(approximately 28% in AUC) compared to young healthy men. A similar effect of age on pharmacokinetics was seen in patients with candidemia or other Candida infections (intra-abdominal abscesses, peritonitis, or pleural space infections). No dose adjustment is recommended for the elderly; however, greater sensitivity of some older individuals cannot be ruled out.
8.6 Patients with Hepatic Insufficiency
Adult patients with mild hepatic insufficiency (Child-Pugh score 5 to 6) do not need a dosage adjustment. For adult patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), CANCIDAS 35 mg daily is recommended based upon pharmacokinetic data [see Clinical Pharmacology (12.3)]. However, where recommended, a 70-mg loading dose should still be administered on Day 1 [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. There is no clinical experience in adult patients with severe hepatic insufficiency (Child-Pugh score >9) and in pediatric patients with any degree of hepatic insufficiency.
8.7 Patients with Renal Insufficiency
No dosage adjustment is necessary for patients with renal insufficiency. Caspofungin is not dialyzable; thus, supplementary dosing is not required following hemodialysis [see Clinical Pharmacology (12.3)].
10. OVERDOSAGE
In adult clinical studies the highest dose was 210 mg, administered as a single dose to 6 healthy subjects. This dose was generally well tolerated. In addition, 100 mg once daily for 21 days has been administered to 15 healthy subjects and was generally well tolerated. Caspofungin is not dialyzable. The minimum lethal dose of caspofungin in rats was 50 mg/kg, a dose which is equivalent to 10 times the recommended daily dose based on relative body surface area comparison.
In clinical trials, one pediatric patient (16 years of age) received a single dose of caspofungin of 113 mg (on Day 1), followed by 80 mg daily for an additional 7 days. These dosages were generally well tolerated.
11. DESCRIPTION
CANCIDAS is a sterile, lyophilized product for intravenous (IV) infusion that contains a semisynthetic lipopeptide (echinocandin) compound synthesized from a fermentation product of Glarea lozoyensis. CANCIDAS is the first of a new class of antifungal drugs (echinocandins) that inhibit the synthesis of β (1,3)-D-glucan, an integral component of the fungal cell wall.
CANCIDAS (caspofungin acetate) is 1-[(4R,5S)-5-[(2-aminoethyl)amino]-N2-(10,12-dimethyl-1-oxotetradecyl)-4-hydroxy-L-ornithine]-5-[(3R)-3-hydroxy-L-ornithine] pneumocandin B0 diacetate (salt). CANCIDAS 50 mg also contains: 39 mg sucrose, 26 mg mannitol, glacial acetic acid, and sodium hydroxide. CANCIDAS 70 mg also contains 54 mg sucrose, 36 mg mannitol, glacial acetic acid, and sodium hydroxide. Caspofungin acetate is a hygroscopic, white to off-white powder. It is freely soluble in water and methanol, and slightly soluble in ethanol. The pH of a saturated aqueous solution of caspofungin acetate is approximately 6.6. The empirical formula is C52H88N10O15•2C2H4O2 and the formula weight is 1213.42. The structural formula is:
12. CLINICAL PHARMACOLOGY
12.1 Mechanism Of Action
Caspofungin acetate, an echinocandin, is an antifungal agent [see Clinical Pharmacology (12.4)].
12.3 Pharmacokinetics
Distribution
Plasma concentrations of caspofungin decline in a polyphasic manner following single 1-hour IV infusions. A short α-phas
