POSACONAZOLE

General Pharmacokinetic Characteristics Posaconazole delayed-release tablets exhibit dose proportional pharmacokinetics after single and multiple dosing up to 300 mg. The mean pharmacokinetic parameters of posaconazole at steady state following administration of posaconazole delayed-release tablets 300 mg twice daily on Day 1, then 300 mg once daily thereafter in healthy volunteers and in neutropenic patients who are receiving cytotoxic chemotherapy for AML or MDS or HSCT recipients with GVHD ar...

14.2 Prophylaxis of Aspergillus and Candida Infections with Noxafil ® Oral Suspension Two randomized, controlled studies were conducted using posaconazole as prophylaxis for the prevention of invasive fungal infections (IFIs) among patients at high risk due to severely compromised immune systems. The first study (Noxafil ® Oral Suspension Study 1) was a randomized, double-blind trial that compared Noxafil ® oral suspension (200 mg three times a day) with fluconazole capsules (400 mg once daily) as prophylaxis against invasive fungal infections in allogeneic hematopoietic stem cell transplant (...

The following serious and otherwise important adverse reactions are discussed in detail in another section of the labeling: Hypersensitivity [see Contraindications (4.1) ] Arrhythmias and QT Prolongation [see Warnings and Precautions (5.2) ] Hepatic Toxicity [see Warnings and Precautions (5.5) ] Adult Patients: Common adverse reactions in studies with posaconazole in adults are diarrhea, nausea, fever, vomiting, headache, coughing, and hypokalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTION...

Known hypersensitivity to posaconazole or other azole antifungal agents. ( 4.1 ) Coadministration of posaconazole with the following drugs is contraindicated; posaconazole increases concentrations and toxicities of: Sirolimus ( 4.2 , 5.1 , 7.1 ) CYP3A4 substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of torsades de pointes (TdP) ( 4.3 , 5.2 , 7.2 ) HMG-CoA Reduct...

Calcineurin-Inhibitor Toxicity : Posaconazole increases concentrations of cyclosporine or tacrolimus; reduce dose of cyclosporine and tacrolimus and monitor concentrations frequently. ( 5.1 ) Arrhythmias and QTc Prolongation : Posaconazole has been shown to prolong the QTc interval and cause cases of TdP. Administer with caution to patients with potentially proarrhythmic conditions. Do not administer with drugs known to prolong QTc interval and metabolized through CYP3A4. ( 5.2 ) Electrolyte Dis...

7 DRUG INTERACTIONS Posaconazole is primarily metabolized via UDP glucuronosyltransferase and is a substrate of p-­glycoprotein (P-gp) efflux. Therefore, inhibitors or inducers of these clearance pathways may affect posaconazole plasma concentrations. Coadministration of drugs that can decrease the plasma concentrations of posaconazole should generally be avoided unless the benefit outweighs the r...