New drug
Fosaprepitant dimeglumine
- Aust Prescr 2008;31:108-11
- 1 August 2008
- DOI: 10.18773/austprescr.2008.060
ISSUE 4 AUGUST
Emend IV (Merck Sharp & Dohme)
vials containing 115 mg as powder for reconstitution
Approved indication: chemotherapy-induced nausea and vomiting
Australian Medicines Handbook section 12.3.4
Aprepitant is an oral antiemetic which was marketed for use in chemotherapy in 2004 (see 'New drugs' 2004;27:76-9). Fosaprepitant is an intravenous formulation of aprepitant which can be given on the first day of chemotherapy. The dose is infused over 15 minutes, 30 minutes before chemotherapy.
Fosaprepitant is a prodrug. It is rapidly converted by many tissues into aprepitant. An intravenous dose of 115 mg fosaprepitant is equivalent to an oral dose of 125 mg aprepitant.1Although the concentrations are similar after 24 hours, the maximum concentration of aprepitant is higher when fosaprepitant is used.
There appear to be few published clinical trials of fosaprepitant. Its product information only contains pivotal efficacy studies of aprepitant. The adverse effects of the two drugs are similar, but fosaprepitant has some extra warnings: the intravenous formulation is incompatible with Hartmann's or Ringer's lactate solution.
A dose of fosaprepitant does not stop vomiting, immediately after cisplatin-based chemotherapy, in as many patients as ondansetron, but it does reduce delayed emesis.2A similar result occurred when intravenous fosaprepitant and dexamethasone, followed by oral aprepitant, were compared to ondansetron and dexamethasone, followed by placebo.3
As aprepitant is metabolised by the cytochrome P450 system, especially 3A4, fosaprepitant can interact with other drugs with similar metabolism such as cyclosporin and tacrolimus. Aprepitant can reduce concentrations of warfarin and oral contraceptives. Inhibition of P450 3A4 by ketoconazole will increase concentrations of aprepitant.
manufacturer provided additional useful information
The Transparency Score is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
References
- Lasseter KC, Gambale J, Jin B, Bergman A, Costanzer M, Dru J, et al. Tolerability of fosaprepitant and bio-equivalency to aprepitant in healthy subjects. J Clin Pharmacol 2007;47:834-40.
- Cocquyt V, Van Belle S, Reinhardt RR, Decramer MLA, O'Brien M, Schellens JHM, et al. Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis. Eur J Cancer 2001;37:835-42.
- Van Belle S, Lichinitser MR, Navari R, Garin AM, Decramer MLA, Riviere A, et al. Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. A randomized controlled trial. Cancer 2002;94:3032-41.
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
