Anidulafungin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Eraxis: 50 mg (1 ea); 100 mg (1 ea) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Noncompetitive inhibitor of 1,3-beta-D-glucan synthase resulting in reduced formation of 1,3-beta-D-glucan, an essential polysaccharide comprising 30% to 60% of Candida cell walls (absent in mammalian cells); decreased glucan content leads to osmotic instability and cellular lysis

Pharmacokinetics/Pharmacodynamics

Distribution

30-50 L

Metabolism

No hepatic metabolism observed; undergoes slow chemical hydrolysis to open-ring peptide lacking antifungal activity

Excretion

Feces (30%, 10% as unchanged drug); urine (<1%)

Half-Life Elimination

Terminal: 40-50 hours

Protein Binding

>99%

Use in Specific Populations

Special Populations: Children

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

Use: Labeled Indications

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

Use: Off Label

Candidiasis, intravascular infectionsyes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, anidulafungin is an effective and recommended treatment for patients with candida intravascular infections, including patients with endocarditis (native or prosthetic valve), infections of implantable cardiac devices (pacemaker, implantable cardiac defibrillator), and Candida suppurative thrombophlebitis.

Candidiasis, osteoarticular infectionsyes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, anidulafungin is an effective and recommended treatment for patients with Candida osteoarticular infections, including Candida osteomyelitis and Candida septic arthritis.

Candidiasis, chronic disseminated (hepatosplenic)yes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, anidulafungin is an effective and recommended treatment for patients with chronic disseminated (hepatosplenic) candidiasis.

Candidiasis empiric therapy (non-neutropenic ICU patients)yes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, anidulafungin is an effective and recommended agent for empiric therapy of suspected invasive candidiasis in non-neutropenic ICU patients.

Candidiasis, oropharyngeal (refractory disease)yes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, anidulafungin may be considered as an alternative for patients with oropharyngeal candidiasis refractory to other antifungals.

Candidiasis, prophylaxis against invasive candidiasis (high-risk ICU patients in units with a high rate of invasive candidiasis)yes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the management of candidiasis, anidulafungin may be considered as an alternative agent for prophylaxis against invasive candidiasis in high-risk patients in adult ICUs with a high rate of invasive candidiasis (>5%).

Contraindications

Hypersensitivity to anidulafungin, other echinocandins, or any component of the formulation

Dosage and Administration

Dosing: Adult

Candidemia, intra-abdominal or peritoneal candidiasis: IV: Initial dose: 200 mg on day 1; subsequent dosing: 100 mg daily; treatment should continue until 14 days after last positive culture. Note: IDSA Candidiasis guidelines recommend transition to fluconazole (eg, after 5 to 7 days in nonneutropenic patients) in clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures (IDSA [Pappas 2016])

Candidiasis, chronic disseminated (hepatosplenic) (off-label use): IV: 200 mg on day 1; subsequent dosing: 100 mg daily for several weeks, followed by oral fluconazole therapy (IDSA [Pappas 2016])

Candidiasis, empiric therapy (suspected invasive candidiasis in nonneutropenic ICU patients) (off-label use): IV: 200 mg on day 1; subsequent dosing: 100 mg daily; treatment should continue for 14 days in patients with clinical improvement. Consider discontinuing after 4 to 5 days in patients with no clinical response (IDSA [Pappas 2016])

Candidiasis, intravascular infections (native or prosthetic valve endocarditis, infection of implantable cardiac devices, suppurative thrombophlebitis) (off-label use): IV: 200 mg daily. For native or prosthetic valve endocarditis, therapy should continue for at least 6 weeks after valve replacement surgery (longer durations in patients with abscesses or other complications); for patients with implantable cardiac devices, therapy should continue for 4 to 6 weeks after surgery (4 weeks for infections limited to generator pockets and at least 6 weeks for infections involving the wires); for suppurative thrombophlebitis, continue for at least 2 weeks after candidemia has cleared. Note: Step-down to fluconazole therapy is recommended in clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures (IDSA [Pappas 2016])

Candidiasis, osteoarticular infections (osteomyelitis or septic arthritis) (alternative therapy) (off-label use): IV: 100 mg daily for at least 14 days, followed by fluconazole (IDSA [Pappas 2016])

Candidiasis, prophylaxis against invasive candidiasis (high-risk ICU patients in units with a high incidence of invasive candidiasis) (alternative therapy; off-label use): IV: Initial dose: 200 mg on day 1; subsequent doses: 100 mg daily (IDSA [Pappas 2016])

Candidiasis, esophageal: IV: 200 mg daily; may transition to oral fluconazole therapy once oral intake tolerable. In patients with fluconazole-refractory disease, continue anidulafungin for 14 to 21 days (IDSA [Pappas 2016]).

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice. Initial dose: 100 mg on day 1; subsequent dosing: 50 mg daily

Candidiasis, oropharyngeal (refractory disease) (alternative therapy) (off-label use): IV: Initial dose: 200 mg on day 1; subsequent dosing: 100 mg daily (IDSA [Pappas 2016])

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Aseptically add 15 mL (50 mg vial) or 30 mL (100 mg vial) of sterile water for injection to each vial. Further dilute 50 mg or 100 mg vials in 50 mL or 100 mL, respectively, of D5W or NS.

Administration

IV: For intravenous use only; infusion rate should not exceed 1.1 mg/minute (1.4 mL/minute or 84 mL/hour).

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); excursions at 25°C (77°F) are permitted for 96 hours and the vial may be returned to storage at 2°C to 8°C (36°F to 46°F). Do not freeze. The reconstituted solution can be stored for up to 24 hours at temperatures up to 25°C (77°F) prior to dilution into the infusion solution (D5W or NS). The infusion solution may be stored for up to 48 hours at temperatures up to 25°C (77°F) or stored in the freezer for at least 72 hours prior to administration.

Drug Interactions

Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Avoid combination

Adverse Reactions

>10%:

Cardiovascular: Hypotension (15%), hypertension (12%), peripheral edema (11%)

Central nervous system: Insomnia (15%)

Endocrine & metabolic: Hypokalemia (≤25%), hypomagnesemia (12%)

Gastrointestinal: Nausea (7% to 24%), diarrhea (9% to 18%), vomiting (7% to 18%)

Genitourinary: Urinary tract infection (15%)

Hepatic: Increased serum alkaline phosphatase (12%)

Infection: Bacteremia (18%)

Respiratory: Dyspnea (12%)

Miscellaneous: Fever (9% to 18%)

2% to 10%:

Cardiovascular: Deep vein thrombosis (10%), chest pain (5%)

Central nervous system: Confusion (8%), headache (8%), depression (6%)

Dermatologic: Decubitus ulcer (5%)

Endocrine & metabolic: Hypoglycemia (7%), dehydration (6%), hyperglycemia (6%), hyperkalemia (6%)

Gastrointestinal: Constipation (8%), dyspepsia (7%), abdominal pain (6%), oral candidiasis (5%)

Hematologic & oncologic: Anemia (8% to 9%), leukocytosis (5% to 8%), thrombocythemia (6%)

Hepatic: Increased serum transaminases (≤5%)

Infection: Sepsis (7%)

Neuromuscular & skeletal: Back pain (5%)

Renal: Increased serum creatinine (5%)

Respiratory: Pleural effusion (10%), cough (7%), pneumonia (6%), respiratory distress (6%)

<2%, postmarketing, and/or case reports: Anaphylactic shock, anaphylaxis, angioedema, atrial fibrillation, blood coagulation disorder, blurred vision, bronchospasm, cholestasis, clostridium infection, diaphoresis, dizziness, ECG abnormality (including ECG changes – prolonged Q-T interval), erythema, eye pain, flushing, hepatic insufficiency, hepatic necrosis, hepatitis, hot flash, increased amylase, increased blood urea nitrogen, increased creatine phosphokinase, increased gamma-glutamyl transferase, increased serum bilirubin, increased serum lipase, infusion related reaction, prolonged prothrombin time, pruritus, right bundle branch block, rigors, seizure, sinus arrhythmia, skin rash, thrombocytopenia, thrombophlebitis, urticaria, ventricular premature contractions, visual disturbance

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic reactions: Severe hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported; immediate treatment for hypersensitivity reactions should be available. Discontinue treatment immediately if reactions occur.
• Hepatic effects: Elevated liver function tests, hepatitis, and hepatic failure have been reported; monitor for progressive hepatic impairment if increased transaminase enzymes noted.
• Infusion reactions: Infusion reactions (eg, bronchospasm, dyspnea, flushing, hypotension, pruritus, rash, urticaria) may occur; do not exceed recommended rate of infusion.

Disease-related concerns:

• Candidal infections: Safety and efficacy have not been established in other Candida infections (eg, endocarditis, osteomyelitis, meningitis).

Monitoring Parameters

Liver function tests

Pregnancy

Pregnancy Considerations

Adverse effects were observed in animal reproduction studies. Other agents are currently preferred for the treatment of Candida infections in pregnant women (IDSA [Pappas 2016]).

Patient Education

What is this drug used for?

• It is used to treat fungal infections.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Back pain
• Trouble sleeping

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, fast heartbeat, increased thirst, seizures, loss of strength and energy, lack of appetite, not able to pass urine or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting
• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood
• Confusion
• Depression
• Severe loss of strength and energy
• Mouth irritation
• Severe dizziness
• Passing out
• Vision changes
• Chills
• Sore throat
• Flushing
• Severe headache
• Swelling of arms or legs
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.