Clinical Trials Adverse Events

The overall safety of aprepitant was evaluated in approximately 5,300 individuals.

The overall safety of fosaprepitant was evaluated in approximately 1,100 individuals. Since EMEND for Injection is converted to aprepitant, those adverse reactions associated with aprepitant might also be expected to occur with EMEND for Injection.

Because clinical trials are conducted under widely varying conditions, adverse-reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

EMEND:
Most common adverse reactions: highly emetogenic chemotherapy (HEC)

Percentage of patients receiving HEC with clinical adverse experiences (incidence ≥3%) — Cycle 1

  Aprepitant regimen (N=544) Standard therapya (N=550)
Body as a whole/site unspecified    
Asthenia/fatigue 17.8 11.8
Dizziness 6.6 4.4
Dehydration 5.9 5.1
Abdominal pain 4.6 3.3
Fever 2.9 3.5
Mucous membrane disorder 2.6 3.1
Digestive system    
Nausea 12.7 11.8
Constipation 10.3 12.2
Diarrhea 10.3 7.5
Vomiting 7.5 7.6
Heartburn 5.3 4.9
Gastritis 4.2 3.1
Epigastric discomfort 4.0 3.1
Eyes, ears, nose, and throat    
Tinnitus 3.7 3.8
Hemic and lymphatic system    
Neutropenia 3.1 2.9
Metabolism and nutrition    
Anorexia 10.1 9.5
Nervous system    
Headache 8.5 8.7
Insomnia 2.9 3.1
Respiratory system    
Hiccups 10.8 5.6

aStandard therapy regimen included ondansetron 32 mg IV and dexamethasone 20 mg PO on day 1, and dexamethasone 8 mg PO twice daily on days 2 through 4. Ondansetron 32 mg IV was used in the clinical trials of aprepitant. Although this dose was used in clinical trials, this is no longer the currently recommended dose. Refer to the ondansetron package insert for the current dosing.

In addition, isolated cases of serious adverse experiences, regardless of causality, of bradycardia, disorientation, and perforating duodenal ulcer were reported in highly emetogenic chemotherapy clinical studies.

A listing of additional clinical adverse experiences in the aprepitant regimen in either HEC or moderately emetogenic chemotherapy studies (incidence >0.5% and greater than with standard therapy, regardless of causality) is included in the Prescribing Information for EMEND.

EMEND for Injection:
Most common adverse reactions: highly emetogenic chemotherapy (HEC)

Percentage of patients receiving HEC with clinical adverse experiences (incidence ≥1% and greater than with standard therapy)

  Aprepitant regimen (N=544) Standard therapyb (N=550)
Respiratory system    
Hiccups 4.6 2.9
Body as a whole/site unspecified    
Asthenia/fatigue 2.9 1.6
Investigations
Increased ALT 2.8 1.5
Increased AST 1.1 0.9
Digestive system
Constipation 2.2 2.0
Dyspepsia 1.5 0.7
Diarrhea 1.1 0.9
Nervous system    
Headache 2.2 1.8
Metabolism and nutrition
Anorexia 2.0 0.5

bStandard therapy regimen included ondansetron 32 mg IV and dexamethasone 20 mg PO on day 1, and dexamethasone 8 mg PO twice daily on days 2 through 4. Ondansetron 32 mg IV was used in the clinical trials of aprepitant. Although this dose was used in clinical trials, this is no longer the currently recommended dose. Refer to the ondansetron package insert for the current dosing.

A listing of additional adverse experiences in the aprepitant regimen (incidence <1% and greater than with standard therapy) is included in the Less Common Adverse Reactions subsection of the Prescribing Information for EMEND for Injection.

In an additional active-controlled clinical study in 1,169 patients receiving aprepitant and highly emetogenic chemotherapy, the adverse-experience profile was generally similar to that seen in the other HEC studies with aprepitant.

CINV=chemotherapy-induced nausea and vomiting.

EMEND and EMEND for Injection, in combination with other antiemetic agents, are indicated in adults for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin.

EMEND and EMEND for Injection have not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND or EMEND for Injection is not recommended.

Selected Important Safety Information

  • EMEND is contraindicated in patients who are hypersensitive to any component of the product. Aprepitant, when administered orally, is a moderate or dose-dependent inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4). EMEND should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. EMEND for Injection is contraindicated in patients who are hypersensitive to EMEND for Injection, aprepitant, polysorbate 80, or any other components of the product. Known hypersensitivity reactions include flushing, erythema, dyspnea, and anaphylactic reactions. Because fosaprepitant is rapidly converted to aprepitant, neither drug should be used concurrently with pimozide or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

View additional Selected Important Safety Information

Selected Important Safety Information (continued)

  • EMEND and EMEND for Injection should be used with caution in patients receiving concomitant medications, including chemotherapy agents, that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND or EMEND for Injection could result in elevated plasma concentrations of these concomitant medications. Conversely, when EMEND or EMEND for Injection is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND or EMEND for Injection is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant.
  • 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 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 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.

  • There have been isolated reports of immediate hypersensitivity reactions, including flushing, erythema, dyspnea, and anaphylaxis, during infusion of fosaprepitant. These hypersensitivity reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. It is not recommended to reinitiate the infusion in patients who have experienced these symptoms during first-time use.
  • Coadministration of EMEND or EMEND for Injection with warfarin (a CYP2C9 substrate) 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 EMEND or EMEND for Injection with each chemotherapy cycle.
  • The efficacy of hormonal contraceptives (including birth control pills, skin patches, implants and certain IUDs) may be reduced during coadministration with and for 28 days after the last dose of EMEND or EMEND for Injection. Alternative or backup methods of contraception should be used during treatment with and for 1 month after the last dose of EMEND or EMEND for Injection.
  • Chronic continuous use of EMEND or EMEND for Injection 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.
  • In clinical trials of EMEND in patients receiving highly emetogenic chemotherapy, the most common adverse events reported at a frequency greater than with standard therapy, and at an incidence of 1% or greater, were hiccups (4.6% EMEND vs 2.9% standard therapy), asthenia/fatigue (2.9% vs 1.6%), increased ALT (2.8% vs 1.5%), increased AST (1.1% vs 0.9%), constipation (2.2% vs 2.0%), dyspepsia (1.5% vs 0.7%), diarrhea (1.1% vs 0.9%), headache (2.2% vs 1.8%), and anorexia (2.0% vs 0.5%).
  • In a clinical trial evaluating safety of the 1-day regimen of EMEND for Injection compared with the 3-day regimen of EMEND, the safety profile was generally similar to that seen in prior highly emetogenic chemotherapy studies with aprepitant. However, infusion-site reactions occurred at a higher incidence in patients who received fosaprepitant (3.0%) than in those who received aprepitant (0.5%). Those infusion-site reactions included infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site thrombophlebitis.
  • In clinical drug interaction studies, EMEND did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of dolasetron).

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

EMEND® (aprepitant) 80 mg, 125 mg capsules and EMEND® (fosaprepitant dimeglumine) 150 mg for Injection