REZZAYO: Uses, Dosage & Side Effects

What Is REZZAYO and What Is It Used For?

REZZAYO contains the active substance rezafungin, a next-generation semisynthetic echinocandin antifungal developed to treat serious fungal infections caused by Candida species. Echinocandins are a class of antifungal drugs that specifically target the fungal cell wall, a structure that has no counterpart in human cells. Rezafungin is structurally related to anidulafungin but has been chemically modified to produce a molecule with greater chemical and metabolic stability, a long plasma half-life, and high front-loaded plasma exposure after the first dose. These properties enable once-weekly intravenous dosing, which is unique within the echinocandin class.

Rezafungin works by inhibiting the enzyme 1,3-β-D-glucan synthase, which is responsible for producing 1,3-β-D-glucan, a structural polysaccharide that is essential for the integrity of the Candida cell wall. When glucan synthesis is blocked, the cell wall becomes weak and loses its ability to withstand osmotic pressure. As a result, susceptible fungal cells swell and rupture, producing a fungicidal effect against most Candida species. Because mammalian cells do not have cell walls and do not contain 1,3-β-D-glucan, rezafungin selectively targets fungi with a low likelihood of host-mediated toxicity at therapeutic doses.

REZZAYO is authorized for the treatment of invasive candidiasis in adult patients. Invasive candidiasis is a broad term that includes candidemia (the presence of Candida species in the bloodstream) as well as deep-seated Candida infections such as intra-abdominal abscesses, peritonitis, infections of the liver and spleen, and disseminated candidiasis involving multiple organs. These infections are most common in critically ill, immunocompromised, or postoperative patients and are associated with substantial morbidity and mortality if not treated promptly and effectively. Invasive candidiasis remains one of the most frequent causes of healthcare-associated bloodstream infections worldwide.

The efficacy and safety of REZZAYO in invasive candidiasis were demonstrated in the international Phase 3 ReSTORE trial, a randomized, double-blind, multicenter study that compared rezafungin (400 mg loading dose followed by 200 mg once weekly) with the standard-of-care intravenous caspofungin (70 mg loading followed by 50 mg daily), with optional step-down to oral azole therapy in both groups. In this trial, rezafungin demonstrated non-inferiority to caspofungin for the primary endpoint of global cure at Day 14, with similar outcomes across secondary endpoints including all-cause mortality at Day 30 and mycologic response. Earlier Phase 2 STRIVE data supported the selected dosing regimen and demonstrated a comparable safety profile to caspofungin. Together, these trials form the basis of REZZAYO’s approval by the U.S. Food and Drug Administration (FDA) in March 2023 and by the European Medicines Agency (EMA) in December 2023.

In clinical practice, REZZAYO represents a welcome addition to the antifungal armamentarium for several reasons. First, resistance to fluconazole and other azoles is increasing in several Candida species, particularly Candida glabrata and the emerging multidrug-resistant pathogen Candida auris. Echinocandins, including rezafungin, remain active against most of these organisms and are therefore recommended as first-line empiric therapy for invasive candidiasis in many patients. Second, the once-weekly dosing schedule of REZZAYO is a major practical advantage over existing echinocandins (caspofungin, micafungin, anidulafungin) that require daily intravenous administration. This may simplify care delivery, reduce the burden on hospital infusion services, and potentially facilitate earlier hospital discharge with outpatient parenteral antifungal therapy (OPAT) in appropriately selected patients.

What Should You Know Before Taking REZZAYO?

Contraindications

The primary contraindication to REZZAYO use is hypersensitivity (allergy) to rezafungin or to any of the other ingredients in the formulation. The excipients in REZZAYO include mannitol, fructose, citric acid monohydrate, sodium hydroxide (for pH adjustment) and hydrochloric acid (for pH adjustment). Patients with a known allergy to any of these substances must not receive REZZAYO. In addition, because REZZAYO contains fructose, it is contraindicated in patients with hereditary fructose intolerance (HFI), a rare genetic condition in which the body is unable to metabolize fructose. Administration of fructose-containing products to individuals with HFI can result in severe hypoglycemia, liver failure, and life-threatening metabolic disturbances.

Serious hypersensitivity reactions, including anaphylaxis, have been reported with echinocandins as a class. Signs and symptoms can include rash, urticaria (hives), pruritus (itching), facial swelling, throat tightness, wheezing, hypotension, and, rarely, loss of consciousness. If a patient experiences signs of a severe allergic reaction during or shortly after infusion, the infusion must be stopped immediately and appropriate emergency treatment provided.

Warnings and Precautions

Before starting REZZAYO, the treating physician will review several clinical factors:

• Hepatic function: Dose-related, transient and asymptomatic elevations in liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase) have been observed with rezafungin in clinical trials. Rare cases of more pronounced hepatic abnormalities, including clinically significant liver injury, have also been described with echinocandins as a class. Liver function should be monitored periodically during treatment, especially in patients with pre-existing hepatic impairment or those receiving concomitant hepatotoxic medications. REZZAYO has not been specifically studied in patients with severe hepatic impairment (Child-Pugh C).
• Photosensitivity: In clinical studies, a small proportion of patients treated with rezafungin experienced phototoxic reactions following sun exposure, typically presenting as an erythematous rash on sun-exposed areas. Patients should be advised to avoid prolonged or intense sun exposure and to use high-factor broad-spectrum sunscreen and protective clothing during treatment and for a period after the last dose.
• Intended patient population: REZZAYO is indicated for adult patients (aged 18 years and older). Its use is appropriate when invasive candidiasis has been diagnosed or is strongly suspected based on clinical, mycologic, and laboratory findings. As with other antifungals, it is important to obtain specimens for fungal culture and susceptibility testing before starting therapy to confirm diagnosis and guide eventual step-down or targeted therapy.
• Limitations of use: REZZAYO is not recommended for the treatment of fungal endocarditis, osteomyelitis, meningitis, endophthalmitis, or central nervous system infections because clinical data in these scenarios are limited. Echinocandins penetrate poorly into the central nervous system, cerebrospinal fluid, and the vitreous humor, which may limit their effectiveness at these sites.
• Breakthrough infections and resistance: Although uncommon, breakthrough candidiasis may occur during echinocandin therapy, particularly with Candida glabrata and certain Candida parapsilosis strains. If clinical deterioration occurs during treatment, susceptibility testing should be performed, and the treatment strategy re-evaluated.

Children and Adolescents

REZZAYO is not currently authorized for use in patients under 18 years of age. The safety and efficacy of rezafungin in children and adolescents have not been established. Pediatric clinical trials are ongoing, and dosing recommendations for younger patients may become available in the future. For children and adolescents with invasive candidiasis, healthcare providers should consider age-appropriate alternatives, which may include micafungin, caspofungin, anidulafungin, liposomal amphotericin B, or azoles, depending on the clinical scenario and local resistance patterns.

Pregnancy and Breastfeeding

Data on the use of REZZAYO in pregnant women are limited or unavailable. Animal reproductive studies have shown embryofetal toxicity, including lower fetal weights and skeletal variations, at exposures in excess of those achieved at the recommended clinical dose. As a precaution, REZZAYO should be avoided during pregnancy unless the clinical condition of the woman requires treatment with rezafungin and no suitable alternative is available. The decision to use REZZAYO during pregnancy should be made by a specialist physician on a case-by-case basis after careful consideration of the potential risks to the fetus and the benefits for the mother.

Women of childbearing potential should use effective contraception during treatment with REZZAYO and for a period after the last dose, in line with the duration required for the drug to be eliminated from the body (several weeks, given its long half-life). Discuss the appropriate duration of contraception with your treating physician.

It is not known whether rezafungin is excreted in human milk. Based on animal data, rezafungin is likely to be present in breast milk. A risk to the breastfed infant cannot be excluded. The decision to discontinue breastfeeding during REZZAYO treatment should be made in consultation with the treating physician, weighing the benefits of breastfeeding for the infant against the benefits of REZZAYO treatment for the mother and the possible adverse effects on the infant.

There are no human data on the effects of rezafungin on male or female fertility. Animal studies have not identified any effects on fertility at clinically relevant exposures.

Driving and Operating Machinery

REZZAYO is not expected to affect the ability to drive or operate machinery. No studies on the effects of rezafungin on the ability to drive and use machines have been performed. However, because REZZAYO is administered to patients with serious underlying infections that may themselves impair cognition and alertness, patients should only drive or operate machinery when they feel clinically well enough to do so.

Important Information About Ingredients

REZZAYO contains fructose and therefore should not be given to patients with hereditary fructose intolerance. It also contains sodium; the exact sodium content per vial depends on the preparation and diluent used. For patients on a controlled sodium diet (for example those with severe heart failure or advanced chronic kidney disease), the total sodium load from intravenous therapy, including any diluents, should be considered. Discuss any known intolerances or dietary restrictions with your healthcare team before starting treatment.

How Does REZZAYO Interact with Other Drugs?

A practical advantage of REZZAYO in the treatment of invasive candidiasis is its comparatively clean drug-drug interaction profile, particularly when set against azole antifungals such as fluconazole, voriconazole, itraconazole, and posaconazole, which have many clinically important interactions mediated by cytochrome P450 enzymes. Rezafungin, like other echinocandins, is eliminated primarily through biliary excretion and slow chemical degradation rather than through hepatic metabolism, which minimizes classic pharmacokinetic interactions.

In vitro and clinical interaction studies have characterized the main transporter and enzyme interactions of rezafungin. Rezafungin is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters, but it is not considered a clinically relevant inhibitor or inducer of the major cytochrome P450 enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5). Rezafungin is, however, a weak inhibitor of BCRP and P-glycoprotein, which can potentially increase plasma concentrations of sensitive substrates of these transporters. These potential interactions may be clinically relevant for a small number of medications that have a narrow therapeutic index or are highly dependent on these transporters.

The table below summarizes the key known or potential drug interactions and coadministration considerations for REZZAYO, based on current regulatory information. This list is not exhaustive; always inform your treating physician and pharmacist about all concurrent medications.

Minor Interactions and General Considerations

Most commonly used medications in hospitalized patients – including antibiotics, proton pump inhibitors, analgesics, corticosteroids, and cardiovascular drugs – do not have clinically significant pharmacokinetic interactions with rezafungin based on current data. Nevertheless, the patients most likely to receive REZZAYO are often critically ill or immunocompromised, with complex medication regimens. As a routine precaution, a full medication reconciliation should be performed by the treating physician and hospital pharmacist before initiating REZZAYO to identify any medications that may require additional monitoring or dose adjustment. Over-the-counter drugs and herbal products should also be disclosed, since some may affect the same transporters or hepatic pathways.

What Is the Correct Dosage of REZZAYO?

REZZAYO should always be used exactly as prescribed by a specialist physician experienced in the management of invasive fungal infections. It is administered by trained healthcare professionals as an intravenous infusion, either in a hospital or in an outpatient infusion clinic setting. Each vial contains 200 mg of rezafungin as a white to off-white lyophilized powder that must be reconstituted and then diluted in a compatible intravenous solution before administration.

Adults

The approved dosing regimen for adults with invasive candidiasis consists of two phases:

The once-weekly schedule is made possible by rezafungin’s long terminal half-life of approximately 133 hours and its front-loaded pharmacokinetic profile, which produces high plasma and tissue exposures rapidly after the loading dose. The total duration of treatment depends on the specific clinical scenario: for most cases of candidemia and invasive candidiasis, international guidelines from ESCMID and IDSA recommend at least 14 days of appropriate systemic antifungal therapy from the first negative follow-up blood culture, along with resolution of signs and symptoms. Patients with more complex infections (for example intra-abdominal abscesses, septic thrombophlebitis, or endophthalmitis when rezafungin is used in combination with other agents) often require longer treatment, and the decision should be individualized based on source control, microbiologic response, and clinical judgement.

Children and Adolescents

Safety and efficacy of REZZAYO in children and adolescents under 18 years of age have not yet been established, and dosing recommendations are not available in this population. Clinical development programs evaluating rezafungin in pediatric patients are ongoing.

Elderly Patients

No dose adjustment is required based on age alone. Population pharmacokinetic analyses have not identified clinically meaningful differences in rezafungin exposure in elderly patients compared with younger adults. However, older patients are more likely to have underlying comorbidities (including cardiovascular, renal, and hepatic conditions) and to be taking multiple concurrent medications; these factors should be considered when prescribing REZZAYO, and routine clinical and laboratory monitoring is advisable.

Renal and Hepatic Impairment

No dose adjustment is required in patients with mild, moderate, or severe renal impairment, including those receiving intermittent hemodialysis. Rezafungin is not cleared to a clinically relevant extent by renal excretion and is not significantly removed by hemodialysis, so it can be given without regard to the dialysis schedule. In patients with mild to moderate hepatic impairment (Child-Pugh A and B), no dose adjustment is required. REZZAYO has not been specifically studied in patients with severe hepatic impairment (Child-Pugh C), so its use in these patients requires careful benefit-risk assessment.

Missed Dose

If a scheduled weekly dose of REZZAYO is missed, it should be administered as soon as possible. Subsequent doses should be given at least 7 days after the most recent dose. Because REZZAYO is given by a healthcare professional in a clinical setting, missed doses are usually identified and managed by the treating team, who will adjust the schedule as needed. Patients and caregivers should promptly notify the healthcare team if an appointment has been missed or rescheduled so that antifungal coverage is not interrupted.

Overdose

There is limited clinical experience with overdose of rezafungin. In clinical trials, single doses of up to 400 mg and repeated weekly doses at the approved regimen were generally well tolerated, with an adverse event profile consistent with the known safety profile of echinocandins. There is no specific antidote for rezafungin overdose. Management of suspected overdose is symptomatic and supportive, with monitoring of vital signs, hepatic function, and clinical status. Hemodialysis is unlikely to be effective for removing rezafungin because the drug is highly protein-bound and has a large volume of distribution. Given the long half-life, monitoring may need to be continued over an extended period.

How REZZAYO Is Prepared and Administered

REZZAYO is prepared and administered by trained hospital staff. The general process is as follows:

1. Reconstitution: Each 200 mg vial is reconstituted with sterile water for injection following the instructions in the Summary of Product Characteristics. The vial is swirled gently to dissolve the powder; vigorous shaking should be avoided.
2. Dilution: The reconstituted concentrate is further diluted in a compatible intravenous solution (for example 5% dextrose in water) to the volume specified in the product labeling.
3. Inspection: The final solution is visually inspected for particulate matter and discoloration prior to administration. It should be clear to slightly opalescent and colorless to pale yellow.
4. Administration: The infusion is given via a dedicated intravenous line over approximately 1 hour. The infusion rate may be slowed if the patient experiences infusion-related symptoms. REZZAYO should not be mixed in the same line with other medicinal products unless compatibility has been established.
5. Storage and stability: Unopened vials are stored refrigerated. Reconstituted and diluted solutions have limited in-use stability, so they should be used as soon as possible after preparation and discarded if not used within the recommended time.

What Are the Side Effects of REZZAYO?

Like all medicines, REZZAYO can cause side effects, although not every patient will experience them. In clinical trials and post-marketing experience, REZZAYO has demonstrated a safety profile broadly similar to that of other echinocandin antifungals. The most frequent adverse events reflect both the effects of rezafungin itself and the complex clinical circumstances of patients with invasive candidiasis, who are often critically ill, recently hospitalized, or immunocompromised. The side effects listed below are presented by frequency of occurrence. Frequency categories follow the MedDRA convention (very common, common, uncommon, rare).

The Phase 3 ReSTORE trial and its open-label and extension data provide the main evidence base for REZZAYO’s safety profile. In these studies, the overall rates of treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events were generally comparable between rezafungin and caspofungin. Infusion-related reactions and transient liver enzyme elevations were specifically noted.

Gastrointestinal symptoms, particularly nausea, diarrhea, and vomiting, are among the most common adverse events reported during REZZAYO treatment. These symptoms are usually mild to moderate in severity and may be related both to the medication and to the underlying illness (for example sepsis, critical illness, recent surgery, or concomitant antibiotic therapy). Supportive care, including antiemetics and adequate hydration, is usually sufficient. Persistent or severe symptoms should be reported to the medical team for evaluation.

Electrolyte disturbances, especially hypokalemia and hypomagnesemia, are frequently observed in patients receiving REZZAYO. These abnormalities are often multifactorial in critically ill patients and may be influenced by concurrent diuretics, gastrointestinal losses, or the underlying infection itself. Routine monitoring of serum electrolytes is standard during treatment, and replacement is provided as needed.

Transient, dose-related elevations of liver enzymes have been consistently reported with rezafungin and other echinocandins. These elevations are usually mild, asymptomatic, and reversible on continuation or after treatment completion. Rarely, more pronounced hepatic reactions, including cholestasis or hepatitis, may occur and warrant closer monitoring or treatment modification. Baseline and periodic liver function tests are part of routine care during prolonged therapy.

Infusion-related reactions such as flushing, warm sensations, and mild rash may occur during or shortly after the infusion. These reactions are generally rate-related and are often managed by slowing or pausing the infusion. Severe reactions are uncommon but should be recognized and treated immediately. Photosensitivity has been described with rezafungin; patients should be advised to avoid prolonged direct sunlight and to use adequate sun protection.

How Should You Store REZZAYO?

REZZAYO is a hospital-administered medicine, so its storage and handling are the responsibility of the pharmacy, infusion center, or specialist clinic where it is used. Patients do not store REZZAYO at home. Nevertheless, it is useful to understand the general storage conditions that ensure the quality, safety, and efficacy of the medication, as rezafungin – like other sterile, lyophilized biologics – is sensitive to temperature, light, and physical stress.

Key storage and handling principles include:

• Refrigerated storage (unopened vials): Store in a refrigerator at 2–8 °C. Keep the vial in the outer carton to protect from light. Do not freeze.
• Protect from light: Rezafungin is photolabile and should be kept in its outer carton until ready for use to minimize light exposure.
• Check expiration date: Do not use REZZAYO beyond the expiration date printed on the vial and carton. The expiration date refers to the last day of that month.
• Single-use vial: Each vial is for single use only. Any unused portion must be discarded in accordance with local regulations for pharmaceutical waste.
• Reconstitution and dilution: REZZAYO must be reconstituted and diluted in accordance with the Summary of Product Characteristics. The product labeling specifies which diluents are compatible and provides in-use stability times.
• In-use stability: After reconstitution and dilution, the prepared infusion solution has a limited in-use shelf life. From a microbiological point of view, the product should be used immediately unless reconstitution and dilution are performed under validated aseptic conditions. If not used immediately, in-use storage times and conditions are the responsibility of the user.
• Inspection before use: The prepared solution should be visually inspected before administration. Do not use if the solution is cloudy, discolored, or contains visible particulate matter.
• Disposal: Any unused product or waste material must be disposed of in accordance with local pharmaceutical waste disposal regulations.

If you have any questions about storage, handling, or stability of REZZAYO, the hospital pharmacist or treating infection specialist is the most appropriate contact. Patients receiving outpatient parenteral antifungal therapy (OPAT) with REZZAYO should be given clear instructions on what to do if a home infusion appointment is missed, delayed, or cancelled, and how to contact the care team.

What Does REZZAYO Contain?

Understanding the composition of REZZAYO is important, particularly for patients with known allergies, intolerances, or rare metabolic conditions. The information below provides a detailed breakdown of the active and inactive ingredients in REZZAYO.

Active Ingredient

The active substance is rezafungin (as rezafungin acetate), a semisynthetic echinocandin antifungal. Each vial contains 200 mg of rezafungin as a lyophilized (freeze-dried) powder. After reconstitution and dilution as described in the product labeling, the resulting solution is administered intravenously.

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

REZZAYO is supplied as a sterile, white to off-white lyophilized powder in a single-dose glass vial. Each vial contains 200 mg of rezafungin. After reconstitution, the solution is clear to slightly opalescent and colorless to pale yellow. Vials are typically supplied in cartons containing one or more single-dose vials. Not all pack sizes may be available in every country.

Marketing Authorization Holder and Manufacturer

REZZAYO is developed and marketed by Melinta Therapeutics (United States) and, for the European Union, by Napp Pharmaceuticals Limited (under authorization granted via the European Medicines Agency). Manufacturing is performed at approved pharmaceutical facilities operating under current good manufacturing practice (cGMP) standards. Regional regulatory approvals may vary; the marketing authorization holder for each country, together with local label information, is displayed on the product packaging.