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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

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.

aprepitant (oral)

(a-prep-i-tant) ,

Emend

(trade name)

fosaprepitant (injection)

(fos-a-prep-i-tant) ,

Emend

(trade name)

Classification

Therapeutic: antiemetics
Pharmacologic: neurokinin antagonists
Pregnancy Category: B

Indications

Oral: Intravenous: Prevention of:
  • 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.
Oral: Prevention of postoperative nausea and vomiting.

Action

Acts as a selective antagonist at substance P/neurokinin 1 (NK1) receptors in the brain.

Therapeutic effects

Decreased nausea and vomiting associated with chemotherapy.
Augments the antiemetic effects of dexamethasone and 5-HT3 antagonists (ondansetron).

Pharmacokinetics

Absorption: 60–65% absorbed following oral administration. Following IV administration, fosaprepitant is rapidly converted to aprepitant, the active component.
Distribution: Crosses the blood brain barrier; remainder of distribution unknown.
Metabolism and Excretion: Mostly metabolized by the liver (CYP3A4 enzyme system); not renally excreted.
Half-life: Aprepitant—9–13 hr.

Time/action profile (antiemetic effect)

ROUTEONSETPEAKDURATION
PO1 hr4 hr*24 hr
IVrapidend of infusion*24 hr
*Blood level

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Concurrent use with pimozide (risk of life-threatening adverse cardiovascular reactions); Lactation: May cause unwanted effects in nursing infants.
Use Cautiously in: Concurrent use with any agents metabolized by CYP3A4; Obstetric: Use only if clearly needed; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Cardiovascular

  • dizziness
  • fatigue
  • weakness

Dermatologic

  • stevens-johnson syndrome (life-threatening)

Gastrointestinal

  • diarrhea

Miscellaneous

  • hiccups
  • hypersensitivity reaction (flushing, erythema, dyspnea) (IV)

Interactions

Drug-Drug interaction

Aprepitant 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.

Route/Dosage

Prevention of Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy

Oral (Adults) 125 mg 1 hr prior to chemotherapy (Day 1) (with dexamethasone 12 mg PO 30 min prior to chemotherapy and a 5-HT3 antagonist prior to chemotherapy), then 80 mg once daily for 2 days (Days 2 and 3) (with dexamethasone 8 mg once daily for 3 days [Days 2–4]).
Intravenous (Adults) Single-dose regimen—150 mg 30 min prior to chemotherapy on Day 1 (with dexamethasone 12 mg PO 30 min prior to chemotherapy and a 5-HT3 antagonist prior to chemotherapy). Continue dexamethasone on Days 2–4 (8 mg PO on Day 2, 8 mg twice daily on Days 3 and 4); 3–day regimen—115 mg 30 min prior to chemotherapy on Day 1 (with dexamethasone 12 mg PO 30 min prior to chemotherapy and a 5-HT3 antagonist prior to chemotherapy). Continue aprepitant 80 mg PO on Days 2 and 3. Continue dexamethasone 8 mg once daily on Days 2–4.

Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy

Oral (Adults) 125 mg 1 hr prior to chemotherapy (Day 1) (with dexamethasone 12 mg PO 30 min prior to chemotherapy and a 5-HT3 antagonist), then 80 mg once daily for 2 days (Days 2 and 3).
Intravenous (Adults) 115 mg 30 min prior to chemotherapy on Day 1 (should be given with dexamethasone 12 mg PO 30 min prior to chemotherapy and a 5-HT3 antagonist). Continue aprepiptant 80 mg PO once daily on Days 2 and 3.

Prevention of Postoperative Nausea and Vomiting

Oral (Adults) 40 mg given within 3 hr prior to induction of anesthesia.

Availability

Capsules: 40 mg, 80 mg, 125 mg
Lyophilized solid (requires reconsititution prior to injection): 115 mg/vial, 150 mg/vial

Nursing implications

Nursing assessment

  • 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 Diagnoses

Risk for deficient fluid volume (Indications)
Imbalanced nutrition: less than body requirements (Indications)

Implementation

  • 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.
  • Intravenous Administration
  • 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.

Patient/Family Teaching

  • 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).

Evaluation/Desired Outcomes

  • Decreased nausea and vomiting associated with chemotherapy.
  • Prevention of postoperative nausea and vomiting.

Emend

a trademark for aprepitant.

Emend

A brand name for the drug APREPITANT.
References in periodicals archive ?
Although two of the three characters in this explanatory phrase are emended, Graham manages to draw this conclusion,
It has been argued that Gwent should be emended to Ceint 'Kent' on the grounds of alliteration and readings of the triad in the fifteenth-century National Library of Wales, MSS Peniarth 47 and 50.
Whether Tender is the Night will in fact appear with its text emended according to what is proposed here is much less clear.
18) Unlike the two passages in Aristophanes, the fragment of Antiphanes, as emended by either Casaubon or Ruhnken, offers nothing explicit about the length of the moustaches but instead requires that it be understood from the context; this understanding is perhaps easier with Ruhnken's text.
The board also emended two other regulations to update them to match with latest developments in the financial markets and to the best international practices on the advanced markets of the world.
and emended descriptions of Acinetobacter calcoaceticus and Acinetobacter Iwofii.
There is a growing interest in Las Casas himself and those who study him know that he habitually emended his work in an ongoing effort to integrate and consolidate the different sources to which he had access; it is very useful to have an edition of the Historia de Las Indias that gives access to this detail.
Instead, there is a conflated version of the two; an edition of the Quarto as emended by the Oxford editors with reference, in part, to the Folio; parallel to this, an edition of the Folio as emended by the Oxford editors with reference, in part, to the Quarto.
If so then perhaps 'swell' should be emended to 'smell'.
85) vafraiiasca is emended to vafrauuasca without considering the rhyming name frapaiiasca in 19.
These emended proofs must have been the basis of at least a second proof, or revises; these have not survived but their existence can be posited because, on six occasions, 1894L has a reading which is different from the emended galley proofs and which must have been introduced at a later stage.