Theophylline is a methylxanthine derivative used primarily as a bronchodilator for the management of chronic obstructive pulmonary disease (COPD) and asthma. It is a non-selective phosphodiesterase inhibitor and adenosine receptor antagonist. The 400mg strength is typically available as a sustained-release tablet or capsule, designed for twice-daily dosing to maintain therapeutic serum levels (10-20 mcg/mL) and improve patient compliance in the Indian context.
Adult: Initial: 200-300 mg/day in divided doses (SR formulation: 200-300 mg once or twice daily). Usual maintenance: 400-600 mg/day in divided doses (e.g., 400mg SR tablet every 12 hours). Dose MUST be individualized based on ideal body weight, smoking status, and TDM. Maximum initial dose should not exceed 400 mg/day in non-smoking adults.
Note: Sustained-release tablets/capsules must be swallowed WHOLE, without crushing, chewing, or splitting. Take at the same times each day, preferably on an empty stomach (1 hour before or 2 hours after meals) for consistent absorption. However, if GI upset occurs, it may be taken with a small amount of food, but consistency is key. Avoid taking with a high-fat meal, which can cause dose-dumping. Maintain adequate hydration.
Theophylline's primary mechanism is non-selective inhibition of phosphodiesterase (PDE) enzymes, particularly PDE3 and PDE4, leading to increased intracellular cyclic AMP (cAMP) and cyclic GMP (cGMP). This results in relaxation of bronchial smooth muscle, inhibition of inflammatory cell activation, and modulation of immune responses. It is also a competitive antagonist of adenosine receptors (A1, A2a, A2b), which contributes to bronchodilation and may mediate some CNS and cardiac effects.
Pregnancy: Pregnancy Category C. Crosses placenta. Use only if potential benefit justifies potential fetal risk. Neonatal tachycardia, irritability, and apnea have been reported. Clearance may increase in 3rd trimester. TDM essential.
Driving: May cause dizziness, nervousness, or visual disturbances. Patients should not drive or operate machinery until they know how the drug affects them, especially during dose titration.
| Ciprofloxacin, Enoxacin | Markedly decreases theophylline clearance, increasing levels by 30-100%. High risk of toxicity. | Major |
| Erythromycin, Clarithromycin | Decreases clearance, increases levels by 20-40%. Requires dose reduction and monitoring. | Major |
| Phenytoin, Carbamazepine, Phenobarbital | Increases theophylline clearance, decreasing levels by 30-50%. May lead to therapeutic failure. | Major |
| Cimetidine | Decreases clearance, increases levels by 40-70%. Use Famotidine or Ranitidine instead. | Major |
| Fluvoxamine | Potent CYP1A2 inhibitor; can double theophylline levels. | Major |
| Rifampicin | Dramatically increases clearance, decreasing levels by 50-60%. | Major |
| Beta-blockers (Propranolol) | Antagonize bronchodilator effect; may also reduce clearance. | Moderate |
| Lithium | Theophylline increases renal lithium excretion, decreasing lithium levels. | Moderate |
| Warfarin | Theophylline may slightly potentiate anticoagulant effect. | Moderate |
Same composition (Theophylline (400mg)), different brands: