Micafungin

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Micafungin
Micafungin.svg
Micafungin ball-and-stick.png
Clinical data
Trade names Mycamine
AHFS/Drugs.com Monograph
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding 99.8%
Metabolism Via catechol-O-methyltransferase pathway
Elimination half-life 11–17 hours
Excretion 40% feces, <15% urine
Identifiers
  • {5-[(1S,2S)-2-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-3-[(1R)-2-carbamoyl-1-hydroxyethyl]-11,20,21,25-tetrahydroxy-15-[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-18-[(4-{5-[4-(pentyloxy)phenyl]-1,2-oxazol-3-yl}benzene)amido]-1,4,7,13,16,22-hexaazatricyclo[22.3.0.09,13]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C56H71N9O23S
Molar mass 1270.28 g·mol−1
3D model (JSmol)
  • CCCCCOc1ccc(-c2cc(-c3ccc(C(=O)N[C@H]4C[C@@H](O)[C@@H](O)N=C(O)[C@@H]5[C@@H](O)[C@@H](C)CN5C(=O)[C@H]([C@H](O)CC(=N)O)N=C(O)[C@H]([C@H](O)[C@@H](O)c5ccc(O)c(OS(=O)(=O)O)c5)N=C(O)[C@@H]5C[C@@H](O)CN5C(=O)[C@H]([C@H](C)O)N=C4O)cc3)no2)cc1
  • InChI=1S/C56H71N9O23S/c1-4-5-6-17-86-32-14-11-28(12-15-32)39-21-33(63-87-39)27-7-9-29(10-8-27)49(75)58-34-20-38(70)52(78)62-54(80)45-46(72)25(2)23-65(45)56(82)43(37(69)22-41(57)71)60-53(79)44(48(74)47(73)30-13-16-36(68)40(18-30)88-89(83,84)85)61-51(77)35-19-31(67)24-64(35)55(81)42(26(3)66)59-50(34)76/h7-16,18,21,25-26,31,34-35,37-38,42-48,52,66-70,72-74,78H,4-6,17,19-20,22-24H2,1-3H3,(H2,57,71)(H,58,75)(H,59,76)(H,60,79)(H,61,77)(H,62,80)(H,83,84,85)/t25-,26-,31+,34-,35-,37+,38+,42-,43-,44-,45-,46-,47-,48-,52+/m0/s1 Yes check.svgY
  • Key:PIEUQSKUWLMALL-NFGJWQNFSA-N Yes check.svgY
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Micafungin, sold under the brand name Mycamine, is an echinocandin antifungal medication used to treat and prevent invasive fungal infections including candidemia, abscesses, and esophageal candidiasis. It inhibits the production of beta-1,3-glucan, an essential component of fungal cell walls that is not found in mammals.

Contents

Administered intravenously, Micafungin received final approval from the U.S. Food and Drug Administration (FDA) in March 2005, and gained approval in the European Union in April 2008. It is on the World Health Organization's List of Essential Medicines . [1]

In August 2023, Mycamine was acquired from Astellas Pharma by Sandoz. [2]

Indications

Micafungin is indicated for the treatment of candidemia, acute disseminated candidiasis, Candida peritonitis, abscesses and esophageal candidiasis.

Micafungin works by way of concentration-dependent inhibition of 1,3-beta-D-glucan synthase resulting in reduced formation of 1,3-beta-D-glucan, which is an essential polysaccharide comprising one-third of the majority of Candida spp. cell walls. This decreased glucan production leads to osmotic instability and thus cellular lysis. [3] [4]

Dosage

The metabolism of micafungin occurs hepatically via acryp sulfatase followed by secondary metabolism by a transferase. Precautions should be taken with regards to dosing, as micafungin weakly inhibits CYP3A4. [5] [6]

Dosage forms

Micafungin is a natural antifungal product derived from other fungi as a defense mechanism for competition of nutrients, etc. To be specific, micafungin is derived from FR901379, and is produced by Coleophoma empetri . [7] [8]

Related Research Articles

<span class="mw-page-title-main">Candidiasis</span> Fungal infection due to any type of Candida

Candidiasis is a fungal infection due to any species of the genus Candida. When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers, among other symptoms.

<span class="mw-page-title-main">Antifungal</span> Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

<span class="mw-page-title-main">Nystatin</span> Antifungal medication

Nystatin, sold under the brand name Mycostatin among others, is an antifungal medication. It is used to treat Candida infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin.

<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

<span class="mw-page-title-main">Caspofungin</span> Antifungal medication

Caspofungin is a lipopeptide antifungal drug from Merck & Co., Inc.. It is a member of a class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall.

<span class="mw-page-title-main">Terconazole</span> Chemical compound

Terconazole is an antifungal drug used to treat vaginal yeast infection. It comes as a lotion or a suppository and disrupts the biosynthesis of fats in a yeast cell. It has a relatively broad spectrum compared to azole compounds but not triazole compounds. Testing shows that it is a suitable compound for prophylaxis for those that suffer from chronic vulvovaginal candidiasis.

<span class="mw-page-title-main">Fungemia</span> Internal, blood-borne infection by fungi, including yeasts.

Fungemia is the presence of fungi or yeast in the blood. The most common type, also known as candidemia, candedemia, or systemic candidiasis, is caused by Candida species. Candidemia is also among the most common bloodstream infections of any kind. Infections by other fungi, including Saccharomyces, Aspergillus and Cryptococcus, are also called fungemia. It is most commonly seen in immunosuppressed or immunocompromised patients with severe neutropenia, cancer patients, or in patients with intravenous catheters. It has been suggested that otherwise immunocompetent patients taking infliximab may also be at a higher risk.

<span class="mw-page-title-main">Anidulafungin</span> Antifungal medication

Anidulafungin (INN) is a semisynthetic echinocandin used as an antifungal drug. It was previously known as LY303366. It may also have application in treating invasive Aspergillus infection when used in combination with voriconazole. It is a member of the class of antifungal drugs known as the echinocandins; its mechanism of action is by inhibition of (1→3)-β-D-glucan synthase, an enzyme important to the synthesis of the fungal cell wall.

<i>Nakaseomyces glabratus</i> Species of fungus

Nakaseomyces glabratus is a species of haploid yeast of the genus Nakaseomyces, previously known as Candida glabrata. Despite the fact that no sexual life cycle has been documented for this species, N. glabratus strains of both mating types are commonly found. C. glabrata is generally a commensal of human mucosal tissues, but in today's era of wider human immunodeficiency from various causes, N. glabratus is often the second or third most common cause of candidiasis as an opportunistic pathogen. Infections caused by N. glabratus can affect the urogenital tract or even cause systemic infections by entrance of the fungal cells in the bloodstream (Candidemia), especially prevalent in immunocompromised patients.

<span class="mw-page-title-main">Esophageal candidiasis</span> Medical condition

Esophageal candidiasis is an opportunistic infection of the esophagus by Candida albicans. The disease usually occurs in patients in immunocompromised states, including post-chemotherapy and in AIDS. However, it can also occur in patients with no predisposing risk factors, and is more likely to be asymptomatic in those patients. It is also known as candidal esophagitis or monilial esophagitis.

<span class="mw-page-title-main">Beta-glucan</span> Class of chemical compounds

Beta-glucans, β-glucans comprise a group of β-D-glucose polysaccharides (glucans) naturally occurring in the cell walls of cereals, bacteria, and fungi, with significantly differing physicochemical properties dependent on source. Typically, β-glucans form a linear backbone with 1–3 β-glycosidic bonds but vary with respect to molecular mass, solubility, viscosity, branching structure, and gelation properties, causing diverse physiological effects in animals.

<span class="mw-page-title-main">Echinocandin</span> Group of chemical compounds

Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.

1,3-Beta-glucan synthase is a glucosyltransferase enzyme involved in the generation of beta-glucan in fungi. It serves as a pharmacological target for antifungal drugs such as caspofungin, anidulafungin, and micafungin, deemed 1,3-Beta-glucan synthase inhibitors. Under the CAZy classification system, fungi and plant members fall in the glycosyltransferase 48 family (GT48). Some members of the glycosyltransferase 2 family, such as the curdlan synthase CrdS, also has a similar activity.

<span class="mw-page-title-main">Aminocandin</span> Chemical compound

Aminocandin is an echinocandin antifungal. It works by targeting the glucan in fungal cell walls.

Pneumocandin B<sub>0</sub> Chemical compound

Pneumocandin B0, also known as pneumocandin B0, pneumocandin B(0), and hydroxy echinocandin, is an organic chemical compound with the formula C50H80N8O17, produced by the fungus Glarea lozoyensis.

<i>Candida auris</i> Species of fungus

Candida auris is a species of fungus that grows as yeast. It is one of the few species of the genus Candida which cause candidiasis in humans. Often, candidiasis is acquired in hospitals by patients with weakened immune systems. C. auris can cause invasive candidiasis (fungemia) in which the bloodstream, the central nervous system, and internal organs are infected. It has attracted widespread attention because of its multiple drug resistance. Treatment is also complicated because it is easily misidentified as other Candida species.

Invasive candidiasis is an infection (candidiasis) that can be caused by various species of Candida yeast. Unlike Candida infections of the mouth and throat or vagina, invasive candidiasis is a serious, progressive, and potentially fatal infection that can affect the blood (fungemia), heart, brain, eyes, bones, and other parts of the body.

<i>Candida tropicalis</i> Species of fungus

Candida tropicalis is a species of yeast in the genus Candida. It is a common pathogen in neutropenic hosts, in whom it may spread through the bloodstream to peripheral organs. For invasive disease, treatments include amphotericin B, echinocandins, or extended-spectrum triazole antifungals.

<span class="mw-page-title-main">Ibrexafungerp</span> Medication

Ibrexafungerp, sold under the brand name Brexafemme, is an antifungal medication used to treat vulvovaginal candidiasis (VVC). It is taken orally. It is also currently undergoing clinical trials for other indications via an intravenous (IV) formulation. An estimated 75% of women will have at least one episode of VVC and 40 to 45% will have two or more episodes in their lifetime.

<span class="mw-page-title-main">Rezafungin</span> Chemical compound

Rezafungin, sold under the brand name Rezzayo, is a medication used for the treatment of invasive candidiasis. It is an echinocandin antifungal.

References

  1. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  2. Dharma RK (28 August 2023). "Sandoz concludes acquisition of Mycamine antifungal agent". Pharmaceutical Technology. Retrieved 29 August 2023.
  3. Pappas PG, Rotstein CM, Betts RF, Nucci M, Talwar D, De Waele JJ, et al. (October 2007). "Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis". Clinical Infectious Diseases. 45 (7): 883–93. doi: 10.1086/520980 . PMID   17806055.
  4. Pettengell K, Mynhardt J, Kluyts T, Lau W, Facklam D, Buell D, et al. (FK463 South African Study Group) (August 2004). "Successful treatment of oesophageal candidiasis by micafungin: a novel systemic antifungal agent". Alimentary Pharmacology & Therapeutics. 20 (4): 475–81. doi: 10.1111/j.1365-2036.2004.02083.x . PMID   15298643. S2CID   31500007.
  5. Carver PL (October 2004). "Micafungin". The Annals of Pharmacotherapy. 38 (10): 1707–21. doi:10.1345/aph.1D301. PMID   15340133. S2CID   265942428.
  6. Kohno S, Masaoka T, Yamaguchi H, Mori T, Urabe A, Ito A, et al. (2004). "A multicenter, open-label clinical study of micafungin (FK463) in the treatment of deep-seated mycosis in Japan". Scandinavian Journal of Infectious Diseases. 36 (5): 372–9. doi:10.1080/00365540410020406. PMID   15287383. S2CID   10873612.
  7. Hashimoto S (January 2009). "Micafungin: a sulfated echinocandin". The Journal of Antibiotics. 62 (1): 27–35. doi: 10.1038/ja.2008.3 . PMID   19132058.
  8. Fujie A (2007). "Discovery of micafungin (FK463): A novel antifungal drug derived from a natural product lead". Pure and Applied Chemistry. 79 (4): 603–614. doi: 10.1351/pac200779040603 .

Further reading