Emetogenic Chemotherapy

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The regimen with EMEND was studied for prevention of CINV in patients with breast cancer

Study design*
chart
*
Study design: Data from a multicenter, randomized, double-blind, parallel-group clinical trial that compared the regimen including EMEND with a multiple-day 5-HT3 receptor antagonist regimen in chemotherapy-naive breast cancer patients (N=866, 99.5% women) receiving an initial cycle of chemotherapy that included cyclophosphamide and doxorubicin/epirubicin. Patients in the group who received the regimen including EMEND ranged from 25 to 78 years of age, with a mean age of 53. Approximately 80% of the patients were white, 8% black, 8% Asian, 4% Hispanic, and <1% other.

The regimen with EMEND offered superior protection vs a multiple-day 5-HT3 receptor antagonist regimen

Complete response (no vomiting, no rescue medication†)—Cycle 1
chart
Continued 
†
Because patients could use rescue medication for nausea and/or vomiting, the end point “no use of rescue medication” is a surrogate for “no nausea.”21,22
  • The difference between treatment groups was driven primarily by the “no emesis” end point, a principal component of this composite primary end point. In addition, a higher proportion of patients receiving the regimen with EMEND in Cycle 1 had a complete response during the acute (0–24 hours) and delayed (25–120 hours) phases compared with patients receiving the multiple-day 5-HT3 receptor antagonist regimen; however, after multiplicity adjustments, the treatment group differences failed to reach statistical significance.

Selected Important Risk Information

EMEND, when administered orally, is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Because fosaprepitant is rapidly converted to aprepitant, neither drug should be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

EMEND should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND could result in elevated plasma concentrations of these concomitant medications. Conversely, when EMEND is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated.

Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine. In clinical studies, EMEND 125 mg/80 mg was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, EMEND 125 mg/80 mg did not influence the pharmacokinetics of docetaxel or vinorelbine.

Because a small number of patients in clinical studies received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied.

The efficacy of hormonal contraceptives may be reduced during coadministration with EMEND and for 28 days after the last dose of EMEND. Alternative or backup methods of contraception should be used during treatment with EMEND and for 1 month after the last dose of EMEND.

Chronic continuous use of EMEND for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use.

Coadministration of EMEND with warfarin may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of EMEND with each chemotherapy cycle.

The most frequent adverse events reported in clinical trials of EMEND for highly emetogenic chemotherapy were asthenia/fatigue (17.8%), nausea (12.7%), hiccups (10.8%), constipation (10.3%), diarrhea (10.3%), and anorexia (10.1%).

The most frequent adverse events reported in clinical trials of EMEND for moderately emetogenic chemotherapy were alopecia (24.0%), fatigue (21.9%), headache (16.4%), constipation (12.3%), neutropenia (8.9%), dyspepsia (8.4%), stomatitis (5.3%), hot flush (3.0%), and pharyngolaryngeal pain (3.0%).

The most frequent clinical adverse events reported in patients receiving EMEND for Injection were infusion site pain (7.6%), headache (3.0%), and infusion site induration (1.5%).

Before prescribing EMEND and EMEND for Injection, please read the Prescribing Information. The Patient Information also is available.

For information about Merck products or services, please call 866-448-7590. The Merck National Service Center will be pleased to assist you Monday through Friday from 8 AM to 7 PM ET.

20850663(2)-05/08-EME