Usage
Caspofungin is prescribed for the treatment of invasive candidiasis (including candidemia), invasive aspergillosis in patients refractory to or intolerant of other antifungal therapies (amphotericin B, lipid formulations of amphotericin B, and/or itraconazole), and empirical therapy for presumed fungal infections (like Candida or Aspergillus) in febrile neutropenic patients. It is classified as an antifungal agent, specifically an echinocandin.
Caspofungin non-competitively inhibits the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall. This leads to cell wall disruption and fungal cell death.
Alternate Names
While Caspofungin acetate is the generic name, it is commonly marketed under the brand name Cancidas.
How It Works
Pharmacodynamics: Caspofungin exerts its antifungal effect by disrupting fungal cell wall integrity. The weakened cell wall becomes susceptible to osmotic stress, ultimately leading to fungal cell lysis and death.
Pharmacokinetics:
- Absorption: Caspofungin is administered intravenously and exhibits concentration-independent, linear pharmacokinetics. Distribution occurs rapidly, with a distribution half-life of 9-11 hours.
- Metabolism: Caspofungin undergoes slow peptide hydrolysis and N-acetylation. It does not appear to involve cytochrome P450 enzyme activity.
- Elimination: Caspofungin is primarily eliminated via hepatic metabolism, with a terminal half-life of 40-50 hours. A small amount is excreted unchanged in the urine.
Mode of Action: Caspofungin selectively targets the enzyme 1,3-β-D-glucan synthase, which is responsible for synthesizing 1,3-β-D-glucan, a key component of the fungal cell wall. It inhibits this enzyme non-competitively.
Elimination Pathways: Primarily hepatic metabolism with minimal renal excretion.
Dosage
Standard Dosage
Adults:
- Loading dose: 70 mg IV infused over 1 hour on Day 1.
- Maintenance dose: 50 mg IV infused over 1 hour once daily. For patients weighing over 80 kg, or if there is an inadequate response, the maintenance dose can be increased to 70 mg IV once daily.
Children (12 months to 17 years):
- Loading dose: 70 mg/m² IV infused over 1 hour on Day 1 (not to exceed 70 mg total dose).
- Maintenance dose: 50 mg/m² IV infused over 1 hour once daily (not to exceed 70 mg total dose). If tolerated but clinical response is inadequate, increase to 70 mg/m² IV once daily (not to exceed 70 mg total dose).
- Children <3 months: Safety and efficacy not established. Consider amphotericin B deoxycholate as the initial treatment of choice when clinically feasible.
- Children 3 to 11 months and infants <2 months: In rare cases when CNS involvement has been excluded, use caspofungin or micafungin with caution. Amphotericin B deoxycholate is generally recommended.
Special Cases:
- Elderly Patients: No specific dose adjustments are needed, though clinical monitoring is advised due to potential age-related physiological changes in organ function.
- Patients with Renal Impairment: No dose adjustment is required.
- Patients with Hepatic Dysfunction:
- Mild Impairment (Child-Pugh score 5-6): No dose adjustment.
- Moderate Impairment (Child-Pugh score 7-9): 35 mg IV once daily after the initial 70 mg loading dose.
- Severe Impairment (Child-Pugh score >9): Not recommended. Limited clinical data and experience.
- Patients with Comorbid Conditions: Consider the specific comorbidity and its impact on drug metabolism and clearance when adjusting dosage.
Clinical Use Cases
Dosing for invasive candidiasis, invasive aspergillosis in refractory patients, and empirical therapy in febrile neutropenia follows the standard dosage guidelines. Caspofungin isn’t indicated for specific use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations independently. Instead, it is used in these settings as part of a broader treatment strategy for confirmed or suspected fungal infections.
Dosage Adjustments
For patients receiving concomitant inducers of hepatic CYP enzymes (e.g., rifampin, nevirapine, efavirenz, carbamazepine, dexamethasone, phenytoin), an increased daily dose of caspofungin to 70 mg (after a 70 mg loading dose in adults) should be considered. For children on these medications, consider 70 mg/m² daily (not exceeding 70 mg total).
Side Effects
Common Side Effects:
Phlebitis, fever, chills, rash, nausea, vomiting, diarrhea, headache, elevated liver enzymes (AST, ALT), hypokalemia.
Rare but Serious Side Effects:
Hepatotoxicity (including hepatic failure), anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, bronchospasm, histamine-mediated reactions.
Long-Term Effects:
Potential for chronic liver disease with prolonged use.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe hepatotoxicity, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Contraindications
Hypersensitivity to caspofungin or any component of the formulation.
Drug Interactions
Concomitant use of caspofungin with cyclosporine can increase the risk of hepatotoxicity, so this combination should be avoided unless the potential benefit clearly outweighs the risk. Inducers of drug clearance (rifampin, efavirenz, nevirapine, phenytoin, dexamethasone, carbamazepine) can reduce caspofungin levels. Caspofungin has interactions with tacrolimus, azathioprine and other drugs that are metabolised by or induce CYP450 enzymes. Always check for potential interactions with concomitant medications before starting treatment.
Pregnancy and Breastfeeding
Pregnancy: Limited human data is available. Animal studies suggest potential embryo-fetal toxicity. Use only if the potential benefit outweighs the potential risk to the fetus.
Breastfeeding: It is unknown whether caspofungin is excreted in human milk. However, given its high protein binding and low oral bioavailability, significant exposure to a breastfed infant is unlikely. A decision to continue or discontinue breastfeeding should be made in consultation with the patient, weighing the risks and benefits.
Drug Profile Summary
- Mechanism of Action: Inhibits 1,3-β-D-glucan synthase, disrupting fungal cell wall synthesis.
- Side Effects: Phlebitis, fever, rash, nausea, vomiting, diarrhea, headache, elevated liver enzymes, hypokalemia. Serious side effects include hepatotoxicity and anaphylaxis.
- Contraindications: Hypersensitivity to caspofungin.
- Drug Interactions: Cyclosporine, inducers of drug clearance (rifampin, etc.), tacrolimus, azathioprine, and others.
- Pregnancy & Breastfeeding: Limited human data; potential fetal risk; unknown if excreted in breast milk. Exercise caution.
- Dosage: Adults: 70 mg loading dose followed by 50 mg daily (or 70 mg daily for patients >80 kg or inadequate response); Children: 70 mg/m² loading dose followed by 50 mg/m² daily (not exceeding 70 mg/dose), with potential dose increases depending on response and concomitant medications. Special adjustments for moderate hepatic impairment.
- Monitoring Parameters: Liver function tests (AST, ALT), potassium levels, complete blood count (CBC), and signs/symptoms of hypersensitivity.
Popular Combinations
Caspofungin is often used in combination with other antifungal agents for difficult-to-treat infections or in cases of antifungal resistance. However, due to its mechanism of action and limited CYP450 interaction profile, it generally does not have synergistic effects when combined with other antifungal drug classes.
Precautions
- General Precautions: Monitor liver function, potassium levels, and CBC. Observe for hypersensitivity reactions.
- Specific Populations: Use with caution in pregnant or breastfeeding patients, children, and patients with hepatic impairment. In the elderly, dose adjustments are not necessary.
- Lifestyle Considerations: No specific lifestyle considerations.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Caspofungin?
A: Adults: 70 mg IV loading dose, then 50 mg IV daily (70 mg daily in patients >80 kg or with inadequate response). Children (12 months - 17 years): 70 mg/m² loading dose, then 50 mg/m² daily, adjusting according to clinical response and concomitant medications. Dosage modification is needed for patients with moderate hepatic impairment.
Q2: How is Caspofungin administered?
A: Administer via slow intravenous infusion over approximately 1 hour. Do not administer as an IV bolus.
Q3: What is the mechanism of action of Caspofungin?
A: Caspofungin non-competitively inhibits 1,3-β-D-glucan synthase, an enzyme crucial for fungal cell wall synthesis.
Q4: What are the most common side effects of Caspofungin?
A: Phlebitis, fever, chills, rash, nausea, vomiting, diarrhea, headache, and elevated liver enzymes.
Q5: Is Caspofungin safe to use during pregnancy?
A: Limited human data is available. Animal studies suggest potential risk. Use only if the benefit clearly outweighs the risk.
Q6: Can Caspofungin be used in patients with renal impairment?
A: Yes, no dose adjustment is needed for renal impairment.
Q7: What are the key drug interactions to be aware of with Caspofungin?
A: Concomitant use with cyclosporine can increase hepatotoxicity risk. Inducers of drug clearance (rifampin, etc.) can decrease caspofungin levels. Monitor drug interaction information for drugs such as tacrolimus, azathioprine.
Q8: What should be monitored in patients receiving Caspofungin?
A: Liver function tests, potassium levels, complete blood count, and signs/symptoms of hypersensitivity.
Q9: Can Caspofungin be used in children?
A: Yes, for children aged 12 months to 17 years, the dosage is weight-based (mg/m²), not to exceed a maximum dose of 70mg. Safety and efficacy haven’t been established in neonates and infants under 3 months. Extreme caution must be exercised if administered to infants between 3 to 11 months and infants <2 months.
Q10: How should Caspofungin be reconstituted and diluted?
A: Reconstitute with sterile water or sodium chloride, then dilute in sodium chloride for infusion. Do not use diluents containing dextrose. Consult the full prescribing information for specific instructions on reconstitution and dilution.
