Peptide education
Echinocandins
Echinocandin antifungals
Echinocandins are a family of intravenous antifungal medicines. US-approved drugs include caspofungin, micafungin, anidulafungin, and rezafungin.
Echinocandins treat selected fungal infections, especially Candida infections. Caspofungin, micafungin, anidulafungin, and rezafungin have distinct product labels and are administered intravenously.
Overview
Quick answer
These are related lipopeptides, not a single standardized molecule. Their labeled uses and patient groups differ, as do their doses and schedules.
What do echinocandins do?
They inhibit the production of beta-1,3-D-glucan, a component of susceptible fungal cell walls.
Which drugs are in this group?
Caspofungin, micafungin, anidulafungin, and rezafungin are separate drugs sold as CANCIDAS, MYCAMINE, ERAXIS, and REZZAYO, respectively.
Do they all have the same uses?
No. For example, CANCIDAS includes treatment of invasive aspergillosis in people whose disease is refractory to, or who cannot tolerate, other therapies. MYCAMINE includes Candida prophylaxis in hematopoietic stem-cell transplant recipients.
What is different about rezafungin?
REZZAYO is given weekly. Its US label covers candidemia and invasive candidiasis in people aged 12 years or older who have limited or no alternative options. Approval was based on limited clinical data.
What should clinicians monitor?
Product labels describe hypersensitivity, infusion reactions, and liver effects. Monitoring and other precautions depend on the particular drug.
Evidence
Evidence snapshot
In adults with invasive candidiasis, global response at the end of intravenous treatment was 75.6% with anidulafungin and 60.2% with fluconazole in the primary analysis.
A randomized trial in adults with candidemia or invasive candidiasis reported day-14 global cure in 55 of 93 rezafungin recipients and 57 of 94 caspofungin recipients.
Caspofungin includes selected aspergillosis and febrile neutropenia uses; micafungin includes Candida prophylaxis for hematopoietic stem-cell transplant recipients.
REZZAYO is labeled for patients aged 12 or older with candidemia or invasive candidiasis who have limited or no alternative options.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| All echinocandins are the same drug. | The products contain four different active drugs. Their labels describe different doses, schedules, and in some cases different indications. | Class membership does not make the products interchangeable. |
| Every echinocandin has the same aspergillosis indication. | The CANCIDAS label includes invasive aspergillosis when a patient is refractory to or intolerant of other therapies. It states that the drug has not been studied as initial therapy for that infection. | This is a caspofungin-specific indication, not a class-wide approval. |
| Echinocandins cannot cause serious adverse effects. | Product labels describe hypersensitivity reactions, liver abnormalities, and infusion reactions. MYCAMINE also lists renal and blood-related effects; REZZAYO includes a photosensitivity precaution. | The safety profile depends on the named drug and the patient's condition. |
Bottom line
Main takeaway
These intravenous antifungals treat certain Candida infections. The prescriber selects a specific drug for the infection and patient.
The adult candidemia labels use daily schedules for caspofungin, micafungin, and anidulafungin. Rezafungin is given weekly and has a limited-alternative indication.
Randomized invasive candidiasis trials compared anidulafungin with fluconazole and rezafungin with caspofungin. The populations and endpoints differ between studies.
Identity
What it is
Echinocandins inhibit an enzyme needed to make fungal cell-wall glucan. Each named drug has its own product label.
CANCIDAS has a selected invasive aspergillosis indication. MYCAMINE has a Candida prophylaxis indication in hematopoietic stem-cell transplant recipients. REZZAYO has a limited-alternative indication for candidemia and invasive candidiasis.
Use context
Routes, doses, and cycle patterns
All four products are given by intravenous infusion. The adult candidemia label schedules below differ in loading dose and interval; pediatric dosing and other indications have separate label provisions.
Human studies and product labels
Caspofungin, adult candidemia
- Purpose
- Candidemia and specified invasive Candida infections
- Context
- CANCIDAS US label
- Route
- Intravenous infusion
- Amount
- 70 mg on day one, then 50 mg once daily
- Frequency
- Daily
The label specifies a 35 mg daily maintenance dose for adults with moderate hepatic impairment and different dosing for esophageal candidiasis.
Micafungin, adult candidemia
- Purpose
- Candidemia and specified invasive Candida infections
- Context
- MYCAMINE US label
- Route
- Intravenous infusion
- Amount
- 100 mg once daily
- Frequency
- Daily
The adult label lists different amounts for esophageal candidiasis and Candida prophylaxis in hematopoietic stem-cell transplant recipients.
Anidulafungin, adult candidemia
- Purpose
- Candidemia and specified invasive Candida infections
- Context
- ERAXIS US label
- Route
- Intravenous infusion
- Amount
- 200 mg on day one, then 100 mg once daily
- Frequency
- Daily
The adult esophageal candidiasis schedule uses different amounts. The label limits infusion rate to reduce infusion-related reactions. ERAXIS contains fructose and is contraindicated in known or suspected hereditary fructose intolerance.
Rezafungin, candidemia or invasive candidiasis
- Purpose
- Patients aged 12 or older with limited or no alternative options
- Context
- REZZAYO US label
- Route
- Intravenous infusion
- Amount
- 400 mg initially, then 200 mg once weekly
- Frequency
- Weekly
The label states that safety beyond four weekly doses has not been established and lists photosensitivity among its precautions.
Rezafungin versus caspofungin trial
- Purpose
- Candidemia or invasive candidiasis in adults
- Context
- Randomized phase 3 study
- Route
- Intravenous infusion
- Amount
- Rezafungin 400 mg then 200 mg; caspofungin 70 mg then 50 mg
- Frequency
- Weekly rezafungin compared with daily caspofungin
- Duration
- Up to four weeks in the trial
The study assessed day-14 global cure and day-30 all-cause mortality.
What varies
- CANCIDAS specifies dose reduction for adults with moderate hepatic impairment and dose changes with certain interacting medicines.
- The labels specify different age ranges and precautions. Liver tests and infusion reactions are relevant to each product's safety assessment.
Research
Research evidence
A trial compared anidulafungin with fluconazole in invasive candidiasis. A separate trial compared weekly rezafungin with daily caspofungin in adults with candidemia or invasive candidiasis.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Anidulafungin versus fluconazole | Adults with invasive candidiasis and a positive baseline culture | Randomized, double-blind comparison | Intravenous anidulafungin compared with intravenous fluconazole | Global response at the end of intravenous therapy was 75.6% versus 60.2% among 245 patients in the primary analysis. | Most participants had candidemia only and 97% were not neutropenic. | Controlled human evidence |
| Rezafungin versus caspofungin | Adults with candidemia or invasive candidiasis | Randomized, double-blind phase 3 comparison | Weekly rezafungin compared with daily caspofungin | Day-14 global cure occurred in 55 of 93 and 57 of 94 patients, respectively. Day-30 death or unknown survival occurred in 22 of 93 and 20 of 94, respectively. | The trial enrolled adults and used a 20-percentage-point noninferiority margin. The REZZAYO label has specific age and limited-alternative criteria. | Controlled human evidence |
Cautions
Safety and unknowns
- ERAXIS contains fructose and is contraindicated in patients with known or suspected hereditary fructose intolerance because it can cause a life-threatening metabolic crisis.
- Each product label lists hypersensitivity contraindications. MYCAMINE, ERAXIS, and REZZAYO also list known hypersensitivity to another echinocandin; CANCIDAS specifies hypersensitivity to its components.
- Serious hypersensitivity and infusion reactions can occur. The product labels include monitoring and infusion precautions.
- Liver test abnormalities are described in the labels. MYCAMINE also warns about renal impairment and blood-related effects, including hemolysis.
- REZZAYO may cause photosensitivity. Its label also states that safety beyond four weekly doses has not been established.
Product quality
Product identity and quality
Each medicine has its own vial, preparation, infusion, and dosing instructions. The drugs have different concentrations and schedules.
Named drug
Caspofungin, micafungin, anidulafungin, and rezafungin have different doses and labeled indications.
Infusion conditions
The labels set product-specific infusion instructions and precautions.
Mechanism
How it is proposed to work
These medicines interfere with the construction of a structural sugar in fungal cell walls, weakening the wall of susceptible fungi.
Anidulafungin inhibits glucan synthase and thereby the formation of beta-1,3-D-glucan. The ERAXIS label also describes mutations associated with echinocandin resistance.
FAQ
Common questions
Are all echinocandins given on the same schedule?
No. Adult candidemia schedules in the cited labels are daily for caspofungin, micafungin, and anidulafungin, but weekly for rezafungin.
Are all echinocandins approved for invasive aspergillosis?
CANCIDAS is labeled for patients whose invasive aspergillosis is refractory to other therapies or who cannot tolerate them. Its label says it has not been studied as initial therapy for that infection.
Details
Technical details
Sources
References
- 1.
- 2.
- 3.
- 4.
- 5.
PubMed. Anidulafungin versus fluconazole for invasive candidiasis
doi:10.1056/NEJMoa066906 PMID:17568028
- 6.
PubMed. Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis
doi:10.1016/S0140-6736(22)02324-8 PMID:36442484 NCT03667690