Fosaprepitant


Concise Prescribing Info
Indications/Uses
Prophylaxis of chemotherapy-induced nausea and vomiting.
Dosage/Direction for Use
Adult : IV In combination therapy w/ a corticosteroid (e.g. dexamethasone) and 5-HT3 antagonist: 150 mg over 20-30 min, approx 30 min prior to chemotherapy on day 1 of cycle only.
Dosage Details
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.
Reconstitution
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.
Incompatibility
Incompatible w/ soln containing divalent cations (e.g. Ca, Mg, Hartmann’s soln, lactated Ringer’s inj).
Contraindications
Hypersensitivity. Concomitant use w/ pimozide, cisapride, terfenadine.
Special Precautions
Moderate to severe hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Nervous: Asthenia, fatigue, malaise, dizziness, somnolence, peripheral neuropathy, headache, weakness, anxiety.
CV: Palpitations, hot flush.
GI: Nausea, anorexia, constipation, diarrhoea, abdominal pain, GERD, dry mouth, flatulence, eructation, dyspepsia.
Resp: Hiccups.
Hepatic: Increased ALT/AST, alkaline phosphatase.
Genitourinary: UTI, dysuria.
Haematologic: Neutropenia, anaemia, leucopenia.
Musculoskeletal: Limb pain.
Dermatologic: Pruritus, acne, urticaria.
Others: Infusion site reactions (e.g. pain, induration).
Potentially Fatal: Hypersensitivity reactions (e.g. Steven-Johnson syndrome/toxic epidermal necrolysis, anaphylaxis and anaphylactic shock).
IV/Parenteral: B
Patient Counseling Information
This drug may cause dizziness and fatigue, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor INR (in patients taking warfarin) for 2 wk (particularly at 7-10 days) following admin; signs or symptoms of hypersensitivity reaction.
Drug Interactions
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.
Food Interaction
Increased serum concentration w/ grapefruit and grapefruit juice. Decreased serum concentration w/ St John’s wort.
Action
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.
Chemical Structure

Chemical Structure Image
Fosaprepitant

Source: National Center for Biotechnology Information. PubChem Database. Fosaprepitant, CID=135413538, https://pubchem.ncbi.nlm.nih.gov/compound/Fosaprepitant (accessed on Jan. 21, 2020)

Storage
Store between 2-8°C.
MIMS Class
References
Anon. Fosaprepitant. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/09/2017.

Buckingham R (ed). Fosaprepitant. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/09/2017.

Emend Injection Powder, Lyophilized for Solution (Merck Sharp and Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/09/2017.

Joint Formulary Committee. Fosaprepitant. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/09/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Aprepitant/Fosaprepitant Dimeglumine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 08/09/2017.

Preston CL (ed). Interactions Search Results for Fosaprepitant Pimozide. Stockley’s Drug Interactions [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/09/2017.

Disclaimer: This information is independently developed by MIMS based on Fosaprepitant from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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