What is the correct dosage of Posaconazole (posaconazole) for treating aspergillosis with a positive bronchoscopy?

Posaconazole Dosing for Aspergillosis with Positive Bronchoscopy

For treating aspergillosis with positive bronchoscopy findings, posaconazole should be dosed as follows: oral tablets 300 mg twice daily on day 1 (loading dose), followed by 300 mg once daily; or for intravenous formulation, 300 mg twice daily on day 1, followed by 300 mg once daily.

Dosing Recommendations Based on Formulation

Intravenous Formulation

• Loading dose: 300 mg IV twice daily on day 1
• Maintenance dose: 300 mg IV once daily 1

Oral Tablet Formulation

• Loading dose: 300 mg PO twice daily on day 1
• Maintenance dose: 300 mg PO once daily 1

Oral Suspension (less preferred due to variable absorption)

• Initial dose: 200 mg (5 mL) four times daily
• After disease stabilization: 400 mg (10 mL) twice daily 1
• Note: Oral suspension should be taken with fatty food to maximize absorption

Treatment Duration and Monitoring

• Treatment should continue until resolution or stabilization of all clinical and radiographic manifestations 1
• For invasive aspergillosis: minimum treatment duration of 6-12 weeks
• For chronic pulmonary aspergillosis: minimum 6 months of therapy is recommended (AI) 1
• Therapeutic drug monitoring is strongly recommended to ensure adequate plasma concentrations:
  • Target trough concentration for treatment: ≥1.0 mg/L 2, 3
  • Target trough concentration for prophylaxis: ≥0.7 mg/L 4

Special Considerations

Refractory Disease

For patients with refractory aspergillosis, posaconazole is recommended with a strength of recommendation B, quality of evidence II 1. In this setting, the same dosing regimen applies.

Patient Weight Considerations

• For patients ≥100 kg with invasive disease, consider a more intensive loading regimen of 300 mg every 8 hours for the first two days of treatment 2
• For maintenance therapy in critically ill patients, some evidence suggests 400 mg daily may be more effective for achieving target concentrations 2

Formulation Selection

• Tablet and IV formulations provide more reliable bioavailability compared to oral suspension 3, 4
• The delayed-release tablet achieves target concentrations in 92% of patients versus 47% with oral suspension 4

Efficacy and Safety

• Posaconazole has been shown to be non-inferior to voriconazole for primary treatment of invasive aspergillosis with potentially fewer treatment-related adverse events 5
• For chronic pulmonary aspergillosis, posaconazole demonstrated clinical response in 61% of patients at 6 months 6
• Common adverse effects include increased liver enzymes, nausea, hypokalaemia, and vomiting 5

Treatment Algorithm

1. Confirm aspergillosis diagnosis with positive bronchoscopy
2. Assess patient's ability to take oral medications and weight
3. Select appropriate formulation (tablet preferred over suspension if oral route possible)
4. Administer loading dose on day 1
5. Continue with maintenance dose
6. Monitor drug levels after 5-7 days of therapy (target >1.0 mg/L)
7. Adjust dose if necessary based on therapeutic drug monitoring
8. Continue treatment until clinical and radiological resolution

Remember that therapeutic drug monitoring is essential to ensure optimal treatment outcomes, particularly when using posaconazole for treatment rather than prophylaxis.