Indications for: NOXAFIL
Treatment of invasive aspergillosis in patients aged ≥13yrs. Prophylaxis against invasive Aspergillus and Candida infections, in patients at high risk due to being severely immunocompromised, such as hematopoietic stem cell transplant recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia due to chemotherapy.
Swallow whole. Invasive aspergillosis treatment: ≥13yrs: 300mg twice a day on Day 1, then 300mg once daily starting on Day 2; total duration: 6–12 weeks. Invasive fungal prophylaxis: 300mg twice a day on Day 1, then 300mg once daily starting on Day 2 until recovery from neutropenia or immunosuppression.
Invasive aspergillosis treatment: <13yrs: not established. Invasive fungal prophylaxis: <2yrs (≤40kg): not applicable. Swallow whole. 2–<18yrs (>40kg): 300mg twice a day on Day 1, then 300mg once daily thereafter until recovery from neutropenia or immunosuppression.
Concomitant sirolimus, ergot alkaloids, or HMG-CoA reductase inhibitors (eg, atorvastatin, lovastatin, simvastatin). Drugs that cause QT prolongation and are metabolized by CYP3A4 (eg, quinidine, pimozide). Concomitant venetoclax (at initiation and during the ramp-up phase) in those with leukemia or lymphoma. PowderMix: known or suspected hereditary fructose intolerance (HFI).
Tabs, oral susp, and PowderMix susp are not interchangeable. Proarrhythmic conditions. Correct potassium, calcium, magnesium levels before and during therapy. Evaluate and monitor LFTs before and during therapy; consider discontinuing if liver disease occurs. Patients who cannot eat a full meal or tolerate an oral nutritional supplement, or those with severe renal impairment, severe diarrhea, vomiting, or >120kg: monitor for breakthrough fungal infections. Inj: avoid in moderate or severe renal impairment (eGFR <50mL/min); if needed, monitor and consider switching to oral therapy if creatinine levels increase. PowderMix: may precipitate a metabolic crisis due to presence of sorbitol; obtain history of HFI symptoms (with sorbitol/fructose/sucrose) exposure prior to initiation. Pregnancy. Nursing mothers.
See Contraindications. Avoid drugs that lower posaconazole levels (eg, rifabutin, phenytoin, efavirenz, fosamprenavir); monitor for breakthrough fungal infections. Potentiates calcineurin-inhibitors (eg, cyclosporine, tacrolimus); monitor trough levels frequently during and at discontinuation of posaconazole; adjust tacrolimus or cyclosporine doses. Potentiates CYP3A4 substrates (eg, ritonavir, atazanavir, calcium channel blockers, vinca alkaloids, rifabutin, phenytoin), digoxin; monitor and consider dose reduction. Neurotoxicity with concomitant vincristine; reserve azole antifungals for those who have no alternative treatment options. Prolonged hypnotic and sedative effects with concomitant midazolam or other benzodiazepines (eg, alprazolam, triazolam). Monitor glucose levels with glipizide. May increase venetoclax toxicities with concomitant use. Susp: avoid concomitant cimetidine, esomeprazole, metoclopramide; if needed, monitor for breakthrough fungal infections. PowderMix: avoid concomitant alcohol.
Fever, diarrhea, nausea, vomiting, headache, hypokalemia, cough; also children: febrile neutropenia, mucosal inflammation, pruritus, hypertension, stomatitis; lab abnormalities (eg, anemia, neutropenia, thrombocytopenia, increased liver enzymes), arrhythmias, QT prolongation.
Fecal (71%), renal (13%). Half-life: 27 hours (inj); 26–31 hours (tabs); 35 hours (oral susp).
Generic Drug Availability:
Tabs, Susp, Vials (YES); Packets (NO)
Tabs—60; Susp—105mL (w. dosing spoon); Vials—1; Packets—1, 8, Kit (8 packets w. supplies)