What are the side effects of caspofungin?

Side Effects of Caspofungin

Caspofungin is generally well-tolerated with minimal adverse effects, primarily consisting of increased liver aminotransferase levels, gastrointestinal upset, headaches, fever, and infusion-related reactions. 1

Common Adverse Effects

The most frequently reported side effects in clinical practice include:

• Hepatic effects: Elevated liver transaminase levels (AST/ALT) are among the most common laboratory abnormalities, though typically mild and reversible 1, 2
• Gastrointestinal symptoms: Nausea, vomiting, and diarrhea occur commonly, with diarrhea reported in 14% of pediatric patients 1, 2
• Fever and pyrexia: Reported in 29% of pediatric patients and commonly in adults 2
• Headache: Frequently reported across clinical trials 1, 3
• Infusion-related reactions: Including phlebitis at the infusion site 3, 4

Histamine-Mediated Reactions

Possible histamine-related adverse reactions have been documented, though they are rare and typically related to infusion rates faster than recommended:

• Cutaneous manifestations: Rash (12% in pediatric patients), pruritus, facial swelling 1, 2
• Angioedema and sensation of warmth 2
• Bronchospasm (rare) 2
• These reactions emphasize the importance of administering caspofungin slowly over approximately 1 hour 1

Serious Hypersensitivity Reactions

Anaphylaxis and severe hypersensitivity reactions have been reported and require immediate discontinuation:

• Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some with fatal outcomes, have been documented 2
• Caspofungin is contraindicated in patients with known hypersensitivity to any component 2
• Discontinue immediately at the first sign or symptom of hypersensitivity and administer appropriate treatment 2

Hepatobiliary Adverse Effects

Laboratory abnormalities in liver function tests warrant close monitoring:

• Isolated cases of clinically significant hepatic dysfunction, hepatitis, and hepatic failure have been reported in patients with serious underlying conditions receiving multiple concomitant medications, though a causal relationship has not been definitively established 2
• Monitor patients who develop abnormal liver function tests for evidence of worsening hepatic function 2
• In liver transplant recipients, Grade IV liver enzyme elevations occurred in 27.7% of patients 5

Special Concern with Cyclosporine

Elevated liver enzymes occur more frequently when caspofungin is used concomitantly with cyclosporine:

• Cyclosporine increases caspofungin AUC by approximately 35% and can cause transient hepatic aminotransferase elevations 1, 5
• Use this combination only when potential benefit outweighs risk 5, 2
• Close monitoring of liver enzymes is mandatory during concomitant therapy 2

Electrolyte Abnormalities

Hypokalemia is a notable adverse effect, particularly in pediatric populations:

• Decreased blood potassium was reported in 15% of pediatric patients 2
• In a retrospective evaluation of 25 immunocompromised children, hypokalemia occurred in 3 patients (12%) as a possible drug-related adverse event 6
• Potassium levels should be monitored and corrected during treatment 7

Other electrolyte disturbances reported include:

• Elevated bilirubin (in 2 of 3 affected pediatric patients with adverse events) 6
• Decreased hemoglobin 6

Cardiovascular Effects

• Hypotension: Reported in 11% of pediatric patients 2
• Chills: Occurred in 11% of pediatric patients 2

Renal Effects

Unlike amphotericin B, caspofungin has minimal nephrotoxicity:

• Drug-related nephrotoxicity is rare in clinical studies 8
• No dose adjustment is required for renal impairment, including acute kidney injury, as caspofungin does not accumulate in renal impairment 1, 2
• Caspofungin is not dialyzable, so supplementary dosing is not required following hemodialysis 2

Comparative Safety Profile

Caspofungin demonstrates superior tolerability compared to amphotericin B:

• In a study of 128 patients, fewer caspofungin recipients (1.4%) had elevated serum creatinine levels compared to amphotericin B recipients (15%) 9
• Discontinuation due to adverse effects occurred in 4% of caspofungin patients versus 22% of amphotericin B patients 9
• Caspofungin was better tolerated than amphotericin B deoxycholate with fewer clinical and laboratory drug-related adverse events 6

Drug Interactions Affecting Adverse Event Profile

Caspofungin has minimal CYP450-mediated drug interactions, reducing the risk of interaction-related adverse effects:

• Caspofungin reduces tacrolimus AUC by approximately 20%, requiring monitoring of tacrolimus levels 1, 5
• Enzyme inducers (efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone, carbamazepine) may reduce caspofungin concentrations, potentially requiring dose escalation to 70 mg daily 1, 5

Pediatric-Specific Considerations

In pediatric patients (3 months to 17 years), the adverse event profile is similar to adults:

• Most common adverse reactions: pyrexia (29%), decreased blood potassium (15%), diarrhea (14%), increased AST (12%), rash (12%), increased ALT (11%), hypotension (11%), and chills (11%) 2
• Postmarketing hepatobiliary adverse reactions have been reported in pediatric patients with serious underlying medical conditions 2
• The drug was well-tolerated in a retrospective evaluation of 25 immunocompromised children, with only 3 patients experiencing adverse events possibly related to the drug 6

Clinical Monitoring Recommendations

Based on the adverse effect profile, the following monitoring is essential:

• Liver function tests should be monitored throughout therapy, particularly in patients with baseline hepatic abnormalities or those receiving cyclosporine 2
• Electrolytes, especially potassium, should be checked regularly 7, 2
• Infusion should be administered slowly over approximately 1 hour to minimize histamine-related reactions 1
• Patients should be observed for signs of hypersensitivity, with immediate discontinuation if symptoms develop 2