NOXAFIL POWDERMIX for ORAL SUSP Dosage & Rx Info

Noxafil Powdermix For Oral Susp Generic Name & Formulations

Legal Class

General Description

Posaconazole 300mg; per packet; pwd for delayed-release oral susp after reconstitution; berry citrus sweet flavor; contains sorbitol.

Pharmacological Class

Azole antifungal.

How Supplied

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

Manufacturer

Merck & Co., Inc.

Generic Availability

Tabs, Susp, Vials (YES); Packets (NO)

Mechanism of Action

Blocks synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14α-demethylase responsible for the conversion of lanosterol to ergosterol in the fungal cell membrane.

Noxafil Powdermix For Oral Susp Indications

Indications

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.

Noxafil Powdermix For Oral Susp Dosage and Administration

Adult

Not applicable.

Children

<2yrs: not established; >40kg: not recommended. Take with food. Ensure delivery of correct dose using provided notched tip syringes. 2–<18yrs (10–<12kg): 90mg twice daily on Day 1, then 90mg once daily; (12–<17kg): 120mg twice daily on Day 1, then 120mg once daily; (17–<21kg): 150mg twice daily on Day 1, then 150mg once daily; (21–<26kg): 180mg twice daily on Day 1, then 180mg once daily; (26–<36kg): 210mg twice daily on Day 1, then 210mg once daily; (36–40kg): 240mg twice daily on Day 1, then 240mg once daily. Continue treatment until recovery from neutropenia or immunosuppression.

Administration

Swallow whole. Take with food. Not interchangeable with oral suspension.

Nursing Considerations

Swallow whole. Take with food. Not interchangeable with oral suspension. Monitor for breakthrough fungal infections in patients who cannot eat a full meal, or tolerate an oral nutritional supplement, or those with severe renal impairment, severe diarrhea, vomiting, or >120kg.

Noxafil Powdermix For Oral Susp Contraindications

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 Powdermix For Oral Susp Boxed Warnings

Not Applicable

Noxafil Powdermix For Oral Susp Warnings/Precautions

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 Powdermix For Oral Susp Pharmacokinetics

Metabolism

Hepatic (CYP3A4).

Elimination

Fecal (71%), renal (13%). Half-life: 27 hours (inj); 26–31 hours (tabs); 35 hours (oral susp).

Noxafil Powdermix For Oral Susp Interactions

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.

Noxafil Powdermix For Oral Susp Adverse Reactions

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.

Noxafil Powdermix For Oral Susp Clinical Trials

See Literature

Noxafil Powdermix For Oral Susp Note