Rezafungin (Monograph)

Brand name: Rezzayo
Drug class: Echinocandins

Introduction

Rezafungin acetate is an echinocandin antifungal agent.

Uses for Rezafungin

Rezafungin acetate has the following uses:

Rezafungin is indicated in patients 18 years of age or older who have limited or no alternative options for the treatment of candidemia and invasive candidiasis. Approval of this indication is based on limited clinical safety and efficacy data for the drug.

Specimens for culture and other laboratory data (e.g., histopathology, non-culture diagnostics) should be obtained prior to initiating antifungal therapy. Therapy may be initiated before the results of the cultures and other laboratory tests are known. However, once these results become available, antifungal therapy should be adjusted accordingly.

Rezafungin has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida.

Rezafungin Dosage and Administration

General

Rezafungin acetate is available in the following dosage form(s) and strength(s):

For injection: 200 mg of rezafungin as a solid (cake or powder) in a single-dose vial for reconstitution and further dilution prior to IV administration.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Administer the recommended dosage of rezafungin once weekly by IV infusion, with an initial 400 mg loading dose, followed by a 200 mg dose once weekly thereafter. The safety of rezafungin has not been established beyond 4 weekly doses.
See full prescribing information for reconstitution, dilution, and administration instructions.

Cautions for Rezafungin

Contraindications

Known hypersensitivity to rezafungin or other echinocandins.

Warnings/Precautions

Infusion-related Reactions

Infusion-related reactions, including flushing, sensation of warmth, urticaria, nausea, and chest tightness have been observed in clinical trials with rezafungin. If these reactions occur, slow or pause the infusion and restart at a lower rate.

Photosensitivity

Rezafungin may cause photosensitivity. Patients should be advised to use protection from sun exposure and other sources of UV radiation during rezafungin treatment.

Hepatic Adverse Reactions

Abnormalities in liver tests have been seen in clinical trial patients treated with rezafungin. In some patients with serious underlying medical conditions who were receiving multiple concomitant medications along with rezafungin, clinically significant hepatic abnormalities have occurred. Monitor patients who develop abnormal liver tests during rezafungin therapy and evaluate patients for their risk/benefit of continuing rezafungin therapy.

Specific Populations

Pregnancy

There are no data on the use of rezafungin during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No adverse embryofetal outcomes were observed when rezafungin was dosed intravenously to pregnant rats or rabbits during the period of organogenesis up to approximately 5 or 3 times the clinical exposure based on AUC comparison. In a pre- and post- natal study, there were no adverse effects on offspring growth, maturation, or measures of neurobehavioral or reproductive function in rats at doses up to about 5 times the recommended human dose based on AUC comparisons.

The background risk of major birth defects and miscarriage for the indicated population 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.

Lactation

There are no data on the presence of rezafungin or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production. Rezafungin was 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 rezafungin and any potential adverse effects on the breastfed infant from rezafungin or from the underlying maternal condition.

Females and Males of Reproductive Potential

Based on rat studies, rezafungin could lead to decreased sperm motility, decreased sperm numbers, and increased incidence of sperm with abnormal morphology. The effect of rezafungin on human fertility is unknown.

Pediatric Use

The safety and effectiveness of rezafungin have not been established in pediatric patients.

Geriatric Use

Of the 151 rezafungin-treated patients at the proposed dose in Trials 1 and 2, 64 patients (42%) were 65 years of age and older, while 26 patients (17%) were 75 years of age and older.

Clinical studies of rezafungin did not include sufficient numbers of older adult patients to determine if patients 65 years and older respond differently than younger adult patients.

Common Adverse Effects

Most common adverse reactions (incidence ≥ 5%) are hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions and Spectrum

Mechanism of Action

Rezafungin is a semi-synthetic echinocandin. Rezafungin inhibits the 1,3-β-D-glucan synthase enzyme complex, which is present in fungal cell walls but not in mammalian cells. This results in inhibition of the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall of many fungi, including Candida species (spp.). Inhibition of 1,3-β-D-glucan synthesis results in concentration-dependent in vitro fungicidal activity against Candida spp.; however, the clinical significance of this activity is unknown.

Spectrum

Rezafungin has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections: Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis.

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following fungi exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for rezafungin against isolates of a similar genus or organism group: Candida krusei, Candida auris, Candida dubliniensis, Candida fabianii, Candida guilliermondii, Candida inconspicua, Candida kefyr, Candida lusitaniae, Candida metapsilosis, Candida orthopsilosis, Candida pulcherrima, Candida rugosa, Candida sojae. However, the efficacy of rezafungin in treating clinical infections caused by these fungi has not been established in adequate and well-controlled clinical trials.

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: [Web].

Resistance

Reduced susceptibility to echinocandins predominantly arises from mutations in glucan synthase catalytic subunit-encoding FKS genes (FKS1 and/or FKS2) that impact residues comprising "hot spot" (HS) regions of the Fks protein. Rezafungin exhibits some degree of cross-resistance to all fks mutations that confer reduced susceptibility to echinocandins. The relevance of fks-based reduced susceptibility to clinical outcome has not been fully characterized for rezafungin.

Advice to Patients

Advise patients to use protection against sun exposure and other sources of UV radiation during treatment because rezafungin acetate may cause photosensitivity.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.