Rezzayo Drug Information

Recommended Dosage for Adults and Pediatric Patients 12 Years of Age or Older 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. REZZAYO is for intravenous infusion only.

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. 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. 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. Table 1: Dilution Requirements for REZZAYO Prior to Administration 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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of REZZAYO cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions Leading to Discontinuation in Patients with Candidemia and Invasive Candidiasis The number of patients with an adverse reaction leading to discontinuation of study medication was 9.3% in the REZZAYO arm and 9.0% in the caspofungin arm. In Trial 2, patients with a history (or presenting with significant symptoms) of severe ataxia, tremor, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's Disease or Huntington's Disease) or currently taking a known neurotoxic medication were excluded from the trial.

Most Common Adverse Reactions in Patients with Candidemia and Invasive Candidiasis Selected adverse reactions occurring in 5% or more of the patients, who received a 400 mg loading dose followed by a 200 mg dose of REZZAYO once weekly are shown in Table 2. Table 2: Adverse Reactions Reported in ≥5% of Adult Patients Receiving REZZAYO Therapy for Candidemia/Invasive Candidiasis s in Patients with Candidemia and Invasive Candidiasis The following selected adverse reactions occurred in <5% of patients receiving REZZAYO: infusion-related reactions, tremor, disseminated intravascular coagulation, dysphagia, gastrointestinal hemorrhage, fluid overload, insomnia, erythema, headache, dizziness, acute kidney injury, abnormal liver tests (including hypertransaminasemia and increased gamma-glutamyltransferase), peripheral neuropathy (includes neuropathy peripheral, polyneuropathy, and peroneal nerve palsy). All tremors developed in the second or third week after initiation of REZZAYO treatment and resolved within a month of onset.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of REZZAYO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders: drug hypersensitivity, anaphylactic reaction

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 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).

Pediatric Use The safety and effectiveness of REZZAYO have been established in pediatric patients 12 years of age or older who have limited or no alternative options for the treatment of candidemia and invasive candidiasis. Use of REZZAYO in this age group, for this indication, is supported by evidence from adequate and well-controlled studies of REZZAYO in adults, along with additional population pharmacokinetic analyses demonstrating that age or body weight had no clinically meaningful effect on rezafungin exposures. There have been no clinical studies conducted with REZZAYO in pediatric patients.

The safety and effectiveness of REZZAYO have not been established in pediatric patients younger than 12 years old.

REZZAYO is contraindicated in patients with known hypersensitivity to rezafungin or other echinocandins. Known hypersensitivity to rezafungin or other echinocandins.

No cases of overdose were reported during the clinical studies. Rezafungin is highly protein bound and not anticipated to be dialyzable.