anidulafungin (Rx)

1-10%

Adults (candidemia)

• Hypokalemia (25%)
• Nausea (24%)
• Diarrhea (18%)
• Pyrexia (18%)
• Hypotension (15%)
• Insomnia (15%)
• Hypertension (12%)
• Dyspnea (12%)
• Increased alkaline phosphatase (12%)
• Hypomagnesemia (12%)
• Peripheral edema (11%)

Pediatric (candidemia)

• Pyrexia (18%)
• Diarrhea (16%)
• Vomiting (16%)

1-10%

Adults (candidemia)

• Deep vein thrombosis (10%)
• Pleural effusion (10%)
• Anemia (9%)
• Constipation (8%)
• Increased WBCs (8%)
• Confusional state (8%)
• Headache (8%)
• Cough (7%)
• Hypoglycemia (7%)
• Hyperkalemia (6%)
• Hyperglycemia (6%)
• Dehydration (6%)
• Respiratory distress (6%)
• Abdominal pain (6%)
• Depression (6%)
• Thrombocythemia (6%)
• Leukocytosis (5%)
• Chest pain (5%)
• Increased hepatic enzymes (5%)
• Increased blood creatinine (5%)
• Back pain (5%)

Adults (esophageal candidiasis)

• Diarrhea (9%)
• Pyrexia (9%)
• Anemia (8%)
• Headache (8%)
• Nausea (7%)
• Dyspepsia (7%)
• Vomiting (7%)
• Hypokalemia (5%)
• Oral candidiasis (5%)

• Adults esophageal candidiasis <2%

  • Blood and lymphatic: Coagulopathy, thrombocytopenia
  • Cardiac: Atrial fibrillation, bundle branch block (right), sinus arrhythmia, ventricular extrasystoles
  • Eye: Eye pain, vision blurred, visual disturbance
  • General and administration site: Infusion related reaction, peripheral edema, rigors
  • Hepatobiliary: Abnormal liver function tests, cholestasis, hepatic necrosis
  • Infections: Clostridial infection
  • Investigations: Amylase increased, bilirubin increased, CPK increased, electrocardiogram QT prolonged, GGT increased, lipase increased, potassium decreased, prothrombin time prolonged, urea increased
  • Nervous system: Convulsion, dizziness
  • Respiratory, thoracic and mediastinal: Cough
  • Skin and subcutaneous tissue: Angioneurotic edema, erythema, pruritus, sweating increased, urticaria
  • Vascular: Flushing, hot flushes, thrombophlebitis superficial

Pediatric (candidemia)

• Anemia (10%)
• Abdominal pain (9%)
• Epistaxis (9%)
• Rash (9%)
• ALT increased (9%)
• AST increased (6%)
• Thrombocytopenia (6%)
• Hypoglycemia (6%)

• Pediatric <5%

  • Blood and lymphatic system disorders: Pancytopenia, thrombocytosis, febrile neutropenia, leukopenia, neutropenia
  • Eye disorders: Periorbital edema
  • Gastrointestinal disorders: Gastroesophageal reflux disease, abdominal distension, nausea, stomatitis, dry mouth
  • General disorders and administrative site conditions: Chest pain, edema peripheral
  • Infections and infestations: Bacteremia, device related infection, gastroenteritis, lower respiratory tract infection, upper respiratory tract infection, urinary tract infection
  • Laboratory investigations: GGT increased, transaminases increased
  • Metabolism and nutrition disorders: Hypocalcemia, hypokalemia, hyponatremia, hypoproteinemia
  • Musculoskeletal and connective tissue disorders: Back pain, pain in extremity
  • Nervous system disorders: Headache, tremor, seizure
  • Psychiatric disorders: Agitation
  • Respiratory, thoracic and mediastinal disorders: Hemoptysis
  • Vascular disorders: Hypotension

Contraindications

Hypersensitivity to any component or other echinocandins

Known or suspected hereditary fructose intolerance

Cautions

Abnormal LFTs observed; if elevated liver tests develop, monitor for evidence of worsening hepatic tests and evaluate risk benefit of continuing anidulafungin monitor for potential hepatic problems

Anaphylactic reactions, including shock, reported; discontinue and initiate appropriate treatment if this occurs

Infusion-related adverse reactions (possibly histamine-mediated) reported, including rash, urticaria, flushing, pruritus, bronchospasm, dyspnea, and hypotension; reduce risk by not exceeding recommended infusion rate

Contains polysorbate 80, an inactive ingredient; thrombocytopenia, renal dysfunction, hepatomegaly, cholestasis, ascites, hypotension, and metabolic acidosis reported in low-birth weight infants receiving high doses of polysorbate; toxicity has not been reported with anidulafungin

Contains fructose; may precipitate a metabolic crisis (eg, life-threatening hypoglycemia, hypophosphatemia, lactic acidosis, hepatic failure) in patients with hereditary fructose intolerance

Pregnancy

Based on findings from animal studies, therapy can cause fetal harm when administered to pregnant females; there are no available human data on use in pregnant females to inform a drug-associated risk of adverse developmental outcomes

Animal studies

• Fetal toxicity observed in animal reproduction studies in the presence of maternal toxicity when anidulafungin was administered to pregnant rabbits during organogenesis at 4 times the proposed therapeutic maintenance dose of 100 mg/day (dose based on relative body surface area)

Lactation

There are no data on presence of drug in human milk, effects on breastfed infant or on milk production

Drug found in milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk

Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Echinocandin - inhibits synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls

Absorption

Peak plasma concentration

• 70mg/35mg: 3.55 mg/L
• 200mg/100mg: 8.6 mg/L

AUC

• 70mg/35mg: 42.3 mg⋅hr/L
• 200mg/100mg: 111.8 mg⋅hr/L

Distribution

Distribution half-life: 30-60 minutes

Protein bound: >99% (plasma proteins)

Vd: 30-50 L

Metabolism

Not metabolized by liver

Undergoes slow chemical degradation to peptide lacking antifungal activity

Degradation half-life: ~24 hr

Elimination

Excretion: Feces (30% over 9 days [<10% intact drug]); urine (<1%)

Terminal half-life

• 70mg/35mg: 43.2 hr
• 200mg/100mg: 52 hr

Clearance

• 70mg/35mg: 0.84 L/hr
• 200mg/100mg: 0.94 L/hr

IV Preparation

Reconstitute lyophilized powder

• Reconstitute vial with sterile water for injection (SWI)
• 50-mg vial: Add 15 mL SWI to provide concentration of 3.33 mg/mL
• 100-mg vial: Add 30 mL SWI to provide concentration of 3.33 mg/mL

Further dilution required

• Adults: Aseptically transfer contents from reconstituted vial(s) to appropriately sized IV bag/bottle of D5W or 0.9% NaCl

• Pediatric patients

  • Infusion solution volume required is dependent on child’s weight
  • Reconstituted solution must be further diluted to 0.77 mg/mL for final infusion solution
  • See prescribing information for how to calculate dilution for doses <50 mg

IV Administration

Visually inspect solution for particulate matter and discoloration; if identified, discard solution

IV infusion rate: Not to exceed 1.1 mg/min

Do not give as IV bolus

Storage

Unopened vials: Store at 25°C (77°F)

Reconstituted vials: May store at 25°C (77°F) for up to 24 hr

Diluted solution: May store at 25°C (77°F) for up to 48 hr

Do not freeze