Anidulafungin
Anidulafungin is an antifungal medication that fights infections caused by fungus.
Mechanism of effect
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.
Pharmacodynamic
Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product of Aspergillus nidulans. Anidulafungin is an echinocandin, a class of antifungal drugs that inhibits the synthesis of 1,3-β-D-glucan, an essential component of fungal cell walls. Anidulafungin is active in vitro against many Candida, as well as some Aspergillus. Like other echinocandins, anidulafungin is not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes.
Pharmacokinetics
-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 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
-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
Drug indications
Candidemia, intra-abdominal or peritoneal candidiasis: Treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and peritonitis) in adults and pediatric patients ≥1 month of age.
Candidiasis, esophageal: Treatment of esophageal candidiasis in adults
Dosage
Candidemia
Indicated for treatment of candidemia and intra-abdominal abscess and peritonitis caused by Candida infections
Day 1: 200 mg IV infusion, THEN
Day 2 and thereafter: 100 mg/day IV
Generally continue 14 days after last positive culture
Esophageal Candidiasis
Indicated for treatment of esophageal candidiasis
Day 1: 100 mg IV infusion, THEN
Day 2 and thereafter: 50 mg/day IV
Minimum 14 day treatment, at least 7 days following resolution of symptoms
Owing to risk of relapse of esophageal candidiasis in patients with HIV infection, consider suppressive antifungal therapy after treatment course
PEDIATRIC
Candidemia
Indicated for treatment of candidemia and intra-abdominal abscess and peritonitis caused by Candida infections in pediatric patients aged ≥1 month
Day 1: 3 mg/kg (not to exceed 200 mg/dose) IV infusion, THEN
Day 2 and thereafter: 1.5 mg/kg (not to exceed 100 mg/dose) IV
Generally continue 14 days after last positive culture
Drug contraindications
Hypersensitivity to this drugHypersensitivity to any component or other echinocandins
Known or suspected hereditary fructose intolerance
Side effects
anemia , depression , Insomnia , Diarrhea , Headache , chest pain , abdominal pain , dizziness , Seizures , Blurred vision , Angioedema , flushing , vertigo , Dyspnea , Hypertension , hypotension , dyspepsia , Urinary tract infection , Peripheral edema , fever , deep vein thrombosis , Injection-site reaction , Hyperkalemia , Hyperglycemia , eye pain , liver failure , pneumonia , itching , atrial fibrillation , Hypoglycemia , skin rush , Back pain , Increased prothrombin timeHypotension , hypertension , peripheral edema ,Insomnia ,Hypokalemia , hypomagnesemia ,Nausea , diarrhea , vomiting ,Urinary tract infection ,Increased serum alkaline phosphatase ,Bacteremia ,Dyspnea ,Fever ,Deep vein thrombosis , chest pain ,Confusion , headache , depression ,Decubitus ulcer ,Hypoglycemia , dehydration , hyperglycemia , hyperkalemia ,Constipation , dyspepsia , abdominal pain , oral candidiasis ,Anemia ,leukocytosis , thrombocythemia ,Increased serum transaminases ,Sepsis ,Back pain ,Increased serum creatinine ,Pleural effusion , cough , pneumonia,respiratory distress ,Anaphylactic shock, anaphylaxis, angioedema, atrial fibrillation, blood coagulation disorder, blurred vision, bronchospasm, cholestasis, clostridium infection, diaphoresis, dizziness, ECG abnormality (including ECG changes – prolonged QT 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
Interactions
Saccharomyces boulardii
Alerts
- Abnormal LFTs observed;
-Anaphylactic reactions, including shock, reported;
-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
Points of recommendation
- if elevated liver tests develop, monitor for evidence of worsening hepatic tests and evaluate risk benefit of continuing anidulafungin monitor for potential hepatic problems.
- discontinue and initiate appropriate treatment if Anaphylactic reactions occurs.
- Monitoring Parameters:LFTs; anaphylaxis or infusion reactions (eg, bronchospasm, dyspnea, flushing, hypotension, pruritus, rash, urticaria).
Pregnancy level
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.
This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.
Breast feeding warning
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
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