APONVIE

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE APONVIE is indicated for the prevention of postoperative nausea and vomiting (PONV) in adults. APONVIE is a substance P/neurokinin-1 (NK 1 ) receptor antagonist, indicated for the prevention of postoperative nausea and vomiting (PONV) in adults. Limitations of Use : APONVIE has not been studied for treatment of established nausea and vomiting. ( 1 ) Limitations of Use APONVIE has not been studied for the treatment of established nausea and vomiting. Dosage and administration 2 DOSAGE AND ADMINISTRATION The recommended dose is 32 mg administered as a 30 second intravenous injection prior to induction of anesthesia. ( 2.1 ) 2.1 Recommended Dosage The recommended dose in adults of APONVIE is 32 mg administered as a 30 second intravenous injection prior to induction of anesthesia. 2.2 Preparation and Administration Inspect the vial for particulate matter and discoloration prior to administration; discard if present. APONVIE is opaque and off-white to amber in color. Aseptically withdraw 4.4 mL from the vial. Flush the infusion line with normal saline before and after administration of APONVIE. 2.3 Compatibilities APONVIE is compatible with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP, and solutions containing divalent cations (e.g., calcium, magnesium), including Lactated Ringer's Solution. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions (including anaphylaxis) : May occur during or soon after administration. If symptoms occur, administer appropriate medical therapy. ( 4 , 5.1 ) CYP3A4 Interactions : Aprepitant is a substrate, weak-to-moderate inhibitor, and inducer of CYP3A4; see full prescribing information. ( 5.2 , 7.2 ) Warfarin (a CYP2C9 substrate) : Risk of decreased INR of prothrombin time; monitor INR in 2-week period, particularly at 7 to 10 days, following administration of APONVIE. ( 5.3 , 7.1 ) Hormonal Contraceptives : Efficacy of contraceptives may be reduced for 28 days following administration of aprepitant. Use effective alternative or back-up methods of non-hormonal contraception. ( 5.4 , 7.1 , 8.3 ) 5.1 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, during or soon after administration of aprepitant have occurred. Symptoms including dyspnea, eye swelling, flushing, pruritus, and wheezing have been reported [see Adverse Reactions (6.2) ] . Monitor patients during and after administration. If hypersensitivity reactions occur, administer appropriate medical therapy. Do not administer APONVIE in patients who experience these symptoms with previous use of aprepitant. 5.2 Clinically Significant CYP3A4 Drug Interactions Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Use of pimozide, a CYP3A4 substrate, with APONVIE is contraindicated [see Contraindications (4) ] . Use of APONVIE with strong CYP3A4 inhibitors (e.g., ketoconazole) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to APONVIE [see Drug Interactions (7.2) ] . Use of APONVIE with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of APONVIE [see Drug Interactions (7.2) ]. 5.3 Decrease in INR with Concomitant Warfarin Use of aprepitant with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in the International Normalized Ratio (INR) of prothrombin time [see Clinical Pharmacology (12.3) ] . Monitor the INR in patients on chronic warfarin therapy in the 2-week period, particularly at 7 to 10 days, following administration of APONVIE [see Drug Interactions (7.1) ] . 5.4 Risk of Reduced Efficacy of Hormonal Contraceptives The efficacy of hormonal contraceptives may be reduced for 28 days following administration of APONVIE [see Clinical Pharmacology (12.3) ] . Advise patients to use effective alternative or back-up methods of non-hormonal contraception for 1 month following administration of APONVIE [see Drug Interactions (7.1) and Use in Specific Populations (8.3) ] . Drug interactions 7 DRUG INTERACTIONS See full prescribing information for a list of clinically significant drug interactions. ( 4 , 5.2 , 5.3 , 5.4 , 7.1 , 7.2 ) 7.1 Effect of Aprepitant on the Pharmacokinetics of Other Drugs Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 [see Clinical Pharmacology (12.3) ] . Table 2 includes drug interactions affecting drugs co-administered with APONVIE and instructions for preventing or managing them. Table 2: Drug Interactions Affecting Drugs When Co-Administered with APONVIE Pimozide Clinical Impact Increased pimozide exposure. Intervention APONVIE is contraindicated [see Contraindications (4) ] . Hormonal Contraceptives Clinical Impact Decreased hormonal exposure for 28 days after administration of APONV