Caspofungin increased

In patients who have failed initial therapy (i.e., salvage), liposomal amphotericin products, itraconazole, or the echinocandin caspofungin can be used. Itraconazole has a response rate of approximately 40%.100 Oral itraconazole exhibits erratic absorption the IV formulation is suspended in cyclodextrin, which is eliminated renally, and thus IV itraconazole should be avoided in patients with a creatinine clearance of less than 30 mL/minute (0.29 mL/s m2).103 Itraconazole also has negative inotropic cardiac effects and increases the serum concentrations of medications (e.g., cyclophosphamide, etopo-side, calcineurin inhibitors, and sirolimus). 

Concomitant medication with inducers of drug c/earance. Patients on rifampin should receive caspofungin 70 mg/day. Patients on nevirapine, efavirenz, carbamazepine, dexamethasone, or phenytoin may require an increase in dosage to caspofungin 70 mg/day. 

Caspofungin Blocks 3-glucan synthase Prevents synthesis of fungal cell wall Fungicidal Candida sp also used in aspergillosis IV only duration, 11-15 h Toxicity Minor gastrointestinal effects, flushing Interactions Increases cyclosporine levels (avoid combination)... 

Caspofungin bits good activity against Candida, and is currently being reviewed by the FDA for this indication. In two clinical studies, cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) increased the AUC of caspofungin by approximately 35%. CANCIDAS did not increase the plasma levels of cyclosporine. There were transient increases in liver ALT and AST when caspofungin and cyclosporine were coadministered. 

Cyclosporine may increase caspofungin levels and the risk of hepatotoxicity... 

Caspofungin is not absorbed orally. After intravenous injection, caspofungin is eliminated from the bloodstream with a tj of- lO hours. Catabolism is largely by hydrolysis and 14-acetylation, followed by excretion in urine and feces. Mild or moderate hepatic insufficiency increases the AUC by 55% and 76%, respectively. About 97% of serum drug is bound to albumin. Dose adjustment is unnecessary for renal insufficiency or hemodialysis. 

Caspofungin is administered intravenously once daily over 1 hour. In candidemia and salvage therapy of aspergillosis, the initial dose is 70 mg, followed by 50 mg daily. The dose may be increased to 70 mg daily in patients failing to respond. Esophageal candidiasis is treated with 50 mg daily. 

Ciclosporin appears to modestly increase caspofungin levels, and concurrent use can apparently result in raised liver enzymes. Ciclosporin slightly raised anidulafungin levels in one study, without any serious adverse events. 

Rifampicin modestly reduces the trough levels of caspofungin after 2 weeks of concurrent use, but this is not thought to be due to increased metabolism. One case of caspofungin treatment failure has been reported in a patient taking rifampicin. Other enzyme inducers (carbamazepine, dexamethasone, efavirenz, nevirapine, and phenytoin) also appeared to reduce caspofungin levels. Rifampicin and other unnamed enzyme inducers did not appear to alter anidulafungin clearance. 

The manufacturers recommend that consideration should be given to increasing the dose of caspofungin from 50 to 70 mg daily in patients taking rifampicin. - This dose has been generally well tolerated in clinical studies. . However, bear in mind the case report of possible caspofungin failure, even at this dose. The manufacturers also say that a population pharmacokinetic analysis suggested that the concurrent use of other met-... 

A cohort study investigating the incidence of thrombocytopenia in subjects receiving linezolid reported a rate of critical thrombocytopenia (<20,000 cells/nun) of 0.8%. A >50% decline in platelets was seen in 17.1% of patients. High trough concentrations were associated with an increased risk of low platelets [79 ]. This is supported somewhat by a retrospective case study which noted a rate of thrombocytopenia of (27.2%) in adult Chinese patients. Multivariate analysis noted that a daily dose of linezolid of >18.75mg/kg, a baseline platelet count of <181 x 10 /L, therapy >10 days and concomitant use of caspofungin and levofloxacin as predictors for low platelets with linezolid treatment [12H]. 

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