FOSAPREPITANT DIMEGLUMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FOSAPREPITANT DIMEGLUMINE (FOSAPREPITANT DIMEGLUMINE).
Fosaprepitant dimeglumine is a prodrug of aprepitant, a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. It inhibits emesis by blocking NK1 receptors in the central nervous system, particularly in the area postrema and the nucleus tractus solitarius.
| Metabolism | Fosaprepitant is rapidly converted to aprepitant via hydrolysis. Aprepitant is metabolized primarily by CYP3A4, with minor contributions from CYP2C19 and CYP1A2. |
| Excretion | Fosaprepitant is rapidly converted to aprepitant. Aprepitant is eliminated primarily by metabolism; <5% of the dose is excreted unchanged in urine. Fecal excretion accounts for approximately 58% of the dose, and urinary excretion accounts for 43% (mostly as metabolites). |
| Half-life | Terminal elimination half-life of aprepitant is approximately 9 to 13 hours; clinical significance includes once-daily dosing for prevention of chemotherapy-induced nausea and vomiting. |
| Protein binding | Aprepitant is >95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution of aprepitant is approximately 70 L (≈1 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Intravenous: 100% (fosaprepitant is a prodrug that is rapidly converted to aprepitant). Oral aprepitant bioavailability is approximately 60-65%. |
| Onset of Action | Intravenous: Within 30 minutes (as aprepitant). |
| Duration of Action | Duration of action is approximately 24 hours, allowing once-daily dosing for the 3-day regimen. |
150 mg intravenous over 30 minutes on day 1, combined with dexamethasone and a 5-HT3 antagonist; alternatively, 115 mg IV on day 1 followed by 80 mg IV on day 2 and 80 mg IV on day 3, or 150 mg oral (as fosaprepitant dimeglumine or aprepitant) on day 1 and 80 mg oral on days 2 and 3.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; insufficient data for GFR <30 mL/min or ESRD (dialysis not expected to remove the drug). |
| Liver impairment | Child-Pugh Class A or B: no dose adjustment; Child-Pugh Class C: avoid use (no data). |
| Pediatric use | Approved for patients aged 12 years and older: 150 mg IV on day 1; for pediatric patients (aged 6 months to <12 years): weight-based dosing of 5 mg/kg IV on day 1 (not to exceed 150 mg) and 3 mg/kg oral aprepitant on days 2 and 3 (not to exceed 80 mg) per clinical trials. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor for adverse effects such as fatigue and dizziness; consider renal and hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FOSAPREPITANT DIMEGLUMINE (FOSAPREPITANT DIMEGLUMINE).
| Breastfeeding | It is unknown if fosaprepitant or its metabolite aprepitant is excreted in human breast milk. No M/P ratio is available. Caution should be exercised when administered to a nursing woman, as effects on the infant are unknown. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need. |
| Teratogenic Risk | Fosaprepitant dimeglumine is classified as Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies exist. In the first trimester, risk cannot be ruled out; in the second and third trimesters, use only if clearly needed. No known teratogenic effects have been reported in humans. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with pimozide (risk of QT prolongation and cardiac arrhythmias)","History of hypersensitivity to any component of the formulation"]
| Precautions | ["Clinically significant CYP3A4 interactions: may increase plasma concentrations of CYP3A4 substrates (e.g., pimozide, midazolam, oral contraceptives); coadministration with pimozide is contraindicated","Chronic use of warfarin: may decrease INR; monitor INR closely","Hormonal contraceptives may be less effective during and for 28 days after treatment; alternative non-hormonal contraception should be used"] |
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| Fetal Monitoring | No specific maternal-fetal monitoring is required beyond standard prenatal care. Clinical monitoring for adverse effects such as infusion site reactions, hypersensitivity, or gastrointestinal disturbances is recommended. Fetal monitoring should follow routine obstetric practice. |
| Fertility Effects | Reproductive studies in animals have shown no impairment of fertility. Human data are insufficient to determine effects on fertility. No adverse effects on male or female fertility have been reported. |