CASPOFUNGIN ACETATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Caspofungin acetate is an echinocandin antifungal that inhibits the synthesis of 1,3-beta-D-glucan, an essential component of the fungal cell wall, by noncompetitively inhibiting the enzyme 1,3-beta-D-glucan synthase. This leads to osmotic instability and cell lysis, primarily against Candida and Aspergillus species.
| Metabolism | Caspofungin is slowly metabolized via hydrolysis and N-acetylation, primarily in the liver. It undergoes spontaneous chemical degradation and is not significantly metabolized by cytochrome P450 enzymes. The drug is a poor substrate for CYP3A4 and does not inhibit or induce major CYP enzymes. |
| Excretion | Primarily hepatic: slow metabolism with subsequent biliary and fecal excretion. ~35% of administered dose excreted in feces and ~41% in urine over 27 days, with <2% unchanged in urine. Minimal renal excretion as unchanged drug. |
| Half-life | Terminal elimination half-life ~9-11 hours in adults, with a prolonged terminal phase (beta half-life 40-50 hours) due to slow tissue distribution and redistribution. Clinically, dosing interval is 24 hours. |
| Protein binding | ~97% bound, primarily to albumin. |
| Volume of Distribution | Volume of distribution (Vd) at steady state approx. 0.14 L/kg (range 0.12-0.15 L/kg), reflecting limited extravascular distribution and high protein binding. |
| Bioavailability | Only available as intravenous formulation; oral bioavailability is negligible (<1%). |
| Onset of Action | Intravenous infusion: Onset of antifungal activity is immediate upon achieving therapeutic serum concentrations (within 1-2 hours after start of infusion). |
| Duration of Action | Duration of antifungal effect persists for at least 24 hours, supporting once-daily dosing. The extended terminal half-life contributes to prolonged activity against susceptible fungi. |
| Molecular Weight | 1092.3 |
Adults: 70 mg IV loading dose on day 1, then 50 mg IV once daily.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | Child-Pugh Class B: 70 mg loading dose on day 1, then 35 mg IV once daily. Child-Pugh Class C: 70 mg loading dose on day 1, then 35 mg IV once daily. |
| Pediatric use | 3 months to <18 years: 70 mg/m2 IV loading dose on day 1 (max 70 mg), then 50 mg/m2 IV once daily (max 50 mg). |
| Geriatric use | No specific dose adjustment; use with caution due to age-related hepatic, renal, or cardiac impairment. |
| 1st trimester | Limited human data; animal studies show fetal harm. Use only if potential benefit justifies risk. |
| 2nd trimester | Limited human data; animal studies show fetal harm. Use only if potential benefit justifies risk. |
| 3rd trimester | Limited human data; animal studies show fetal harm. Use only if potential benefit justifies risk. |
Clinical note
Cyclosporine increases caspofungin exposure and may cause elevated liver enzymes Not for use in hepatic impairment.
| Placental transfer | Crosses placenta in animals; human data limited. |
| Breastfeeding | Caspofungin is excreted in animal milk; not known if excreted in human milk. Caution advised due to potential for serious adverse reactions in nursing infants. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Common Effects | Fever |
| Serious Effects |
Hypersensitivity to caspofungin or any component of the formulation
| Precautions | Hypersensitivity reactions (e.g., anaphylaxis) have been reported; discontinue if severe reaction occurs., Hepatotoxicity: Elevations of liver enzymes and bilirubin; monitor liver function tests. Use with caution in patients with hepatic impairment., Infusion-related reactions (e.g., flushing, fever, phlebitis) – may require slow infusion or premedication., Concomitant use with cyclosporine increases risk of elevated liver enzymes and should be used with caution., Not recommended for use in pregnancy unless benefit outweighs risk; limited human data., Dose adjustment required in patients with moderate hepatic insufficiency (Child-Pugh score 7-9). |
| Food/Dietary |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | Caspofungin acetate is classified as pregnancy category C. Animal studies have shown fetal developmental toxicity (e.g., increased resorptions, skeletal variations) at doses below human exposures. No adequate human data exist; risk cannot be excluded. Avoid use in first trimester unless benefit outweighs risk. Use in second and third trimesters only if clearly needed. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, alkaline phosphatase, bilirubin), renal function (serum creatinine, BUN), and complete blood count with differential. Assess for hypersensitivity reactions (fever, rash, flushing, pruritus, anaphylaxis). Monitor fetal growth and development if used during pregnancy. In neonates, monitor infusion-related reactions and hepatic function. |
| Fertility Effects | No dedicated fertility studies in humans. Animal studies in rats at up to 3x human exposure showed no impairment of fertility. Theoretical concern for endocrine disruption due to echinocandin class? Not confirmed. Advise caution in patients planning pregnancy; need for contraception during therapy should be discussed. |
| Grapefruit and grapefruit juice may decrease metabolism of caspofungin; avoid concurrent use. No other known food interactions. |
| Clinical Pearls | Caspofungin is an echinocandin that inhibits β-(1,3)-D-glucan synthase; it is fungicidal against Candida spp. and fungistatic against Aspergillus spp. Dose reduction required for moderate hepatic impairment (Child-Pugh 7-9); no loading dose adjustment. Monitor LFTs during therapy. Not effective against Cryptococcus, Fusarium, or Zygomycetes. Infusion-related reactions (histamine-mediated) may occur; premedicate if needed. Drug interactions: decreases tacrolimus levels (monitor); may reduce sirolimus and nifedipine levels. Not dialyzable; no supplemental dose after hemodialysis. |
| Patient Advice | This medication is given intravenously (IV) to treat serious fungal infections. · You may experience infusion-related reactions such as flushing, rash, or itching during administration; tell your healthcare provider right away. · Avoid grapefruit and grapefruit juice while on this medication as it may affect how the drug works. · Report any signs of liver problems: yellowing of skin or eyes, dark urine, severe nausea/vomiting, or unusual bleeding/bruising. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |