Theophylline exerts its therapeutic effects through multiple mechanisms:

1. Phosphodiesterase Inhibition:
   • Inhibits phosphodiesterase enzymes, increasing intracellular cyclic AMP (cAMP) levels, which relaxes bronchial smooth muscles (BNF).
2. Adenosine Receptor Antagonism:
   • Blocks adenosine receptors, preventing bronchoconstriction and reducing inflammation (Lippincott).
3. Histone Deacetylase Activation:
   • Enhances the anti-inflammatory effects of corticosteroids in the airways (Lange).
4. Central Respiratory Stimulation:
   • Improves diaphragmatic contractility and respiratory drive, particularly in patients with COPD (Lippincott).

Theophylline is indicated for:

1. Asthma:
   • Used as an add-on therapy for patients with severe or refractory asthma.
2. Chronic Obstructive Pulmonary Disease (COPD):
   • Improves lung function and reduces exacerbations in stable COPD.
3. Apnea of Prematurity (Off-Label):
   • Stimulates breathing in premature infants with apnea (not BNF-approved).
4. Chronic Lung Diseases:
   • May be used in other conditions like bronchiectasis or chronic bronchitis.

Theophylline dosage varies based on the formulation, patient age, and clinical condition. Always follow the prescribing physician’s instructions.

Adults:

• Oral: 200–400 mg daily in divided doses (immediate-release) or once daily (extended-release).
• IV (Aminophylline): Loading dose of 5 mg/kg, followed by 0.5 mg/kg/hour infusion (BNF).

Children:

• Oral: 10–16 mg/kg/day in divided doses (immediate-release).
• IV (Aminophylline): Loading dose of 5 mg/kg, followed by 0.5–0.7 mg/kg/hour infusion.

Administration Tips:

• Take with food to reduce gastrointestinal irritation.
• Avoid crushing or chewing extended-release formulations.
• Monitor serum theophylline levels regularly (therapeutic range: 10–20 mg/L).

Theophylline has a narrow therapeutic index, and side effects are common, especially at higher doses:

Common:

• Gastrointestinal: Nausea, vomiting, diarrhea.
• Central nervous system: Headache, insomnia, restlessness.
• Cardiovascular: Tachycardia, palpitations.

Rare but Serious:

• Seizures: Particularly with serum levels >20 mg/L.
• Cardiac Arrhythmias: Atrial fibrillation, ventricular tachycardia.
• Hypotension or Shock: With rapid IV administration.

Before using theophylline, inform your healthcare provider if you have:

• Liver or kidney disease (reduces drug clearance).
• Heart disease or arrhythmias.
• Peptic ulcer disease or gastroesophageal reflux disease (GERD).
• Seizure disorders.
• Allergies to theophylline or methylxanthines.

Special Populations:

• Pregnancy: Use only if benefits outweigh risks (BNF Category: C).
• Breastfeeding: Theophylline passes into breast milk; monitor infant for irritability or insomnia.
• Elderly: Increased risk of toxicity due to reduced clearance.

Theophylline interacts with numerous medications, altering its metabolism and effects:

1. CYP1A2 Inhibitors (e.g., ciprofloxacin, fluvoxamine):
   • Increase theophylline levels, raising the risk of toxicity (BNF).
2. CYP1A2 Inducers (e.g., rifampicin, phenytoin):
   • Decrease theophylline levels, reducing efficacy (Lippincott).
3. Beta-Blockers (e.g., propranolol):
   • May counteract bronchodilator effects.
4. Lithium:
   • Theophylline may increase lithium excretion, reducing its efficacy.
5. Stimulants (e.g., caffeine):
   • Additive CNS stimulation, increasing side effects.

Generic Names in Pharmacy

• Theophylline (active ingredient)
• Aminophylline (a theophylline derivative)
• Common brand names: Theo-24®, Uniphyl®, Slo-Bid®