THEOPHYLLINE- theophylline anhydrous tablet, extended release
Glenmark Pharmaceuticals Inc., USA
DESCRIPTION
Theophylline (anhydrous) tablets in a controlled-release system allows a 24-hour dosing interval for appropriate patients.
Theophylline is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous theophylline has the chemical name 1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyL.
The molecular formula of anhydrous theophylline is C7 H8 N4 O2 with a molecular weight of 180.17.
Each controlled-release tablet for oral administration, contains 400 mg or 600 mg of anhydrous theophylline.
Inactive Ingredients: cetostearyl alcohol, hydroxyethyl cellulose, magnesium stearate, povidone and talc.
CLINICAL PHARMACOLOGY
Mechanism of Action
Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). While the mechanisms of action of theophylline are not known with certainty, studies in animals suggest that bronchodilatation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors. Some of the adverse effects associated with theophylline appear to be mediated by inhibition of PDE III (e.g., hypotension, tachycardia, headache, and emesis) and adenosine receptor antagonism (e.g., alterations in cerebral blood flow).
Theophylline increases the force of contraction of diaphragmatic muscles. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel.
INDICATIONS AND USAGE
Theophylline is indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.
CONTRAINDICATIONS
Theophylline is contraindicated in patients with a history of hypersensitivity to theophylline or other components in the product.
WARNINGS
Concurrent Illness
Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition:
Active peptic ulcer disease
Seizure disorders
Cardiac arrhythmias (not including bradyarrhythmias)
DOSAGE AND ADMINISTRATION
Theophylline 400 or 600 mg tablets can be taken once a day in the morning or evening. It is recommended that theophylline be taken with meals. Patients should be advised that if they choose to take theophylline with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food.
Theophylline tablets are not to be chewed or crushed because it may lead to a rapid release of theophylline with the potential for toxicity. The tablet may be split. Infrequently, patients receiving theophylline tablets 400 or 600 mg may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual theophylline.
Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release theophylline product may be transferred to once-daily administration of 400 mg or 600 mg theophylline tablets on a mg-for-mg basis.
It must be recognized that the peak and trough serum theophylline levels produced by the once-daily dosing may vary from those produced by the previous product and/or regimen.
The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects.