Rezzayo

Indication

REZZAYO 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 [see Microbiology ]. Approval of this indication is based on limited clinical safety and efficacy data for REZZAYO [see Clinical Studies ].

Limitations of Use
REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida.

Usage

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.

Recommended Dosage

Administer the recommended dosage of REZZAYO once weekly by intravenous (IV) infusion, with an initial 400 mg loading dose, followed by a 200 mg dose once weekly thereafter. The safety of REZZAYO has not been established beyond 4 weekly doses [see Adverse Reactions ]. REZZAYO is for intravenous infusion only [see Dosage and Administration ].

Missed Doses

If a scheduled dose is missed (not taken on the assigned day), administer the missed dose as soon as possible.

• If the missed dose is administered within 3 days of the assigned day, the next weekly dose may be given on schedule.
• If the missed dose is administered more than 3 days after the assigned day, revise the dosing schedule to ensure there are at least 4 days before the next dose.
• If restarting after at least 2 weeks of missed dosing, the dosing should be started again at the 400 mg loading dose.

Preparation and Administration of REZZAYO

Reconstitution

REZZAYO is supplied as a single-dose vial containing 200 mg of rezafungin.

For the 400 mg dose, aseptically reconstitute two vials each with 9.5 mL of sterile Water for Injection, to provide a concentration of 20 mg/mL in each vial.

For the 200 mg dose, aseptically reconstitute one vial with 9.5 mL of sterile Water for Injection, to provide a concentration of 20 mg/mL.

Swirl gently to dissolve the white to pale yellow cake or powder. Avoid shaking to minimize foaming. The solution should be clear to pale yellow after dissolution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the reconstituted solution is cloudy or has precipitated. The reconstituted solution is not for direct injection and must be diluted before intravenous infusion.

Storage of the Reconstituted Solution

REZZAYO reconstituted solution can be stored between 5°C to 25°C (41°F to 77°F). Stability of the reconstituted solution has been demonstrated for 24 hours when stored at 5°C to 25°C (41°F to 77°F).

Preparation of Intravenous Infusion Solution

See Table 1 for the dilution requirements for infusion solution. First, aseptically withdraw and discard the appropriate volume of diluent from the intravenous bag containing 250 mL of 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, or 5% Dextrose Injection. Next, aseptically transfer the indicated volume of reconstituted solution (10 mL per vial) into the intravenous bag.

REZZAYO vials are single-dose vials. Discard any unused portion.

Storage of the Intravenous Infusion Solution

Store REZZAYO infusion solution between 5°C to 25°C (41°F to 77°F). Stability of the infusion solution has been demonstrated for 48 hours at 5°C to 25°C (41°F to 77°F).

The infusion solution must not be frozen.

Administration of Intravenous Infusion Solution

Administer REZZAYO by intravenous infusion over approximately one hour (~250 mL/h). If infusion-related reactions occur, the infusion may be slowed, or paused and restarted at a lower rate [see Warnings and Precautions ].

Pregnancy

Risk Summary

There are no data on the use of REZZAYO 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 (see Data). 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.

Data

Animal Data

In an embryofetal development study, intravenous rezafungin was administered at doses up to 45 mg/kg, once every 3 days to female rats one week prior to pairing with untreated males, and dosing was continued through mating to gestation day 17. Maternal toxicity included a transient histamine-release response (hypoactivity, ataxia, flushed extremities, dilated pupils and/or swollen facial area) at rezafungin doses of 15 mg/kg and above. No adverse embryofetal outcomes were observed in rat pups at rezafungin doses of 45 mg/kg, equivalent to 5 times the clinical exposure based on AUC comparisons.

No adverse outcomes were observed when rezafungin was dosed intravenously once every 3 days to pregnant rabbits during the period of organogenesis (GD 7 to 19) at doses up to 35 mg/kg (approximately 3 times the clinical exposure) despite maternal toxicity (reduced bodyweight gain).

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 administered rezafungin intravenously once every 3 days from 1 week prior to mating through weaning (LD20), at doses up to 45 mg/kg/day (about 5 times the recommended human dose based on AUC comparisons).

Lactation

Risk Summary

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 REZZAYO and any potential adverse effects on the breastfed infant from REZZAYO or from the underlying maternal condition.

Females and Males of Reproductive Potential

Infertility

Males

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 REZZAYO on human fertility is unknown [see Nonclinical Toxicology ].

Pediatric Use

The safety and effectiveness of REZZAYO 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 REZZAYO did not include sufficient numbers of older adult patients to determine if patients 65 years and older respond differently than younger adult patients.

Infusion-Related Reactions

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

Photosensitivity

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

Hepatic Adverse Reactions

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