactive 4-0-sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. The majority of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. Salbutamol is bound to plasma proteins to the extent of 10%. After administration by the inhaled route between 10 and 20% of the dose reaches the lower airways. The remainder is retained in the delivery system or is deposited in the oropharynx from where it is swallowed The traction deposited in the airways is absorbed into the pulmonary tissues and circulation but is not metabolised by the lung. On reaching the systemic circulation it becomes accessible to hepatic metabolism and is excreted, primarily in the urine, as unchanged drug and as the phenolic sulphate. The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulphate. Both unchanged drug and conjugate are excreted primarily in the unne. Pre-clinical Safety Data In common with other potent selective 02 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 2.5 mg/kg, 4 times the maximum human oral dose. In rate, treatment at the levels of 0.5, 2.32, 10.75 and 50mgikgiclay 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 50ing/kg/day, 78 times the maximum human oral dose.