Isavuconazonium

Isavuconazonium, a second-generation triazole antifungal drug, was authorised by the FDA on March 6, 2015. It is used to treat dangerous fungal infections such invasive aspergillosis, which starts in the lungs and spreads to other organs via the bloodstream, and invasive mucormycosis, which typically starts in the sinuses, brain, or lungs.

BRAND NAME:

Cresemba - Cresemba contains each vial of isavuconazonium sulfate 200mg as the major active ingredient.

MECHANISM OF ACTION:

Isavuconazole targets and inhibits lanosterol 14α-demethylase, a cytochrome P450-dependent enzyme vital for producing ergosterol, an essential component of the fungal cell membrane. This inhibition disrupts membrane integrity and function, ultimately resulting in fungal cell death. Structurally, isavuconazole possesses a side arm that aligns the molecule in a way that allows its triazole ring to fit precisely into the binding pocket of the fungal CYP51 enzyme.

PHARMACODYNAMICS:

Absorption: The mean peak plasma concentration of isavuconazole at steady state was 7,499 ng/mL. After a single oral dose of 600 mg, the Cmax reached 20,028 ng/mL. Isavuconazole has a high oral bioavailability, with an absolute bioavailability of 98% following a single oral dose.

Distribution: The mean steady volume of distribution was approximately 450 L for intravenous administration.

Metabolism: Isavuconazonium, the prodrug of isavuconazole, is converted to its active form through esterase-mediated hydrolysis. In addition to isavuconazole and the inactive cleavage product, several minor metabolites are formed during this process. The primary enzymes responsible for the metabolism of isavuconazole are CYP3A4 and CYP3A5, followed by further processing via uridine diphosphate-glucuronosyltransferases (UGTs).

Excretion: For oral administration, 46.1% of total radiolabelled isavuconazole was detected in the feces, and about 45.5% was recovered in urine.

DOSAGE AND ADMINISTRATION:

The dosage for each patient differs according to the patient’s condition, and age.

For the treatment of invasive aspergillosis and mucormycosis in patients 18 years and older, the recommended loading dose is 2 capsules by mouth every 8 hours for 6 doses. The maintenance dose is 2 capsules once daily. Start maintenance dose 12 to 24 hours after the last loading dose.

For intravenous doses, 200mg isavuconazole IV is recommended every hour for 6 doses. The maintenance dose is 200mg of isavuconazole IV once daily. Start maintenance dose 12 to 24 hours after the last loading dose.

DRUG INTERACTIONS:

Taking other drugs along with isavuconazole can cause adverse effects. So some drugs should be avoided while taking isavuconazole and the doctor should inform the doctor while prescribing the medicines. Below are the few drugs that interact with the isavuconazole.