Focinvez

Uses and Indications

FOCINVEZ is indicated for use in adults and pediatric patients aged 6 months and older, in conjunction 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

The recommended adult dosage of FOCINVEZ is 150 mg, administered 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, weighing at least 6 kg, dosing regimens vary by age and should be referenced 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, consisting of FOCINVEZ on Day 1, followed by aprepitant capsules or aprepitant for oral suspension on Days 2 and 3.

FOCINVEZ should be administered through a central venous catheter on Day 1. 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 the adult regimen, 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

Fosaprepitant is associated with several important warnings and precautions that healthcare professionals must consider to ensure safe administration and patient management.

CYP3A4 Interactions Fosaprepitant acts as a weak inhibitor of CYP3A4, while its active metabolite, aprepitant, serves as a substrate, inhibitor, and inducer of this enzyme. It is essential to consult the Full Prescribing Information for detailed recommendations regarding contraindications, potential adverse reactions, and necessary dosage adjustments for FOCINVEZ and any concomitant medications.

Hypersensitivity Reactions Patients may experience hypersensitivity reactions, including anaphylaxis and anaphylactic shock, during or shortly after the infusion of FOCINVEZ. Should any symptoms of hypersensitivity arise, the infusion must be discontinued immediately. Reinitiation of FOCINVEZ is contraindicated in patients who have previously experienced such reactions.

Infusion Site Reactions 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. In the event of a severe reaction, the infusion should be stopped, and appropriate treatment should be administered.

Monitoring of Warfarin Therapy When FOCINVEZ is administered alongside warfarin, a CYP2C9 substrate, there is a risk of decreased INR (International Normalized Ratio) of prothrombin time. It is crucial to monitor the INR closely during the two weeks following the initiation of FOCINVEZ, particularly around days 7 to 10, to ensure safe anticoagulation management.

Hormonal Contraceptives 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 providers should advise patients to utilize effective alternative or backup contraceptive methods during this period to prevent unintended pregnancy.

Side Effects

Patients receiving treatment with FOCINVEZ may experience a range of adverse reactions. The most common adverse reactions reported in clinical trials among adults, occurring in 2% or more of participants, include fatigue, diarrhea, neutropenia, asthenia, anemia, peripheral neuropathy, leukopenia, dyspepsia, urinary tract infection, and pain in extremities.

Serious adverse reactions may include hypersensitivity reactions, which can manifest as anaphylaxis or anaphylactic shock. These reactions may occur during or shortly after infusion. If any symptoms of hypersensitivity arise, the drug should be discontinued immediately, and reinitiation of FOCINVEZ is contraindicated in patients with a history of such reactions.

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. In the event of a severe reaction, the infusion should be discontinued, and appropriate treatment should be administered.

Patients on warfarin, a CYP2C9 substrate, should be monitored for a potential decrease in INR of prothrombin time, particularly during the 2-week period following the initiation of FOCINVEZ, with particular attention at 7 to 10 days post-initiation.

Additionally, the efficacy of hormonal contraceptives may be reduced during treatment with FOCINVEZ and for one month following the last dose of either fosaprepitant or oral aprepitant. It is recommended that patients use effective alternative or back-up methods of contraception during this time.

Other important considerations include the potential for known hypersensitivity to any component of FOCINVEZ and the concurrent use of pimozide, which should be avoided.

Drug Interactions

Clinically significant drug interactions may occur with the use of this medication. It is essential for healthcare professionals to refer to the full prescribing information for a comprehensive list of these interactions.

Pharmacodynamic interactions may lead to enhanced effects or increased toxicity when this medication is used concurrently with other agents. Careful monitoring of the patient's clinical status is advised to mitigate potential adverse effects.

Pharmacokinetic interactions may alter the absorption, distribution, metabolism, or excretion of this medication or the concomitant drugs. Dosage adjustments may be necessary based on the specific interaction and the clinical scenario.

Healthcare providers should remain vigilant and consider both the pharmacodynamic and pharmacokinetic profiles of all medications prescribed to ensure patient safety and therapeutic efficacy.

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 initial and repeat courses of 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 pediatric patients within this age range.

Efficacy and safety findings are further corroborated by an adequate and well-controlled study of a 3-day oral aprepitant regimen in the same pediatric population. 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.

It is important to note that while additional pediatric use information is available for Merck Sharp & Dohme LLC’s EMEND (fosaprepitant) for injection, this drug product does not include that information due to marketing exclusivity rights held by Merck Sharp & Dohme LLC.

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 indicate that there are no clinically meaningful differences in the pharmacokinetics of oral aprepitant when comparing healthy adult subjects aged 65 years and older 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 consider the developmental and health benefits of breastfeeding alongside the mother's clinical need for FOCINVEZ. Additionally, potential adverse effects on the breastfed infant from FOCINVEZ or from the underlying maternal condition should be carefully evaluated.

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. 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

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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 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 exposure in female rats 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 increase in the incidences 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 a systemic exposure approximately two times 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 tests, 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

Reports of hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been documented in patients receiving fosaprepitant. Patients are advised to seek immediate medical attention if they experience signs or symptoms indicative of a hypersensitivity reaction. These 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.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling (Patient Information) to ensure they are well-informed about the medication.

Patients should be made aware of the potential for hypersensitivity reactions associated with fosaprepitant, including severe reactions such as anaphylaxis and anaphylactic shock. It is crucial to instruct patients to seek immediate medical attention if they experience any 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, healthcare providers should inform patients about the possibility of infusion site reactions. Patients should be advised to seek medical attention if they notice new or worsening signs or symptoms at or near the infusion site, such as erythema, edema, pain, necrosis, vasculitis, or thrombophlebitis.

It is important for patients to discuss all medications they are currently taking with their healthcare provider, including prescription medications, nonprescription medications, and herbal products, to avoid potential drug interactions.

For patients on chronic warfarin therapy, healthcare providers should instruct them to adhere to their provider's guidance regarding blood draws to monitor their INR during the two-week period following the initiation of FOCINVEZ with each chemotherapy cycle, particularly around days 7 to 10.

Lastly, patients should be informed that the administration of FOCINVEZ may reduce the efficacy of hormonal contraceptives. Healthcare providers should instruct patients 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 last dose of fosaprepitant or oral aprepitant.

Storage and Handling

FOCINVEZ is supplied in vials that should be refrigerated at a temperature range of 2°C to 8°C (36°F to 46°F). When stored in the original carton, FOCINVEZ vials may be kept 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 handled with care to maintain product integrity.

Additional Clinical Information

Patients should be advised to read the FDA-approved patient labeling for important information regarding their treatment. Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported in patients taking fosaprepitant. Patients experiencing signs or symptoms such as hives, rash, itching, skin peeling, difficulty breathing or swallowing, dizziness, or rapid heartbeat should seek immediate medical attention.

Additionally, patients should be vigilant for new or worsening signs of infusion site reactions, including erythema, edema, pain, necrosis, vasculitis, or thrombophlebitis, and seek medical attention if these occur. It is crucial for patients to discuss all medications they are taking, including prescription, nonprescription, and herbal products, with their healthcare provider. Those on chronic warfarin therapy should follow their healthcare provider's instructions regarding INR monitoring during the 2-week period after starting FOCINVEZ with each chemotherapy cycle. Furthermore, patients should be informed that FOCINVEZ may reduce the efficacy of hormonal contraceptives and are advised to use effective alternative or back-up contraception methods during treatment and for one month following the last dose of fosaprepitant or oral aprepitant.

FDA Insert (PDF)

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

View full prescribing information (PDF)