Trade Names:Emend- Injection, lyophilized powder for solution 115 mg
Fosaprepitant is a prodrug of aprepitant, which is a selective high-affinity antagonist of human substance P/neurokinin 1 receptors.
Following a single IV injection, mean AUC and mean C max are 31.7 mcg•h/mL and 3.27 mcg/mL, respectively.
Rapidly converted to aprepitant, which is more than 95% bound to plasma proteins. Mean Vd at steady state is approximately 70 L.
Primarily metabolized by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19.
Recovery in the urine and feces is 57% and 45%, respectively. Terminal t ½ ranges from approximately 9 to 13 h.
No dosage adjustment is needed for patients with renal function impairment or end-stage renal disease undergoing hemodialysis.Hepatic Function Impairment
No dosage adjustment is needed in patients with mild to moderate hepatic function impairment.Elderly
No dosage adjustment is needed.Gender or race
No dosage adjustment is needed.
Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin; prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
Coadministration of cisapride or pimozide; hypersensitivity to any component of the product.
IV Fosaprepitant 115 mg infused over 15 min may be substituted for aprepitant 125 mg orally 30 min prior to chemotherapy on day 1 only of the chemotherapy-induced nausea and vomiting regimen.
Store at 36° to 46°F. Reconstituted final solution is stable for 24 h at or below 77°F.
Contraceptive efficacy may be reduced. Use alternative methods of contraception during aprepitant treatment and for 1 mo after the last dose of aprepitant.CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin)
Plasma concentrations of these drugs may be reduced. In patients receiving warfarin, closely monitor anticoagulation parameters for 14 days after initiation of the 3-day antiemetic regimen.CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin)
Plasma concentrations of aprepitant may be reduced, decreasing the efficacy.CYP3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir)
Plasma concentrations of aprepitant may be elevated, increasing the pharmacologic effects and adverse reactions.CYP3A4 substrates (eg, alprazolam, cisapride, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, methylprednisolone, midazolam, paclitaxel, pimozide, vinblastine, vincristine, vinorelbine)
Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and adverse reactions. Cisapride and pimozide are contraindicated with coadministration of aprepitant. Reduce the dexamethasone dose by 50%; reduce the oral and IV doses of methylprednisolone by 50% and 25%, respectively, when coadministering aprepitant.Paroxetine
Plasma concentrations of both aprepitant and paroxetine may be reduced.
None well documented.
Asthenia/fatigue (18%); headache (16%); dizziness (7%); insomnia (4%).
Alopecia (24%); hot flush (3%); angioedema, Stevens-Johnson syndrome, urticaria.
Tinnitus (4%); pharyngolaryngeal pain (3%).
Nausea (13%); constipation (12%); anorexia, diarrhea (10%); dyspepsia, vomiting (8%); abdominal pain, heartburn, stomatitis (5%); epigastric discomfort, gastritis (4%).
Decreased WBC (9%); proteinuria (7%); increased ALT (6%); increased BUN (5%); increased serum creatinine (4%); increased AST (3%); decreased hemoglobin (2%).
Fever, mucosal inflammation, mucous membrane disorder (3%).
Monitor for antiemetic effects.
Category B .
Safety and efficacy not established.
Copyright © 2009 Wolters Kluwer Health.