Isavuconazonium
Isavuconazonium Uses, Dosage, Side Effects, Food Interaction and all others data.
Isavuconazonium is a second-generation triazole antifungal approved on March 6, 2015 by the FDA for the treatment of invasive aspergillosis and invasive mucormycosis, marketed by Astellas under the brand Cresemba. It is the prodrug form of isavuconazole, the active moiety, and it is available in oral and parenteral formulations. Due to low solubility in water of isavuconazole on its own, the isovuconazonium formulation is favorable as it has high solubility in water and allows for intravenous administration. This formulation also avoids the use of a cyclodextrin vehicle for solubilization required for intravenous administration of other antifungals such as voriconazole and posaconazole, eliminating concerns of nephrotoxicity associated with cyclodextrin. Isovuconazonium has excellent oral bioavailability, predictable pharmacokinetics, and a good safety profile, making it a reasonable alternative to its few other competitors on the market.
| Trade Name | Isavuconazonium |
| Availability | Prescription only |
| Generic | Isavuconazonium |
| Isavuconazonium Other Names | Isavuconazonium |
| Related Drugs | itraconazole, amphotericin b, voriconazole, posaconazole, Cresemba |
| Weight | 372mg, 186mg, |
| Type | Intravenous Powder For Injection, Oral Capsule, Intravenous |
| Formula | C35H35F2N8O5S |
| Weight | Average: 717.77 Monoisotopic: 717.241370179 |
| Protein binding | >99% |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Isavuconazonium is a triazole antifungal used for the treatment of invasive aspergillosis and mucormycosis.
Indicated in the treatment of invasive aspergillosis and invasive mucormycosis.
Isavuconazonium is also used to associated treatment for these conditions: Disseminated mucormycosis, Invasive Aspergillosis
How Isavuconazonium works
Antifungals in the triazole class, such as isavuconazonium, target and inhibit the sterol 14-α-demethylase (Erg11p) which is a key player in the demethylation step of the ergosterol biosynthetic pathway. This inhibition results in a halt in production of ergosterol, a molecule typically found in the membranes of fungi such as Aspergillus, Candida, and Mucorales that plays a role in regulation of membrane integrity, fluidity and permeability. The inhibition of Erg11p also causes the buildup of ergosterol precursors, which are toxic and cause cell death.
Toxicity
Isavuconazole, the active moiety of isavuconazonium, is classified as Pregnancy Class C and should be avoided in pregnant women. It was also found to be excreted in breast milk in animal studies in rats, therefore it should be avoided in breastfeeding women.
Food Interaction
- Avoid grapefruit products. Grapefruit is a moderate to strong inhibitor of CYP3A4. Strong CYP3A4 inhibitors are contraindicated with isavuconazonium.
- Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of isavuconazonium and may reduce its serum concentration. Co-administration of isavuconazonium with St. John's Wort is contraindicated.
- Take with or without food. The bioavailability of isavuconazonium is not significantly impacted by food.
Isavuconazonium Drug Interaction
Moderate: tacrolimusMinor: citalopramUnknown: hydromorphone, penicillin v potassium, prednisolone ophthalmic, risperidone, fat emulsion, intravenous electrolyte solution, valganciclovir
Isavuconazonium Disease Interaction
Volume of Distribution
450 L
Elimination Route
When administered intravenously as isavuconazonium, >99% of the prodrug is quickly converted to active isavuconazole (catalyzed by plasma esterases). Oral administration of isavuconazonium shows 98% oral bioavailability, however administration with food results in a 20% decrease in AUC (area under concentration-time curve) as well as decreasing maximum serum concentration (Cmax) by 50% and increasing time to Cmax by 1.5 hours.
Half Life
80 to 130 hours.
Elimination Route
45% excreted in feces and bile, and 45% excreted in urine as inactive metabolites. Less than 1% of active isavuconazole is excreted unchanged in urine.
Innovators Monograph
You find simplified version here Isavuconazonium
