Dulaedge

Uses

Dulaedge is an echinocandin antifungal used for the treatment of the following infections:

• Candidemia and other forms of Candida infections (intra-abdominal abscess and peritonitis) in adults and pediatric patients (1 month of age and older).
• Esophageal candidiasis in adults.

• Dulaedge has not been studied in adult and pediatric patients with endocarditis, osteomyelitis, and meningitis due to Candida or in sufficient numbers of neutropenic patients. The dosage of Dulaedge for the treatment of Candida dissemination into the CNS and the eye has not been established.
• Dulaedge is associated with high relapse rates in esophageal candidiasis.

Dulaedge is also used to associated treatment for these conditions: Bloodstream Infections, Candidemia, Candidiasis, Esophageal Candidiasis, Fungal peritonitis caused by Candida, Intraabdominal Abscess caused by Candida, Invasive Aspergillosis, Oropharyngeal Candidiasis

How Dulaedge works

Dulaedge is a semi-synthetic echinocandin with antifungal activity. Dulaedge inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall, ultimately leading to osmotic instability and cell death.

Dosage

Dulaedge dosage

Candidemia and other forms of Candida infections-

• Adults: 200 mg loading dose on Day 1, followed by 100 mg once daily maintenance dose thereafter for at least 14 days after the last positive culture.
• Pediatric Patients 1 Month of Age and Older: 3 mg/kg (not to exceed 200 mg) loading dose on Day 1, followed by 1.5 mg/kg (not to exceed 100 mg) once daily maintenance dose thereafter for at least 14 days after the last positive culture.

• Adults: 100 mg loading dose on Day 1, followed by 50 mg once daily maintenance dose thereafter for a minimum of 14 days and for at least 7 days following resolution of symptoms.
• Pediatric Patients 1 Month of Age and Older: Not Approved.

Side Effects

Adults-

• Candidemia and other forms of Candida infections: Most common adverse reactions (≥15%) are hypokalemia, nausea, diarrhea, vomiting, pyrexia, insomnia, hypotension.
• Esophageal candidiasis: Most common adverse reactions (≥5%) are diarrhea, pyrexia, anemia, headache, vomiting, nausea, dyspepsia, oral candidiasis, and hypokalemia. 

Toxicity

During clinical trials a single 400 mg dose of anidulafungin was inadvertently administered as a loading dose. No clinical adverse events were reported. The maximum non-lethal dose of anidulafungin in rats was 50 mg/kg, a dose which is equivalent to 10 times the recommended daily dose for esophageal candidiasis (50mg/day).

Precaution

Hepatic Effects: Risk of abnormal liver tests, hepatitis, hepatic failure; monitor hepatic function during therapy.

Hypersensitivity: Anaphylaxis, including shock has been reported. Risk of infusion-related adverse reactions, possibly histamine-mediated, including rash, urticaria, flushing, pruritus, bronchospasm, dyspnea, and hypotension; to reduce occurrence, do not exceed a rate of infusion of 1.1 mg/minute.

Risk of Neonatal Toxicity Associated with Polysorbates: Dulaedge contains polysorbate 80, an inactive ingredient. Thrombocytopenia, renal dysfunction, hepatomegaly, cholestasis, ascites, hypotension and metabolic acidosis haves been reported in low-birth weight infants receiving high doses of polysorbate. Dulaedge is not approved in pediatric patients younger than 1 month of age.

Hereditary Fructose Intolerance (HFI): Dulaedge contains fructose. Risk of metabolic crisis with life-threatening hypoglycemia, hypophosphatemia, lactic acidosis, and hepatic failure. Obtain history of HFI symptoms in pediatric patients before Dulaedge administration.

Interaction

Cyclosporine: Administration of multiple doses of anidulafungin and cyclosporine to healthy subjects resulted in no significant alteration in the steady state pharmacokinetics of either drug. No dosage adjustment of cyclosporine or anidulafungin is needed when the two drugs are co-administered.

Voriconazole: Administration of multiple doses of anidulafungin and voriconazole to healthy subjects resulted in no significant alteration in the steady state pharmacokinetics of either drug. No dosage adjustment of voriconazole or anidulafungin is needed when the two drugs are co-administered.

Tacrolimus: Administration of multiple doses of anidulafungin and a single-dose of tacrolimus to healthy subjects resulted in no significant alteration in the steady state pharmacokinetics of either drug. No dosage adjustment of tacrolimus or anidulafungin is needed when the two drugs are co-administered.

Rifampin: Administration of multiple doses of anidulafungin and rifampin to patients resulted in no significant alteration in the steady state pharmacokinetics of anidulafungin. No dosage adjustment of anidulafungin is needed when it is co administered with rifampin.

Amphotericin B Liposome for Injection: Administration of multiple doses of anidulafungin and liposomal amphotericin B to patients resulted in no significant alteration in the steady state pharmacokinetics of anidulafungin. No dosage adjustment of anidulafungin is needed when it is co-administered with liposomal amphotericin B.

Food Interaction

Dulaedge Disease Interaction

Moderate: hepatotoxicity

Volume of Distribution

• 30 to 50 L

Half Life

40-50 hours

Clearance

• 1 L/h

Elimination Route

Less than 1% of the administered radioactive dose was excreted in the urine. Dulaedge is not hepatically metabolized.

Pregnancy & Breastfeeding use

Pregnancy: Based on findings from animal studies, Dulaedge can cause fetal harm when administered to a pregnant woman. There are no available human data on the use of Dulaedge in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies fetal toxicity was observed 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 on the basis of relative body surface area. Inform pregnant woman of the risk to the fetus.

Lactation: There are no data on the presence of anidulafungin in human milk, the effects on the breastfed infant or the effects on milk production. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Dulaedge was found in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Dulaedge and any potential adverse effects on the breastfed child from Dulaedge or from the underlying maternal condition.

Contraindication

Dulaedge is contraindicated in:

• Patients with known hypersensitivity to anidulafungin, any component of Dulaedge, or other echinocandins.
• Patients with known or suspected Hereditary Fructose Intolerance (HFI).

Acute Overdose

During clinical trials a single 400 mg dose of Dulaedge was inadvertently administered as a loading dose. No clinical adverse events were reported. In a study of 10 healthy subjects administered a loading dose of 260 mg followed by 130 mg daily; 3 of the 10 subjects experienced transient, asymptomatic transaminase elevations (≤3 x ULN)

Dulaedge is not dialyzable. The maximum non-lethal dose of anidulafungin in rats was 50 mg/kg, a dose which is equivalent to 10 times the recommended daily dose for esophageal candidiasis (50 mg/day) or equivalent to 5 times the recommended daily dose for candidemia and other Candida infections (100 mg/day), based on relative body surface area comparisons.

Storage Condition

Dulaedge vials: Dulaedge vials should be stored in a refrigerator at 2°C-8°C. Do not freeze. Excursions for 96 hours up to 25ºC are permitted, and the vial can be returned to storage at 2°C-8°C.

Reconstituted solution: Dulaedge reconstituted solution can be stored at up to 25°C for up to 24 hours.

Infusion Solution: Dulaedge infusion solution can be stored at temperatures up to 25°C for up to 48 hours. Do not freeze.

Innovators Monograph

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