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Isavuconazonium, sold under the brand name Cresemba, is a systemic antifungal medication of the triazole class which is used to treat invasive aspergillosis and mucormycosis. It is used as the sulfate. It is taken by mouth or given via intravenous.
The most common side effects include abnormal liver enzyme tests, nausea, vomiting, difficulty breathing, abdominal pain, diarrhea, injection site reactions, headache, Hypokalemia, and skin rash.
Isavuconazonium is a prodrug of isavuconazole.
In preclinical studies, isavuconazonium caused birth defects in animals; it has not been tested in pregnant women.
In addition, isavuconazole induces CYP2B6 and can decrease the amount of drugs metabolized by the enzyme. Isavuconazole inhibits P-glycoprotein (P-gp), BCRP, SLC22A2, and uridine diphosphate-glucuronosyltransferases, each of which remove drugs from circulation; isavuconazonium will increase the amount of drugs that are affected by those proteins and may increase their toxicities.
Isavuconazole works by inhibition of lanosterol 14α-demethylase, the enzyme responsible for converting lanosterol to ergosterol via a demethylation reaction. The resulting depletion of ergosterol and buildup of lanosterol compromise the fungal cell membrane. Mammalian lanosterol 14α-demethylase is more resistant to inhibition by , making the drug's effects mostly specific to fungi.
In 2014, Basilea and Astellas amended the agreement to give Astellas sole marketing authority in North America, and Basilea the rights to market in the rest of the world.
The US Food and Drug Administration (FDA) granted approval in March 2015,
In 2017, Basilea licensed rights to Pfizer to market isavuconazole in Europe and other regions.
Chemistry
Isavuconazonium comprises an N-(3-acetoxypropyl)- N-methylamino-carboxymethyl group linked through an ester moiety to the triazole nitrogen in isavuconazole.
In the aquatic media of the body, the isavuconazole molecule is transformed into monohydrate.
History
Isavuconazole and isavuconazonium were discovered in Japan by researchers at Roche's research center in Kamakura. Basilea Pharmaceutica, which had been spun out of Roche to develop antimicrobial assets, developed isavuconazonium through Phase II clinical trials. In February 2010, Basilea partnered with Astellas Pharma to complete Phase III trials, obtain regulatory approvals, and market the drug. In 2013 and 2014, the partners won orphan drug designation in the US for isavuconazonium for treating invasive aspergillosis, mucormycosis, and invasive candidiasis.
and the European Medicines Agency (EMA) approved it in October 2015. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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