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Anidulafungin


General


Pronunciation

(ay nid yoo la FUN jin)


Brand Names: U.S.

  • Eraxis

Indications


Use: Labeled Indications

Treatment of candidemia and other forms of Candida infections (including those of intra-abdominal, peritoneal, and esophageal locus)


Contraindications


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


Dosing and Administration


Dosing: Adult

Aspergillosis (invasive) in HIV-infected patients: IV: 200 mg on day 1, then 100 mg once daily until infection resolution and CD4 count >200 cells/mm3 (HHS [OI adult 2015])

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

Esophageal candidiasis: IV: Initial dose: 100 mg on day 1; subsequent dosing: 50 mg daily; treatment should continue for a minimum of 14 days and for at least 7 days after symptom resolution


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Aspergillosis (invasive) in HIV-infected patients (off-label use): Adolescents: IV: Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment necessary, including dialysis patients.


Dosing: Hepatic Impairment

No dosage adjustment necessary.


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

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


Storage

Store 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 ≥72 hours prior to administration.


Dosage Forms/Strengths


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]


Compatibility

Stable in D5W, NS.

Y-site administration: Incompatible with ertapenem, sodium bicarbonate.


Drug Interactions

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


Monitoring Parameters

Liver function tests


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% (Limited to important or life-threatening): Anaphylactic shock, anaphylaxis, angioedema, atrial fibrillation, blood coagulation disorder, blurred vision, cholestasis, clostridium infection, ECG abnormality (including ECG changes " “ prolonged Q-T interval), hepatic insufficiency, hepatic necrosis, hepatitis, increased amylase, infusion related reaction, prolonged prothrombin time, right bundle branch block, seizure, sinus arrhythmia, thrombocytopenia, thrombophlebitis, ventricular premature contractions


Warnings/Precautions


Special Populations: Elderly

Clearance differed slightly between the elderly group and the nonelderly group, and the range of clearance was similar.


Special Populations: Children

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


Special Populations: Gender

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


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 rate of infusion.

Disease-related concerns:

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


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse effects were observed in animal reproduction studies. Other agents are currently preferred for the treatment of Candida infections in pregnant women (Pappas 2009).


Actions


Pharmacology

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


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%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, diarrhea, or insomnia. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of low magnesium (mood changes; muscle pain or weakness; muscle cramps or spasms; seizures; tremors; lack of appetite; severe nausea or vomiting; or an abnormal heartbeat), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), angina, vomiting blood, difficult urination, pain with urination, severe dizziness, passing out, chills, pharyngitis, flushing, severe headache, shortness of breath, or swelling of arms or legs (HCAHPS).

- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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