Mitapivat and Sildenafil: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sildenafil
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
Reduced sildenafil exposure
Interaction Deep Dive
Avoid concomitant use of mitapivat with sildenafil (sensitive CYP3A substrates with a narrow therapeutic index). Coadministration of mitapivat (a CYP3A inducer) with sildenafil reduces exposure of the sildenafil1. If coadministration is required, monitor for loss of therapeutic effect 2. Dose up-titration of sildenafil may be needed when initiating treatment with mitapivat. Reduce the dose of sildenafil to 20 mg three times a day when discontinuing treatment with mitapivat 3.
Why it happens (mechanism)
Induction of CYP3A-mediated metabolism of sildenafil
Literature reports
4 reports — tap to read
a) In normal volunteers, coadministration of multiple doses of 125 mg twice daily bosentan and 80 mg three times daily sildenafil resulted in a reduction of sildenafil plasma concentrations by 63% and increased bosentan plasma concentrations by 50%. The changes in plasma concentrations were not considered clinically relevant 4.
b) Population pharmacokinetic analysis of data from patients in clinical trials indicated approximately 3-fold the sildenafil clearance when it was coadministered with mild CYP3A inducers 3.
c) In a randomized, double-blind, parallel-group, placebo-controlled study in healthy males (n=55), concomitant use of bosentan and sildenafil led to increased bosentan AUC and Cmax and decreased sildenafil AUC and Cmax. Study participants were randomized to receive either sildenafil, bosentan, or combination of the two drugs. Dosing regimens were sildenafil three times daily on days 1 to 6 and 11 to 16 (20 mg initially and then 80 mg after 3 days) and bosentan 125 mg twice daily on days 7 to 17. On day 16, mean pharmacokinetic parameters revealed bosentan Cmax and AUC were 42% (90% confidence interval (CI) 15.4-74.8%) and 49.8% (90% CI 28.7-74.5%) higher with concomitant administration of sildenafil verses placebo, (Cmax, 1547 nanogram/mL vs 912 nanogram/mL), and (AUC, 6925 nanogram-hr/mL vs 4355 nanogram-hr/mL). On day 16, mean pharmacokinetic parameters revealed sildenafil Cmax, and AUC were 55.4% (90% CI 40.3-66.6%) and 62.6% (90% CI 56.8-67.7%) lower with concomitant administration of bosentan verses placebo, (Cmax, 275 nanogram/mL vs 585 nanogram/mL), and (AUC, 634 nanogram-hr/mL vs 1847 nanogram-hr/mL). No serious adverse events occurred, and greater than 96% of reported events were mild. The most common adverse event with combination treatment was headache (43 reports). Other commonly reported events with combination treatment were nasal congestion, backache, and myalgia 5.
d) In drug interaction studies, coadministration of mitapivat with midazolam (a sensitive CYP3A substrate) decreased midazolam AUC (inf) and Cmax by 21% and 19% with mitapivat 5 mg twice daily, by 43% and 39% with mitapivat 20 mg twice daily, and by 57% and 52% with mitapivat 50 mg twice daily, respectively 2. Similarly, midazolam AUC (inf) and Cmax decreased by 65% and 59%, respectively, with mitapivat 100 mg twice daily 1.
Common questions
Can I take Mitapivat and Sildenafil together?
Reduced sildenafil exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mitapivat and Sildenafil 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Mitapivat or Sildenafil 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 (5)
- Product Information: AQVESME™ oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
- Product Information: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
- Product Information: REVATIO(R) oral tablets, oral suspension, intravenous injection, sildenafil oral tablets, oral suspension, intravenous injection. Pfizer Labs (per FDA), New York, NY, 2023. DailyMed
- Product Information: TRACLEER(R) oral tablets, bosentan oral tablets. Actelion Pharmaceuticals US (per FDA), South San Francisco, CA, 2015. DailyMed
- Burgess G, Hoogkamer H, Collings L, et al: Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol 2008; 64(1):43-50. PubMed
Keep reading about Sildenafil
Keep reading about Mitapivat
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