Fosaprepitant dosing

Is 150 mg IV the best dose for prevention of PONV?

Fosaprepitant, an IV prodrug of aprepitant, was approved for prevention of chemotherapy-induced nausea and vomiting at a dose of 150 mg IV. Considering that oral aprepitant is usually given at a dose of 40 mg to prevent postoperative nausea and vomiting (PONV), what dose of fosaprepitant should be given? The 2020 PONV consensus guidelines only mention the 150 mg dose.

Aprepitant given at a dose of 40 mg is non-inferior to ondansetron in preventing nausea but superior in preventing vomiting with effects lasting 24-48 hours. A higher dose of 125 mg of aprepitant was not more effective than the 40 mg dose.

When looking at the pharmacokinetics, you see that 150 mg of fosaprepitant yields an area under the concentration-time curve (AUC) of 37.4 (± 14.8) mcg•hr/mL at 20 minutes after infusion. Compare this to the AUC of 7.8 mcg•hr/mL for 40 mg of oral aprepitant. Fosaprepitant results in a level ~4.8x higher than aprepitant suggesting a dose closer to ~31 mg IV would be effective at preventing PONV.

Fortunately for us, we don’t need to guess at the dosing. In 2022, Aponvie, an IV version of aprepitant (not a prodrug like fosaprepitant), was approved for prevention of PONV at a dose of 32 mg IV. The AUC at that dose was 7.8 mcg•hr/mL—the same as aprepitant.

All this suggests that when using fosaprepitant for the prevention or treatment of PONV, a reasonable dose would be 32 mg or perhaps 40 mg IV. Doses higher than that are unlikely to confer additional benefit.