AXOFIL

What it is

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

Approved indications —

Invasive aspergillosis in patients intolerant of, or with disease that is refractory to, alternative therapy. — Fusariosis, zygomycosis, coccidioidomycosis, chromoblastomycosis, and mycetoma in patients intolerant of, or with disease that is refractory to, alternative therapy. — 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 (HSCT) recipients.

Dosing overview

For refractory invasive fungal infections or intolerant patients with invasive fungal infections, the loading dose is 300 mg (three 100 mg modified release tablets) twice a day on the first day, then 300 mg (three 100 mg modified release tablets) once a day thereafter, and each dose may be taken without regard to food intake. 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, the loading dose is 300 mg (three 100 mg modified release tablets) twice a day on the first day, then 300 mg (three 100 mg modified release tablets) once a day thereafter, with duration of therapy based on recovery from neutropenia or immunosuppression, and modified release tablets can be taken without regard to food intake.

Key safety warnings

Hepatic reactions including mild to moderate elevations in liver enzymes have been reported during treatment with posaconazole, and elevated liver function tests were generally reversible on discontinuation 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. Some azoles have been associated with prolongation of the QT interval on the electrocardiogram. Posaconazole should be administered with caution to patients with potentially proarrhythmic conditions and should not be administered with medicines that are known to prolong the QTc interval and are metabolised through the CYP3A4. Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary, before and during posaconazole therapy. Concomitant administration of azole antifungals, including posaconazole, 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. Azole antifungals, including posaconazole, should be reserved for patients receiving a vinca alkaloid, including vincristine, who have no alternative treatment options. Posaconazole may cause increased risk of photosensitivity reaction. Patients should be advised to avoid sun exposure during treatment without adequate protection such as protective clothing and sunscreen with a high sun protection factor.

Contraindications

AXOFIL is contraindicated in patients with known hypersensitivity to posaconazole or to any of the excipients. Coadministration of posaconazole and ergot alkaloids (ergotamine, dihydroergotamine) is contraindicated as posaconazole may increase the plasma concentration of ergot alkaloids, which may lead to ergotism. Coadministration with the 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 posaconazole with rivaroxaban or apixaban is contraindicated, as posaconazole may increase the plasma concentration of these medicines, which may increase the risk of bleeding.

Regulatory history

AXOFIL posaconazole 100 mg modified release tablets were first listed on the ARTG on 12 November 2020.