1.1. Adults
Aprepitant is FDA-approved for prevention of CINV due to high and moderate emetogenic agents including high dose cisplatin, as well as prevention for PONV [1-3]. When used to prevent CINV with highly emetogenic chemotherapy, aprepitant and rolapitant are prescribed as triple or quadruple therapy in combination with a 5-HT3 receptor antagonist, dexamethasone, and olanzapine based on product labeling, clinical trial data, as well as data from available published antiemetic guidelines [6, 7]. Rolapitant is indicated to manage delayed CINV seen with initial and repeat courses of chemotherapy, including, but not limited to, highly emetogenic chemotherapy [1, 4]. Netupitant (substance P/NK1 receptor antagonist) and palonosetron (selective 5-HT3 receptor antagonist), as combination therapy, are FDA-approved to prevent acute and delayed CINV seen with initial and repeat courses of chemotherapy, including, but not limited to, highly emetogenic chemotherapy [1, 5]. Maximum recommended adult dosages for substance P/NK1 receptor antagonists are summarized in Tables 1 and 2. Dosages exceeding those listed in Tables 1 and 2 will be reviewed.
| Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage |
|---|---|---|---|
| aprepitant (Emend) | 40 mg, 80 mg, 125 mg capsules 125 mg/5 ml oral suspension | preventing CINV: highly or moderately emetogenic chemotherapy: day 1 (one hour before chemotherapy) | 125 mg/day (as capsule or suspension)*! |
| preventing CINV: highly or moderately emetogenic chemotherapy: days 2 and 3 | 80 mg/day (as capsule or suspension)+@ ¥α | ||
| PONV: within 3 hours of anesthesia induction | 40 mg as a single dose (as capsule) | ||
| rolapitant (Varubi) | 90 mg tablet | preventing delayed CINV seen with highly emetogenic chemotherapy | 180 mg as a single dose 1 to 2 hours before chemotherapy on day 1 (2 x 90 mg tablets)^!@ |
| preventing delayed CINV seen with non-highly emetogenic chemotherapy and combinations of anthracycline and cyclophosphamide | 180 mg as a single dose 1 to 2 hours before chemotherapy on day 1 (2 x 90 mg tablets)#α |
Legend:
- * for high and moderate emetic risk regimens, use in conjunction with a 5-HT3 receptor antagonist plus dexamethasone on day 1 (product labeling)
- ! for high emetic risk regimens, use in conjunction with a 5-HT3 receptor antagonist, dexamethasone, and olanzapine on day 1 (guideline recommendation) [6, 7]
- + for high emetic risk regimens, use in conjunction with dexamethasone on days 2-3; dexamethasone monotherapy is given on day 4 (product labeling)
- @ for high emetic risk regimens, administer dexamethasone and olanzapine on days 2-4 (guideline recommendation) [6, 7]
- α for moderate emetic risk regimens; consider dexamethasone through day 3 (guideline recommendation) [6, 7]
- ^ in conjunction with dexamethasone and a 5-HT3 receptor antagonist on day 1, and dexamethasone on days 2-4 (product labeling)
- # for moderate emetic risk regimens, use in conjunction with dexamethasone and a 5-HT3 receptor antagonist on day 1. Continue 5-HT3 receptor antagonist therapy on days 2-4 (product labeling)
- PONV = postoperative nausea and vomiting
- CINV = chemotherapy-induced nausea and vomiting
- PONV = postoperative nausea and vomiting
| Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage |
|---|---|---|---|
| netupitant/palonosetron (Akynzeo®) | 300 mg netupitant/ 0.5 mg palonosetron capsules | preventing acute and delayed CINV seen with chemotherapy (highly emetogenic) | 1 capsule on day 1 (one hour before chemotherapy)**# |
| 300 mg netupitant/ 0.5 mg palonosetron capsules | preventing acute and delayed CINV seen with chemotherapy (NOT highly emetogenic) | 1 capsule on day 1 (one hour before chemotherapy)++ α |
Legend:
- ** in conjunction with dexamethasone 30 minutes before chemotherapy on day 1, and dexamethasone once daily on days 2-4 (product labeling)
- # for high emetic risk regimens, use in conjunction with dexamethasone and olanzapine on day 1. Continue dexamethasone and olanzapine on days 2-4 (guideline recommendation)8,9
- ++ for regimens that are not considered high emetic risk, use in conjunction with dexamethasone 30 minutes before chemotherapy on day 1 (product labeling)
- α for moderate emetic risk regimens; consider dexamethasone through day 3 (guideline recommendation)8,9
- CINV = chemotherapy-induced nausea and vomiting