Diazepam Rectal and Netupitant: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Netupitant
No brand names on recordDiazepam Rectal
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 exposure of CYP3A4 substrate
Interaction Deep Dive
Avoid concomitant use of CYP3A4 substrates with netupitant or fosnetupitant (prodrug of netupitant) (a moderate inhibitor of CYP3A4) for 1 week. Concomitant use of netupitant or fosnetupitant and CYP3A4 substrates may increase the exposure of these substrates. The mean AUC and Cmax of the CYP3A4 substrate erythromycin was increased following the coadministration of netupitant in a pharmacokinetic study. Increases in the AUC of dexAMETHasone, a CYP3A4 probe substrate, remained for up to 8 days following a single dose of netupitant. The concomitant use of CYP3A4 substrates with netupitant should be avoided for 1 week. If a CYP3A4 substrate must be administered within 1 week of netupitant, consider reducing the dose of the CYP3A4 substrate1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism by netupitant
Literature reports
2 reports — tap to read
a) In one study where the duration of CYP3A4 inhibition was assessed using dexAMETHasone as a CYP3A4 probe substrate, the mean AUC of dexAMETHasone increased by 1.6-fold on day 1, 2.4-fold on day 4, 1.5-fold on day 6, and 1.2-fold on day 8 after a single dose of the combination netupitant 300 mg/palonosetron 0.5 mg was coadministered to participants on day 1. The participants had been treated with a dexAMETHasone regimen of 12 mg on day 1 followed by 8 mg on days 2, 3, 4, 6, 8, and 10 1.
b) A pharmacokinetic study demonstrated that when erythromycin 500 mg was coadministered with netupitant 300 mg, the mean AUC of erythromycin increased by 56% and the Cmax increased by 92% 1.
Common questions
Can I take Diazepam Rectal and Netupitant together?
Increased exposure of CYP3A4 substrate Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam Rectal and Netupitant 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Diazepam Rectal or Netupitant 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: AKYNZEO(R) oral capsules, netupitant palonosetron oral capsules. Helsinn Therapeutics (US), Inc (per FDA), Iselin, NJ, 2018. DailyMed
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