Mitapivat and Voriconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Voriconazole
Mitapivat
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 mitapivat exposure, an increased risk of mitapivat-related adverse effects, reduced voriconazole exposure and an reduced efficacy of voriconazole
Interaction Deep Dive
Avoid coadministration of mitapivat (CYP3A4 substrate) and voriconazole (strong CYP3A4 inhibitor) as concomitant use increases mitapivat exposure, which may increase the risk of adverse effects1. Reduce dosage of mitapivat and monitor adverse reactions. Coadministration of voriconazole with mitapivat (CYP3A4 inducer) may also result in reduced voriconazole exposure. Adjust voriconazole dosage and monitor for lack of efficacy 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of mitapivat; induction of CYP3A4-mediated metabolism of voriconazole
Literature reports
7 reports — tap to read
a) Coadministration of mitapivat with itraconazole, a strong CYP3A4 inhibitor, increased mitapivat AUC(infinity) and Cmax by 4.9-fold and 1.7-fold, respectively, following a single dose of mitapivat 20 mg. Following administration of mitapivat 50 mg twice daily with itraconazole, mitapivat AUC(0 to 12) and Cmax increased by 3.6-fold and 2.2-fold, respectively 1.
b) Coadministration of mitapivat with ketoconazole, a strong CYP3A4 inhibitor, increased mitapivat AUC(0 to 12) and Cmax by approximately 3.9-fold and 2.4-fold, respectively, following administration of mitapivat 5, 20 or 50 mg twice daily 1.
c) In an independent published study, concomitant use of voriconazole (400 mg every 12 hours on Day 1, then 200 mg every 12 hours on Day 2) with a single intravenous dose of fentaNYL (CYP3A4 substrate) (5 microgram/kg) resulted in an increase in the mean AUC (0 to inf) of fentaNYL by 1.4-fold (range 0.81- to 2.04-fold) 2.
d) In another independent published study, coadministration of multiple doses of oral voriconazole (400 mg every 12 hours, on Day 1 followed by five doses of 200 mg every 12 hours on Days 2 to 4) with a single 10 mg oral dose of oxyCODONE (CYP3A4 substrate) on Day 3 resulted in an increase in the mean Cmax and AUC (0 to inf) of oxyCODONE by 1.7-fold (range 1.4- to 2.2-fold) and 3.6- fold (range 2.7- to 5.6-fold), respectively. The mean elimination half-life of oxyCODONE was also increased by 2.0-fold (range 1.4- to 2.5-fold) 2.
e) In stable renal transplant recipients receiving chronic cycloSPORINE (CYP3A4 substrate) therapy, concomitant administration of oral voriconazole (200 mg every 12 hours for 8 days) increased cycloSPORINE Cmax and AUC (tau) an average of 1.1 times (90% CI: 0.9, 1.41) and 1.7 times (90% CI: 1.5, 2.0), respectively, as compared to when cycloSPORINE was administered without voriconazole 2.
f) In a drug interaction study, rifAMPin (CYP3A4 inducer) (600 mg once daily) decreased the steady state Cmax and AUC(tau) of voriconazole (200 mg every 12 hours x 7 days) by an average of 93% and 96%, respectively, in healthy subjects. Doubling the dose of voriconazole to 400 mg every 12 hours does not restore adequate exposure to voriconazole during coadministration with rifAMPin 2.
g) In an independent published study in healthy volunteers who were given multiple oral doses of St. John’s Wort (CYP3A4 inducer) (300 mg LI 160 extract three times daily for 15 days) followed by a single 400 mg oral dose of voriconazole, a 59% decrease in mean voriconazole AUC(0 to inf) was observed. In contrast, coadministration of single oral doses of St. John’s Wort and voriconazole had no appreciable effect on voriconazole AUC(0 to inf). Long-term use of St. John’s Wort could lead to reduced voriconazole exposure 2.
Common questions
Can I take Mitapivat and Voriconazole together?
Increased mitapivat exposure, an increased risk of mitapivat-related adverse effects, reduced voriconazole exposure and an reduced efficacy of voriconazole Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mitapivat and Voriconazole 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 Mitapivat or Voriconazole 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: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2022. DailyMed
- Product Information: VFEND(R) oral tablets, oral suspension, intravenous injection, voriconazole oral tablets, oral suspension, intravenous injection. Roerig (per FDA), New York, NY, 2025. DailyMed
Keep reading about Voriconazole
Keep reading about Mitapivat
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