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Drugs reference index «Fosaprepitant Dimeglumine»

Fosaprepitant Dimeglumine

Pronunciation: (FOS-ap-RE-pi-tant dye-MEG-loo-meen)Class: Antiemetic

Trade Names:Emend- Injection, lyophilized powder for solution 115 mg

Pharmacology

Fosaprepitant is a prodrug of aprepitant, which is a selective high-affinity antagonist of human substance P/neurokinin 1 receptors.

Pharmacokinetics

Absorption

Following a single IV injection, mean AUC and mean C max are 31.7 mcg•h/mL and 3.27 mcg/mL, respectively.

Distribution

Rapidly converted to aprepitant, which is more than 95% bound to plasma proteins. Mean Vd at steady state is approximately 70 L.

Metabolism

Primarily metabolized by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19.

Elimination

Recovery in the urine and feces is 57% and 45%, respectively. Terminal t ½ ranges from approximately 9 to 13 h.

Special Populations

Renal Function Impairment

No dosage adjustment is needed for patients with renal function impairment or end-stage renal disease undergoing hemodialysis.

Hepatic Function Impairment

No dosage adjustment is needed in patients with mild to moderate hepatic function impairment.

Elderly

No dosage adjustment is needed.

Gender or race

No dosage adjustment is needed.

Indications and Usage

Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin; prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

Contraindications

Coadministration of cisapride or pimozide; hypersensitivity to any component of the product.

Dosage and Administration

Adults

IV Fosaprepitant 115 mg infused over 15 min may be substituted for aprepitant 125 mg orally 30 min prior to chemotherapy on day 1 only of the chemotherapy-induced nausea and vomiting regimen.

General Advice

  • Fosaprepitant is incompatible with any solutions containing divalent cations (eg, calcium, magnesium), including Ringer's lactate solution and Hartmann's solution.
  • Chronic, continuous administration is not recommended.

Storage/Stability

Store at 36° to 46°F. Reconstituted final solution is stable for 24 h at or below 77°F.

Drug Interactions

Contraceptives, hormonal

Contraceptive efficacy may be reduced. Use alternative methods of contraception during aprepitant treatment and for 1 mo after the last dose of aprepitant.

CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin)

Plasma concentrations of these drugs may be reduced. In patients receiving warfarin, closely monitor anticoagulation parameters for 14 days after initiation of the 3-day antiemetic regimen.

CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin)

Plasma concentrations of aprepitant may be reduced, decreasing the efficacy.

CYP3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir)

Plasma concentrations of aprepitant may be elevated, increasing the pharmacologic effects and adverse reactions.

CYP3A4 substrates (eg, alprazolam, cisapride, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, methylprednisolone, midazolam, paclitaxel, pimozide, vinblastine, vincristine, vinorelbine)

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and adverse reactions. Cisapride and pimozide are contraindicated with coadministration of aprepitant. Reduce the dexamethasone dose by 50%; reduce the oral and IV doses of methylprednisolone by 50% and 25%, respectively, when coadministering aprepitant.

Paroxetine

Plasma concentrations of both aprepitant and paroxetine may be reduced.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Asthenia/fatigue (18%); headache (16%); dizziness (7%); insomnia (4%).

Dermatologic

Alopecia (24%); hot flush (3%); angioedema, Stevens-Johnson syndrome, urticaria.

EENT

Tinnitus (4%); pharyngolaryngeal pain (3%).

GI

Nausea (13%); constipation (12%); anorexia, diarrhea (10%); dyspepsia, vomiting (8%); abdominal pain, heartburn, stomatitis (5%); epigastric discomfort, gastritis (4%).

Hematologic-Lymphatic

Neutropenia (9%).

Lab Tests

Decreased WBC (9%); proteinuria (7%); increased ALT (6%); increased BUN (5%); increased serum creatinine (4%); increased AST (3%); decreased hemoglobin (2%).

Metabolic-Nutritional

Dehydration (6%).

Respiratory

Hiccups (11%).

Miscellaneous

Fever, mucosal inflammation, mucous membrane disorder (3%).

Precautions

Monitor

Monitor for antiemetic effects.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Overdosage

Symptoms

Drowsiness, headache.

Patient Information

  • Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
  • Advise patient to report the use of any other prescription or nonprescription medication or herbal product to health care provider.
  • Instruct patients on chronic warfarin therapy to have their clotting status closely monitored during the 2-wk period following initiation of the 3-day regimen, particularly at 7 to 10 days after initiation.
  • Advise patient to use nonhormonal form of contraceptive while taking fosaprepitant and for 1 mo following the last dose of the 3-day regimen.

Copyright © 2009 Wolters Kluwer Health.

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