AHFS/Drugs.com cresemba ATC code J02AC05 (WHO) | Routes of
administration Oral, intravenous Molar mass 437.47 g/mol | |
 | ||
Trade names Cresemba (prodrug form) Pregnancy
category US: C (Risk not ruled out) Legal status US: ℞-only
In general: ℞ (Prescription only) | ||
Isavuconazole (BAL4815; trade name Cresemba) is a triazole antifungal drug. Its prodrug, isavuconazonium sulfate (BAL8557), was granted approval by the U.S. Food and Drug Administration (FDA) on March 6, 2015
Contents
During its Phase III drug trials, Astellas partnered with Basilea Pharmaceutica, the developer of the drug, for rights to co-development and marketing of isavuconazole.
On May 28, 2013, Basilea Pharmaceutica announced it had been granted orphan drug status by the FDA for treatment of aspergillosis. Since then, it has also been granted orphan drug status for the treatment of invasive candidiasis.
Medical uses
Isavuconazole has been approved by the FDA for treatment of invasive aspergillosis and invasive mucormycosis in adults ages 18 years and older. Both infections are caused by mold and fungi common to the environment, and occur in individuals who are immunosuppressed or have other complicating conditions, such as diabetes or lung disease.
Side effects
Common
Rare
Warnings
Isavuconazole should not be administered with other medications that strongly inhibit or induce the enzyme CYP3A4 due to the effect on plasma concentration. CYP3A4 inducers can result in subtherapeutic drug levels, and CYP3A4 inhibitors can cause supratherapeutic levels with increased adverse events and toxicity.
Isavuconazole is not recommended in people with pre-sensitized immune state to other heterocyclic compound antifungal agents and infusion-related reactions.
Studies have shown isavuconazole to have a dose dependent effect of shortening the QTc interval. It is contraindicated for use in individuals with familial short QT syndrome. Additive effects with other drugs that shorten the QTc have not been evaluated.
Mechanism of action
Isavuconazole works by inhibiting lanosterol 14 alpha-demethylase, the enzyme responsible for converting lanosterol to ergosterol by demethylation. The resulting depletion of ergosterol and build up of lanosterol compromise the structure of the fungal cell membrane. Mammalian cells are resistant to demethylation inhibition by azoles, making the drug effects specific to fungi.
Clinical trials
There have been three phase III clinical trials of isavuconazole, ACTIVE, VITAL and SECURE. As of June 2015, SECURE and VITAL have been presented in abstract form and results from ACTIVE have not been released.
The SECURE trial compared voriconazole and isavuconazole in invasive fungal infections due to aspergillus. Isuvaconazole was found to be non-inferior to voriconazole, another triazole antifungal, with all cause mortality at 18.6%, compared to 20.2% in the voriconazole group. It additionally demonstrated a similar side effect profile. A commentary on the study noted that "Isavuconazole will probably achieve an equivalent recommendation to voriconazole for the initial treatment of invasive aspergillosis in clinical guidelines. However, voriconazole will become off-patent in many countries from 2016 and new formulations of posaconazole are now available, broadening therapeutic options and affecting cost."