Focinvez

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 administered as an intravenous infusion on Day 1. The infusion should be delivered over a period of 20 to 30 minutes and must be completed 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 to be 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.

Administration of FOCINVEZ for pediatric patients should be conducted through a central venous catheter. For patients aged 12 years to 17 years, the intravenous infusion should be administered over 30 minutes, while for those aged 6 months to less than 12 years, the infusion duration should be extended to 60 minutes. 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.

Patients taking warfarin, a CYP2C9 substrate, should be closely monitored for a potential decrease in INR (International Normalized Ratio) of prothrombin time. It is recommended to monitor INR during a 2-week period, with particular attention at 7 to 10 days following the initiation of FOCINVEZ.

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 case of hypersensitivity reactions, patients should be instructed to discontinue the drug and seek emergency medical assistance. It is crucial for healthcare providers to emphasize the importance of immediate action should such symptoms arise.

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 soon after infusion. In the event of such symptoms, it is imperative to discontinue the drug immediately and not to reinitiate FOCINVEZ if similar symptoms have occurred with previous use.

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

Additional considerations include potential drug interactions. For instance, when FOCINVEZ is used concurrently with warfarin, a CYP2C9 substrate, there is a risk of decreased INR of prothrombin time. It is recommended to monitor INR closely during the two-week period following the initiation of FOCINVEZ, particularly around days 7 to 10. Furthermore, the efficacy of hormonal contraceptives may be reduced during treatment and for one month following the last dose of either fosaprepitant or oral aprepitant; therefore, effective alternative or back-up methods of contraception should be employed.

Patients with known hypersensitivity to any component of this drug or those using pimozide concurrently should not use FOCINVEZ.

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 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), 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 indication 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 pediatric patients aged 6 months to 17 years. 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.

Given these findings, no specific dosage adjustments are recommended for geriatric patients. However, healthcare providers should continue to monitor elderly patients closely for any potential adverse effects, as individual responses may vary.

Pregnancy

There is no specific information available regarding the use of this medication during pregnancy, including safety concerns, dosage modifications, or special precautions that should be taken. Healthcare professionals are advised to consider the lack of data when prescribing this medication to pregnant patients and to weigh the potential risks and benefits. Women of childbearing potential should be counseled accordingly, and alternative treatments may be considered in the absence of established safety profiles.

Lactation

Lactation studies have not been conducted to assess the presence of aprepitant in human milk, the effects on the breastfed infant, or the effects on milk production. However, aprepitant is present in rat milk, suggesting that it is likely to be present in human milk as well.

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 removed from the body through hemodialysis, which may influence management decisions in cases of significant overdose. Continuous assessment and supportive care remain the cornerstone of managing any potential complications arising from an overdose.

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 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 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 conducted with 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. Reported symptoms may include erythema, edema, pain, necrosis, vasculitis, or thrombophlebitis at or near the infusion site.

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. 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 encourage 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.

It is essential for patients to discuss all medications they are currently taking, including prescription and nonprescription medications, as well as herbal products, with their healthcare provider. For patients on chronic warfarin therapy, providers should instruct them to follow specific guidelines regarding blood draws to monitor their INR during the 2-week period, particularly around 7 to 10 days after initiating FOCINVEZ with each chemotherapy cycle.

Lastly, healthcare providers should inform patients that the administration of FOCINVEZ may reduce the efficacy of hormonal contraceptives. Patients 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 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 the vials are kept in their original carton, they 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.

It is essential for patients to discuss all medications they are taking, including prescription and over-the-counter 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 effectiveness of hormonal contraceptives, and they should use alternative or backup contraceptive 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 Spes Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)