Drug interactions
Phenobarbital + Theophylline
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Overview
Phenobarbital induces hepatic enzymes and can increase the clearance of theophylline, lowering serum concentrations and reducing efficacy; discontinuation of phenobarbital can increase theophylline levels and risk toxicity.
Mechanism of action
Phenobarbital induces CYP1A2 (primary for theophylline metabolism) and other hepatic enzymes, accelerating theophylline metabolism and reducing half-life.
Clinical management
Monitor theophylline serum concentrations and clinical response after starting, stopping, or changing the dose of phenobarbital; adjust theophylline dose accordingly (often upward when adding phenobarbital, downward when stopping). Recheck levels within ~3–5 days and again after steady-state (up to 1–2 weeks). Monitor for reduced efficacy and for toxicity (nausea, vomiting, insomnia, tachyarrhythmias, seizures) when phenobarbital is withdrawn.
Drug reference
References
- Theophylline: Drug Information (including drug interactions with enzyme inducers such as barbiturates) — UpToDate
- Theophylline Monograph (interaction with enzyme-inducing anticonvulsants such as phenobarbital) — Lexicomp
- Theophylline (e.g., Theo-24) Prescribing Information – Drug Interactions (effects of enzyme inducers including barbiturates) — FDA Label
Frequently asked questions
Can I take Phenobarbital with Theophylline?
The interaction is rated: Moderate. Phenobarbital induces hepatic enzymes and can increase the clearance of theophylline, lowering serum concentrations and reducing efficacy; discontinuation of phenobarbital can increase theophylline levels and risk toxicity.
How serious is the interaction between Phenobarbital and Theophylline?
The interaction is rated: Moderate. Evidence level: Moderate.
How is the interaction between Phenobarbital and Theophylline managed?
Monitor theophylline serum concentrations and clinical response after starting, stopping, or changing the dose of phenobarbital; adjust theophylline dose accordingly (often upward when adding phenobarbital, downward when stopping). Recheck levels within ~3–5 days and again after steady-state (up to 1–2 weeks). Monitor for reduced efficacy and for toxicity (nausea, vomiting, insomnia, tachyarrhythmias, seizures) when phenobarbital is withdrawn.
Why do Phenobarbital and Theophylline interact?
Phenobarbital induces CYP1A2 (primary for theophylline metabolism) and other hepatic enzymes, accelerating theophylline metabolism and reducing half-life.
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