Ketoconazole Topical and Levomethadyl: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Levomethadyl
No brand names on record
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
Increased levomethadyl exposure
Interaction Deep Dive
Concomitant use of ketoconazole together with a CYP3A4 substrate, such as levomethadyl may result in elevated levomethadyl exposure and may also increase levomethadyl-related adverse reactions1. This increase in serum concentration could potentially prolong QT intervals while simultaneously provoking symptoms of opiate withdrawal 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of levomethadyl
Literature reports
1 report — tap to read
a) Concurrent use of ketoconazole with levomethadyl (LAAM) resulted in a significant increase in levomethadyl parent compound while significantly reducing exposure of both active metabolites (norLAAM and dinorLAAM). In a single-blind, randomized, cross-over study, healthy subjects (n=13) were entered into a 1-month washout period prior to receiving a single oral dose of either ketoconazole 400 mg or placebo. 1 hour later, each subject received a single oral dose of LAAM 5 mg/70 kg body weight. Serial blood analysis was then performed over 240 hours in conjunction with subject-rated measures of LAAM effect. Following a 1-month washout, each subject crossed over the opposing study arm. Concurrent use of ketoconazole increased the LAAM mean Cmax and AUC (0-240 hours) by 322% and 529%, respectively (p less than 0.001) while simultaneously reducing the norLAAM mean Cmax by 23% and extending the Tmax by 243% (p less than 0.005 and 0.001, respectively). DinorLAAM mean Cmax also declined (by 45%) with concomitant ketoconazole use, and Tmax increased simultaneously by 1160% (p less than 0.001). AUC (0-240 hours) for norLAAM and dinorLAAM were both increased, by 225% and 121%, respectively (p less than 0.001 and 0.005, respectively). Subjects receiving concurrent ketoconazole reported significantly less sedation (p less than 0.05) while showing an upwards trend (over baseline) toward subjectively reported feelings of stomach distress, shaking tremors of hands, and other opiate withdrawal effects 2.
Common questions
Can I take Ketoconazole Topical and Levomethadyl together?
Increased levomethadyl exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Levomethadyl 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.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Levomethadyl 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 (2)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Moody DE, Walsh SL, Rollins DE, et al: Ketoconazole, a cytochrome P450 3A4 inhibitor, markedly increases concentrations of levo-acetyl-alpha-methadol in opioid-naive individuals. Clin Pharmacol Ther 2004; 76(2):154-166.
Keep reading about Ketoconazole Topical
Keep reading about Levomethadyl
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