Noxafil Posaconazole Enteric-coated Tablets

1. Indications and Usage
Invasive Aspergillosis: Treatment of invasive aspergillosis in adult patients who are refractory to or intolerant of other antifungal agents (e.g., amphotericin B, itraconazole, voriconazole).
Oropharyngeal Candidiasis (OPC): Treatment of oropharyngeal candidiasis, including refractory cases.
Prophylaxis of Invasive Fungal Infections (IFI): Prophylaxis in adult patients who are at high risk of developing IFIs due to severe immunosuppression (e.g., hematopoietic stem cell transplant recipients with graft-versus-host disease or patients with hematologic malignancies and prolonged neutropenia).
Empirical Therapy: Empirical therapy for presumed fungal infection in febrile neutropenic adult patients.
2. Dosage and Administration
Administration: Oral administration. Tablets must be swallowed whole and should not be chewed or crushed.
Food Requirement: Unlike the oral suspension, the enteric-coated tablets provide consistent absorption under fasting conditions; administration with food is not required.
Dosing (Adults):
Treatment of Invasive Aspergillosis: 300 mg twice daily on Day 1 (loading dose), followed by 300 mg once daily thereafter.
Treatment of OPC:
Susceptible: 100 mg once daily on Day 1 (loading dose), followed by 100 mg once daily for 13 days.
Refractory: 400 mg twice daily on Day 1 (loading dose), followed by 400 mg once daily thereafter.
Prophylaxis: 300 mg twice daily on Day 1 (loading dose), followed by 300 mg once daily thereafter.
Empirical Therapy: 300 mg twice daily on Day 1 (loading dose), followed by 300 mg once daily thereafter.
3. Mechanism of Action
Triazole Antifungal: Posaconazole is a synthetic broad-spectrum triazole antifungal agent.
Pathway: It inhibits the fungal cytochrome P450-dependent enzyme 14α-demethylase. This enzyme is responsible for converting lanosterol to ergosterol.
Physiological Effect: Inhibition of ergosterol biosynthesis disrupts the integrity and function of the fungal cell membrane, leading to fungal cell growth arrest or death.
4. Safety and Warnings
QTc Prolongation: Posaconazole may cause QT interval prolongation and is a known cause of Torsades de Pointes. It should be used with caution in patients with cardiovascular disease or those taking other QT-prolonging drugs.
Hepatotoxicity: Cases of severe liver toxicity (including liver failure) have been reported. Liver function tests (ALT, AST) should be monitored during therapy.
Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, skin reactions (e.g., Stevens-Johnson syndrome), and angioedema, may occur.
Embryo-Fetal Toxicity: Based on animal data, may cause fetal harm.
5. Adverse Reactions
Most Common: Nausea, vomiting, diarrhea, headache, pyrexia, cough, and increased hepatic enzymes (ALT/AST).
Other: Hypokalemia, hypomagnesemia, hypophosphatemia, rash, and fatigue.
6. Drug Interactions
CYP3A4 Substrates: Posaconazole is a potent inhibitor of CYP3A4. Concomitant use with CYP3A4 substrates (e.g., midazolam, sirolimus, tacrolimus, cyclosporine, simvastatin) can significantly increase their plasma concentrations.
Contraindicated: Sirolimus, simvastatin, lovastatin, quinine, terfenadine, astemizole.
Dose Adjustment/Monitoring Required: Tacrolimus, cyclosporine, midazolam.
CYP3A4 Inducers: Strong inducers (e.g., rifampin, phenytoin) may significantly decrease posaconazole plasma concentrations and are generally not recommended.
Acid-Reducing Agents: PPIs or H2 blockers may decrease the exposure of the oral suspension but generally have no clinically significant effect on the enteric-coated tablets.
7. Pharmaceutical Information
Chemical Name: ‌4-{4-[4-(4-{[(3R,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydrofuran-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one‌