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aprepitant fosaprepitant dimeglumine
Emend, Emend for Injection
Pharmacologic class: Substance P and neurokinin-1 antagonist
Therapeutic class: Adjunctive antiemetic
Pregnancy risk category B
Augments antiemetic activity of ondansetron (a 5-hydroxytryptamine3-receptor antagonist) and dexamethasone. Also inhibits cisplatin-induced emesis.
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
• Hypersensitivity to drug
• Concurrent pimozide, terfenadine, astemizole, or cisapride therapy
Use cautiously in:
• patients receiving concurrent warfarin or CYP3A4 inhibitors
• pregnant patients.
• 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.
CNS: dizziness, neuropathy, headache, insomnia, asthenia, fatigue
GI: nausea, vomiting, constipation, diarrhea, epigastric discomfort, gastritis, heartburn, abdominal pain, anorexia
Other: fever, dehydration, hiccups
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
• Monitor neurologic status. Institute measures to prevent injury as needed.
• Assess nutritional and hydration status.
• Monitor CBC.
• 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.
aprepitant (oral)(a-prep-i-tant) ,
fosaprepitant (injection)(fos-a-prep-i-tant) ,
Pharmacologic: neurokinin antagonists
- Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy,
- Nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy.
Time/action profile (antiemetic effect)
|PO||1 hr||4 hr*||24 hr|
|IV||rapid||end of infusion*||24 hr|
Adverse Reactions/Side Effects
- stevens-johnson syndrome (life-threatening)
- hypersensitivity reaction (flushing, erythema, dyspnea) (IV)
Drug-Drug interactionAprepitant inhibits, induces, and is metabolized by the CYP3A4 enzyme system; it also induces the CYP2C9 system. Concurrent use with other medications that are metabolized by CYP3A4 may result in ↑ toxicity from these agents including docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine, midazolam, triazolam, and alprazolam ; concurrent use should be undertaken with caution.Concurrent use with drugs that significantly inhibit the CYP3A4 enzyme system including (ketoconazole, itraconazole, nefazodone, clarithromycin, ritonavir, nelfinavir, and diltiazem ) may ↑ blood levels and effects of aprepitant.Concurrent use with drugs that induce the CYP3A4 enzyme system including rifampin, carbamazepine, and phenytoin may ↓ blood levels and effects of aprepitant.↑ blood levels and effects of dexamethasone (regimen reflects a 50% dose reduction); a similar effect occurs with methylprednisolone (↓ IV dose by 25%, ↓ PO dose by 50% when used concurrently).May ↓ the effects of warfarin (careful monitoring for 2 wk recommended), oral contraceptives (use alternate method), and phenytoin.
Prevention of Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy
Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy
Prevention of Postoperative Nausea and Vomiting
- Assess nausea, vomiting, appetite, bowel sounds, and abdominal pain prior to and following administration.
- Monitor hydration, nutritional status, and intake and output. Patients with severe nausea and vomiting may require IV fluids in addition to antiemetics.
- Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
- Lab Test Considerations: Monitor clotting status closely during the 2 wk period, especially at 7–10 days, following aprepitant therapy in patients on chronic warfarin therapy.
- May cause mild, transient ↑ in alkaline phosphatase, AST, ALT, and BUN.
- May cause proteinuria, erythrocyturia, leukocyturia, hyperglycemia, hyponatremia, and ↑ leukocytes.
- May cause ↓ hemoglobin and WBC.
Potential Nursing DiagnosesRisk for deficient fluid volume (Indications)
Imbalanced nutrition: less than body requirements (Indications)
- For chemotherapy, aprepitant is given as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist (see Route/Dosage).
- Oral: Administer daily for 3 days. Day 1—administer 125 mg 1 hr prior to chemotherapy. Days 2 and 3—administer 80 mg once in the morning. May be administered without regard to food.
- Single-Dose Regimen: Intermittent Infusion: Inject 5 mL of 0.9% NaCl for Injection into vial. Swirl gently; avoid shaking or jetting saline into vial. Diluent: Prepare an infusion bag of 145 mL 0.9% NaCl. Withdraw entire volume from vial, and transfer to infusion bag for a total volume of 150 mL. Concentration: 1 mg/mL. Gently invert bag 2–3 times. Solution is stable for 24 hr at room temperature. Inspect solution for particulate matter. Do not administer solutions that are discolored or contain particulate matter.
- Rate: Infuse over 20–30 min.
- 3-Day Regimen: Intermittent Infusion: Inject 5 mL of 0.9% NaCl for Injection into vial. Swirl gently; avoid shaking or jetting saline into vial. Diluent: Prepare an infusion bag of 110 mL 0.9% NaCl. Withdraw entire volume from vial, and transfer to infusion bag for a total volume of 115 mL. Concentration: 1 mg/mL. Gently invert bag 2–3 times. Solution is stable for 24 hr at room temperature. Inspect solution for particulate matter. Do not administer solutions that are discolored or contain particulate matter.
- Rate: Administer over 15 min.
- Y-Site Compatibility: dexamethasone, granisetron, methylprednisolone, ondansetron, palonosetron
- Solution Incompatibility: Incompatible with solutions containing divalent cations (calcium, magnesium) including LR and Hartmann's solution.
- Instruct patient to take aprepitant as directed. Direct patient to read the Patient Package Insert before starting therapy and to reread it each time the prescription is renewed.
- Instruct patient to notify health care professional if nausea and vomiting occur prior to administration.
- Advise patient to notify health care professional immediately if symptoms of hypersensitivity reaction (hives, rash, itching, redness of the face/skin, difficulty in breathing or swallowing) occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Caution patient that fosaprepitant may decrease the effectiveness of oral contraceptives. Advise patient to use alternate nonhormonal methods of contraception during and for 1 mo following treatment. Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
- Advise patient and family to use general measures to decrease nausea (begin with sips of liquids and small, nongreasy meals; provide oral hygiene; remove noxious stimuli from environment).
- Decreased nausea and vomiting associated with chemotherapy.
- Prevention of postoperative nausea and vomiting.