Didanosine and Methadone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methadone
Didanosine
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.
What happens
Reduced didanosine exposure
Interaction Deep Dive
Concomitant administration of didanosine and methadone appear to decrease the serum concentrations of didanosine21. In opiate-dependent patients, the coadministration of didanosine and methadone may result in decreased area under the concentration-time curve (AUC) and peak drug concentrations (Cmax) for didanosine. If administered in the tablet formulation, a larger dose of didanosine may be required in patients maintained on methadone 3. Do not coadminister methadone with didanosine pediatric powder for solution formulation due to significant decreases in didanosine concentrations. If coadministration of methadone and didanosine is warranted, the delayed release, enteric-coated beadlet formulation is preferred and monitor the patients closely for adequate clinical response, including monitoring for changes in the HIV RNA viral load21.
Why it happens (mechanism)
Reduced didanosine bioavailability
Literature reports
3 reports — tap to read
a) Sixteen patients received chronic maintenance dose of methadone and didanosine 200 mg as a single dose. Steady-state area under the concentration-time curve (AUC) for didanosine decreased 57% and Cmax by 66%. When methadone was administered concomitantly with didanosine 400 mg the steady-state AUC of didanosine was decreased 29% and Cmax by 41% 21.
b) Treatment with didanosine may be negatively affected if administered in patients maintained on methadone therapy. The effects of methadone on the pharmacokinetics of the tablet formulation of didanosine and stavudine were examined in seventeen patients stabilized on methadone therapy and in ten untreated controls. A 66% reduction (p equals 0.007) in peak didanosine concentration (Cmax) and an approximately 60% reduction in the area under the concentration-time curve (AUC) was observed. The authors of the report hypothesized that methadone slows gastrointestinal motility, decreasing the absorption rate of didanosine. The result is decreased bioavailability since didanosine degradation increases in the gastrointestinal tract, or greater loss due to first-pass metabolism 3.
c) Experimental evidence demonstrated that methadone decreased the AUC and peak levels for didanosine. Methadone disposition was not substantially altered 456.
Common questions
Can I take Didanosine and Methadone together?
Reduced didanosine exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Didanosine and Methadone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Didanosine or Methadone 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 a safer alternative to one of these medications for me?
References (6)
- Product Information: VIDEX(R) oral powder for solution, didanosine oral powder for solution. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2014. DailyMed
- Product Information: VIDEX EC oral delayed-release capsules, enteric-coated beadlets, didanosine oral delayed-release capsules, enteric-coated beadlets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2018.
- Rainey P, Friedland G, McCance-Katz E, et al: Interaction of methadone with didanosine and stavudine. JAIDS 2000; 24(3):241-248. DOI
- Product Information: DISKETS dispersible tablets, methadone HCl dispersible tablets. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley, NJ, 2023.
- Product Information: METHADOSE oral concentrate, methadone HCl oral concentrate. SpecGx LLC (per FDA), Webster Groves, MO, 2023. DailyMed
- Product Information: Methadone HCl injection, methadone HCl injection. Mylan Institutional LLC (per FDA), Morgantown, WV, 2023. DailyMed
Keep reading about Methadone
Keep reading about Didanosine
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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