Rezzayo
(Rezafungin)By using PrescriberAI, you agree to the AI Terms of Use.
Rezzayo Prescribing Information
REZZAYO is an echinocandin antifungal 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 REZZAYO. (
REZZAYO is an echinocandin antifungal 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 REZZAYO.
REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida.
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
REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to
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 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
Reduced susceptibility to echinocandins predominantly arises from mutations in glucan synthase catalytic subunit-encoding
In vitro studies have not demonstrated antagonism between rezafungin and azoles, amphotericin B, or flucytosine. In vitro studies have not demonstrated antagonism for rezafungin versus bacteria in combination with the following antibacterial drug classes: aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, glycopeptides, macrolides, monobactams, oxazolidinones, polypeptides, rifamycins, sulfonamides, and tetracyclines, as well as daptomycin.
Rezafungin has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections.
Candida glabrata
Candida parapsilosis
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. However, the efficacy of rezafungin in treating clinical infections caused by these fungi has not been established in adequate and well-controlled clinical trials.
Candida auris
Candida dubliniensis
Candida fabianii
Candida guilliermondii
Candida inconspicua
Candida kefyr
Candida lusitaniae
Candida metapsilosis
Candida orthopsilosis
Candida pulcherrima
Candida rugosa
Candida sojae
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.
The safety and efficacy of REZZAYO in the treatment of patients with candidemia and/or invasive candidiasis (IC) were evaluated in a multicenter, randomized, double-blind study (Trial 1; NCT03667690). Patients were randomized in a 1:1 ratio to receive REZZAYO or caspofungin. Randomization was stratified based on diagnosis (candidemia only; IC) and by Acute Physiology and Chronic Health Evaluation II score (APACHE II)/absolute neutrophil count (ANC) at screening. Patients with septic arthritis in a prosthetic joint, osteomyelitis, endocarditis or myocarditis, meningitis, endophthalmitis, chorioretinitis, or any central nervous system infection, chronic disseminated candidiasis, or urinary tract candidiasis due to ascending
Patients in the REZZAYO arm were to receive a single 400 mg loading dose on Day 1 of Week 1, followed by 200 mg once weekly, for a total of two to four doses. Patients in the caspofungin arm were to receive a single 70 mg IV loading dose, followed by caspofungin 50 mg IV once daily treatment for a total of 2 to 4 weeks. After ≥3 days of IV therapy, patients in the caspofungin group could be switched to oral step-down therapy (fluconazole), if the patient met the criteria for cure and was preparing to be discharged.
One hundred and ninety-nine patients in the intent-to-treat (ITT) population were randomized. The age range was 19-91 years, the gender distribution was 62% male and 38% female, and the race distribution was 61% White, 5% Black, 29% Asian, and 5% other races or not reported. The median duration of therapy was 14 days in the two treatment arms.
The modified ITT (mITT) population included 187 patients with a culture positive for
Efficacy was assessed by all-cause mortality at Day 30. The number and percentage of patients in each treatment group who were alive and deceased/unknown survival status at Day 30 was determined in the mITT population. Additional efficacy outcomes were global cure (mycological eradication/presumed eradication, clinical cure, and radiological cure [for patients with documented IC by radiologic or other imaging findings at baseline]), mycological eradication/presumed eradication, and investigator's assessment of clinical cure. Results of the efficacy endpoints are shown in Table 4.
| REZZAYO 400 mg/200 mg N = 93 n (%) | Caspofungin 70 mg/50 mg N = 94 n (%) | Difference (95% CI)Two-sided 95% confidence intervals (CIs) for the observed differences in cure rates (REZZAYO minus caspofungin) is calculated using the unadjusted methodology of Miettinen and Nurminen. | |
|---|---|---|---|
All-Cause Mortality (Day 30) Patients who died on or before Day 30, or with unknown survival status. | 22 (23.7) | 20 (21.3) | 2.4 (-9.7, 14.4) |
Global Cure Patients with a mycological eradication/presumed eradication, clinical cure and radiologic cure (for patients with IC documented by radiologic or other imaging findings at baseline), as adjudicated by the Data Review Committee. | |||
| Day 5 | 52 (55.9) | 49 (52.1) | 3.8 (-10.5, 17.9) |
| Day 14 | 55 (59.1) | 57 (60.6) | -1.5 (-15.4, 12.5) |
Clinical Cure Investigator's assessment of clinical response based on resolution of attributable systemic signs and symptoms of candidemia/IC, no new systemic signs or symptoms attributable to candidemia/IC, no new systemic antifungal therapy to treat candidemia/IC, and the subject is alive. | |||
| Day 5 | 59 (63.4) | 70 (74.5) | -11.0 (-24.0, 2.3) |
| Day 14 | 62 (66.7) | 63 (67.0) | -0.4 (-13.8, 13.1) |
| Day 30 | 51 (54.8) | 52 (55.3) | -0.5 (-14.6, 13.7) |
Mycological eradication/presumed eradication Negative blood culture or culture from a normally sterile site and no change in antifungal therapy for the treatment of candidemia and/or IC. For IC patients, if the normally sterile baseline site ofCandida infection was not accessible, the patient was presumed to have an eradication if the clinical outcome and radiologic outcome (if assessed) was a cure. | |||
| Day 5 | 64 (68.8) | 58 (61.7) | 7.1 (-6.6, 20.6) |
| Day 14 | 63 (67.7) | 62 (66.0) | 1.8 (-11.7, 15.2) |
A multicenter, randomized, dose-finding, exploratory, double-blind study was conducted in subjects with candidemia and/or invasive candidiasis (Trial 2: NCT02734862). The primary objectives of this study were to evaluate safety and tolerability of rezafungin and overall success (mycological eradication and resolution of systemic signs attributable to candidemia and/IC) at Day 14. The study provides safety and supportive efficacy data.
REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida. (
REZZAYO is an echinocandin antifungal 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 REZZAYO.
REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida.
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
REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to
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.
For injection: 200 mg of rezafungin as a sterile white to pale yellow solid (cake or powder) for reconstitution in a single-dose glass vial.
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
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.
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).
REZZAYO is contraindicated in patients with known hypersensitivity to rezafungin or other echinocandins.
- Infusion-related Reactions:REZZAYO may cause infusion-related reactions, including flushing, sensation of warmth, urticaria, nausea, or chest tightness. If these reactions occur, slow or pause the infusion. ()
5.1 Infusion-Related ReactionsInfusion-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. Advise patients to use protection from sun exposure and other sources of UV radiation. ()
5.2 PhotosensitivityREZZAYO 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. Monitor patients who develop abnormal liver tests and evaluate patients for their risk/benefit of continuing REZZAYO therapy. ()
5.3 Hepatic Adverse ReactionsAbnormalities 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.
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Infusion-related Reactions [see Warnings and Precautions ()]
5.1 Infusion-Related ReactionsInfusion-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 ]. - Hepatic Adverse Reactions [see Warnings and Precautions ()]
5.3 Hepatic Adverse ReactionsAbnormalities 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.