Levoketoconazole and Clindamycin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Clindamycin
Levoketoconazole
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.
Here's what's going on. Your body uses a liver enzyme called CYP3A4 to break down clindamycin. Levoketoconazole (Recorlev) blocks that enzyme. When the enzyme is blocked, clindamycin can build up in your body to higher levels than intended, which can raise the chance of side effects like stomach upset, diarrhea, or other reactions.
Because this combination can push drug levels quite high, it is labeled as one to avoid together. Please don't stop or change either medicine on your own. Instead, let your pharmacist or doctor know you've been prescribed both. They can pick a safer option or watch you closely, and this is very manageable once your care team knows.
Mechanism: Levoketoconazole is a strong CYP3A4 inhibitor. Clindamycin is metabolized substantially by CYP3A4, so concurrent use is expected to reduce clindamycin clearance and increase its systemic exposure (AUC/Cmax), raising the risk of concentration-related adverse effects (GI intolerance, diarrhea).
- Direction: increased clindamycin exposure (neither drug is a prodrug requiring 3A4 activation).
- Magnitude: not quantified for clindamycin; labeling cites felodipine AUC/Cmax increases of ~1007%/937%, illustrating inhibitor potency.
- Evidence: probable. Onset: unspecified.
- Management: combination is contraindicated per labeling; select a non-CYP3A4-dependent alternative or defer one agent.
What happens
Increased CYP3A4 substrate exposure and an increased risk of sensitive CYP3A4 substrate-related adverse reaction
Interaction Deep Dive
The combined use of levoketoconazole with sensitive CYP3A4 substrates is contraindicated. Because levoketoconazole inhibits CYP3A4, giving it alongside a sensitive CYP3A4 substrate can raise the substrate's exposure, thereby heightening the likelihood of adverse reactions linked to that substrate. A drug interaction study demonstrated that administering levoketoconazole 400 mg once daily together with felodipine (a sensitive CYP3A4 substrate) raised felodipine AUC by 1007% and Cmax by 937%1.
Why it happens (mechanism)
Inhibition of CYP3A4-substrate metabolism by levoketoconazole
How to manage this interaction
Keep taking both exactly as prescribed for now, and don't stop either on your own. This pairing is flagged as one to avoid because levoketoconazole can raise clindamycin levels.
- Tell your pharmacist and prescriber that you have been prescribed both drugs so they can review it promptly.
- Your care team may choose an alternative antibiotic that does not rely on the same liver enzyme, or adjust your plan and monitor you more closely.
- Report side effects like ongoing diarrhea, severe stomach pain, or feeling unwell.
Once your team is aware, this is very manageable.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study evaluating drug interactions, giving levoketoconazole 400 mg once daily together with felodipine (a sensitive CYP3A4 substrate) raised felodipine AUC by 1007% and Cmax by 937%, respectively, when compared with felodipine given by itself (N=14) 1.
Common questions
Can I take Levoketoconazole and Clindamycin together?
Levoketoconazole can strongly raise clindamycin levels by blocking its breakdown, so this combination is one to avoid; contact your pharmacist or doctor before taking both, but don't stop either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levoketoconazole and Clindamycin interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Levoketoconazole and Clindamycin interaction managed?
Keep taking both exactly as prescribed for now, and don't stop either on your own. This pairing is flagged as one to avoid because levoketoconazole can raise clindamycin levels. Tell your pharmacist and prescriber that you have been prescribed both drugs so they can review it promptly. Your care team may choose an alternative antibiotic that does not rely on the same liver enzyme, or adjust your p… Management is individual — always follow your own care team's guidance.
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 Levoketoconazole or Clindamycin 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 (1)
- Product Information: RECORLEV(R) oral tablets, levoketoconazole oral tablets. Xeris Pharmaceuticals Inc (per FDA), Chicago, IL, 2023. DailyMed
Keep reading about Clindamycin
Keep reading about Levoketoconazole
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