NOXAFIL

What it is

NOXAFIL is a modified release tablet formulation containing 100 mg of posaconazole. Posaconazole is a triazole antifungal agent that inhibits the enzyme lanosterol 14α-demethylase, which catalyses an essential step in ergosterol biosynthesis.

Approved indications

NOXAFIL is indicated for use in the treatment of invasive aspergillosis in patients intolerant of, or with disease that is refractory to, alternative therapy, and for fusariosis, zygomycosis, coccidioidomycosis, chromoblastomycosis, and mycetoma in patients intolerant of, or with disease that is refractory to, alternative therapy in patients 13 years of age or older. — Invasive aspergillosis in patients intolerant of, or with disease that is refractory to, alternative therapy in patients 13 years of age or older. — Fusariosis, zygomycosis, coccidioidomycosis, chromoblastomycosis, and mycetoma in patients intolerant of, or with disease that is refractory to, alternative therapy in patients 13 years of age or older. — Prophylaxis of invasive fungal infections among patients 13 years of age and older who are at high risk of developing these infections, such as patients with prolonged neutropenia or haematopoietic stem cell transplant recipients.

Dosing overview

For refractory invasive fungal infections or in patients intolerant of invasive fungal infections, NOXAFIL is given as a loading dose of 300 mg (three 100 mg modified release tablets) twice a day on the first day, then 300 mg once a day thereafter. Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response. For prophylaxis of invasive fungal infections, NOXAFIL is given as a loading dose of 300 mg (three 100 mg modified release tablets) twice a day on the first day, then 300 mg once a day thereafter, with duration of therapy based on recovery from neutropenia or immunosuppression. NOXAFIL modified release tablets may be taken without regard to food intake.

Key safety warnings

In clinical trials, there were infrequent cases of hepatic reactions (mild to moderate elevations in liver enzymes and bilirubin) during treatment with NOXAFIL. Elevated liver function tests were generally reversible on discontinuation of therapy and in some instances normalised without interruption of therapy. Rarely, more severe hepatic reactions (including cases that have progressed to fatal outcomes) were reported in patients with serious underlying medical conditions such as haematological malignancy during treatment with NOXAFIL. Some azoles have been associated with prolongation of the QT interval on the electrocardiogram. NOXAFIL should be administered with caution to patients with potentially proarrhythmic conditions and should not be administered with medicines that are known to prolong the QT interval and are metabolised through the CYP3A4. Concomitant administration of azole antifungals including NOXAFIL with vincristine has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus. NOXAFIL should be reserved for patients receiving vincristine who have no alternative treatment options. Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during NOXAFIL therapy.

Contraindications

NOXAFIL is contraindicated in patients with known hypersensitivity to posaconazole or to any of the excipients. Coadministration of NOXAFIL and ergot alkaloids (ergotamine, dihydroergotamine) is contraindicated as NOXAFIL may increase the plasma concentration of ergot alkaloids, which may lead to ergotism. Coadministration with HMG-CoA reductase inhibitors that are primarily metabolised through CYP3A4 is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis. Coadministration of NOXAFIL with rivaroxaban or apixaban is contraindicated, as NOXAFIL may increase the plasma concentration of these medicines, which may increase the risk of bleeding.

Regulatory history

NOXAFIL posaconazole 100 mg modified release tablets were first listed on the ARTG on 2014-11-27.