Drug reference

Theophylline

Methylxanthine bronchodilator / phosphodiesterase inhibitor · Bronchodilator

Also known as Aminophylline, Oxtriphylline, Xanthine, Methylxanthine

START

Check baseline theophylline level if prior use, LFTs, caffeine intake, smoking status. Review ALL medications for CYP1A2 interactions. Target 5-15 mcg/mL.

TYPICAL MAX

900mg/day. Toxicity risk increases above 15 mcg/mL; seizures and arrhythmias can occur at 20-30 mcg/mL. Narrow therapeutic index.

STOP IF

Serum level >20 mcg/mL, seizures, life-threatening arrhythmias, severe vomiting with dehydration.

WATCH

Serum theophylline levels: at 2-3 days after start or dose change, then every 6-12 months (more frequently if interacting drugs added). Smoking increases clearance by 50-80% (dose increase needed); smoking cessation decreases clearance (dose reduction needed). Many drug interactions via CYP1A2.

CDSCO approvedHATC R03DA04

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · Onset 30-60 min (IR)
PEAK: 1.5h · Tmax IR 1-2h; SR 4-8h
t½: 8h · t½ ~8h (non-smokers)
DURATION: 8h · 6-8 hours (IR)

EXCRETION

Hepatic metabolism; 10% renal unchanged

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Crosses placenta; may cause neonatal irritability and tachycardia. Use only if benefit outweighs risk—target lower serum levels (5-12 mcg/mL).

FDA category + note

Top interactionssee all 12 →

FebuxostatContraindicatedDatabaseKimi deep-research + Cla
AllopurinolSevereTextbook-citedKDT 7e · p948
AtazanavirSevereTextbook-citedKDT 7e · p948
CiprofloxacinSevereTextbook-citedKDT 7e · p948

Available in India

44 branded formulations and 59 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Mechanism

Non-selective phosphodiesterase inhibitor increasing intracellular cAMP; antagonizes adenosine receptors (A1, A2); stimulates diaphragmatic contractility; has mild anti-inflammatory properties in airways. Bronchodilation plus enhanced respiratory muscle function.

Indications

Chronic asthma (maintenance, not rescue)Chronic obstructive pulmonary disease (COPD)Apnea of prematurity (neonatal)

Dosing

Adult: Immediate-release: 300mg/day divided q6-8h initially x 3 days, then 400mg/day x 3 days, then 600mg/day max. Sustained-release: 150-300mg q12h. Target serum level: 5-15 mcg/mL (bronchodilation); toxic >20 mcg/mL.
Pediatric: <1 year: 0.2 x (age in weeks) + 5 = mg/kg/day divided q6-8h. 1-9 years: 16-24mg/kg/day divided q6h (max 400mg/day). 9-12 years: 12-18mg/kg/day (max 600mg).
Renal adjustment: No adjustment for mild-moderate. Severe: reduce dose 50%.
Hepatic adjustment: Reduce dose 50% in hepatic cirrhosis, acute hepatitis, cholestasis.
Geriatric: Start 150-200mg/day; clearance reduced by ~30%; increased toxicity risk.
Max dose: 900mg/day (adults); 600mg/day (children 1-16 years)

Pharmacokinetics

Onset

Bronchodilation within 1 hour (IR)

Peak effect

Tmax 1-2 hours (IR); 4-8 hours (SR); steady-state in 2-3 days

Duration

6-8 hours (IR); 8-12 hours (SR); 24 hours (some formulations)

Half-life

~8 hours (adults, non-smokers); ~4 hours (smokers); ~24-30 hours (neonates); ~30 hours (CHF, cirrhosis)

Bioavailability

~100% (oral)

Protein binding

~40-60%

Metabolism

Extensive hepatic via CYP1A2 (major), CYP2E1, CYP3A4; many drug interactions

Excretion

~10% unchanged in urine; remainder as metabolites

Contraindications

Hypersensitivity to theophylline or xanthines
Acute porphyria
Uncontrolled arrhythmias
Uncontrolled seizure disorders

Side effects

Common

Nausea and vomitingHeadacheInsomniaTachycardia / palpitationsTremorDyspepsiaIrritability

Serious

Theophylline toxicity (nausea, vomiting, seizures, arrhythmias, death—can occur at 15-20 mcg/mL in sensitive patients)
Ventricular arrhythmias
Seizures (can occur without preceding GI symptoms)
Severe tachycardia
Hypokalemia
Hyperglycemia

Pregnancy & lactation

Pregnancy

Crosses placenta; may cause neonatal irritability and tachycardia. Use only if benefit outweighs risk—target lower serum levels (5-12 mcg/mL).

Lactation

Excreted in breast milk (~1% of maternal dose); may cause infant irritability and insomnia. Generally compatible at moderate doses; monitor infant.

Drug interactions

Febuxostat

Contraindicated

Database

Theophylline is partially metabolized by xanthine oxidase. Febuxostat inhibits this pathway, increasing theophylline levels and risk of toxicity (seizures, arrhythmias, nausea).

Avoid concurrent use. If both needed, use extreme caution, monitor theophylline levels, and reduce theophylline dose.

Source: Kimi deep-research + Cla

Allopurinol

Severe

Textbook-cited

Theophylline toxicity (nausea, arrhythmias, seizures).

Monitor theophylline levels and reduce dose

Source: KDT 7e · p948

Atazanavir

Severe

Textbook-cited

Theophylline toxicity

Monitor levels and reduce dose

Source: KDT 7e · p948

Ciprofloxacin

Severe

Textbook-cited

Theophylline toxicity (nausea, seizures, arrhythmias).

Monitor theophylline levels and reduce dose

Source: KDT 7e · p948

Clarithromycin

Severe

Textbook-cited

Theophylline toxicity.

Monitor levels and reduce dose

Source: KDT 7e · p948

Darunavir

Severe

Textbook-cited

Theophylline toxicity

Monitor levels and reduce dose

Source: KDT 7e · p948

Erythromycin

Severe

Textbook-cited

Theophylline toxicity.

Monitor levels and reduce dose

Source: KDT 7e · p948

Fluconazole

Severe

Textbook-cited

Theophylline toxicity.

Monitor levels and reduce dose

Source: KDT 7e · p948

Itraconazole

Severe

Textbook-cited

Theophylline toxicity.

Monitor levels and reduce dose

Source: KDT 7e · p948

Ketoconazole

Severe

Textbook-cited

Theophylline toxicity

Monitor levels and reduce dose

Source: KDT 7e · p948

Lopinavir

Severe

Textbook-cited

Theophylline toxicity

Monitor levels and reduce dose

Source: KDT 7e · p948

Pefloxacin

Severe

Textbook-cited

Theophylline toxicity (nausea, seizures, arrhythmias)

Monitor theophylline levels and reduce dose

Source: KDT 7e · p948

Related guidelines

Chronic obstructive pulmonary disease

GOLD · Pulmonology · 2025

Chronic obstructive pulmonary disease

ICS · Pulmonology · 2022

Extrapulmonary tuberculosis

ICMR · Infectious Diseases · 2022

Chronic obstructive pulmonary disease

NICE · Pulmonology · 2019

Asthma in adults

GINA · Pulmonology · 2024

Ask House about Theophylline

Continue into a citation-backed clinical answer with the drug context already attached.

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Sources: KD Tripathi 7e, Goodman & Gilman 14e, Katzung, BNF·Verified: 2026-05-19 · House clinical team·Cockpit curated: 2026-05-19