A-Z Drug Facts > Caspofungin Acetate

Caspofungin Acetate

Pronouncation: (KASS-poe-FUN-jin ASS-eh-tate)
Class: Echinocandins, Antifungal agent

Trade Names:
Cancidas
- Powder for injection, lyophilized 50 mg
- Powder for injection, lyophilized 70 mg

Pharmacology

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Inhibits synthesis of β-(1,3)-D-glucan, an integral component of fungal cell wall.

Pharmacokinetics

Distribution

About 97% protein bound (albumin).

Metabolism

Slowly metabolized by hydrolysis and N-acetylation and undergoes spontaneous chemical degradation.

Elimination

The t _½ is 9 to 11 h (beta phase) and 40 to 50 h (gamma phase). 35% is excreted in feces and 41% in urine (about 1.4% as unchanged drug). Renal Cl is about 0.15 mL/min. Total Cl is 12 mL/min. Not dialyzable.

Special Populations

Renal Function Impairment

AUC is increased 30% to 49% in those with Ccr up to 49 mL/min.

Hepatic Function Impairment
Mild (Child-Pugh score 5 to 6)

AUC is increased about 55%.

Moderate (Child-Pugh score 7 to 9)

AUC is increased 76%.

Elderly

AUC is increased about 28%. No dosage adjustment is needed.

Indications and Usage

Treatment of invasive aspergillosis in patients refractory to or intolerant of other antifungal therapies; empirical treatment for presumed fungal infections in febrile, neutropenic patients; treatment of esophageal candidiasis; treatment of candidemia and the following Candida infections: intra-abdominal abscesses, peritonitis, and pleural space infections.

Contraindications

Standard considerations.

Dosage and Administration

Invasive Aspergillosis, Candidemia and other Candida Infections, Empirical Treatment of Fungal Infections
Adults

IV Loading dose: 70 mg given by slow infusion of about 1 h on day 1. Maintenance dose: 50 mg daily by slow infusion of about 1 h thereafter.

Esophageal Candidiasis
Adults

IV 50 mg daily by slow infusion of about 1 h.

Hepatic Function Impairment

Mild hepatic insufficiency (Child-Pugh score 7 to 9), reduce maintenance dose to 35 mg daily.

General Advice

• Follow manufacturer's instructions for reconstitution and administration.
• For IV infusion only. Not for intra-abdominal, intra-pleural, intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration. Do not administer reconstituted solution directly into patient.
• Allow refrigerated vial of caspofungin to come to room temperature before reconstituting. Reconstitute powder for injection by adding 10.5 mL sodium chloride injection 0.9%, sterile water for injection, or bacteriostatic water for injection with benzyl alcohol 0.9% or with methylparaben and propylparaben to the appropriate vial (50 or 70 mg). Mix gently until a clear solution is obtained.
• Transfer 10 mL of reconstituted solution to IV bag or bottle containing 250 mL of sodium chloride injection 0.9%, 0.45%, or 0.225%, or Ringer's lactate injection.
• To prepare 70 mg dose from two 50 mg vials: reconstitute two 50 mg vials with 10.5 mL of diluent each. Transfer a total of 14 mL of the reconstituted solution from the 2 vials to the infusion bag or bottle.
• To prepare 50 mg daily dose at reduced volume, add 10 mL of reconstituted solution to 100 mL of compatible infusion fluid in IV bag or bottle.
• To prepare 35 mg daily dose for patient with moderate hepatic impairment, add 7 mL of reconstituted 50 mg vial to 250 mL or 100 mL of compatible infusion fluid in IV bag or bottle.
• Visually inspect reconstituted solution. Do not use if particulate matter, cloudiness, or discoloration is noted.

Storage/Stability

Store unopened vials in refrigerator (36° to 46°F). Reconstituted caspofungin solution may be stored at temperature less than 77°F for 1 h prior to preparing diluted IV infusion solution. IV infusion solution in IV bag or bottle can be stored at temperatures less than 77°F for 24 h or in refrigerator (36° to 46°F) for 48 h.

Drug Interactions

Cyclosporine

Avoid concurrent use if possible because caspofungin levels may be elevated, increasing the risk of side effects.

Inducers or mixed inducers/inhibitors of drug clearance (eg, carbamazepine, dexamethasone, efavirenz, nelfinavir, nevirapine, phenytoin, rifampin)

Caspofungin blood levels may be decreased, reducing the efficacy. Coadministration may require an increase in dose to 70 mg of caspofungin daily.

Tacrolimus

Tacrolimus blood levels may be decreased, reducing the efficacy.

Incompatibility

Do not mix or co-infuse with other medications. Do not use diluents containing dextrose. Caspofungin is not stable in diluents containing dextrose.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Phlebitis, thrombophlebitis (16%); hypertension, tachycardia (2%); hypotension (1%); swelling and peripheral edema (postmarketing).

CNS

Headache (11%); paresthesia (3%); dizziness, tremor (2%); insomnia (1%).

Dermatologic

Rash (6%); flushing, induration, perspiration/diaphoresis, pruritus, sweating (3%); erythema (2%).

GI

Nausea (6%); abdominal pain, diarrhea, vomiting (4%); anorexia (1%).

Genitourinary

Renal insufficiency (1%).

Hematologic-Lymphatic

Decreased Hgb (12%); decreased Hct (11%); decreased WBC (6%); anemia (4%); decreased neutrophils, decreased platelets, increased eosinophils (3%); increased lymphocytes, increased PT (2%).

Hepatic

Jaundice (1%); hepatic dysfunction (postmarketing).

Lab Tests

Decreased serum potassium, increased alkaline phosphatase (11%); increased alanine aminotransferase and aspartate aminotransferase (10%); decreased serum albumin (9%); increased urine WBC (8%); increased urine protein (5%); increased direct serum bilirubin; increased serum creatinine, increased urine RBC (4%); decreased serum protein, increased total serum bilirubin (3%); decreased serum calcium, hypomagnesemia, increased blood urea, serum sodium decreased (2%); increased serum potassium, decreased serum bicarbonate, serum uric acid increased, urine pH increased (1%).

Local

Infused vein complication (12%).

Metabolic-Nutritional

Hypokalemia (4%); edema, facial (3%); hypercalcemia (postmarketing).

Musculoskeletal

Myalgia (3%); back pain, musculoskeletal pain (1%).

Respiratory

Dyspnea (2%); tachypnea (1%).

Miscellaneous

Fever (26%); chills (14%); pain (5%); flu-like symptoms (3%).

Precautions

Monitor Evaluate LFTs prior to treatment and periodically thereafter. If abnormal LFTs are noted, monitor patients liver function more frequently. If worsening hepatic function is noted, evaluate risk/benefit of continued therapy with caspofungin.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Patient Information

• Advise patient or caregiver that medication will be prepared and administered by health care professionals in a hospital setting.
• Advise patient to immediately report any discomfort at injection site or the vein above the injection site.
• Instruct patient to report any of the following to health care provider: chills, fever, headache, nausea, any unusual or unexplained symptoms.

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