theophylline
Brand: Theo-24, Theochron
Beers Criteria TDM Required Prototype Drug
Drug Class: methylxanthine
Drug Family: bronchodilator
Subclass: non-selective phosphodiesterase inhibitor / adenosine receptor antagonist
Organ Systems: respiratorycardiovascular
Mechanism of Action
Non-selective PDE inhibitor increasing cAMP causing bronchodilation; also adenosine antagonism; anti-inflammatory at lower concentrations; narrow therapeutic index.
phosphodiesterase (non-selective)adenosine A1/A2 receptors
Indications
- COPD (add-on)
- asthma (add-on — third-line)
- apnea of prematurity (IV aminophylline)
Contraindications
- active peptic ulcer
- uncontrolled seizure disorder
- tachyarrhythmias
Adverse Effects
Common
- nausea
- vomiting
- headache
- insomnia
- tachycardia
- tremor
Serious
- seizures (toxicity)
- arrhythmias (ventricular)
- death (toxicity)
Pharmacokinetics (ADME)
| Absorption | well absorbed oral; IV aminophylline (theophylline + ethylenediamine) |
| Distribution | moderate |
| Metabolism | extensive hepatic CYP1A2 (primary), CYP3A4 |
| Excretion | renal (10% unchanged) |
| Half-life | 6-9 hours (varies with age, smoking) |
| Onset | variable |
| Peak | 1-2 hours |
| Duration | variable |
| Protein Binding | 56% |
| Vd | 0.5 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| cimetidine/ciprofloxacin | CYP1A2 inhibition — dramatically increases theophylline — toxicity risk | major |
| rifampin | CYP induction — markedly reduces theophylline | major |
| smoking | induces CYP1A2 — reduces theophylline levels; cessation dramatically raises levels | major |
| macrolide antibiotics (erythromycin) | inhibits CYP1A2 — increases theophylline | major |
Nursing Considerations
- Narrow therapeutic index: target serum level 5-15 mcg/mL
- Monitor serum levels; check after 3-5 days (steady state) and with any dose changes or drug additions
- Signs of toxicity: tachycardia, nausea, restlessness, headache, insomnia; seizures at >20 mcg/mL
- Smoking: dramatically reduces levels — warn about cessation (levels will rise)
- Many drug interactions requiring level monitoring
Clinical Pearls
- NTI: toxicity risk at levels barely above therapeutic; seizures are often the first serious manifestation
- Smoking induction of CYP1A2: smokers require higher doses; quitting raises levels dangerously — monitor closely
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.