Echinocandins are a group of fungicidal agents that target the fungal cell wall. Echinocandins inhibit β-glucan synthase, which in turn inhibits the production of β-glucan, a key structural component of fungal cell walls. The 3 primary drugs in this class include caspofungin, micafungin, and anidulafungin. Echinocandins are mainly used to treat Candida and Aspergillus infections in individuals who are critically ill or have neutropenia. Although echinocandins have a narrower spectrum of activity than some other antifungal classes, they are clinically useful because of their relatively low toxicity profiles and significantly fewer drug interactions than the azoles and amphotericin B. Resistance to echinocandins is generally uncommon, but is emerging in some strains of C. glabrata, usually through mutations that reduce the affinity of this drug to β-glucan synthase.

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Echinocandins are a group of antifungal agents that target the fungal cell wall and are typically used to treat invasive candidiasis in individuals with neutropenia or those who are critically ill.

  • 3 drugs from this class are currently used clinically:
    • Caspofungin
    • Micafungin
    • Anidulafungin
  • Key benefits of echinocandins over other antifungal drug classes (e.g., azoles and amphotericin B):
    • Low potential for renal or hepatic toxicity
    • Few serious drug-drug interactions

Chemistry and Pharmacodynamics

Chemical structure

  • Large cyclic peptides
  • The large ring is linked to a long fatty-acid chain that acts as an anchor, holding the drug in place in the fungal cell membrane.
  • Large molecules → poor penetration into the CSF and eye, and low dissolution in the urine

Mechanism of action

Echinocandins exert their effects by inhibiting fungal cell wall production by interfering with the synthesis of β-glucan, an important structural enzyme.

  • Fungal cell wall is composed of 3 primary layers (in order from outside to inside):
    • Proteins
    • β-Glucans:
      • Form essential crosslinks between the proteins above and chitin below
      • Constitute approximately 30%‒60% of the cell wall mass in Candida spp.
    • Chitin
  • Echinocandins inhibit β-glucan synthase, which is the enzyme that synthesizes β-glucan. Inhibition of this enzyme results in:
    • Impairing the ability of the fungus to create and/or maintain its cell wall
    • Significant ↑ in the susceptibility of the fungal cell to osmotic forces → fungicidal effect
  • Genetics:
    • Key subunits of β-glucan synthase are encoded in the FKS1 and FKS2 genes.
    • Mutations in these genes can lead to resistance to echinocandins.
  • β-glucan and β-glucan synthase are not found in human cells → significantly less toxicity than some other antifungal agents (e.g., amphotericin B)
  • Echinocandin activity complements the antifungal effects of other drug classes → suitability in combination therapy
Antifungal agents and mechanisms of action

Antifungal agents and mechanisms of action

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Common characteristics

Characteristics common to all 3 drugs in this class:

  • Poor oral absorption → IV formulations only
  • High levels of protein binding
  • Poor penetration into:
    • Eyes
    • CNS
  • Neither significantly metabolized by, nor are inducer/inhibitors of cytochrome P450 (CYP450)
  • Do not require dosing adjustments in renal or hepatic impairment
  • Nondialyzable


Caspofungin exhibits complicated, triphasic, nonlinear pharmacokinetics.

  • Absorption and distribution:
    • Significant tissue distribution leads to an initial rapid decline in plasma levels.
    • Next, there is a re-release of the drug from the extravascular tissue.
    • Highly protein bound
  • Metabolism:
    • Slow but extensive hepatic metabolism (somewhat faster in younger individuals)
    • Interferes with cyclosporine metabolism
  • Excretion:
    • Half-life:
      • Distribution: approximately 10 hours
      • Terminal: 40‒50 hours
    • Urine (40%), primarily as metabolites
    • Feces (35%), primarily as metabolites
  • Clinical relevance of caspofungin pharmacokinetics: requires a loading dose followed by lower once-daily dosing


Micafungin exhibits more predictable, linear pharmacokinetics.

  • Metabolism:
    • Slow but extensive hepatic metabolism (somewhat faster in younger individuals)
    • Undergoes minor hydroxylation by CYP3A
    • Interferes with sirolimus metabolism
  • Excretion:
    • Half-life: 11‒21 hours
    • Primarily fecal (71%)


Anidulafungin exhibits more predictable, linear pharmacokinetics.

  • Metabolism:
    • No hepatic metabolism
    • Undergoes slow chemical hydrolysis
  • Excretion:
    • Half-life: 40‒50 hours
    • Fecal (30%)


Echinocandins are generally interchangeable with regard to their activity and indications.

Spectrum of activity

  • Active against:
    • Candida spp., including some fluconazole-resistant strains of C. glabrata and C. krusei
    • Aspergillus spp.
  • Some activity against endemic mycoses (though generally not adequate to be effective treatment agents):
    • Blastomycosis
    • Histoplasmosis
    • Coccidioidomycosis
  • No significant activity against:
    • Cryptococcus spp.
    • Zygomycosis
    • Mucormycosis

Clinical uses

Echinocandins are most commonly used in individuals with neutropenia or Candida infections.

  • Candidiasis:
    • Esophageal
    • Refractory oropharyngeal disease
    • Candida biofilms
    • Candidemia and disseminated disease
    • Intraabdominal abscess, peritonitis, and pleural-space infections
  • Fungal prophylaxis in individuals with neutropenia and cancer
  • Febrile neutropenia (empiric therapy, generally preferred over amphotericin B)
  • Salvage therapy in invasive aspergillosis

Adverse Events and Contraindications

Adverse effects

Echinocandins are generally very well tolerated and have low toxicity compared with other antifungal agents. Adverse effects, if seen, may include:

  • Fever
  • Minor GI side effects: nausea, vomiting, and/or diarrhea
  • Reaction/phlebitis at the infusion site
  • Infusion reactions (generally with rapid infusion):
    • Bronchospasm and dyspnea
    • Flushing
    • Hypotension
    • Urticaria, pruritus, and/or rash
  • Hypokalemia
  • Anemia
  • Hepatotoxicity (rare):
    • ↑ In transaminases
    • Hepatic dysfunction (extremely rare): hepatitis and/or hepatic failure


  • Hypersensitivity to echinocandins
  • Suspected hereditary fructose intolerance (as anidulafungin formulations contain fructose)


  • Resistance in most Candida spp. is rare, but possible.
  • Exception is with C. glabrata:
    • ↑ Resistance in some strains that are also resistant to fluconazole and voriconazole
    • Resistance may be as high as 12%.
  • Primary mechanism of resistance is a mutation in the FKS gene → ↓ affinity of echinocandins to their target, β-glucan synthase

Comparison of Antifungal Medications

Table: Comparison of antifungal medications
Drug class (examples)Mechanism of actionClinical relevance
Azoles (Fluconazole, Voriconazole)Inhibits the production of ergosterol (a critical component of the fungal cell membrane) by blocking the lanosterol 14-α-demethylase enzyme
  • Widely used antifungals with a relatively broad spectrum of activity
  • Many drug-to-drug interactions due to effects on the CYP450 system
  • Hepatotoxicity
  • Overall less toxic than amphotericin B
Polyenes (Amphotericin B, Nystatin)Binds to ergosterol in the fungal cell membrane creating artificial pores in the membrane → results in leakage of cellular components and leads to cell lysis (death)Amphotericin B:
  • Reserved for life-threatening fungal infections
  • Broad spectrum of activity
  • Relatively ↑ toxicity (especially nephrotoxicity)
  • Overall less toxic than amphotericin B

  • Topical use only: skin, mucous membranes, GI lumen
Echinocandins (Caspofungin, Micafungin, Anidulafungin)Inhibits β-glucan synthase (the enzyme synthesizing β-glucan and an important structural component of the fungal cell wall) → weakened cell wall → cell lysis
  • Treats Candida and Aspergillus infections in critically ill and neutropenic patients
  • Minimal toxicity
  • Minimal drug-to-drug interactions
  • Binds to the keratin in newly forming skin, making the human cells resistant to invasion → over time the new, uninfected hair/skin/nail structures replace the old, infected structures
  • Inhibits the assembly of microtubules in dermatophytes → inhibits fungal cell replication
  • Treats dermatophyte infections of the hair, skin, and nails
  • Oral medication only (not topically active)
  • Affects the CYP450 system (more drug-to-drug interactions)
  • Largely replaced by newer agents (e.g., terbinafine)
TerbinafineInhibits the squalene epoxidase enzyme → blocks the production of squalene epoxide, which is a precursor to ergosterol and a critical component of the cell membrane
  • Treats dermatophyte infections of the hair, skin, and nails
  • Agent of choice for onychomycosis
  • Relatively low toxicity
FlucytosineA pyrimidine analog with metabolites:
  • Competing with uracil and disrupting RNA synthesis
  • Irreversibly inhibiting thymidylate synthase → fungus is unable to synthesize or correct DNA
  • Always used in combination with other agents due to:
    • Positive synergistic effects
    • ↑ Resistance with monotherapy
  • Major indications:
    • Cryptococcal meningitis
    • Chromoblastomycosis
  • Toxicity: myelosuppression


  1. Sheppard, D., Lampiris, H.W. (2012). Antifungal Agents. In Katzung, B.G., Masters, S.B., Trevor, A.J. (Eds.), Basic and Clinical Pharmacology (12th Ed., pp. 855).
  2. Lewis, R.E. (2020). Pharmacology of echinocandins. In Bogorodskaya, M (Ed.), UpToDate. Retrieved July 22, 2021, from 
  3. Nivoix, Y., Ledoux, M., Herbrecht, R. (2020). Antifungal therapy: New and evolving therapies. Semin Respir Crit Care Med. 2020; 41, 158-174. Retrieved July 22, 2021, from 
  4. Fotsing, L.D. (2021). Caspofungin. StatPearls. Retrieved July 22, 2021, from 
  5. Lexicomp Drug Information Sheets (2021). In UpToDate. Retrieved July 22, 2021, from:
    1. Caspofungin, 
    2. Micafungin, 
    3. Anidulafungin,

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