Anidulafungin (Monograph)

Brand name: Eraxis
Drug class: Echinocandins
VA class: AM700
Chemical name: 1-[(4R,5R)-4,5-dihydroxy-N2-[[4″-(pentyloxy)[1,1′:4′,1″-terphenyl]-4-yl]carbonyl]-l-ornithine] Echinocandin B
Molecular formula: C₅₈H₇₃N₇O₁₇
CAS number: CAS-166663-25-8

Medically reviewed by Drugs.com on Aug 26, 2024. Written by ASHP.

Introduction

Antifungal; echinocandin.

Uses for Anidulafungin

Candidemia and Other Invasive Candida Infections

Treatment of candidemia and certain other invasive Candida infections (intra-abdominal abscess, peritonitis). A drug of choice.

Manufacturer states safety and efficacy not established for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida.

Manufacturer states efficacy data insufficient to date regarding use of anidulafungin for treatment of candidemia or other invasive Candida infections in neutropenic patients.

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in nonneutropenic patients in intensive care units (ICUs), IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial therapy; IV or oral fluconazole is an acceptable alternative for initial therapy in selected patients, including those who are not critically ill and unlikely to have infections caused by fluconazole-resistant Candida. IV amphotericin B recommended if echinocandin- and azole-resistant Candida suspected and is an alternative when echinocandins and fluconazole have been ineffective or cannot be used. Consider transition from the echinocandin to fluconazole (usually within 5–7 days) in clinically stable patients if strain susceptible to fluconazole (e.g., C. albicans) and initial treatment resulted in negative repeat blood cultures.

For treatment of candidemia in neutropenic patients^{† [off-label]}, IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) or, alternatively, IV amphotericin B for initial therapy. Fluconazole is an alternative for initial therapy in those who are not critically ill and have had no prior exposure to azole antifungals; also can be used for step-down therapy in clinically stable patients who have fluconazole-susceptible isolates and documented bloodstream clearance. Voriconazole can be used as an alternative for initial therapy when broader antifungal coverage is required and also can be used as step-down therapy during neutropenia in clinically stable patients who have voriconazole-susceptible isolates and documented bloodstream clearance. An echinocandin, amphotericin B, or voriconazole recommended for infections known to be caused by C. krusei.

For treatment of osteoarticular infections^{† [off-label]} (e.g., osteomyelitis, septic arthritis) caused by Candida, IDSA recommends initial treatment with fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If septic arthritis involves a prosthetic device that cannot be removed, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended if isolate is susceptible.

For treatment of endocarditis^{† [off-label]} (native or prosthetic valve) or implantable cardiac device infections caused by Candida, IDSA recommends initial treatment with IV amphotericin B (with or without flucytosine) or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If isolate is susceptible, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended to prevent recurrence in those with native valve endocarditis who cannot undergo valve replacement and in those with prosthetic valve endocarditis.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of candidemia and disseminated candida infections.

Esophageal Candidiasis

Treatment of esophageal candidiasis. A drug of choice.

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).

IDSA recommends oral fluconazole as the preferred drug of choice for treatment of esophageal candidiasis; if oral therapy not tolerated, IV fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) recommended. For fluconazole-refractory esophageal candidiasis, IDSA recommends itraconazole oral solution or IV or oral voriconazole; alternatives are an IV echinocandin (anidulafungin, caspofungin, micafungin) or IV amphotericin B. IDSA states oral posaconazole (oral suspension or delayed-release tablets) is another possible alternative for treatment of fluconazole-refractory esophageal candidiasis.

For treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral or IV fluconazole or itraconazole oral solution. Alternatives include oral or IV voriconazole, an IV echinocandin (anidulafungin, caspofungin, micafungin), or IV amphotericin B. For refractory esophageal candidiasis, including fluconazole-refractory infections, in HIV-infected adults and adolescents, itraconazole oral solution or posaconazole oral suspension is recommended; alternatives are IV amphotericin B, an IV echinocandin (anidulafungin, caspofungin, micafungin), or oral or IV voriconazole.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for esophageal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of esophageal candidiasis may benefit from secondary prophylaxis with oral fluconazole or posaconazole oral suspension; however, consider potential for development of azole resistance.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of esophageal candidiasis.

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis^{† [off-label]}. Considered an alternative, not a drug of choice.

For mild oropharyngeal candidiasis, IDSA recommends topical treatment with clotrimazole lozenges or miconazole buccal tablets; nystatin (oral suspension or tablets) is an alternative. For moderate to severe oropharyngeal candidiasis, IDSA recommends oral fluconazole. For fluconazole-refractory oropharyngeal candidiasis, IDSA recommends itraconazole oral solution or posaconazole oral suspension; oral voriconazole or amphotericin B oral suspension (not commercially available in US) recommended as alternatives. Other alternatives for refractory oropharyngeal candidiasis are IV echinocandins (anidulafungin, caspofungin, micafungin) or IV amphotericin B.

For treatment of oropharyngeal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes; if topical therapy used (e.g., mild to moderate episodes), drugs of choice are clotrimazole lozenges or miconazole buccal tablets. Alternatives for systemic treatment are itraconazole oral solution or posaconazole oral suspension; nystatin oral suspension is an alternative for topical treatment. For fluconazole-refractory infections in HIV-infected adults and adolescents, posaconazole oral suspension is preferred; itraconazole oral solution is an alternative.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for oropharyngeal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of oropharyngeal candidiasis may benefit from secondary prophylaxis with oral fluconazole; however, consider potential for development of azole resistance.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of oropharyngeal candidiasis.

Candida auris Infections

Treatment of infections caused by C. auris, an emerging pathogen associated with potentially fatal candidemia or other invasive infections.

First identified in 2009, C. auris has now been reported as the cause of serious invasive infections (including fatalities) in multiple countries worldwide (e.g., Japan, South Korea, India, Kuwait, South Africa, Pakistan, United Kingdom, Venezuela, Colombia, US). As of May 2017, a total of 77 clinical cases of C. auris had been reported to CDC from 7 different US states. May be difficult to identify using standard in vitro methods. Large percentage of C. auris clinical isolates are resistant to fluconazole; multidrug-resistant isolates with reduced susceptibility or resistance to all 3 major classes of antifungal agents (azoles, polyenes, echinocandins) reported.

CDC issued interim recommendations regarding laboratory diagnosis, treatment, and infection control measures for suspected or known C. auris infections. Based on limited data available to date, CDC recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial treatment of invasive C. auris infections (e.g., bloodstream or intra-abdominal infections) in adults. CDC states a switch to IV amphotericin B (lipid formulation) could be considered if patient is clinically unresponsive to the echinocandin or fungemia persists >5 days. Consultation with an infectious disease specialist highly recommended.

CDC recommends that infection control measures be observed for all patients with cultures yielding C. auris, including those with positive cultures only from noninvasive body sites.

If C. auris infection is suspected, immediately contact state or local public health authorities and the CDC (candidaauris@cdc.gov) for guidance. Consult interim recommendations and most recent information from CDC available at [Web] for additional information on diagnosis and management of C. auris infections.

Aspergillosis

Safety and efficacy for treatment of invasive aspergillosis^{† [off-label]} not established; only limited data are available regarding use of the drug for treatment of such infections.

IDSA and other clinicians consider IV voriconazole the drug of choice for primary treatment of invasive aspergillosis in adult and pediatric patients, including HIV-infected patients; IV amphotericin B or isavuconazonium (prodrug of isavuconazole) usually recommended as alternatives for primary treatment.

For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends IV amphotericin B, an IV echinocandin (caspofungin, micafungin), oral or IV posaconazole, or itraconazole oral suspension. IDSA states that echinocandins (either alone or in conjunction with other antifungals) may be effective for salvage therapy of invasive aspergillosis; however, routine use of echinocandin monotherapy not recommended for primary treatment of invasive aspergillosis.

Consult current IDSA clinical practice guidelines available at [Web] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [Web] for additional information on management of aspergillosis.

Anidulafungin Dosage and Administration

Administration

IV Administration

Administer by slow IV infusion. Do not administer by rapid IV injection.

Do not admix or infuse concomitantly with other drugs.

Must be reconstituted and diluted prior to administration. Use strict aseptic technique since the drug contains no preservatives.

Reconstitution

Reconstitute 50- or 100-mg vials of lyophilized anidulafungin with 15 or 30 mL, respectively, of sterile water for injection to provide a solution containing 3.33 mg/mL.

Dilution

Dilute total contents of the required number of reconstituted vials in 50, 100, or 200 mL of 5% dextrose injection or 0.9% sodium chloride injection as directed to provide an IV infusion solution containing 0.77 mg/mL. (See Table.)

Rate of Administration

Administer by IV infusion at a rate not exceeding 1.1 mg/minute (1.4 mL/minute). More rapid infusion may increase risk of histamine-mediated reactions. (See Histamine-mediated Reactions under Cautions.)

Dosage

Pediatric Patients

General Pediatric Dosage†

IV

AAP recommends a loading dose of 1.5–3 mg/kg, followed by 0.75–1.5 mg/kg once daily.

Candidemia and Other Invasive Candida Infections

IV

HIV-infected children ≥2 years of age^†: Some experts recommend an initial loading dose of 3 mg/kg on day 1, followed by 1.5 mg/kg once daily.

IDSA recommends that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 2 weeks after documented clearance of Candida from the bloodstream, resolution of candidemia symptoms, and resolution of neutropenia.

Esophageal Candidiasis

IV

HIV-infected children ≥2 years of age^†: Some experts recommend an initial loading dose of 3 mg/kg on day 1, followed by 1.5 mg/kg (up to 100 mg) once daily.

HIV-infected adolescents^†: A single 100-mg loading dose on day 1, followed by 50 mg once daily.

IDSA and others recommend that antifungal treatment for esophageal candidiasis be continued for 14–21 days.

Adults

Candidemia and Other Invasive Candida Infections

IV

A single 200-mg loading dose on day 1, followed by 100 mg once daily.

IDSA states consider a transition from the echinocandin to fluconazole (usually within 5–7 days) in patients who are clinically stable, have isolates susceptible to fluconazole (e.g., C. albicans), and have negative repeat blood cultures after initial antifungal treatment.

Duration of treatment is based on clinical response. Manufacturer recommends anidulafungin be continued for at least 14 days after last positive culture. IDSA recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 2 weeks after documented clearance of Candida from the bloodstream and resolution of candidemia symptoms and neutropenia.

Osteoarticular infections^†: IDSA recommends 100 mg once daily. After ≥2 weeks, can switch to fluconazole.

Endocarditis^† (native or prosthetic valve) or implantable cardiac device infections^†: IDSA recommends 200 mg once daily. If infection caused by fluconazole-susceptible Candida, can switch to fluconazole after patient stabilized and Candida has been cleared from bloodstream.

Esophageal Candidiasis

IV

A single 100-mg loading dose on day 1, followed by 50 mg once daily is recommended by the manufacturer.

IDSA recommends 200 mg once daily if anidulafungin used for treatment of esophageal candidiasis, including fluconazole-refractory disease (see Esophageal Candidiasis under Uses).

HIV-infected adults: A single 100-mg loading dose on day 1, followed by 50 mg once daily.

Duration of treatment is based on clinical response. Manufacturer recommends a minimum of 14 days and at least 7 days following resolution of symptoms. IDSA and others recommend that antifungal treatment be continued for 14–21 days.

Oropharyngeal Candidiasis†

IV

IDSA recommends a single 200-mg loading dose on day 1, followed by 100 mg once daily for 7–14 days.

Candida auris Infections

IV

CDC recommends a single 200-mg loading dose on day 1, followed by 100 mg once daily.

Aspergillosis†

IV

Some experts recommend a single 200-mg loading dose, followed by 100 mg daily.

Duration of treatment is based on severity of patient's underlying disease, recovery from immunosuppression, and clinical response. IDSA recommends that treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks.

Special Populations

Hepatic Impairment

Mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, or C): Dosage adjustments not necessary.

Renal Impairment

Mild, moderate, or severe renal impairment: Dosage adjustments not necessary.

Not dialyzable; may administer without regard to dialysis timing.

Geriatric Patients

Adults ≥65 years of age: Dosage adjustments not necessary.

Cautions for Anidulafungin

Contraindications

• Known hypersensitivity to anidulafungin, other echinocandin antifungals (e.g., caspofungin, micafungin), or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic reactions, including anaphylactic shock, reported in patients receiving anidulafungin. If such reactions occur, discontinue the drug and administer appropriate treatment.

Possible histamine-mediated symptoms (e.g., rash, urticaria, flushing, pruritus, dyspnea, hypotension). Reported infrequently when infusion rate does not exceed 1.1 mg/minute.

Infusion-related adverse reactions (e.g., rash, urticaria, flushing, pruritus, bronchospasm, dyspnea, hypotension) reported and possibly may be histamine-mediated reactions. To reduce occurrence of such reactions, do not exceed infusion rate of 1.1 mg/minute.

Hepatic Effects

Abnormal liver function test results reported. Clinically important hepatic dysfunction, hepatitis, or worsening hepatic failure reported in patients with serious underlying conditions receiving multiple drugs concomitantly; causal relationship not established.

If abnormal liver function test results occur, monitor for evidence of worsening hepatic function and evaluate benefits versus risks of continuing anidulafungin therapy.

Selection and Use of Antifungals

Obtain specimens for fungal culture and other relevant laboratory studies (e.g., histopathology) prior to initiation of therapy. Therapy may be started pending results; adjust therapy as needed when results available.

Specific Populations

Pregnancy

Category B.

No adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.

In rats, crosses the placenta, is detected in fetal plasma, and has been associated with incomplete ossification of several bones.

Lactation

Distributed into milk in rats; not known whether distributed into human milk.

Use with caution in nursing women.

Pediatric Use

Safety and efficacy not established in pediatric patients ≤16 years of age.

Has been used in a limited number of neutropenic children 2–17 years of age^† without unusual adverse effects.

Although data limited, some experts state anidulafungin can be considered for first-line treatment of invasive candidiasis or for alternative treatment of esophageal candidiasis in HIV-infected children 2–17 years of age^†.

Geriatric Use

No overall differences in efficacy or safety were observed between adults ≥65 years of age and younger adults, but possibility that some older patients may have increased sensitivity to the drug cannot be ruled out.

Hepatic Impairment

Mild, moderate or severe hepatic impairment (Child-Pugh class A, B, or C): No clinically important effects on pharmacokinetics; dosage adjustments not necessary.

Renal Impairment

Mild, moderate, or severe renal impairment: No clinically important effects on pharmacokinetics; dosage adjustments not necessary.

Common Adverse Effects

GI effects (nausea, diarrhea, vomiting , dyspepsia ), phlebitis/thrombophlebitis, hypokalemia, increased ALT, increased alkaline phosphatase, increased γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGPT), pyrexia, headache, rash, insomnia, anemia, neutropenia.

Drug Interactions

Does not inhibit or induce and is not a substrate for CYP isoenzymes.

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely with drugs metabolized by CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A.

Drugs Affecting or Affected by P-glycoprotein Transport

Not an inhibitor or substrate of the P-glycoprotein transport system; pharmacokinetic interactions unlikely.

Specific Drugs

Anidulafungin Pharmacokinetics

Absorption

Plasma Concentrations

Linear relationship between dose and peak plasma concentration and AUC.

Steady state achieved on the first day after an IV loading dose.

Distribution

Extent

Crosses placenta in rats and detected in rat fetal plasma; not known whether crosses placenta in humans.

Distributed into milk of lactating rats; not known whether distributed into human milk.

Plasma Protein Binding

>99%.

Elimination

Metabolism

Slow chemical degradation at physiologic temperature and pH; metabolite exhibits no antifungal activity.

Elimination Route

Eliminated principally in feces via the biliary tract. Following a single IV dose, 30% recovered in feces over 9 days (<10% as unchanged drug); <1% excreted in urine.

Half-life

Distribution half-life is 0.5–1 hour; terminal elimination half-life is 27–52 hours.

Special Populations

Geriatric adults: Median clearance in adults ≥65 years of age slightly less than that in younger adults; dosage adjustments not required.

Hepatic impairment: Not metabolized in the liver; concentrations not increased in adults with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, or C).

Renal impairment or end-stage renal disease: Negligible renal clearance; pharmacokinetics not affected by mild, moderate, or severe renal impairment.

Not removed by hemodialysis.

Stability

Storage

Parenteral

Powder for IV Infusion

2–8°C; may be exposed to temperatures up to 25°C for 96 hours and then returned to 2–8°C. Do not freeze.

Following reconstitution with sterile water for injection, may be stored at temperatures up to 25°C for ≤24 hours.

Following further dilution in 5% dextrose injection or 0.9% sodium chloride injection to a concentration of 0.77 mg/mL, may be stored at temperatures up to 25°C for ≤48 hours or, alternatively, may be stored frozen for at least 72 hours.

Compatibility

Parenteral

Solution Compatibility1

Drug CompatibilityHID

Actions and Spectrum

• Semisynthetic echinocandin antifungal; lipopeptide synthesized from a fermentation product of Aspergillus nidulans.

• Echinocandins (e.g., anidulafungin, caspofungin, micafungin) differ structurally and pharmacologically from other available antifungals.

• Inhibits synthesis of β-d-glucan, an essential component of fungal cell walls that is not present in mammalian cells.

• May be fungistatic or fungicidal in action.

• Active in vitro against Candida, including C. albicans, C. dubliniensis, C. glabrata, C. guilliermondii, C. keyfri, C. krusei, C. lusitaniae, C. metapsilosis, C. orthopsilosis, C. parapsilosis, and C. tropicalis.

• Clinical isolates of C. auris (often misidentified as C. haemulonii, C. famata, or Rhodotorula glutinis) generally inhibited in vitro by anidulafungin concentrations of 0.125–1 mcg/mL.

• Active against some strains of fluconazole-resistant C. albicans, C. glabrata, and C. krusei.

• Active in vitro against Aspergillus, including A. fumigatus, A. flavus, A. niger, and A. terreus.

• Like other echinocandins, not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes.

• Although clinical importance unclear, Candida (e.g., C. glabrata) with reduced susceptibility to echinocandins reported. Some clinical isolates of C. auris have reduced susceptibility or resistance to anidulafungin in vitro (i.e., MICs ≥4 mcg/mL).

• Resistance to echinocandins usually due to point mutations within the genes (FKS1 and FKS2) encoding for subunits in the glucan synthase enzyme complex.

• Potential for development of resistance or for cross-resistance with other echinocandins (caspofungin, micafungin) not known. Active against some strains of C. glabrata resistant to caspofungin and C. parapsilosis resistant to caspofungin and micafungin.

Advice to Patients

• Inform patients about risk of developing abnormal liver function tests and/or hepatic dysfunction and that liver function tests may be monitored during anidulafungin treatment.

• Inform patients that anaphylactic reactions, including shock, reported in patients receiving anidulafungin. Advise patients that the drug may be discontinued and appropriate treatment administered if such reactions occur.

• Inform patients that infusion-related adverse reactions, possibly histamine mediated, may occur; importance of reporting symptoms (e.g., rash, urticaria, flushing, pruritus, dyspnea, hypotension) to their clinician.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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