Intravenous Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: In combination therapy w/ a corticosteroid (e.g. dexamethasone) and 5-HT3 antagonist: 150 mg given via IV infusion over 20-30 min approx 30 min prior to chemotherapy on day 1 of cycle only.
IV infusion: Add 5 mL of NaCl 0.9% soln to a vial labelled as containing 150 mg. Swirl gently to avoid foaming. Dilute further w/ 145 mL of NaCl 0.9% to a total volume of 150 mL, w/ a final concentration of 1 mg/mL.
This drug may cause dizziness and fatigue, if affected, do not drive or operate machinery.
Monitor INR (in patients taking warfarin) for 2 wk (particularly at 7-10 days) following admin; signs or symptoms of hypersensitivity reaction.
Decreased INR of prothrombin time w/ warfarin. Increased plasma concentration of midazolam or other benzodiazepines (e.g. alprazolam, triazolam). May decrease efficacy of OC. May decrease plasma concentration of CYP2C9 substrates (e.g. tolbutamide). Increased exposure w/ CYP3A4 inhibitors (e.g. clarithromycin, ketoconazole, protease inhibitors, nefazodone). Decreased serum concentration w/ phenytoin. Decreased exposure w/ CYP3A4 inducers (e.g. rifampicin, carbamazepine). May increase serum concentration of corticosteroids. Potentially Fatal: Increased serum concentration and risk of QT interval prolongation w/ pimozide, cisapride, terfenadine.
Increased serum concentration w/ grapefruit and grapefruit juice. Decreased serum concentration w/ St John’s wort.
Description: Fosaprepitant is a prodrug of aprepitant. It prevents acute and delayed emesis by inhibiting a substance P/neurokin-1 (NK1) receptor. It also augments antiemetic effect of 5HT3 receptor antagonist and corticosteroids. Pharmacokinetics: Absorption: Time to peak plasma concentration: W/in 30 min. Distribution: Aprepitant: Crosses blood brain barrier. Volume of distribution: Approx 70 L. Plasma protein binding: >95%. Metabolism: Rapidly converted in hepatic and extrahepatic tissues into aprepitant which undergoes extensive metabolism via oxidation primarily by CYP3A4 enzyme and some by CYP1A2 and CYP2C19 enzymes into 7 weakly-active metabolites. Excretion: Mainly via urine (57% as metabolites); faeces (45% as metabolites). Elimination half-life: Approx 9-13 hr.
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