Isavuconazole

Isavuconazole is a triazole antifungal medication used in the treatment of several fungal infections, including aspergillosis and mucormycosis. It is available under the brand name Cresemba. Isavuconazole acts by inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes, thereby exerting its antifungal effects.

Medical Uses

Isavuconazole is indicated for the treatment of invasive Aspergillosis, a serious infection that can occur in people with weakened immune systems, and Mucormycosis, a rare but serious fungal infection caused by molds in the Mucorales family. It is considered an option when other antifungal treatments are not suitable due to resistance, toxicity, or intolerances.

Pharmacology

Mechanism of Action

Isavuconazole works by inhibiting lanosterol 14α-demethylase, an enzyme necessary for converting lanosterol to ergosterol. Without ergosterol, the fungal cell membrane becomes compromised, leading to cell death. This mechanism is similar to other triazole antifungals.

Pharmacokinetics

Isavuconazole is well absorbed orally and has a high bioavailability. It has a long half-life, allowing for once-daily dosing. The drug is extensively metabolized in the liver, primarily through the CYP3A4 pathway, and eliminated in the feces and urine.

Adverse Effects

Common adverse effects of isavuconazole include nausea, vomiting, diarrhea, headache, and abnormal liver function tests. Serious but less common side effects may include QT prolongation, severe hepatic impairment, and severe hypersensitivity reactions.

Drug Interactions

Isavuconazole is a potent inhibitor of CYP3A4, leading to potential interactions with other drugs metabolized by this enzyme. It can increase the plasma concentrations of drugs like cyclosporine, tacrolimus, and certain statins, necessitating dose adjustments and careful monitoring.

Dosage and Administration

Isavuconazole is administered both orally and intravenously. The typical induction dose for adults is 200 mg three times daily for the first two days, followed by a maintenance dose of 200 mg once daily. Dose adjustments may be necessary for patients with hepatic impairment.

History

Isavuconazole was approved for medical use in the United States and the European Union in 2015. Its development was part of an effort to provide more treatment options for serious fungal infections, which are a significant cause of morbidity and mortality in immunocompromised patients.

Society and Culture

Legal status and availability of isavuconazole can vary by country, but it is generally a prescription medication. Its introduction has been welcomed as an important addition to the limited arsenal of antifungal agents, especially for treating infections resistant to other antifungals.