Tulobuterol Hydrochloride

The primary pharmacological action of beta-adrenergic drugs is to stimulate adenyl cyclase, the enzyme which catalyzes the formation of cyclic-3',5' adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP). The cyclic AMP thus formed mediates the cellular response that results in bronchodilation. Tulobuterol, due to its highly selective action on beta-2 adrenoceptors, relaxes the bronchial smooth muscle and has been shown to be clinically successful in the symptomatic treatment of reversible obstructive airways disease (ROAD) such as bronchial asthma, and also in bronchitis and emphysema.

Some bronchodilators stimulate beta-1 (cardiac) receptors in addition to beta-2 receptors and may cause tachycardia, angina, and possibly arrhythmias in susceptible patients. Animal studies and in vitro experiments indicate that tulobuterol is more selective in its beta-2 agonist activity than other agents in this class and, therefore, should produce fewer cardiac side effects.

As long-term clinical studies have demonstrated, tulobuterol continues to be efficacious and does not result in cumulative or toxic side effects. Due to the variability of the disease and the need for individualized dosage requirements, flexibility in dosing is indispensable.

The use of Long-Acting Beta Agonists is contraindicated without the use of an asthma controller medication such as inhaled corticosteroid.

Long-Acting Beta Agonists should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved. Patient should then be maintained on a long-term asthma controller medication (e.g. Corticosteroids).

Tablets: The usual oral adult dose of tulobuterol is one 2 mg tablet twice a day. A convenient starting dose for children 12 years and over and adults is 1 mg twice a day, particularly for elderly patients and those with a history of sensitivity to beta-adrenergic agents. Unless precluded by drug-related side effects, the patient may have the dose increased after seven to ten days to 2 mg twice a day, if necessary, to achieve a greater therapeutic response.

Although most patients can be maintained on a dose of 1 to 2 mg twice daily, the variability of patient response and severity of symptoms may require further adjustment of the dose, as with any bronchodilator treatment. Therefore, if necessary, the adult dose of tulobuterol may be increased to 6 mg a day in divided doses according to clinical response.

Syrup: Based on dose-ranging studies in children, the usual dose of tulobuterol syrup (1 mg/5 mL) for children is 40 to 80 mcg/kg/day in two divided doses.

In clinical studies in children, the effective dose has ranged from 20 to 100 mcg/kg/day.

This leads to the following recommendations on the basis of age:

• For children aged one to six years, 0.25 tsp. (1.25 mL) to 0.5 tsp. (2.5 mL) BID
• For children aged six to twelve years, 0.5 tsp. (2.5 mL) to 1 tsp. (5 mL) BID
• For children aged over twelve years, 1 tsp. (5 mL) to 2 tsp. (10 mL) BID
• The above age recommended doses may have to be modified according to patient response.

Increased risk of arrhythmia with digoxin. Hypokalaemia with concomitant admin of xanthines, corticosteroids and diuretics.

Administration of tulobuterol is contraindicated in patients with known hypersensitivity to sympathomimetic amines or any of the formulation components.

The adverse reactions of tulobuterol are similar in nature to those of other sympathomimetic agents, however the incidence of certain cardiovascular effects is less with tulobuterol. Dose-related finger tremor is common with these agents, but the effects tend to lessen with continued administration of the drug. Oral formulations of tulobuterol, like other sympathomimetic agents, can also cause less frequent adverse reactions such as hypertension, palpitations, angina, tachycardia, vomiting, vertigo, central nervous system stimulation, insomnia and headache.

Safety of this product for use during pregnancy has not been established. It is not known whether tulobuterol is excreted in human breast milk nor whether it has a harmful effect on the newborn. Therefore, as with any medication, the use of the drug in pregnancy, lactation, or women of childbearing potential requires that the expected therapeutic benefit of the drug be weighed against its possible hazards to the mother and child.

Long-Acting Beta Agonists should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medications alone.

Tulobuterol should be used with caution in patients with diabetes mellitus, hypertension, hyperthyroidism, and seizure disorders.

Caution should be observed in patients with renal failure in view of the kidney being the principle route of elimination of the drug. Dosage may also require individualization in patients with impaired liver function as normally tulobuterol is extensively metabolized by the liver.

As with other sympathomimetic bronchodilator agents, tulobuterol should be administered cautiously to cardiac patients, especially those with associated arrhythmias, coronary insufficiency, or myocardial ischemia.

Short-acting selective & β2-adrenoceptor stimulants