In the prospective invasive aspergillosis and compassionate use studies, there were 4 adult patients treated with CANCIDAS (50 mg/day) and cyclosporine for 2 to 56 days. None of these patients experienced increases in hepatic enzymes.

Given the limitations of these data, CANCIDAS and cyclosporine should only be used concomitantly in those patients for whom the potential benefit outweighs the potential risk. Patients who develop abnormal liver function tests during concomitant therapy should be monitored and the risk/benefit of continuing therapy should be eva luated.
5.2 Hepatic Effects
Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with CANCIDAS. In some patients with serious underlying conditions who were receiving multiple concomitant medications with CANCIDAS, isolated cases of clinically significant hepatic dysfunction, hepatitis, and hepatic failure have been reported; a causal relationship to CANCIDAS has not been established. Patients who develop abnormal liver function tests during CANCIDAS therapy should be monitored for evidence of worsening hepatic function and eva luated for risk/benefit of continuing CANCIDAS therapy.
5.3 Duration and Dose of CANCIDAS
The efficacy of a 70-mg dose regimen in adult patients with invasive aspergillosis who are not clinically responding to the 50-mg daily dose is not known. Limited safety data suggest that an increase in dose to 70 mg daily is well tolerated. The safety and efficacy of doses above 70 mg have not been adequately studied in adult patients with Candida infections. However, CANCIDAS was generally well tolerated at a dose of 100 mg once daily for 21 days when administered to 15 adult healthy subjects.

The safety information on treatment durations longer than 4 weeks is limited in adult and pediatric patients; however, available data suggest that CANCIDAS continues to be well tolerated with longer courses of therapy (up to 162 days in adults and up to 87 days in pediatric patients).
6. ADVERSE REACTIONS
Possible histamine-mediated symptoms have been reported including reports of rash, facial swelling, pruritus, sensation of warmth, or bronchospasm. Anaphylaxis has been reported during administration of CANCIDAS.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of CANCIDAS cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does provide a basis for identifying adverse reactions that appear to be related to drug use and for approximating rates.

6.1 Clinical Trials Experience in Adults
The overall safety of caspofungin was assessed in 1661 adult individuals who received single or multiple doses of caspofungin acetate: 564 febrile, neutropenic patients (empirical therapy study); 178 patients with candidemia and/or intra-abdominal abscesses, peritonitis, or pleural space infections (including 4 patients with chronic disseminated candidiasis); 297 patients with esophageal and/or oropharyngeal candidiasis; 228 patients with invasive aspergillosis; and 394 individuals in phase I studies. In the empirical therapy study patients had undergone hematopoietic stem-cell transplantation or chemotherapy. In the studies in