Drug intelligence / Profile preview

fosaprepitant + tropisetron + olanzapine

Development stage
Unknown
Lead developer
Merck
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

Based on the search results, this is a combination antiemetic regimen used primarily for preventing chemotherapy-induced nausea and vomiting (CINV), particularly in patients undergoing high-dose chemotherapy followed by stem cell transplantation. The search results show this combination has been studied and used clinically, especially for patients with lymphoma and multiple myeloma. ## Mechanism of Action The combination works through multiple pathways to prevent nausea and vomiting: - **Fosaprepitant**: A neurokinin-1 (NK1) receptor antagonist that blocks substance P from binding to NK1 receptors in the brain, which helps prevent delayed nausea and vomiting[1]. - **Tropisetron**: A 5-hydroxytryptamine-3 (5-HT3) receptor antagonist that blocks serotonin receptors in the gastrointestinal tract and central nervous system, primarily effective for acute nausea and vomiting[1]. - **Olanzapine**: An atypical antipsychotic that blocks multiple neurotransmitter receptors including dopamine, serotonin, histamine, and muscarinic receptors, which contributes to its antiemetic effect, particularly for nausea control[3][4]. ## Clinical Efficacy The FTO regimen has shown superior efficacy compared to standard antiemetic regimens: - In a retrospective study of patients receiving high-dose chemotherapy before autologous stem cell transplantation, the FTO regimen achieved a 70% complete response rate compared to 36% with a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD)[1]. - The FTO regimen was particularly effective in the delayed phase of CINV, with 74% of patients achieving complete response compared to 38% with the standard regimen[1]. - Multiple-day administration of this combination significantly reduced the percentage of patients unable to eat and the requirement for rescue medications[1]. ## Safety Profile The FTO regimen is generally well-tolerated: - Most adverse events reported were mild and transient[1]. - One study noted a case of hypotension in an elderly female patient weighing less than 50 kg after receiving olanzapine, which resolved without medical intervention[4]. This combination represents an advancement in CINV management, especially for patients undergoing intensive chemotherapy regimens and stem cell transplantation, where nausea and vomiting control remains challenging.

02

Targets

HTR3A (5-hydroxytryptamine receptor 3A)HTR2C (5-hydroxytryptamine 2C receptor)HRH1 (Histamine H1 Receptor)M1 (Muscarinic acetylcholine receptor M1)ADRA1A (α1A)HTR6 (5-hydroxytryptamine receptor 6)HTR2A (Serotonin receptor 5-HT2A)DRD2 (Dopamine D2 Receptor)TACR1 (Neurokinin‑1 Receptor)

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