EMEND SIDE EFFECTS
- Generic Name: aprepitant capsules
- Brand Name: Emend Capsules
- Drug Class: Antiemetic Agents, NK1 Receptor Antagonists
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.
The overall safety of EMEND was evaluated in approximately 6800 individuals.
Adverse Reactions In Adults In The Prevention Of Nausea And Vomiting Associated With HEC And MEC
In 2 active-controlled, double-blind clinical trials in patients receiving highly emetogenic chemotherapy (HEC) (Studies 1 and 2), EMEND in combination with ondansetron and dexamethasone (EMEND regimen) was compared to ondansetron and dexamethasone alone (standard therapy).
In 2 active-controlled clinical trials in patients receiving moderately emetogenic chemotherapy (MEC) (Studies 3 and 4), EMEND in combination with ondansetron and dexamethasone (EMEND regimen) was compared to ondansetron and dexamethasone alone (standard therapy). The most common adverse reaction reported in patients who received MEC in pooled Studies 3 and 4 was dyspepsia (6% versus 4%).
Across these 4 studies there were 1412 patients treated with the EMEND regimen during Cycle 1 of chemotherapy and 1099 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy. The most common adverse reactions reported in patients who received HEC and MEC in pooled Studies 1, 2, 3 and 4 are listed in Table 5.
Table 1: Most Common Adverse Reactions in Patients Receiving HEC and MEC from a Pooled Analysis of HEC and MEC Studies*
| EMEND, ondansetron, and dexamethasone† (N=1412) |
Ondansetron and dexamethasone‡ (N=1396) |
|
| fatigue | 13% | 12% |
| diarrhea | 9% | 8% |
| asthenia | 7% | 6% |
| dyspepsia | 7% | 5% |
| abdominal pain | 6% | 5% |
| hiccups | 5% | 3% |
| white blood cell count decreased | 4% | 3% |
| dehydration | 3% | 2% |
| alanine aminotransferase increased | 3% | 2% |
| * Reported in ≥ 3% of patients treated with the EMEND regimen and at a greater incidence than standard therapy. † EMEND regimen ‡ Standard therapy |
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In a pooled analysis of the HEC and MEC studies, less common adverse reactions reported in patients treated with the EMEND regimen are listed in Table 2.
Table 2: Less Common Adverse Reactions in EMEND-Treated Patients from a Pooled Analysis of HEC and MEC Studies*
| Infection and Infestations | oral candidiasis, pharyngitis |
| Blood and the Lymphatic System Disorders | anemia, febrile neutropenia, neutropenia, thrombocytopenia |
| Metabolism and Nutrition Disorders | decreased appetite, hypokalemia |
| Psychiatric Disorders | anxiety |
| Nervous System Disorders | dizziness, dysgeusia, peripheral neuropathy |
| Cardiac Disorders | palpitations |
| Vascular Disorders | flushing, hot flush |
| Respiratory, Thoracic and Mediastinal Disorders |
cough, dyspnea, oropharyngeal pain |
| Gastrointestinal Disorders | dry mouth, eructation, flatulence, gastritis, gastroesophageal reflux disease, nausea, vomiting |
| Skin and Subcutaneous Tissue Disorders | alopecia, hyperhidrosis, rash |
| Musculoskeletal and Connective Tissue Disorders |
musculoskeletal pain |
| General Disorders and Administration Site Condition |
edema peripheral, malaise |
| Investigations | aspartate aminotransferase increased, blood alkaline phosphatase increased, blood sodium decreased, blood urea increased, proteinuria, weight decreased |
| * Reported in > 0.5% of patients treated with the EMEND regimen, at a greater incidence than standard therapy and not previously described in Table 5. | |
In an additional active-controlled clinical study in 1169 patients receiving EMEND and HEC, the adverse reactions were generally similar to that seen in the other HEC studies with EMEND.
In another CINV study, Stevens-Johnson syndrome was reported as a serious adverse reaction in a patient receiving the EMEND regimen with cancer chemotherapy.
Adverse reactions in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were generally similar to that observed in Cycle 1.
Adverse Reactions In Pediatric Patients 6 Months To 17 Years Of Age In The Prevention Of Nausea And Vomiting Associated With HEC Or MEC
In a pooled analysis of 2 active-controlled clinical trials in pediatric patients aged 6 months to 17 years who received highly or moderately emetogenic cancer chemotherapy (Study 5 and a safety study, Study 6), EMEND in combination with ondansetron with or without dexamethasone (EMEND regimen) was compared to ondansetron with or without dexamethasone (control regimen).
There were 184 patients treated with the EMEND regimen during Cycle 1 and 215 patients received open-label EMEND for up to 9 additional cycles of chemotherapy.
In Cycle 1, the most common adverse reactions reported in pediatric patients treated with the EMEND regimen in pooled Studies 5 and 6 are listed in Table 3.
Table 3: Most Common Adverse Reactions in EMEND-Treated Pediatric Patients in HEC and MEC Pooled Studies 5 and 6*
| EMEND and ondansetron† (N=184) |
Ondansetron‡ (N=168) |
|
| neutropenia | 13% | 11% |
| headache | 9% | 5% |
| diarrhea | 6% | 5% |
| decreased appetite | 5% | 4% |
| cough | 5% | 3% |
| fatigue | 5% | 2% |
| hemoglobin decreased | 5% | 4% |
| dizziness | 5% | 1% |
| hiccups | 4% | 1% |
| * Reported in ≥3% of patients treated with the EMEND regimen and at a greater incidence than control regimen. † EMEND regimen ‡ Control regimen |
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Forty-nine patients were treated with ifosfamide chemotherapy in each arm. Two of the patients treated with ifosfamide in the aprepitant arm developed behavioral changes (agitation = 1; abnormal behavior = 1), whereas no patient treated with ifosfamide in the control arm developed behavioral changes. Aprepitant has the potential for increasing ifosfamide-mediated neurotoxicity through induction of CYP3A4.
Adverse Reactions In Adult Patients In The Prevention Of PONV
In 2 active-controlled, double-blind clinical studies in patients receiving general anesthesia (Studies 7 and 8), 40-mg oral EMEND was compared to 4-mg intravenous ondansetron.
There were 564 patients treated with EMEND and 538 patients treated with ondansetron.
The most common adverse reactions reported in patients treated with EMEND for PONV in pooled Studies 7 and 8 are listed in Table 8.
Table 4: Most Common Adverse Reactions in EMEND-Treated Patients in a Pooled Analysis of PONV Studies*
| EMEND 40 mg (N = 564) |
Ondansetron (N = 538) |
|
| constipation | 9% | 8% |
| hypotension | 6% | 5% |
| * Reported in ≥ 3% of patients treated with the EMEND 40 mg and at a greater incidence than ondansetron. | ||
In a pooled analysis of PONV studies, less common adverse reactions reported in patients treated with EMEND are listed in Table 5.
Table 5: Less Common Adverse Reactions in EMEND-Treated Patients in a Pooled Analysis of PONV Studies*
| Infections and Infestations | postoperative infection |
| Metabolism and Nutrition Disorders | hypokalemia, hypovolemia |
| Nervous System Disorders | dizziness, hypoesthesia, syncope |
| Cardiac Disorders | bradycardia |
| Vascular Disorders | hematoma |
| Respiratory, Thoracic and Mediastinal Disorders |
dyspnea, hypoxia, respiratory depression |
| Gastrointestinal Disorders | abdominal pain, dry mouth, dyspepsia |
| Skin and Subcutaneous Tissue Disorders | urticaria |
| General Disorders and Administration Site Conditions |
hypothermia |
| Investigations | blood albumin decreased, bilirubin increased, blood glucose increased, blood potassium decreased |
| Injury, Poisoning and Procedural Complications |
operative hemorrhage, wound dehiscence |
| * Reported in > 0.5% of patients treated with EMEND and at a greater incidence than ondansetron | |
In addition, two serious adverse reactions were reported in PONV clinical studies in patients taking a higher than recommended dose of EMEND: one case of constipation, and one case of sub-ileus.
Other Studies
Angioedema and urticaria were reported as serious adverse reactions in a patient receiving EMEND in a non-CINV/non-PONV study (EMEND is only approved in the CINV and PONV populations).
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of EMEND. 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 drug exposure.
Skin and subcutaneous tissue disorders: pruritus, rash, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis.
Immune system disorders: hypersensitivity reactions including anaphylactic reactions.
Nervous system disorders: ifosfamide-induced neurotoxicity reported after EMEND and ifosfamide coadministration.
SRC: NLM .