Caspofungin

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Cacidas

ICU INDICATIONS:

1. Invasive or oesophageal candidiasis

Treatment of candidaemia and the following Candida infections: intra-abdominal abscesses, peritonitis and pleural space infections. Caspofungin acetate has not been studied in endocarditis, osteomyelitis, or meningitis due to Candida

2. Aspergillus infection

Caspofungin is indicated for treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e. amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). However, it has not been studied as initial therapy for invasive aspergillosis

3. Empirical therapy for presumed fungal infections in febrile, neutropaenic patients

PRESENTATION AND ADMINISTRATION:

IV:

50 mg and 70 mg vials of white powder

Refrigerate at 2-8°C. Do not freeze

Bring vial to room temperature and reconstitute by adding 10.5 mL of water for injection. Mix gently until completely dissolved producing a clear solution. Concentrations of reconstituted vials are 7 mg/mL (70 mg vial) or 5 mg/mL (50 mg vial).

Add required volume of reconstituted solution to 250 mL of compatible IV fluid and administer slowly over approximately 1 hour. A reduced volume of 100 mL may be used for 50 mg or 35mg doses only.

Reconstituted solution and diluted infusion solution are stable for 24 hours at or below 25°C

Compatible with:

Normal saline, Hartmanns

DOSAGE:

IV:

Loading dose of 70 mg followed by 50 mg once daily

See also IMPORTANT DRUG INTERACTIONS FOR THE INTENSIVE CARE UNIT as dosage adjustment is required when co-administered with particular medicines

Note: dosage adjustment is required in liver failure. Patients with mild hepatic insufficiency (Child-Pugh score 5-6) do not need a dosage adjustment. For moderate hepatic insufficiency (Child-Pugh score 7-9), caspofungin acetate 35 mg daily is recommended. However a 70-mg loading dose should still be administered on Day 1. There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score >9)

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

Dosage is base on body surface area which should be calculated using the Mosteller formula

70 mg/m² day 1, then 50 mg/m² once daily IV

Note: The safety and efficacy of Caspofungin in the paediatric population is not established

CLINICAL PHARMACOLOGY:

Caspofungin is the first of a new class of antifungal drugs (echinocandins) that inhibit the synthesis of an integral component of the fungal cell wall.

Caspofungin exhibits in vitro activity against Aspergillus species (Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus) and Candida species (Candida albicans, Candida glabrata, Candida guilliermondii, Candida krusei, Candida parapsilosis, and Candida tropicalis).

Based on available evidence from clinical studies, it appears that caspofungin is as effective as amphotericin B in empirical therapy of persistent febrile neutropaenia and in patients with invasive Candidiasis.

CONTRAINDICATIONS:

1. Hypersensitivity to caspofungin.

WARNINGS:

Concomitant use of caspofungin acetate with cyclosporin is not recommended unless the potential benefit outweighs the potential risk to the patient due to an increased risk of liver toxicity

PRECAUTIONS:

General:

The efficacy of a 70 mg dose regimen in patients with invasive aspergillosis who are not clinically responding to the 50 mg daily dose is not known. Limited safety data suggest that an increase in dose to 70 mg daily is well tolerated.

Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with caspofungin acetate. In some patients with serious underlying conditions who were receiving multiple concomitant medications along with caspofungin acetate, clinical hepatic abnormalities have also occurred. Isolated cases of significant hepatic dysfunction, hepatitis, or worsening hepatic failure have been reported in patients. A causal relationship to caspofungin acetate has not been established.

Laboratory Tests:

No tests in addition to standard tests are indicated

Drug/Laboratory Test Interactions: None known

IMPORTANT DRUG INTERACTIONS IN ICU:

Caspofungin with:

Tacrolimus: Caspofungin acetate reduces the blood levels of tacrolimus. For patients receiving both therapies, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended.

Cyclosporin: See WARNINGS

Rifampicin: a drug-drug interaction study with rifampin in healthy volunteers has shown a 30% decrease in caspofungin trough concentrations. Patients on rifampin should receive 70 mg of caspofungin acetate daily.

Dexamethasone: increases clearance of caspofungin. Use 70 mg daily of caspofungin.

Phenytoin: increases clearance of caspofungin. Use 70 mg daily of caspofungin.

Carbamazepine: increases clearance of caspofungin. Use 70 mg daily of caspofungin.

ADVERSE REACTIONS:

Body as a whole:

Chills, Fever, Flushing, Perspiration/diaphoresis

Cardiovascular System:

Hypertension, tachycardia

Gastrointestinal System:

Abdominal pain, diarrhoea, nausea, vomiting

Musculoskeletal System:

Back pain

Respiratory System:

Dyspnoea, tachypnoea

Nervous System:

Headache

Metabolic:

Hypokalaemia

Skin:

Rash