aprepitant fosaprepitant dimeglumine

Action

Augments antiemetic activity of ondansetron (a 5-hydroxytryptamine₃-receptor antagonist) and dexamethasone. Also inhibits cisplatin-induced emesis.

Availability

Capsules: 40 mg, 80 mg, 125 mg

Powder for injection, lyophilized: 115 mg, 150 mg in single-dose vials

Indications and dosages

➣ To prevent acute and delayed nausea and vomiting caused by highly emetogenic cancer chemotherapy

Adults: 125 mg P.O. 1 hour before chemotherapy on day 1; then 80 mg P.O. once daily in morning on days 2 and 3. Give with 12 mg dexamethasone P.O. and 32 mg ondansetron I.V. on day 1, and with 8 mg dexamethasone P.O. on days 2 to 4.

Adults: Single-dose regimen: 150 mg (fosaprepitant dimeglumine) by I.V. infusion over 20 to 30 minutes starting 30 minutes before chemotherapy, with 12 mg dexamethasone P.O. once daily and 32 mg ondansetron I.V. 30 minutes before chemotherapy once daily on day 1. On day 2, give dexamethasone 8 mg P.O. once daily in the morning. On days 3 and 4, give dexamethasone 8 mg P.O. b.i.d.

Adults: Three-day dosing regimen; 115 mg (fosaprepitant dimeglumine) by I.V. infusion over 15 minutes starting 30 minutes before chemotherapy, with 12 mg dexamethasone P.O. 30 minutes before chemotherapy once daily and 32 mg ondansetron I.V. once daily on day 1. On days 2 and 3, give 80 mg (aprepitant) capsules P.O. once daily and dexamethasone 8 mg P.O. once daily. On day 4, give dexamethasone 8 mg P.O. once daily.

➣ To prevent nausea and vomiting caused by moderately emetogenic cancer chemotherapy

Adults: Three-day dosing regimen; 115 mg (fosaprepitant dimeglumine) by I.V. infusion over 15 minutes starting 30 minutes before chemotherapy, with 12 mg dexamethasone P.O. 30 minutes before chemotherapy once daily and 8 mg ondansetron P.O. b.i.d. (one capsule 30 to 60 minutes before chemotherapy and one capsule 8 hours after first dose) on day 1. Give 80 mg (aprepitant) capsules P.O. once daily on days 2 and 3.

➣ Prevention of postoperative nausea and vomiting

Adults: 40 mg P.O. once within 3 hours before induction anesthesia

Contraindications

• Hypersensitivity to drug

• Concurrent pimozide, terfenadine, astemizole, or cisapride therapy

• Breastfeeding

Precautions

Use cautiously in:

• patients receiving concurrent warfarin or CYP3A4 inhibitors

• pregnant patients.

Administration

• Give with other antiemetics as prescribed.

• For the 115-mg and 150-mg I.V. dose, reconstitute powder with 5 ml normal saline solution in vial and inject in infusion bag containing 110 ml and 145 ml normal saline solution, respectively, to yield a final concentration of 1 mg/ml. Then gently invert I.V. bag two or three times. Don't mix with other solutions, including lactated Ringer's and Hartmann's solutions.

Adverse reactions

CNS: dizziness, neuropathy, headache, insomnia, asthenia, fatigue

EENT: tinnitus

GI: nausea, vomiting, constipation, diarrhea, epigastric discomfort, gastritis, heartburn, abdominal pain, anorexia

Hematologic: neutropenia

Other: fever, dehydration, hiccups

Interactions

Drug-drug. CYP3A4 inducers (carbamazepine, phenytoin, rifampin): decreased aprepitant blood level

CYP3A4 inhibitors (azole antifungals, clarithromycin, nefazodone, ritonavir): increased aprepitant blood level

Dexamethasone, methylprednisolone: increased steroid exposure

Docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine: increased blood levels of these drugs

Hormonal contraceptives: decreased contraceptive efficacy

Paroxetine: decreased efficacy of either drug

Pimozide: increased blood level and toxic effects of aprepitant

Tolbutamide, warfarin: CYP2C9 induction, decreased efficacy of these drugs

Patient monitoring

• Monitor neurologic status. Institute measures to prevent injury as needed.

• Assess nutritional and hydration status.

• Monitor CBC.

Patient teaching

• Tell patient that drug may cause CNS effects. Explain that he'll be monitored to ensure his safety.

• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, hearing, strength, balance, and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.