aprepitant

(redirected from fosaprepitant)

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.

aprepitant

an antiemetic agent.
indications This drug is used to prevent nausea and vomiting associated with cancer chemotherapy (including high-dose cisplatin). It is used in combination with other antiemetics.
contraindications Known hypersensitivity to this drug prohibits its use.
adverse effects Adverse effects of this drug include insomnia, anxiety, depression, confusion, peripheral neuropathy, bradycardia, deep vein thrombosis, hypertension, abdominal pain, anorexia, gastritis, vomiting, heartburn, serum creatine, proteinuria, dysuria, anemia, asthenia, fatigue, dehydration, fever, hiccups, tinnitus, and increased aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen. Life-threatening side effects include thrombocytopenia and neutropenia. Common side effects include headache, dizziness, diarrhea, constipation, and nausea.

aprepitant

A neurokinin receptor antagonist drug used to prevent the nausea and vomiting, whether current or delayed, associated with cisplatin-based anticancer therapy. Aprepitant is an orally active antagonist of substance P neurokinin-1 receptors and is the first of a new class of antiemetic drugs.
References in periodicals archive ?
Tenders are invited for Supply of medicines for use of individual patients,inj docetaxel 120mg 1 nos,inj carboplatin450mg 1 nos,inj pegfilgrastim 6mg 1 nos,tab mycophenolate mofetil 500mg 720 nos,inj octreotide acetate 30 mg 1 nos,cap lycosafe 30 nos,tab everolimus5mg 30 nos,inj cisplatin 50mg 8 nos,inj cisplatin 10mg 8 nos,inj fosaprepitant 150mg 4 nos,inj pemetrexed 500mg 8 nos,colostomy bag -13986 (colopast) 24 nos,flange-13196 (coloplast) 24 nos,belt-0421 (coloplast) 6 nos,tab digemax 1100 nos,capd 1.
Compounds that block NK-1 receptors, including vofopitant, CP-122,721, CJ-11,794, fosaprepitant (L758,298), aprepitant (MK-869), and casopitant, reduce emesis following cisplatin, ipecac, apomorphine, and radiation therapy (8), (11).
Fosaprepitant 115 mg IV on d 1 only, and then aprepitant 80 mg [d.
25 mg IV on day 1) plus aprepitant (125 mg PO on day 1, and 80 mg PO daily on days 2 and 3; on day 1, aprepitant may be substituted by fosaprepitant 115 mg IV) plus dexamethasone (12 mg PO or IV on days 1 to 4).
1mg,Tab Crean 25000iu,Inj Cisplatin 50mg,Inj Cisplatin 10mg,Inj Fosaprepitant 150mg,Cap Norpace 100mg (same Brand),Inj Gemcitabin 1.
CHICAGO -- Merck announced today results from a new non-inferiority trial of an antiemetic regimen containing fosaprepitant dimeglumine administered as a single intravenous (IV) 150-mg dose in combination with a 5-HT3 antagonist and dexamethasone compared with a three-day regimen of aprepitant with a 5-HT3 antagonist and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving a first cycle of cisplatin-based chemotherapy.
The results of this study demonstrate that an antiemetic-regimen with a single, 150-mg injection of fosaprepitant provides similar protection against CINV as a three-day regimen of oral EMEND([R]) (aprepitant), which has become part of the standard of care for patients receiving highly emetogenic chemotherapy," said Steven Grunberg, M.
9 percent of patients who received an antiemetic regimen that included a single, 150 mg dose of fosaprepitant , ondansetron 32 mg IV, and dexamethasone 12 mg orally on Day 1, and dexamethasone 8 mg orally on Day 2, and dexamethasone 8 mg orally twice daily on Days 3 and 4 achieved a complete response, defined as no vomiting and no use of rescue medication, in the overall phase of chemotherapy (0 to 120 hours post-initiation of cisplatin-based chemotherapy) compared to 72.
Tenders are invited for for Supply of Medicine, Inj Fosaprepitant 150 mg 5 NOS2 Inj Cisplatin 50mg 10 NOS3 Inj 5 Fluorouracil 500Mg 30 NOS1 Inj Albumin bound Paclitaxel etc.
MEDICATIONS: caspofungin, Ertapenem, Posaconazole, Sugammadex, Fosaprepitant
EMEND for Injection is an intravenous prodrug of the oral formulation of EMEND([R]) (aprepitant), which means that when EMEND for Injection is administered, fosaprepitant is rapidly converted in the body to aprepitant.
Outside the United States, fosaprepitant dimeglumine is approved for use in the European Union and Australia, with marketing applications under review by a number of other regulatory agencies.