Anidulafungin

Pronunciation: (an-ID-ue-la-FUN-jin)
Class: Antifungal

Trade Names

Eraxis
- Injection, lyophilized powder for solution 50 mg
- Injection, lyophilized powder for solution 100 mg

Pharmacology

Inhibits formation of an essential component of fungal cell walls by inhibiting glucan synthase, an enzyme present in fungal cells.

Pharmacokinetics

Absorption

C _max ranges from 3.55 to 10.9 mg/L; AUC ranges from 42.3 to 168.9 mg•h/L.

Distribution

Vd is 30 to 50 L. Protein binding is greater than 99%.

Metabolism

Undergoes slow chemical degradation at physiologic temperature and pH. Anidulafungin is not a substrate, inducer, or inhibitor of CYP isozymes.

Elimination

Cl is approximately 1 L/h; elimination half-life is 40 to 50 h. Approximately 30% is excreted in the feces over 9 days and less than 1% is excreted in the urine.

Special Populations

Renal Function Impairment

In subjects with mild, moderate, severe, or end-stage (dialysis-dependent) renal impairment, pharmacokinetics were similar to those observed in healthy renal function. Dose adjustments are not necessary based on degree of renal insufficiency, including hemodialysis.

Hepatic Function Impairment

Concentrations were not increased in subjects with any degree of hepatic impairment. Dose adjustment is not necessary based on degree of hepatic insufficiency.

Elderly

Cl differed slightly between the elderly group and the nonelderly group, and the range of Cl was similar. Dose adjustments are not necessary for elderly patients.

Children

Concentration and exposure in children were similar to those observed in adults.

Gender

In multiple-dose patient studies, drug Cl was slightly faster (approximately 22%) in men. Dose adjustments are not necessary based on gender.

Race

Pharmacokinetics were similar among white, black, Asian, and Hispanic patients. Dose adjustments are not necessary based on race.

Fungal infection

Pharmacokinetics in patients with fungal infections are similar to those observed in healthy subjects.

HIV status

Dosage adjustments are not necessary based on HIV status, including coadministration of antiretroviral therapy.

Indications and Usage

Treatment of esophageal candidiasis, candidemia, and other forms of Candida infections (intra-abdominal abscess and peritonitis).

Unlabeled Uses

Catheter-related bloodstream infections caused by the Candida species in pediatric patients.

Contraindications

Hypersensitivity to echinocandins or any component of the product.

Dosage and Administration

Candidemia or Other Candida Infections (intra-abdominal abscess and peritonitis)
Adults

IV Single 200 mg loading dose on day 1 followed by 100 mg/day thereafter, generally for at least 14 days after the last positive culture.

Esophageal Candidiasis
Adults

IV Single 100 mg loading dose on day 1 followed by 50 mg/day thereafter for a minimum of 14 days and at least 7 days following resolution of symptoms.

General Advice

• For IV infusion, not for IV bolus injection.
• Rate of infusion should not exceed 1.1 mg/min.
• Reconstitute 50 mg vial with 15 mL or 100 mg vial with 30 mL of sterile water for injection.
• The reconstituted solution must be further diluted with only dextrose 5% injection or sodium chloride 0.9% injection. Do not dilute with other solutions or co-infuse with other medications or electrolytes.

Storage/Stability

Store unreconstituted vials, reconstituted solution, and diluted solution for infusion between 36° and 46°F. Do not freeze. The reconstituted solution may be stored for up to 1 h; the diluted solution for infusion should be administered within 24 h.

Drug Interactions

Cyclosporine

Anidulafungin AUC may be slightly increased. No dosage adjustment is needed.

Adverse Reactions

Cardiovascular

Atrial fibrillation, ECG early transition, ECG QT prolonged, flushing, hot flushes, hypertension, hypotension, right bundle branch block, sinus arrhythmia, superficial thrombophlebitis, ventricular extrasystoles (less than 2%); deep vein thrombosis (1%).

CNS

Convulsions, dizziness, headache (less than 2%).

Dermatologic

Angioneurotic edema, erythema, increased sweating, pruritus, urticaria (less than 2%); rash (1%).

EENT

Blurred vision, eye pain, visual disturbance (less than 2%).

GI

Diarrhea (3%); constipation, dyspepsia, fecal incontinence, nausea, upper abdominal pain, vomiting (less than 2%).

Hematologic-Lymphatic

Coagulopathy, thrombocytopenia (less than 2%); leukopenia, neutropenia (1%).

Hepatic

Cholestasis, hepatic necrosis (less than 2%).

Lab Tests

Abnormal LFTs, increased alkaline phosphatase, increased ALT, increased hepatic enzyme (2%); decreased magnesium and platelet count, increased amylase, bilirubin, calcium, CPK, creatinine, GGT, lipase, platelet count, and urea, PT prolongation (less than 2%); increased AST.

Local

Infusion-related reaction (less than 2%); phlebitis (1%).

Metabolic-Nutritional

Hypokalemia (3%); hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypomagnesemia (less than 2%).

Musculoskeletal

Back pain, rigors (less than 2%).

Respiratory

Cough (less than 2%).

Miscellaneous

Candidiasis, clostridial infection, fungemia, oral candidiasis, peripheral edema (less than 2%); pyrexia (1%).

Precautions

Monitor Monitor patients developing abnormal LFTs during use of anidulafungin for worsening hepatic function and evaluate for continued therapy.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic effects

Cases of significant hepatic dysfunction, hepatitis, or hepatic failure have been reported.

Overdosage

Symptoms

Generally well tolerated. Transient, asymptomatic transaminase elevations have been reported.

Patient Information

• Advise patient or caregiver that this medication will be prepared and administered by a health care provider in a hospital setting.
• Instruct patients to notify their health care provider if any of the following most common adverse reactions persist or become bothersome: diarrhea; headache; pain, swelling, or redness at the injection site.
• Inform patients that there have been isolated reports of serious hepatic effects.
• Inform patients that the medication may cause hypersensitivity reactions (eg, bronchospasm, dyspnea, flushing, hypotension, rash, urticaria), and to report these immediately to their health care provider.

Copyright © 2009 Wolters Kluwer Health.