SIDE EFFECTS

Clinical Trials Experience

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.

Since EMEND (fosaprepitant dimeglumine injection) for Injection is converted to aprepitant, those adverse reactions associated with aprepitant might also be expected to occur with EMEND (fosaprepitant dimeglumine injection) for Injection.

The overall safety of fosaprepitant was evaluated in approximately 1100 individuals and the overall safety of aprepitant was evaluated in approximately 6500 individuals.

Oral Aprepitant

Highly Emetogenic Chemotherapy (HEC)

In 2 well-controlled clinical trials in patients receiving highly emetogenic cancer chemotherapy, 544 patients were treated with aprepitant during Cycle 1 of chemotherapy and 413 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy. Oral aprepitant was given in combination with ondansetron and dexamethasone.

In Cycle 1, adverse reactions were reported in approximately 17% of patients treated with the aprepitant regimen compared with approximately 13% of patients treated with standard therapy. Treatment was discontinued due to adverse reactions in 0.6% of patients treated with the aprepitant regimen compared with 0.4% of patients treated with standard therapy.

The most common adverse reactions reported in patients treated with the aprepitant regimen with an incidence ≥ 1% and greater than standard therapy are listed in Table 5.

Table 5 : Adverse Reactions (incidence ≥ 1%) in patients receiving HEC with a greater incidence in the Aprepitant Regimen relative to Standard Therapy

A listing of adverse reactions in the aprepitant regimen (incidence < 1%) that occurred at a greater incidence than standard therapy are presented in the Less Common Adverse Reactions subsection below.

In an additional active-controlled clinical study in 1169 patients receiving aprepitant and highly emetogenic chemotherapy, the adverse experience profile was generally similar to that seen in the other HEC studies with aprepitant.

Moderately Emetogenic Chemotherapy (MEC)

In 2 well-controlled clinical trials in patients receiving moderately emetogenic cancer chemotherapy, 868 patients were treated with the aprepitant during Cycle 1 of chemotherapy and 686 of these patients continued into extensions for up to 4 cycles of chemotherapy. In both studies, oral aprepitant was given in combination with ondansetron and dexamethasone (aprepitant regimen).

In the combined analysis of Cycle 1 data for these 2 studies, adverse reactions were reported in approximately 14% of patients treated with the aprepitant regimen compared with approximately 15% of patients treated with standard therapy. Treatment was discontinued due to adverse reactions in 0.7% of patients treated with the aprepitant regimen compared with 0.2% of patients treated with standard therapy.

The most common adverse reactions reported in patients treated with the aprepitant regimen with an incidence ≥ 1% and greater than standard therapy are listed in Table 6.

Table 6: Adverse Reactions (incidence ≥ 1%) in patients receiving MEC with a greater incidence in the Aprepitant Regimen relative to Standard Therapy

A listing of adverse reactions in the aprepitant regimen (incidence < 1%) that occurred at a greater incidence than standard therapy are presented in the Less Common Adverse Reactions subsection below.

Less Common Adverse Reactions

Adverse reactions reported in either HEC or MEC studies in patients treated with the aprepitant regimen with an incidence < 1% and greater than standard therapy are listed in Table 7.

Table 7 : Adverse Reactions (incidence < 1%) in patients observed in either HEC or MEC Studies with a greater incidence in the Aprepitant Regimen relative to Standard Therapy

In another chemotherapy induced nausea and vomiting (CINV) study, Stevens-Johnson syndrome was reported as a serious adverse reaction in a patient receiving aprepitant with cancer chemotherapy.

The adverse experience profiles in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were similar to that observed in Cycle 1.

Fosaprepitant

In an active-controlled clinical study in patients receiving highly emetogenic chemotherapy, safety was evaluated for 1143 patients receiving the 1-day regimen of EMEND (fosaprepitant dimeglumine injection) for Injection 150 mg compared to 1169 patients receiving the 3-day regimen of EMEND (fosaprepitant dimeglumine injection) (aprepitant). The safety profile was generally similar to that seen in prior HEC studies with aprepitant. However, infusion-site reactions occurred at a higher incidence in patients in the fosaprepitant group (3.0%) compared to those in the aprepitant group (0.5%). The reported infusion-site reactions included infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site thrombophlebitis.

The following additional adverse reactions occurred with fosaprepitant 150 mg and were not reported with the oral aprepitant regimen in the corresponding section above.

Table 8 : Adverse Reactions (incidence > 0.1%) in patients receiving Fosaprepitant 150 mg and not reported above for the Oral Aprepitant Regimen

Other Studies with Postoperative Nausea and Vomiting

In well-controlled clinical studies in patients receiving general balanced anesthesia, 564 patients were administered 40 mg aprepitant orallyand 538 patients were administered 4 mg ondansetron intravenously.

Adverse reactions were reported in approximately 4% of patients treated with 40 mg aprepitant compared with approximately 6% of patients treated with 4 mg ondansetron intravenously.

In patients treated with aprepitant, increased ALT (1.1%) was seen at a greater incidence than with ondansetron (1.0%). The following additional adverse reactions were observed in patients treated with aprepitant at an incidence < 1% and greater than with ondansetron.

Table 9 : Adverse Reactions (incidence < 1%) in patients receiving Aprepitant 40 mg with a greater incidence in the Aprepitant group relative to ondansetron

In addition, two serious adverse reactions were reported in postoperative nausea and vomiting (PONV) clinical studies in patients taking a higher dose of aprepitant: one case of constipation, and one case of subileus.

Other Studies

Angioedema and urticaria were reported as serious adverse reactions in a patient receiving aprepitant in a non-CINV/non-PONV study.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of fosaprepitant and aprepitant. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug.

Skin and subcutaneous tissue disorders: pruritus, rash, urticaria.

Immune system disorders: hypersensitivity reactions including anaphylactic reactions.

Read the entire FDA prescribing information for Emend Injection (Fosaprepitant Dimeglumine Injection) »