Focinvez

Description

FOCINVEZ (fosaprepitant injection) is a sterile, ready-to-use, clear and colorless solution formulation containing fosaprepitant dimeglumine, a prodrug of aprepitant. Fosaprepitant is chemically described as 1-Deoxy-1-(methylamino)-D-glucitol[3-[[[2R,3S)-2-[(1R)-1-3,5-bis(trifluoromethyl)phenylethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-2,5-dihydro-5-oxo-1H-1,2,4-triazol-1-yl]phosphonate (2:1) (salt). Its empirical formula is C23H22F7N4O6P ⋅ 2(C7H17NO5), and it has a molecular weight of 1004.83. Fosaprepitant dimeglumine appears as a white to off-white amorphous powder and is freely soluble in water. Each 50 mL vial of FOCINVEZ contains 150 mg of fosaprepitant, which is equivalent to 245.3 mg of fosaprepitant dimeglumine. Inactive ingredients in each vial include Betadex sulfobutyl ether sodium (8 g), edetate disodium (5.4 mg), and sodium hydroxide (for pH adjustment) in water for injection.

Uses and Indications

FOCINVEZ is indicated for use in adults and pediatric patients aged 6 months and older, in combination with other antiemetic agents, 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. Additionally, it is indicated for the prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

Limitations of use: FOCINVEZ has not been studied for the treatment of established nausea and vomiting.

Dosage and Administration

FOCINVEZ is administered as follows:

For adult patients, the recommended dosage is 150 mg, which should be given as an intravenous infusion over a period of 20 to 30 minutes on Day 1. It is essential to complete the infusion approximately 30 minutes prior to the initiation of chemotherapy.

For pediatric patients aged 6 months to 17 years who weigh at least 6 kg, dosing regimens vary by age and are detailed in the Full Prescribing Information. For single dose chemotherapy regimens, a single dose of FOCINVEZ is administered on Day 1. In the case of single or multi-day chemotherapy regimens, a 3-day regimen is recommended, with FOCINVEZ given on Day 1, followed by aprepitant capsules or aprepitant for oral suspension on Days 2 and 3.

On Day 1, FOCINVEZ should be administered through a central venous catheter. The infusion duration is 30 minutes for patients aged 12 years to 17 years, and 60 minutes for those aged 6 months to less than 12 years. Similar to adult patients, the infusion must be completed approximately 30 minutes prior to chemotherapy.

Contraindications

Use of this drug is contraindicated in patients with a known hypersensitivity to any component of the formulation. Additionally, concurrent use with pimozide is contraindicated due to potential drug interactions that may exacerbate adverse effects.

Warnings and Precautions

Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, may occur during or shortly after the infusion of FOCINVEZ. In the event of such symptoms, it is imperative to discontinue the drug immediately. Reinitiation of FOCINVEZ is contraindicated in patients who have experienced hypersensitivity reactions with previous use.

Infusion site reactions, such as thrombophlebitis, necrosis, and vasculitis, have been predominantly reported in patients receiving vesicant chemotherapy. To minimize the risk of these reactions, it is advised to avoid infusing FOCINVEZ into small veins. Should a severe reaction develop, the infusion must be discontinued, and appropriate treatment should be administered.

Caution is warranted when administering FOCINVEZ to patients on warfarin, a CYP2C9 substrate, due to the potential risk of decreased INR of prothrombin time. It is recommended to monitor INR closely during the 2-week period following the initiation of FOCINVEZ, with particular attention at 7 to 10 days post-initiation.

The efficacy of hormonal contraceptives may be diminished during treatment with FOCINVEZ and for one month following the last dose of either fosaprepitant or oral aprepitant. Healthcare professionals should advise patients to utilize effective alternative or backup methods of contraception during this period.

General precautions should be observed regarding CYP3A4 interactions. Fosaprepitant acts as a weak inhibitor of CYP3A4, while aprepitant, the active moiety, serves as a substrate, inhibitor, and inducer of CYP3A4. For detailed recommendations concerning contraindications, potential adverse reactions, and dosage adjustments of FOCINVEZ and concomitant medications, refer to the Full Prescribing Information.

In the event of hypersensitivity symptoms, patients should be instructed to discontinue the drug and seek emergency medical assistance. If hypersensitivity reactions occur, it is crucial for patients to stop taking FOCINVEZ and contact their healthcare provider promptly.

Monitoring of INR is essential during the specified 2-week period, particularly at 7 to 10 days after the initiation of FOCINVEZ, to ensure patient safety and effective management of anticoagulation therapy.

Side Effects

Patients receiving FOCINVEZ may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

The most common adverse reactions observed in clinical trials include fatigue, diarrhea, neutropenia, asthenia, anemia, peripheral neuropathy, leukopenia, dyspepsia, urinary tract infections, and pain in extremities. These reactions were reported with varying frequencies among participants.

Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, may occur during or shortly after infusion. In the event of such symptoms, it is imperative to discontinue FOCINVEZ immediately and not to reinitiate treatment if similar symptoms have occurred with previous use.

Infusion site reactions, such as thrombophlebitis, necrosis, and vasculitis, have been predominantly reported in patients receiving vesicant chemotherapy. To minimize the risk of these reactions, it is advised to avoid infusions into small veins. Should a severe reaction develop, the infusion should be discontinued, and appropriate treatment should be administered.

Additionally, there are important considerations regarding drug interactions. The use of warfarin, a CYP2C9 substrate, may lead to a decreased INR of prothrombin time; therefore, it is essential to monitor INR closely during the two weeks following the initiation of FOCINVEZ, particularly around days 7 to 10. Furthermore, hormonal contraceptives may have reduced efficacy during treatment and for one month after the last dose of either fosaprepitant or oral aprepitant. Patients are advised to use effective alternative or back-up methods of contraception during this period.

Other adverse reactions may include known hypersensitivity to any component of the drug and concurrent use with pimozide, which should be avoided.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Focinvez (fosaprepitant dimeglumine), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of FOCINVEZ have been established in pediatric patients aged 6 months to 17 years for the prevention of acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This is supported by data from adequate and well-controlled studies of intravenous fosaprepitant in adults, along with additional safety, efficacy, and pharmacokinetic data specific to the pediatric population.

Efficacy and safety were further corroborated by a well-controlled study of a 3-day oral aprepitant regimen in pediatric patients within the same age range. However, the safety and effectiveness of FOCINVEZ for the prevention of nausea and vomiting associated with HEC or MEC have not been established in patients younger than 6 months of age.

Toxicity studies in juvenile dogs treated with fosaprepitant from postnatal day 14 to day 42 revealed decreased testicular weight and Leydig cell size in males at a dosage of 6 mg/kg/day, while females exhibited increased uterine weight, hypertrophy of the uterus and cervix, and edema of vaginal tissues at 4 mg/kg/day. Additionally, a study in young rats assessed the effects of aprepitant on growth, neurobehavioral, and sexual development from Postnatal Day 10 to Postnatal Day 58. Although slight changes in the onset of sexual maturation were noted in both male and female rats, there were no observed effects on mating, fertility, embryonic-fetal survival, or the histomorphology of reproductive organs. Neurobehavioral assessments indicated no adverse effects on sensory function, motor function, or learning and memory.

Geriatric Use

Elderly patients, defined as those aged 65 and over, comprised 27% of the 1649 adult cancer patients treated with intravenous fosaprepitant in high emetic risk (HEC) and moderate emetic risk (MEC) clinical studies, with 5% of patients aged 75 and over. Clinical experience with fosaprepitant has not identified any significant differences in treatment responses between elderly and younger adult patients.

Furthermore, pharmacokinetic studies of oral aprepitant have shown no clinically meaningful differences in healthy subjects aged 65 years and older compared to their younger counterparts.

While no specific dosage adjustments are recommended based solely on age, healthcare providers should remain vigilant in monitoring elderly patients for any potential adverse effects, given the general considerations for this population.

Pregnancy

There are no data on the presence of aprepitant in human milk, nor are there any studies assessing the effects on the breastfed infant or on milk production. However, aprepitant has been detected in rat milk, suggesting that it may also be present in human milk. Healthcare professionals should weigh the developmental and health benefits of breastfeeding against the mother's clinical need for FOCINVEZ and any potential adverse effects on the breastfed infant from FOCINVEZ or from the underlying maternal condition. Caution is advised when administering this medication to nursing mothers.

Lactation

There are no data on the presence of aprepitant in human milk, nor are there any known effects on breastfed infants or on milk production in lactating mothers. However, aprepitant has been detected in rat milk, suggesting that it may also be present in human milk.

When considering the use of FOCINVEZ in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for the medication and any potential adverse effects on the breastfed infant from FOCINVEZ or from the underlying maternal condition.

Renal Impairment

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be warranted in these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of overdosage with FOCINVEZ, there is currently no specific information available regarding the treatment of overdose with fosaprepitant or aprepitant.

Upon identification of an overdose, it is imperative that FOCINVEZ be discontinued immediately. Healthcare professionals should ensure that general supportive treatment is initiated, along with appropriate monitoring of the patient’s condition.

It is important to note that aprepitant is not effectively removed from the body through hemodialysis, which should be taken into consideration when managing an overdose situation. Continuous assessment and supportive care remain the cornerstone of management in such cases.

Nonclinical Toxicology

Oral administration of aprepitant did not adversely affect the fertility or general reproductive performance of male or female rats at doses up to the maximum feasible dose of 1000 mg/kg twice daily. This exposure in male rats was lower than the exposure at the recommended adult human dose of 150 mg, while in female rats, it was approximately equivalent to the adult human exposure.

Carcinogenicity studies were conducted in Sprague-Dawley rats and CD-1 mice over a period of 2 years. In the rat studies, animals received oral doses ranging from 0.05 to 1000 mg/kg twice daily. The highest dose resulted in systemic exposures to aprepitant that were approximately equivalent to (in female rats) or less than (in male rats) the adult human exposure at the recommended human dose of 150 mg. Treatment with aprepitant at doses of 5 to 1000 mg/kg twice daily led to an increased incidence of thyroid follicular cell adenomas and carcinomas in male rats. In female rats, the treatment resulted in hepatocellular adenomas at doses of 5 to 1000 mg/kg twice daily, as well as hepatocellular carcinomas and thyroid follicular cell adenomas at doses of 125 to 1000 mg/kg twice daily.

In the mouse carcinogenicity studies, animals were treated with oral doses ranging from 2.5 to 2000 mg/kg/day. The highest dose produced systemic exposure approximately twice that of the adult human exposure at the recommended human dose of 150 mg. Treatment with aprepitant resulted in the development of skin fibrosarcomas at doses of 125 and 500 mg/kg/day in male mice. It is noteworthy that carcinogenicity studies were not conducted with fosaprepitant.

Aprepitant and fosaprepitant were not found to be genotoxic in several assays, including the Ames test, the human lymphoblastoid cell (TK6) mutagenesis test, the rat hepatocyte DNA strand break test, the Chinese hamster ovary (CHO) cell chromosome aberration test, and the mouse micronucleus test. Fosaprepitant, when administered intravenously, is rapidly converted to aprepitant. In fertility studies involving fosaprepitant and aprepitant, the highest systemic exposures to aprepitant were observed following oral administration of aprepitant.

Postmarketing Experience

Hypersensitivity reactions, including cases of anaphylaxis and anaphylactic shock, have been reported in patients receiving fosaprepitant. Patients are advised to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction, which may include hives, rash and itching, skin peeling or sores, flushing, difficulty in breathing or swallowing, dizziness, rapid or weak heartbeat, or feelings of faintness.

Additionally, patients should seek medical attention for new or worsening signs or symptoms of an infusion site reaction. These may include erythema, edema, pain, necrosis, vasculitis, or thrombophlebitis occurring at or near the infusion site.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) to understand the medication fully. It is important to inform patients that hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported in individuals taking fosaprepitant. Patients should be instructed to seek immediate medical attention if they experience any signs or symptoms of a hypersensitivity reaction, such as hives, rash and itching, skin peeling or sores, flushing, difficulty in breathing or swallowing, dizziness, rapid or weak heartbeat, or feelings of faintness.

Healthcare providers should also counsel patients to seek medical attention if they notice new or worsening signs or symptoms of an infusion site reaction. These may include erythema, edema, pain, necrosis, vasculitis, or thrombophlebitis at or near the infusion site.

Patients must be encouraged to discuss all medications they are currently taking, including other prescription medications, nonprescription medications, or herbal products, to ensure safe and effective use of fosaprepitant.

For patients on chronic warfarin therapy, it is essential to follow the healthcare provider's instructions regarding blood draws to monitor their INR during the 2-week period, particularly at 7 to 10 days following the initiation of FOCINVEZ with each chemotherapy cycle.

Lastly, patients should be informed that the administration of FOCINVEZ may reduce the efficacy of hormonal contraceptives. They should be instructed to use effective alternative or back-up methods of contraception, such as condoms and spermicides, during treatment with FOCINVEZ and for one month following the administration of the last dose of fosaprepitant or oral aprepitant.

Storage and Handling

FOCINVEZ is supplied in vials, and the National Drug Code (NDC) numbers are available upon request.

For optimal storage, FOCINVEZ should be refrigerated at a temperature range of 2°C to 8°C (36°F to 46°F). When kept in its original carton, FOCINVEZ vials may be stored at room temperature, between 20°C to 25°C (68°F to 77°F), for a maximum duration of 90 days. It is essential to ensure that the vials are protected from light and maintained in a secure environment to preserve their integrity.

Additional Clinical Information

Patients should be advised to read the FDA-approved patient labeling for important information regarding their treatment. Clinicians should inform patients about the potential for hypersensitivity reactions, including anaphylaxis, associated with fosaprepitant. Patients experiencing symptoms such as hives, rash, difficulty breathing, or dizziness should seek immediate medical attention. Additionally, patients should be monitored for infusion site reactions, including erythema and pain, and report any new or worsening symptoms to their healthcare provider.

Patients are encouraged to discuss all medications they are taking, including prescription and nonprescription drugs, as well as herbal products, to avoid potential drug interactions. Those on chronic warfarin therapy should follow their healthcare provider's instructions for INR monitoring during the two weeks following the initiation of FOCINVEZ with each chemotherapy cycle. Furthermore, patients should be informed that FOCINVEZ may reduce the efficacy of hormonal contraceptives, and they should use effective alternative or back-up contraception methods during treatment and for one month after the last dose.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Focinvez as submitted by Steriscience Specialties Private Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)