Caspofungin
The first echinocandin antifungal, a cyclic lipopeptide that dissolves the fungal cell wall and is first-line intravenous therapy for invasive candidiasis and candidaemia.
Also known as caspofungin acetate, echinocandin lipopeptide, Cancidas, MK-0991, L-743872
Approved drug — Licensed by a major regulator for human use, with phase-3 trial data behind it.
FDA-approved in 2001 with randomised trials showing at least equivalence to amphotericin B in invasive candidiasis and to liposomal amphotericin in empirical neutropenic therapy, with markedly better tolerability. IDSA candidiasis guidelines make echinocandins first-line initial therapy for candidaemia. The evidence base here is solid.
How it works
Caspofungin is a semisynthetic derivative of pneumocandin B0 from Glarea lozoyensis. It inhibits the FKS1-encoded catalytic subunit of 1,3-beta-D-glucan synthase, an enzyme complex with no mammalian equivalent — which is why the echinocandins are the best-tolerated systemic antifungal class. Loss of beta-1,3-glucan leaves the cell wall unable to withstand turgor pressure, producing fungicidal activity against Candida and fungistatic activity against Aspergillus, where it damages growing hyphal tips rather than killing outright. It has no activity against Cryptococcus, which lacks a significant beta-glucan wall component, nor against most Mucorales. Resistance is driven by FKS1 and FKS2 hotspot mutations, notably common in Candida glabrata and in the emerging multidrug-resistant Candida auris. It penetrates the CNS, eye and urine poorly, which limits it in those compartments.
Targets: Beta-1,3-D-glucan synthase (FKS1), Fungal cell wall
Dosing
| Protocol | Dose | Frequency | Route |
|---|---|---|---|
| Candidaemia and invasive candidiasisInfused slowly over about 1 hour. | 70 mg | once on day 1, then 50 mg once daily | intravenous |
| Empirical therapy in persistent febrile neutropeniaOnce daily infusion. | 70 mg | once on day 1, then 50 mg once daily | intravenous |
| Moderate hepatic impairment dosingOnce daily. | 35 mg | once daily after the standard 70 mg load | intravenous |
- · 70 mg loading dose on day 1, then 50 mg once daily. Patients over 80 kg stay on 70 mg daily. Treat for at least 14 days after the first negative blood culture and resolution of symptoms.
- · Same regimen. Continued until neutrophil recovery, and for at least 14 days if a fungal infection is confirmed.
- · Child-Pugh 7-9 requires the maintenance dose to drop to 35 mg daily. No adjustment for renal impairment or dialysis.
Titration
Maintenance dose increases to 70 mg daily with concomitant rifampin or other strong inducers, and drops to 35 mg daily in moderate hepatic impairment.
Cycling
Courses are dictated by the infection: at least 14 days beyond the first negative blood culture in candidaemia, longer for endocarditis, osteomyelitis or hepatosplenic disease. Step-down to oral fluconazole is standard once the isolate is known to be susceptible and the patient is stable.
Pharmacology
- Half-life
- Beta-phase half-life of roughly 9 to 11 hours, with a slower gamma phase over 40 to 50 hours; once-daily dosing.
- Onset
- Fungicidal against Candida within hours in vitro; blood cultures typically clear over 2 to 5 days in candidaemia.
- Routes
- intravenous
- Molecule
- Semi-synthetic cyclic hexapeptide lipopeptide (echinocandin)
- Sequence length
- 6 amino acids
- Molecular weight
- 1093.3 Da
Handling
- Diluent
- Sterile water for injection, then diluted in 0.9% or 0.45% sodium chloride or lactated Ringer's
- Typical mix
- 10.5 or 10.8 mL
- Vial sizes
- 50, 70 mg
- Lyophilised
- Refrigerated at 2-8°C.
- Reconstituted
- The reconstituted vial can sit at up to 25°C for 1 hour; the diluted infusion bag is stable for 24 hours at room temperature or 48 hours refrigerated.
Mixing
Each vial takes 10.8 mL of sterile water (10.5 mL of usable volume). Do not use dextrose-containing diluents — caspofungin is unstable in glucose solutions.
Side effects
- commonInfusion-related histamine reaction— Flushing, rash, facial swelling and itching if infused quickly. Slow the infusion to at least an hour.
- commonTransaminase elevation— Usually modest and reversible; more pronounced when combined with cyclosporine.
- commonFever and chills
- commonPhlebitis at the infusion site
- commonHypokalaemia
- rareAnaphylaxis— Reported during infusion; requires immediate discontinuation.
Do not use if
- Known hypersensitivity to caspofungin or other echinocandins.
- Not effective against Cryptococcus, most Mucorales or Fusarium — choosing an echinocandin for these is a treatment failure by design.
- Poor CNS, vitreous and urinary penetration make it a bad choice for fungal meningitis, endophthalmitis or urinary candidiasis.
Combining it
- cautioncyclosporine — Raises caspofungin AUC by about 35% and is associated with transient ALT and AST elevation. Use together only when the benefit is clear, with liver monitoring.
- cautionrifampin — Induces clearance enough that the maintenance dose should be increased to 70 mg daily.
- cautiontacrolimus — Caspofungin lowers tacrolimus trough concentrations by roughly 20%; tacrolimus levels need rechecking.
- redundantmicafungin — Same class, same target — there is no reason to use two echinocandins.
What to monitor
- · Liver function tests at baseline and periodically, especially with cyclosporine.
- · Serum potassium.
- · Follow-up blood cultures every 1-2 days in candidaemia until clearance is documented.
- · Dilated ophthalmological examination in candidaemia, since echinocandins penetrate the eye poorly and endophthalmitis changes the drug choice.
Legal status
Prescription-only injectable, approved in the US, EU and most markets; generic versions are available.
References
- Mora-Duarte et al. 2002, caspofungin versus amphotericin B for invasive candidiasis (trial)
- Pappas et al. 2016, IDSA clinical practice guideline for the management of candidiasis (guideline)
- Cancidas (caspofungin acetate) US prescribing information (label)
Mechanism in depth
An echinocandin: non-competitive inhibition of beta-1,3-glucan synthase, which is essential to fungal cell wall integrity and has no mammalian counterpart. That absence of a human target is why the echinocandins are among the best-tolerated systemic antifungals. Activity is fungicidal against Candida and fungistatic against Aspergillus, a distinction that drives where each is used.
What usually goes wrong
The common failures are organism-related rather than toxicity-related: echinocandins do not cover Cryptococcus, and they have poor penetration into urine, cerebrospinal fluid and the vitreous. A candidaemia complicated by endophthalmitis or meningitis needs something else. Rising echinocandin resistance in Candida glabrata and Candida auris via FKS mutations is the other emerging failure mode.
Bloodwork worth running
| Marker | When | Why it matters |
|---|---|---|
| Liver enzymes and bilirubin | Baseline and periodically. | Clearance is hepatic and the maintenance dose is reduced in moderate hepatic impairment - the only routine dose adjustment this drug needs.Act if: Child-Pugh B warrants a reduced maintenance dose. |
Pharmacokinetics
- Protein binding
- 97%
- Crosses blood-brain barrier
- no
- Elimination
- Hepatic
Receptor targets
- Beta-1,3-glucan synthase (FKS subunit) — Non-competitive
Fungal cell wall synthesis failure; no mammalian homologue
What to expect, and when
A loading dose on day one is required because of the long half-life; without it, therapeutic concentrations take several days.
Stacking and comparisons
Micafungin needs no loading dose and has fewer interactions; caspofungin requires hepatic dose adjustment and interacts with rifampicin and cyclosporine. Rezafungin is the long-acting once-weekly member of the class.
Genuinely uncertain
- Whether echinocandin dose escalation overcomes low-level FKS-mediated resistance is not established.