xafil delayed-release tablets should be used only for the prophylaxis indication. Noxafil delayed-release tablets provide higher plasma drug exposures than Noxafil oral suspension under fasted conditions.
• In patients who cannot eat a full meal and for whom Noxafil delayed-release tablets are not an option, each dose of Noxafil oral suspension should be administered with a liquid nutritional supplement or an acidic carbonated beverage.
• For patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage and who do not have the option of taking Noxafil delayed-release tablets, an alternative antifungal therapy should be considered or patients should be monitored closely for breakthrough fungal infections.
3 DOSAGE FORMS AND STRENGTHS
Noxafil 100 mg delayed-release tablets are available as yellow, coated, oblong tablets, debossed with "100" on one side.
Noxafil oral suspension is available in 4-ounce (123 mL) amber glass bottles with child-resistant closures containing 105 mL of suspension (40 mg of posaconazole per mL).
4 CONTRAINDICATIONS
4.1 Hypersensitivity
Noxafil is contraindicated in persons with known hypersensitivity to posaconazole, any component of Noxafil, or other azole antifungal agents.
4.2 Use with Sirolimus
Noxafil is contraindicated with sirolimus. Concomitant administration of Noxafil with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
4.3 QT Prolongation with Concomitant Use with CYP3A4 Substrates
Noxafil is contraindicated with CYP3A4 substrates that prolong the QT interval. Concomitant administration of Noxafil with the CYP3A4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and cases of torsades de pointes [see Warnings and Precautions (5.2) and Drug Interactions (7.2)].
4.4 HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4
Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].
4.5 Use with Ergot Alkaloids
Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions (7.4)].
5 WARNINGS AND PRECAUTIONS
5.1 Calcineurin-Inhibitor Drug Interactions
Concomitant administration of Noxafil with cyclosporine or tacrolimus increases the whole blood trough concentrations of these calcineurin-inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Nephrotoxicity and leukoencephalopathy (including deaths) have been reported in clinical efficacy studies in patients with elevated cyclosporine or tacrolimus concentrations. Frequent monitoring of tacrolimus or cyclosporine whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the tacrolimus or cyclosporine dose adjusted accordingly.
5.2 Arrhythmias and QT Prolo
