Gastrointestinal disorders: pancreatitis
Hepatobiliary disorders: hepatic necrosis
Skin and subcutaneous tissue disorders: erythema multiforme, Stevens-Johnson, skin exfoliation
Renal and urinary disorders: clinically significant renal dysfunction
General disorders and administration site conditions: swelling and peripheral edema

7. DRUG INTERACTIONS
[See Clinical Pharmacology (12.3).]

In clinical studies, caspofungin did not induce the CYP3A4 metabolism of other drugs. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes.

Clinical studies in adult healthy volunteers show that the pharmacokinetics of CANCIDAS are not altered by itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus. CANCIDAS has no effect on the pharmacokinetics of itraconazole, amphotericin B, or the active metabolite of mycophenolate.

Tacrolimus: For patients receiving CANCIDAS and tacrolimus, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended.

Cyclosporine: In two adult 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 CANCIDAS and cyclosporine were co-administered [see Warnings and Precautions (5.1) and Adverse Reactions, Concomitant Therapy (6.1)].

Rifampin: Adult patients on rifampin should receive 70 mg of CANCIDAS daily.

Other inducers of drug clearance:

Adults: When CANCIDAS is co-administered to adult patients with inducers of drug clearance, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, use of a daily dose of 70 mg of CANCIDAS should be considered.

Pediatric Patients: When CANCIDAS is co-administered to pediatric patients with inducers of drug clearance, such as rifampin, efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a CANCIDAS dose of 70 mg/m2 daily (not to exceed an actual daily dose of 70 mg) should be considered.
8. USE IN SPECIFIC POPULATIONS

8.1 Pregnancy
Pregnancy Category C

There are no adequate and well-controlled studies with the use of CANCIDAS in pregnant women. In animal studies, caspofungin caused embryofetal toxicity, including increased resorptions, increased peri-implantation loss, and incomplete ossification at multiple fetal sites. CANCIDAS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In offspring born to pregnant rats treated with caspofungin at doses comparable to the human dose based on body surface area comparisons, there was incomplete ossification of the skull and torso and increased incidences of cervical rib. There was also an increase in resorptions and peri-implantation losses. In pregnant rabbits treated with caspofungin at doses comparable to 2 times the human dose based on body surface area comparisons, there was an increased incidence of incomplete ossification of the talus/calcaneus in offspring and increases in fetal resorptions. Caspofungin crossed the p