Theophylline
Methylxanthines
Methylxanthines
An oral bronchodilator for asthma and COPD with a narrow therapeutic range and many interactions; levels are checked to avoid toxicity.
Quick facts
- Group
- Methylxanthines
- Target
- Adenosine A2A receptor (and phosphodiesterases PDE3, PDE4)
- Used for
- Add-on treatment of chronic asthma
- Key effects
- Nausea · Headache and insomnia · Nervousness
- Monitor
- Heart rate and rhythm · Smoking status
- ATC
- R03DA04
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows theophylline bound to the human adenosine A2A receptor (stabilised crystal construct); theophylline also inhibits phosphodiesterases.
Theophylline relaxes bronchial smooth muscle mainly by inhibiting phosphodiesterases (PDE3 and, less, PDE4), which raises cyclic AMP. It also blocks adenosine receptors, stimulates the respiratory centre and strengthens the diaphragm. Its adverse effects come from the same actions: PDE inhibition causes tachycardia, headache and vomiting, and adenosine blockade causes arrhythmias and seizures. Its clearance by the liver (mostly CYP1A2) varies widely between people and becomes saturated, so small dose changes can cause large changes in serum levels.
- Theophylline inhibits phosphodiesterases in airway muscle
- Cyclic AMP rises and the muscle relaxes
- Adenosine receptor block stimulates breathing
- The same actions in heart and brain cause toxicity
Indications
- Add-on treatment of chronic asthma Asthma →
- Chronic airflow obstruction in COPD (emphysema, chronic bronchitis) Chronic obstructive pulmonary disease (COPD) →
Adverse effects
Common
- Nausea, vomiting and stomach upset
- Headache and insomnia
- Nervousness, irritability and tremor
- Palpitations and fast heartbeat
- Increased urination
Contraindications
- Hypersensitivity to theophylline
- Extreme caution in active peptic ulcer, seizure disorders and tachyarrhythmias
- Caution where clearance is reduced: heart failure, liver disease, old age, fever with viral illness, hypothyroidism
Key interactions
- CYP1A2 inhibitors: ciprofloxacin, erythromycin, clarithromycin, cimetidine, fluvoxamine
- Slow theophylline clearance and raise levels into the toxic range
- Smoking, rifampicin, carbamazepine, phenobarbital, phenytoin, St John's wort
- Speed clearance and lower levels; levels rise when they are stopped (including quitting smoking)
- Lithium
- Theophylline increases lithium clearance and can lower its effect
- Benzodiazepines
- Theophylline counteracts their sedation (adenosine antagonism)
- Halothane and other agents that sensitise the heart to catecholamines; ketamine
- Higher risk of ventricular arrhythmias; ketamine may lower the seizure threshold
What is monitored
- Serum theophylline concentration at the start, after dose changes, with new interacting drugs or illness, and when toxicity is suspected
- Heart rate and rhythm
- Potassium and glucose in toxicity
- Smoking status
Administration and safety
- Extended-release tablets are swallowed whole, not crushed or chewed
- Different extended-release products are not interchangeable without checking levels
- Large amounts of coffee, tea, cola or chocolate add methylxanthine effects
Pregnancy and breastfeeding
Theophylline crosses the placenta; its protein binding falls in the third trimester, so toxicity can appear at usual total levels and monitoring is closer.
Nursing care
- Ask about smoking, new medicines (especially antibiotics), fever and heart or liver disease
- Treat new nausea or vomiting as possible toxicity and check a level
- Monitor pulse and rhythm; report palpitations
- Teach not to change brand or dose and to report when stopping smoking
Pharmacokinetics
- Absorption
- Well absorbed by mouth; extended-release forms smooth the levels
- Distribution
- Into body water, crosses the placenta and enters breast milk
- Metabolism
- Liver, mostly CYP1A2, with saturable (non-linear) kinetics; a small part becomes caffeine
- Half-life
- Varies widely with age, smoking, heart and liver disease and interacting drugs
Test yourself
Think of the answer, then tap the question to see it.
Why is theophylline monitored with serum levels?
Its therapeutic range is narrow and its clearance varies widely and saturates, so toxicity is easy to reach.
Which liver enzyme metabolises theophylline, and which two drugs inhibit it?
CYP1A2; ciprofloxacin and fluvoxamine (also cimetidine, erythromycin).
What are the most dangerous signs of theophylline toxicity?
Tachyarrhythmias and seizures; vomiting is often the earliest warning.
What happens to theophylline levels when a patient stops smoking?
They rise, because smoking had been inducing CYP1A2.
Which molecular actions explain theophylline's bronchodilation?
Phosphodiesterase inhibition (higher cyclic AMP) plus adenosine receptor blockade.
Connections
← Back to the class: Methylxanthines
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - THEOPHYLLINE tablet, extended release (DailyMed (U.S. National Library of Medicine), 2026); Theophylline: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2019); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.