Drug Interaction Report

Theophylline and Allopurinol: Interaction Details

A pharmacist-reviewed analysis of the Theophylline and Allopurinol interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Theophylline

Accurbron® Aerolate® Aquaphyllin® Asbron® Bronkodyl® Duraphyl® Elixicon® Elixomin®
+

Allopurinol

Aloprim Lopurin® Zyloprim Zyloprim®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Jul 11, 2026
Editorial policy · Data sources
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Interaction severity
Moderate
Can be significant — usually manageable with monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 46 documented Theophylline interactions, 18 are rated moderate — including this one.
Onset
delayed
Evidence
theoretical
Severity
Moderate

What happens

Theophylline toxicity (nausea, vomiting, palpitations, seizures)

Interaction Deep Dive

Large doses of allopurinol (ie, 300 mg twice daily) have been shown to reduce theophylline clearance by approximately 20%. The onset of this interaction takes from two to four weeks3. Monitor theophylline levels two to three weeks after adding or deleting allopurinol to theophylline therapy and adjust theophylline dose if required.

Why it happens (mechanism)

Decreased theophylline metabolism

Literature reports

1 report — tap to read

a) Although early reports indicated that the pharmacokinetics and disposition of theophylline were not significantly affected by concomitant allopurinol administration 12, a more recent study 3 reported that allopurinol 300 mg administered q12h for 14 to 28 days inhibited theophylline metabolism, with a corresponding reduction in the mean clearance and an increase in the half-life, despite failure of allopurinol in smaller doses given for only 7 days to alter theophylline disposition. When allopurinol is given in these doses, theophylline dose reductions should be initiated to avoid toxicity.

Common questions

Can I take Theophylline and Allopurinol together?

Theophylline toxicity (nausea, vomiting, palpitations, seizures) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Theophylline and Allopurinol interaction?

It is rated moderate. Can be significant — usually manageable with monitoring.

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Theophylline or Allopurinol need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there anything you'd monitor while I'm on both?

References (3)

  1. Vozeh S, Powell JR, Cupit GC, et al: Influence of allopurinol on theophylline disposition in adults. Clin Pharmacol Ther 1980; 27:194-197. PubMed
  2. Grygiel JJ, Wing LMH, Farkas J, et al: Effects of allopurinol on theophylline metabolism and clearance. Clin Pharmacol Ther 1979; 26:660-667. DOI
  3. Manfredi RL & Vesell ES: Inhibition of theophylline metabolism by long-term allopurinol administration. Clin Pharmacol Ther 1981; 29:224-228. DOI
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Theophylline

Keep reading about Theophylline

All Theophylline interactions (46) Theophylline drug information
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Allopurinol

Keep reading about Allopurinol

All Allopurinol interactions (32) Allopurinol drug information
Also serious with: Fezolinetant Didanosine Acenocoumarol Pegloticase Injection
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Theophylline + Activated Charcoal Ephedra Sida Cordifolia Adrafinil African Wild Potato Ashitaba Bacopa Baikal Skullcap + 118 more
Allopurinol + Activated Charcoal Asarabacca Beer Siberian Cocklebur Wine Aristolochia Ashwagandha Black Cohosh + 52 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.