1. Clinical Overview
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.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral (sustained-release): 1-2 hours for initial effect; peak bronchodilation in 4-8 hours. | Sustained-release formulations: Approximately 12 hours, allowing for twice-daily dosing. | Approximately 96% for oral sustained-release formulations when taken on an empty stomach. |
2. Mechanism of Action
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.
3. Indications & Uses
- Maintenance therapy for symptomatic relief and prevention of chronic asthma
- Maintenance therapy for chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema
4. Dosage & Administration
Adult Dosage: 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.
Administration: 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.
5. Side Effects
Common side effects may include:
- Nausea, vomiting, epigastric pain
- Headache
- Insomnia, restlessness
- Nervousness, irritability
- Tachycardia, palpitations
- Increased diuresis
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| 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 |
7. Patient Counselling
- DO take the medicine at the same times every day.
- DO swallow the sustained-release tablet/capsule whole. Do NOT crush, chew, or break it.
- DO inform all your doctors and pharmacists that you are taking theophylline.
- DO keep all appointments for blood tests to check theophylline levels.
- DONT start or stop any other medicine (including OTC, herbal, Ayurvedic) without consulting your doctor.
- DONT change the brand of theophylline without medical advice, as absorption may differ.
- DONT consume large amounts of caffeine-containing products (coffee, tea, cola, chocolate).
8. Toxicology & Storage
Overdose: Mild toxicity (15-20 mcg/mL): Nausea, vomiting, diarrhea, headache, insomnia, tachycardia. Moderate toxicity (20-40 mcg/mL): Persistent vomiting, cardiac arrhythmias (SVTs), hypotension, agitation, tremors. Severe toxicity (>40 mcg/mL): Intractable vomiting, cardiac arrhythmias (ventricular), hypokalemia, hyperglycemia, seizures (often the first sign in children), brain damage, and death. Toxicity can occur with only a small increase above the therapeutic range.
Storage: Store at room temperature (15-30°C), protected from light and moisture. Keep in the original container, tightly closed. Keep out of reach of children. Do not use after the expiry date printed on the pack.