Fosemred Special Precautions

Since fosaprepitant is rapidly converted to aprepitant (a weak to moderate inhibitor of CYP3A4), fosaprepitant should be used with caution in patients receiving concomitant orally administered medicinal products that are primarily metabolized through CYP3A4; some chemotherapy agents are metabolized by CYP3A4 (see Interactions). Weak inhibition of CYP3A4 by fosaprepitant 150 mg could result in elevated plasma concentrations of these concomitant medicinal products administered orally (see Interactions). Consequently, chemotherapeutic agents metabolized via CYP3A4 should be used with caution. Additionally, concomitant administration with irinotecan should be approached with particular caution as the combination may result in increased toxicity.
Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine and vincristine.
Particular caution and careful monitoring are advised in patients receiving CYP3A4 substrates vinblastine, vincristine, or ifosfamide or other chemotherapy agents metabolized primarily by CYP3A4.
There are limited data in patients with moderate hepatic insufficiency and no data in patients with severe hepatic insufficiency. Fosaprepitant should be used with caution in these patients.
Coadministration of fosaprepitant with ergot alkaloid derivatives, which are CYP3A4 substrates, may result in elevated plasma concentrations of these medicinal products. Therefore, caution is advised due to the potential risk of ergot-related toxicity.
Concomitant administration of fosaprepitant with medicinal products that strongly induce CYP3A4 activity (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination results in reductions of the plasma concentrations of aprepitant. Concomitant administration of aprepitant with St. John's wort is not recommended.
Concomitant administration of fosaprepitant with medicinal products that inhibit CYP3A4 activity (e.g., ritonavir, ketoconazole, clarithromycin, telithromycin) should be approached cautiously as the combination results in increased plasma concentrations of aprepitant.
Immediate hypersensitivity reactions including flushing, erythema, dyspnea, and anaphylaxis/anaphylactic shock have occurred during or soon after infusion of fosaprepitant. These hypersensitivity reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. It is not recommended to reinitiate the infusion in patients who experience hypersensitivity reactions.
Infusion site reactions (ISRs) have been reported with the use of FOSEMRED (see Adverse Reactions). The majority of severe ISRs, including thrombophlebitis and vasculitis, were reported with concomitant vesicant (e.g., anthracycline-based) chemotherapy administration, particularly when associated with extravasation. Necrosis was also reported in some patients with concomitant vesicant chemotherapy.
Coadministration of fosaprepitant with warfarin may result in a clinically significant decrease in International Normalized Ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of fosaprepitant with each chemotherapy cycle (see Interactions).
The efficacy of hormonal contraceptives during and for 28 days after administration of fosaprepitant may be reduced. Alternative or back-up methods of contraception should be used during treatment with fosaprepitant and for 1 month following administration of fosaprepitant (see Interactions).
Chronic continuous use of FOSEMRED for injection for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use.
FOSEMRED should not be given as a bolus injection, but should always be diluted and given as a slow intravenous infusion (see Dosage & Administration). FOSEMRED should not be administered intramuscularly or subcutaneously. Mild injection site thrombosis has been observed at higher doses (see Overdosage). If signs or symptoms of local irritation occur, the injection or infusion should be terminated and restarted in another vein.
Effects on ability to drive and use machines: FOSEMRED may have minor influence on the ability to drive and use machines. Dizziness and fatigue may occur following administration of FOSEMRED.
Use in Children: FOSEMRED is not recommended for the use below 12 years of age.