What is the difference between posaconazole (Noxafil) prophylaxis versus treatment dosing?

From the Guidelines

Posaconazole prophylaxis dosing is significantly lower than treatment dosing, with a recommended prophylaxis dose of 300 mg delayed-release tablets once daily (after a loading dose of 300 mg twice daily on the first day) or 200 mg oral suspension three times daily, as opposed to treatment dosing of 300 mg delayed-release tablets twice daily on the first day, followed by 300 mg once daily thereafter, or 400 mg oral suspension twice daily for severe infections 1.

Key Differences in Dosing

• Prophylaxis dosing: 300 mg delayed-release tablets once daily or 200 mg oral suspension three times daily
• Treatment dosing: 300 mg delayed-release tablets twice daily on the first day, followed by 300 mg once daily thereafter, or 400 mg oral suspension twice daily for severe infections

Rationale for Different Dosing

The difference in dosing reflects the distinct goals of prophylaxis and treatment. Prophylactic dosing aims to prevent fungal colonization in high-risk patients, whereas treatment dosing seeks to achieve fungicidal concentrations in tissues to eliminate established infections 1.

Important Considerations

• Therapeutic drug monitoring is often recommended, especially for treatment, with target trough concentrations >0.7 mg/L for prophylaxis and >1.0 mg/L for treatment
• Food significantly enhances absorption of the oral suspension, so timing with meals is important for optimal bioavailability, particularly with the suspension formulation 1

From the FDA Drug Label

Table 1: Dosing Regimens in Adult Patients Indication Dose and Frequency Duration of Therapy Prophylaxis of invasive Aspergillusand Candidainfections Posaconazole Delayed-Release Tablets: Loading dose: 300 mg (three 100 mg delayed-release tablets) twice a day on the first day Maintenance dose: 300 mg (three 100 mg delayed-release tablets) once a day, starting on the second day. Loading dose: 1 day Maintenance dose: Duration of therapy is based on recovery from neutropenia or immunosuppression.

The difference between posaconazole prophylaxis vs treatment dosing is not explicitly stated in the provided drug labels, as treatment dosing is not mentioned. However, the prophylaxis dosing is provided as a loading dose of 300 mg twice a day on the first day, followed by a maintenance dose of 300 mg once a day, starting on the second day 2. Key points to note include:

• The dosing regimen for prophylaxis of invasive Aspergillus and Candida infections
• The importance of administering posaconazole delayed-release tablets with or without food
• The non-substitutability of Noxafil oral suspension with posaconazole delayed-release tablets or Noxafil PowderMix for delayed-release oral suspension due to differences in dosing of each formulation 2.

From the Research

Posaconazole Prophylaxis vs Treatment Dosing

• Posaconazole is approved for prophylaxis against Aspergillus and Candida infections in immunocompromised patients at high risk for these infections 3.
• The European Medicines Agency (EMA) has approved posaconazole for treatment of aspergillosis, fusariosis, chromoblastomycosis, and coccidioidomycosis in patients who are refractory to or intolerant of other azoles or amphotericin B 3.
• Posaconazole has been used with success as salvage therapy for invasive mold infections and endemic mycoses in patients who are refractory to or intolerant of other antifungal agents 3.
• The dosing for posaconazole prophylaxis and treatment may vary, with prophylaxis typically involving a lower dose to prevent invasive fungal infections in high-risk patients 4, 5.
• Treatment dosing for posaconazole is often higher and used for patients with established invasive fungal infections, including aspergillosis, oropharyngeal and esophageal candidiasis 6, 7.

Efficacy and Safety

• Posaconazole has been shown to be effective in preventing invasive fungal infections in immunocompromised patients, with a significantly lower risk of IFIs compared to other antifungal agents 5.
• The safety profile of posaconazole is generally good, with rare serious side effects, even with prolonged use 3, 6.
• However, newer posaconazole formulations may achieve higher blood levels, which could potentially lead to an increase in adverse effects 3.
• Symptomatic adverse events were more common in patients receiving voriconazole compared to posaconazole 4.

Clinical Use

• Posaconazole is used predominantly for prophylaxis and salvage therapy of fungal infections in adults 3.
• Indications for use as initial therapy of fungal infections and for broader use in children will depend on the accrual of additional clinical data 3.
• Posaconazole has pharmacokinetic advantages and a low side effect profile, making it a valuable addition to the family of antifungal agents 6, 7.