Article: Caspofungin

Caspofungin is an antifungal drug, the first of a new class termed the echinocandins. It shows activity against infections with Aspergillus and Candida, and works by inhibiting cell wall synthesis. It is administered intravenously.

Indications

Currently caspofungin acetate has been approved by the FDA for the treatment of invasive aspergillosis in patients whose disease is refractory to, or who are intolerant of, other first-line antifungal agents (i.e. conventional or liposomal amphotericin B preparations and flucytosine or itraconazole). Caspofungin acetate itself has so far not been studied as first-line therapy for aspergillosis or other mycotic diseases.

Empirical therapy of presumed fungal infections in febrile, neutropenic patients has become an additional indication in 2006.

Clinical Efficacy

Thirty six (36) percent of patients refractory to other therapies responded well to caspofungin therapy, while even 70% of patients intolerant to other therapies were classified as responders. Direct comparative studies to other drugs in the treatment of invasive aspergillosis have so far not been undertaken.

Contraindications

Known hypersensitivity to caspofungin acetate or any other ingredient contained in the formulation

Warnings

• Hepatic Effects

The concomitant use of caspofungin and cyclosporine in healthy volunteers led to a more frequent increase of liver enzymes (ALT=SGPT and AST=SGOT) than noted with cyclosporine alone. Combination treatment is only indicated, if the potential benefit for the patient outweighs the potential risk.

Dosage reduction in patients with moderately impaired liver function is recommended. No clinical data exists regarding the use of caspofungin in patients with severely impaired liver function.

• Sensitivity Reactions

Reactions due to histamine release (rash, facial swelling, pruritus, sensation of warmth and one case of anaphylaxis) have been seen. Those reactions should be carefully watched for.

• Drug Resistance

In clinical studies development of resistance in Aspergillus spp., the causative fungus of aspergillosis, has so far not been seen. Likewise, experiments on the emergence of resistance with fungi-cultures and studies in animals were negative. However, the emergence of resistance cannot be excluded.

Pregnancy and Lactation

Caspofungin has been assigned to class C.

Capsofungin is found in the milk of lactating rats; it is not known, whether this effect can be seen in women, too. Lactating women should be treated cautiously.

Geriatric Patients

Ordinarily, no dose adjustments are necessary.

Pediatric Patients

There is no sufficient clinical experience to judge the safety and efficacy in patients younger than 18 years of age.

Side-Effects

Compared to amphotericin B, caspofungin seems to have a relatively low incidence of side-effects. In clinical studies and post-marketing reports the side-effects seen in 1% or more of the patients were as follows:

• Gastrointestinal system : nausea, vomiting, abdominal pain, and diarrhea
• Central nervous system : headache
• Whole body : fever, phlebitis or thrombophlebitis, complications at intravenous cannulation site (e.g. induration), unspecified pain, flu-like-syndrome, myalgia, chills, and paresthesia
• Respiratory : dyspnea
• Renal : increased plasma creatinine
• Hematological : anemia
• Electrolytes : hypokalemia
• Liver : increased liver enzymes (asymptomatic)
• Hypersensitivity : rash, facial edema, pruritus
• Others : tachycardia

Additionally, infrequent cases of symptomatic liver damage, peripheral edema and swelling, and hypercalcemia have been seen. One case of anaphylaxis (severe allergic reaction) has also been noted.

Drug interactions

• Cyclosporine : see under Hepatic Effects
• Tacrolimus : potential pharmacokinetic interactions
• Other systemic antimycotic agents : with amphotericin B, itraconazole and mycophenolate no interactions have been seen
• Inducers of drug clearance (e.g. carbamazepine, phenytoin, rifampin, dexamethason) : consider 70mg i.v. as maintenance dose instead of 50mg

Duration of Treatment

The mean duration of therapy in previous studies was 34 days. Some patients were even healed by a 1-day treatment. However, a few patients were treated for as long as 162 days and tolerated the drug well, indicating that longtime use may be indicated and tolerated favourably in complicated cases of aspergillosis. Generally, the duration of treatment is dictated by the severity of the disease, the clinical response and the improvement of immunecompetence in immunecompromised patients.

Dosage

An initial dose of 70mg by i.v.-infusion is given followed by 50mg i.v. daily. If no response is seen or if inducers of caspofungin clearance (see above) are given as comedication the daily dose may be increased to 70mg i.v. An infusion should take approximately 1 hour.

Dosage Forms

• Cancidas® 50mg for i.v.-infusion (manufacturer Merck)
• Cancidas® 70mg for i.v.-infusion (manufacturer Merck)
• Brand names in countries other than the US may vary.