Caspofungin Acetate

(BANM, USAN, rINNM)
Caspofungin Acetate Chemical formula
Synonyms: Acetato de caspofungina; Caspofungine, Acétate de; Caspofungini Acetas; Kaspofungiiniasetaatti; Kaspofunginacetat; L-743873; MK-0991. (4R,5S)-5-[(2-Aminoethyl)amino]N 2 -(10,12-dimethyltetradecanoyl)-4-hydroxyhydroxydiacetate.
Cyrillic synonym: Каспофунгина Ацетат.

💊 Chemical information

Chemical formula: C52H88N10O15,2C2H4O2 = 1213.4.
CAS — 179463-17-3.
ATC — J02AX04.
ATC Vet — QJ02AX04.

💊 Adverse Effects and Precautions

Adverse experiences reported with caspofungin have included anaemia, diarrhoea, nausea and vomiting, flushing, headache, fever, tachycardia, and venous complications around the infusion site. Possible histamine-mediated symptoms have been rash, facial swelling, pruritus, sensation of warmth, or bronchospasm. Anaphylaxis has occurred. Isolated cases of hepatotoxicity have occurred and patients who develop abnormal liver function tests should be monitored for deterioration in hepatic function. Caspofungin may need to be given in reduced doses to patients with hepatic impairment (see below).

Breast feeding.

Caspofungin is excreted in the breast milk of lactating animals, but the risk to breast-fed infants is suggested to be low. Recommendations in licensed product information vary: in the UK it recommends against use in women who are breast feeding, while in the USA caution is advised.

Pregnancy.

Caspofungin has been shown to cross the placenta in animal studies and was shown to be embryotoxic in rats and rabbits; it was noted that there were no adequate and well-controlled studies in human pregnancy. Caspofungin is generally only recommended in pregnancy if the benefits to the mother are considered to outweigh the risks to the fetus.

💊 Interactions

Although caspofungin is not metabolised by the hepatic cytochrome P450 system, drugs that induce hepatic enzymes may increase its clearance. Such effects have been noted with carbamazepine, dexamethasone, efavirenz, nevirapine, phenytoin, and rifampicin, and an increase in the dose of caspofungin should be considered in patients who are also taking these drugs and who are not clinically responding (see Uses and Administration, below). When caspofungin has been given with ciclosporin, an increase in the area under the concentration-time curve for caspofungin, as well as increases in hepatic enzymes, were observed and use of the two drugs together is not recommended. Caspofungin has resulted in decreased blood concentrations of tacrolimus and therapeutic drug monitoring and appropriate dosage adjustments to tacrolimus are recommended.

💊 Antimicrobial Action

Caspofungin inhibits the synthesis of β-1,3-D-glucan, an essential component of the cell wall of many fungi. Caspofungin exhibits in-vitro activity against many Aspergillus spp. and is fungicidal against Candida spp. including non-albicans strains.

💊 Pharmacokinetics

Plasma concentrations of caspofungin decline in a polyphasic manner after intravenous infusion. The initial short α-phase occurs immediately post-infusion and is followed by a β-phase with a half-life of 9 to 11 hours; an additional longer γ-phase also occurs with a half-life of 40 to 50 hours. Plasma clearance is dependent on distribution rather than on biotransformation or excretion. Caspofungin is highly bound to plasma protein. There is slow metabolism of caspofungin by hydrolysis and N-acetylation and excretion in faeces and urine.

💊 Uses and Administration

Caspofungin is an echinocandin antifungal used in the treatment of invasive aspergillosis in patients who are refractory to, or intolerant of, other therapy. It is also used in the treatment of invasive candidiasis and as empirical therapy for presumed fungal infections in febrile, neutropenic patients. Caspofungin is used as the acetate but doses are expressed in terms of the base; caspofungin acetate 77.7 mg is equivalent to about 70 mg of caspofungin. It is given by slow intravenous infusion over about 1 hour. A loading dose of 70 mg is given on the first day and is followed by 50 mg daily; in adult patients weighing more than 80 kg, and in patients taking hepatic-enzyme inducing drugs who fail to respond, a daily dose of 70 mg is recommended. Doses may need to be reduced in patients with hepatic impairment (see below).
1. Letscher-Bru V, Herbrecht R. Caspofungin: the first representative of a new antifungal class. J Antimicrob Chemother 2003; 51: 513–21
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7. Falagas ME, et al. Caspofungin for the treatment of fungal infections: a systematic review of randomized controlled trials. Int J Antimicrob Agents 2007; 29: 136–43
8. Hope WW, et al. The pharmacology and clinical use of caspofungin. Expert Opin Drug Metab Toxicol 2007; 3: 263–74
9. Waters L, Nelson M. The use of caspofungin in HIV-infected individuals. Expert Opin Invest Drugs 2007; 16: 899–908.

Administration in children.

Caspofungin is not licensed for use in paediatric patients, but has been prescribed.1 A retrospective study2 of 25 immunocompromised children with a median age of 9.8 years, given at least one dose of caspofungin, found that it appeared to be safe and well tolerated. Patients weighing less than 50 kg had a dose of 0.8 to 1.6 mg/kg daily, while those over 50 kg were given 50 to 75 mg daily. Another retrospective review3 of 64 immunocompromised children with a median age of 11.5 years, reported a success rate of 67.7% with caspofungin at a median daily maintenance dose of 1.07 mg/kg, either as monotherapy or with another antifungal. A case series4 of 10 neonates (9 preterm) with invasive candidiasis not responsive to amphotericin B and/or fluconazole reported that Candida spp. were cleared from the blood in all patients in a mean of 4.3 days after starting caspofungin therapy. Nine neonates were given an initial dose of 1 mg/kg daily for the first 2 days followed by 2 mg/kg daily for 15 to 21 days; the other was given a lower dose.
1. Lehrnbecher T, Groll AH. Experiences with the use of caspofungin in paediatric patients. Mycoses 2008; 51 (suppl 1): 58–64
2. Franklin JA, et al. Retrospective study of the safety of caspofungin in immunocompromised pediatric patients. Pediatr Infect Dis J 2003; 22: 747–9
3. Groll AH, et al. Treatment with caspofungin in immunocompromised paediatric patients: a multicentre survey. J Antimicrob Chemother 2006; 57: 527–35
4. Odio CM, et al. Caspofungin therapy of neonates with invasive candidiasis. Pediatr Infect Dis J 2004; 23: 1093–7.

Administration in hepatic impairment.

Patients with mild hepatic impairment do not require dosage adjustment. In patients with moderate hepatic impairment, a daily dose of caspofungin 35 mg should be used after the initial dose of 70 mg; appropriate doses for patients with severe hepatic impairment have not been established.

💊 Preparations

Proprietary Preparations

Arg.: Cancidas; Austral.: Cancidas; Belg.: Cancidas; Braz.: Cancidas; Canad.: Cancidas; Chile: Cancidas; Cz.: Cancidas; Denm.: Cancidas; Fin.: Cancidas; Fr.: Cancidas; Ger.: Cancidas; Gr.: Cancidas; Hong Kong: Cancidas; Hung.: Cancidas; Irl.: Cancidas; Israel: Cancidas; Ital.: Cancidas; Malaysia: Cancidas; Neth.: Cancidas; Norw.: Cancidas; NZ: Cancidas; Philipp.: Cancidas; Pol.: Cancidas; Port.: Cancidas; Rus.: Cancidas (Кансидас); Singapore: Cancidas; Spain: Cancidas; Swed.: Cancidas; Switz.: Cancidas; Thai.: Cancidas; Turk.: Cancidas; UK: Cancidas; USA: Cancidas; Venez.: Cancidas.
Published October 23, 2018.