Aponvie
(aprepitant)Dosage & Administration
The recommended dose is 32 mg administered as a 30 second intravenous injection prior to induction of anesthesia.
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Aponvie Prescribing Information
APONVIE is indicated for the prevention of postoperative nausea and vomiting (PONV) in adults.
Limitations of Use
APONVIE has not been studied for the treatment of established nausea and vomiting.
Recommended Dosage
The recommended dose in adults of APONVIE is 32 mg administered as a 30 second intravenous injection prior to induction of anesthesia.
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.
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.
Injectable emulsion: 32 mg/4.4 mL (7.2 mg/mL) aprepitant as an opaque, off-white to amber emulsion, in a single-dose vial.
Pregnancy
Risk Summary
There are insufficient data on aprepitant use in pregnant women to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Avoid use of APONVIE in pregnant women due to the alcohol content (see Clinical Considerations). In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug concentrations (area under the plasma-concentration time curve [AUC]) of oral aprepitant approximately 4.8 times the exposure at the recommended human dose of APONVIE (see Data).
The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
APONVIE contains alcohol. Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. There is no safe level of alcohol exposure in pregnancy; therefore, avoid use of APONVIE in pregnant women.
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 125 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 125 mg/kg/day were approximately 4.8 times the exposure at the recommended human dose of APONVIE. Aprepitant crosses the placenta in rats and rabbits.
Lactation
Risk Summary
There are no data on 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. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for APONVIE and any potential adverse effects on the breastfed infant from APONVIE or from the underlying maternal condition.
Females and Males of Reproductive Potential
Contraception
Upon administration of APONVIE, 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 or spermicides) for 1 month following administration of APONVIE [see Warnings and Precautions (5.4), Drug Interactions (7.1), and Clinical Pharmacology (12.3)].
Pediatric Use
The safety and effectiveness of APONVIE have not been established in pediatric patients.
Juvenile Animal Study
A study was 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) through Postnatal Day 58. 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.
Geriatric Use
Of the 1120 adult patients treated with oral aprepitant in PONV clinical studies, 7% were aged 65 and over, while 2% were aged 75 and over. Clinical studies of aprepitant did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. No clinically meaningful differences in the pharmacokinetics of oral aprepitant were observed in healthy geriatric subjects compared to younger adult subjects [see Clinical Pharmacology (12.3)].
APONVIE is contraindicated in patients:
- with a history of hypersensitivity to aprepitant or any component of the product [see Description (11)]. Hypersensitivity reactions have included anaphylaxis [see Warnings and Precautions (5.1)].
- taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of pimozide, which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Drug Interactions (7.1)].
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.
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)].
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)].
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)].