FOSAPREPITANT- fosaprepitant dimeglumine injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

FOSAPREPITANT DIMEGLUMINE (UNII: D35FM8T64X) (APREPITANT - UNII:1NF15YR6UY)

Available from:

Athenex Pharmaceutical Division, LLC.

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Fosaprepitant for injection, in combination with other antiemetic agents, is indicated in adults for the prevention of: - acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin. - delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Limitations of Use - Fosaprepitant has not been studied for the treatment of established nausea and vomiting. Pediatric use information is approved for Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.'s Emend (fosaprepitant) for injection. However, due to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Fosaprepitant is contraindicated in patients: - who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions, flushing, erythema, and dyspnea have been reported [see Warnings and Precautions ( 5.2), Adverse Reactions ( 6.2)] . - taking pimozide. Inhibition of CYP3A4 by aprepitant, the active moiety, could result in elevated plasma concentrations of this drug, which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions ( 5.1)]. Risk Summary There are insufficient data on use of fosaprepitant in pregnant women to inform a drug associated risk. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug levels (AUC) approximately equivalent to the exposure at the recommended human dose (RHD) of 150 mg [see Data] . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryofetal development studies in rats and rabbits, aprepitant was administered during the period of organogenesis at oral doses up to 1000 mg/kg twice daily (rats) and up to the maximum tolerated dose of 25 mg/kg/day (rabbits). No embryofetal lethality or malformations were observed at any dose level in either species. The exposures (AUC) in pregnant rats at 1000 mg/kg twice daily and in pregnant rabbits at 25 mg/kg/day were approximately equivalent to the exposure at the RHD of 150 mg. Aprepitant crosses the placenta in rats and rabbits. Risk Summary Lactation studies have not been conducted to assess the presence of aprepitant in human milk, the effects on the breastfed infant, or the effects on milk production. Aprepitant is present in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for fosaprepitant and any potential adverse effects on the breastfed infant from fosaprepitant or from the underlying maternal condition. Contraception Upon administration of fosaprepitant, the efficacy of hormonal contraceptives may be reduced. Advise females of reproductive potential using hormonal contraceptives to use an effective alternative or back-up non-hormonal contraceptive (such as condoms and spermicides) during treatment with fosaprepitant and for 1 month following the last dose [see Drug Interactions ( 7.1), Clinical Pharmacology ( 12.3)] . The safety and effectiveness of fosaprepitant for the prevention of nausea and vomiting associated with HEC or MEC have not been established in patients less than 6 months of age. Juvenile Animal Toxicity Data In juvenile dogs treated with fosaprepitant, changes in reproductive organs were observed. In juvenile rats treated with aprepitant, slight changes in sexual maturation were observed without an effect on reproduction. No effects on neurobehavior, sensory and motor function, or learning and memory were observed in rats. In a toxicity study in juvenile dogs treated with fosaprepitant from postnatal day 14 (equivalent to a newborn human) to day 42 (approximately equivalent to a 2 year old human), decreased testicular weight and Leydig cell size were seen in the males at 6 mg/kg/day and increased uterine weight, hypertrophy of the uterus and cervix, and edema of vaginal tissues were seen in females from 4 mg/kg/day. A study was also conducted in young rats to evaluate the effects of aprepitant on growth and on neurobehavioral and sexual development. Rats were treated at oral doses up to the maximum feasible dose of 1000 mg/kg twice daily from the early postnatal period (Postnatal Day 10 (equivalent to a newborn human) through Postnatal Day 58 (approximately equivalent to a 15 year old human)). Slight changes in the onset of sexual maturation were observed in female and male rats; however, there were no effects on mating, fertility, embryonic-fetal survival, or histomorphology of the reproductive organs. There were no effects in neurobehavioral tests of sensory function, motor function, and learning and memory. Pediatric use information is approved for Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.'s Emend (fosaprepitant) for injection. However, due to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Of the 1649 adult cancer patients treated with intravenous fosaprepitant in HEC and MEC clinical studies, 27% were aged 65 and over, while 5% were aged 75 and over. Other reported clinical experience with fosaprepitant has not identified differences in responses between elderly and younger patients. In general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy [see Clinical Pharmacology ( 12.3)] . The pharmacokinetics of aprepitant in patients with mild and moderate hepatic impairment were similar to those of healthy subjects with normal hepatic function. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 9). There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9). Therefore, additional monitoring for adverse reactions in these patients may be warranted when fosaprepitant is administered [see Clinical Pharmacology ( 12.3)].

Product summary:

Fosaprepitant for Injection is a white to off-white lyophilized powder for reconstitution, supplied as follows: Storage Conditions Fosaprepitant for Injection vials must be refrigerated, store at 2°C to 8°C (36°F to 46°F). The reconstituted final drug solution is stable for 24 hours at ambient room temperature [at or below 25°C (77°F)]. Discard unused portion. Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

FOSAPREPITANT- FOSAPREPITANT DIMEGLUMINE INJECTION, POWDER,
LYOPHILIZED,
FOR SOLUTION
ATHENEX PHARMACEUTICAL DIVISION, LLC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
FOSAPREPITANT FOR
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
FOSAPREPITANT FOR
INJECTION.
FOSAPREPITANT FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2008
INDICATIONS AND USAGE
Fosaprepitant for injection is a substance P/neurokinin-1 (NK
) receptor antagonist, indicated in adults, in
combination with other antiemetic agents, for the prevention of ( 1):
acute and delayed nausea and vomiting associated with initial and
repeat courses of highly emetogenic
cancer chemotherapy (HEC) including high-dose cisplatin.
delayed nausea and vomiting associated with initial and repeat courses
of moderately emetogenic
cancer chemotherapy (MEC).
Limitations of Use ( 1)
Fosaprepitant has not been studied for treatment of established nausea
and vomiting.
DOSAGE AND ADMINISTRATION
Recommended Dosage ( 2.1)
Administer fosaprepitant for injection as an intravenous infusion;
complete the infusion approximately
30 minutes prior to chemotherapy.
Adults: 150 mg on Day 1.
Administer fosaprepitant for injection on Day 1 as an intravenous
infusion over 20 to 30 minutes
(adults).
See Full Prescribing Information for dosages of concomitant
antiemetic(s). ( 2.1)
DOSAGE FORMS AND STRENGTHS
Fosaprepitant for injection: 150 mg fosaprepitant, lyophilized powder
in single-dose vial for reconstitution. (
3)
CONTRAINDICATIONS
Known hypersensitivity to any component of this drug. ( 4, 5.2)
Concurrent use with pimozide. ( 4)
WARNINGS AND PRECAUTIONS
CYP3A4 Interactions:Fosaprepitant is a weak inhibitor of CYP3A4, and
aprepitant, the active moiety, is a
substrate, inhibitor, and inducer of CYP3A4; see Full Prescribing
Information for recommendations
regarding contraindications, risk of adverse reactions, and dosage
adjustment of fosaprepitant and
concomitant drugs. ( 4, 5.1, 7.1,