Defactinib and Nafcillin Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Nafcillin Injection
Defactinib
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
Reduced defactinib exposure and reduced efficacy of defactinib
Interaction Deep Dive
Avoid concomitant use of defactinib (CYP3A4 substrate) with a strong or moderate CYP3A4 inducer. Coadministration of defactinib (a CYP3A4 substrate) with a moderate or strong CYP3A4 inducer reduces defactinib exposure, which may reduce the efficacy of defactinib. Defactinib Cmax decreased by 83% and AUC by 87% following coadministration with phenytoin (strong CYP3A4 inducer) three times daily for 23 days and a single dose of defactinib 200 mg (1.0 times the approved recommended dose) on Day 14. Major metabolite of defactinib, N-desmethyl amide (M4) AUC decreased by 79% and Cmax decreased by 70%1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of defactinib
Literature reports
1 report — tap to read
a) Defactinib Cmax decreased by 83% and AUC by 87% following coadministration with phenytoin (strong CYP3A4 inducer) three times daily for 23 days and a single dose of defactinib 200 mg (1.0 times the approved recommended dose) on Day 14. Major metabolite of defactinib, N-desmethyl amide (M4) AUC decreased by 79% and Cmax decreased by 70% 1.
Common questions
Can I take Defactinib and Nafcillin Injection together?
Reduced defactinib exposure and reduced efficacy of defactinib Always confirm with your pharmacist or prescriber before making any change.
How serious is the Defactinib and Nafcillin Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
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 Defactinib or Nafcillin Injection 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: AVMAPKI(TM) FAKZYNJA(TM) CO-PACK oral capsules, tablets, avutometinib oral capsules, defactinib oral tablets. Verastem, Inc (per manufacturer), Needham, MA, 2025. DailyMed
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