MICAFUNGIN for injection

MICAFUNGIN for injection

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MICAFUNGIN for injection

Micafungin for Injection is a sterile, lyophilized product for intravenous infusion that contains micafungin sodium. Micafungin sodium is a semisynthetic lipopeptide (echinocandin) synthesized by a chemical modification of a fermentation product of Coleophoma empetri F-11899. Micafungin inhibits the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall.

Each single-dose vial contains 50 mg micafungin (equivalent to 50.86 mg micafungin sodium) or 100 mg micafungin (equivalent to 101.73 mg micafungin sodium), 0.21 mg citric acid anhydrous, and 400 mg sucrose. Sodium hydroxide and/or citric acid may be added for pH adjustment. The product is preservative-free and nonpyrogenic. Micafungin for Injection must be diluted with 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP. Following reconstitution with 0.9% Sodium Chloride Injection, USP, the resulting pH of the solution is between 5 to7.

Micafungin sodium is chemically designated as: Pneumocandin A0,1-[(4R,5R)-4,5-dihydroxy-N2 -[4-[5-[4-(pentyloxy) phenyl]-3- isoxazolyl]benzoyl]-Lornithine]-4-[(4S)-4-hydroxy-4-[4-hydroxy-3-(sulfooxy)phenyl]-L-threonine]-, monosodium salt.

The molecular formula is C56H70N9NaO23S and the formula weight is 1292.26.

Micafungin sodium is a light-sensitive, hygroscopic white powder that is freely soluble in water, isotonic sodium chloride solution, N, N-dimethylformamide and dimethylsulfoxide, slightly soluble in methyl alcohol, and practically insoluble in acetonitrile, ethyl alcohol (95%), acetone, diethyl ether and n-hexane.

Indications and usage

Micafungin for Injection is an echinocandin indicated in adult and pediatric patients for:

  • Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses in adult and pediatric patients 4 months of age and older.
  • Treatment of Esophageal Candidiasis in adult and pediatric patients 4 months of age and older.
  • Prophylaxis of Candida Infections in adult and pediatric patients 4 months of age and older undergoing Hematopoietic Stem Cell Transplantation (HSCT).

Limitations of Use

  • Micafungin for Injection has not been adequately studied in patients with endocarditis, osteomyelitis or meningoencephalitis due to Candida.
  • The efficacy of Micafungin for Injection against infections caused by fungi other than Candida has not been established.

Mechanism of Action

Micafungin inhibits the synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls, which is not present in mammalian cells.

Resistance

There have been reports of clinical failures in patients receiving micafungin for injection therapy due to the development of drug resistance. Some of these reports have identified specific mutations in the FKS protein component of the glucan synthase enzyme that are associated with higher MICs and breakthrough infection.

Antimicrobial Activity

Micafungin has been shown to be active against most isolates of the following Candida species, both in vitro and in clinical infections

  • Candida albicans
  • Candida glabrata
  • Candida guilliermondii
  • Candida krusei
  • Candida parapsilosis
  • Candida tropicalis

Susceptibility Testing: For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Contraindications

Micafungin for Injection is contraindicated in persons with known hypersensitivity to micafungin sodium, any component of Micafungin for Injection, or other echinocandins.

Warnings and precautions

  • Hypersensitivity Reactions: Anaphylaxis and anaphylactoid reactions (including shock) have been observed. Discontinue Micafungin for Injection and administer appropriate treatment.
  • Hematological Effects: Isolated cases of acute intravascular hemolysis, hemolytic anemia and hemoglobinuria have been reported. Monitor rate of hemolysis. Discontinue if severe.
  • Hepatic Effects: Abnormalities in liver tests; isolated cases of hepatic impairment, hepatitis, and hepatic failure have been observed. Monitor hepatic function. Discontinue if severe dysfunction occurs.
  • Renal Effects: Elevations in BUN and creatinine; isolated cases of renal impairment or acute renal failure have been reported. Monitor renal function.
  • Infusion and Injection Site Reactions can occur including rash, pruritus, facial swelling, and vasodilatation. Monitor infusion closely, slow infusion rate if necessary
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Adverse reactions

Most common adverse reactions across adult and pediatric clinical trials for all indications include diarrhea, nausea, vomiting, abdominal pain, pyrexia, thrombocytopenia, neutropenia, and headache.

Drug interactions

Monitor for sirolimus, itraconazole or nifedipine toxicity, and dosage of sirolimus, itraconazole or nifedipine should be reduced, if necessary.

Use in specific populations

Pregnancy: Based on findings from animal studies, Micafungin for Injection may cause fetal harm when administered to a pregnant woman. There are insufficient human data on the use of micafungin for injection in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, intravenous administration of micafungin sodium to pregnant rabbits during organogenesis at doses four times the maximum recommended human dose resulted in visceral abnormalities and increased abortion. Advise pregnant women of the risk to the fetus

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

Pediatric

Use Pediatric Patients 4 Months of Age and Older: The safety and effectiveness of micafungin for injection for the treatment of esophageal candidiasis, candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses, esophageal candidiasis, and for prophylaxis of Candida infections in patients undergoing HSCT have been established in pediatric patients 4 months of age and older. Use of micafungin for injection for these indications and in this age group is supported by evidence from adequate and well-controlled studies in adult and pediatric patients with additional pharmacokinetic and safety data in pediatric patients 4 months of age and older.

Pediatric Patients Younger than 4 Months of Age: The safety and effectiveness of micafungin for injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age

Overdosage

Micafungin for Injection is highly protein bound and, therefore, is not dialyzable. No cases of micafungin for injection overdosage have been reported. Repeated daily doses up to 8 mg/kg (maximum total dose of 896 mg) in adult patients and up to 6 mg/kg in pediatric patients 4 months of age and older, and up to 10 mg/kg in pediatric patients younger than 4 months of age have been administered in clinical trials with no reported doselimiting toxicity.

Storage

Storage Store Micafungin for Injection, for intravenous use at room temperature, 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light; do not remove the protective sleeve

  • Store the reconstituted product at 25°C (77°F)
  • Store the diluted solution at 25°C (77°F)
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