Fungal infections:

Indications for: NOXAFIL INJECTION

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.

Adult Dosage:

Give by slow IV infusion over ~90mins via central venous line (including central venous catheter or PICC); if unavailable, may give via peripheral venous catheter over ~30mins only as a single dose in advance of central line placement. 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 thereafter until recovery from neutropenia or immunosuppression.

Children Dosage:

Give by slow IV infusion over ~90mins via central venous line (including central venous catheter or PICC); if unavailable, may give via peripheral venous catheter over ~30mins only as a single dose in advance of central line placement. Invasive aspergillosis treatment: <13yrs: not established. Invasive fungal prophylaxis: <2yrs (≤40kg): not established; 2–<18yrs (>40kg): 6mg/kg (max 300mg) twice a day on Day 1, then 6mg/kg (max 300mg) once daily thereafter until recovery from neutropenia or immunosuppression.

NOXAFIL INJECTION Contraindications:

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).

NOXAFIL INJECTION Warnings/Precautions:

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.

NOXAFIL INJECTION Classification:

Azole antifungal.

NOXAFIL INJECTION Interactions:

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.

Adverse Reactions:

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.

Generic Drug Availability:

NO

How Supplied:

Tabs—60; Susp—105mL (w. dosing spoon); Vials—1; Packets—1, 8, Kit (8 packets w. supplies)