Posaconazole
Mechanism :
Interferes with fungal cytochrome P450 (lanosterol-14a-demethylase) activity, decreasing ergosterol synthesis.
Indication :
- Prophylaxis of invasive Aspergillus and Candida infections
- Oropharyngeal candidiasis (13 years and older)
Contraindications :
Co-administration with sirolimus, ergot alkaloids, HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4, or CYP3A4 substrates that prolong the QT interval; hypersensitivity to posaconazole, other azole antifungal agents, or any component of the formulation.
Dosing :
Candida and aspergillosis prophylaxis:
≥13 years:
Oral: Suspension:
200 mg 3 times daily.
IV:
Initial: 300 mg twice daily on day 1; Maintenance dose: 300 mg once daily on day 2 and thereafter.
Duration of therapy is based on recovery from neutropenia or immunosuppression.
Treatment of Oropharyngeal infection:
≥13 years:
Initial: 100 mg PO twice daily on day 1. Maintenance: 100 mg OD on day 2 and thereafter for 13 days. For infections refractory to
itraconazole and
fluconazole, the FDA-labelled dose is 400 mg PO twice daily.
Mucocutaneous candidiasis:
≥13 years:
400 mg PO twice daily for 14 to 21 days in patients with refractory disease.
Disseminated histoplasmosis:
≥13 years:
400 mg PO twice daily for at least 12 months.
Adverse Effect :
Thrombophlebitis, hypertension, peripheral edema, headache, rigors, fatigue, skin rash, hypokalemia, hypermagnesemia, hyperglycemia, diarrhea, vomiting, nausea, anorexia, constipation, thrombocytopenia, anemia. Neutropenia, increased AST, musculoskeletal pain, cough, dyspnea, fever.
Interaction :
Antineoplastic Agents (Vinca Alkaloids): Posaconazole may enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids).
CYP3A4 Substrates: CYP3A4 Inhibitors may decrease the metabolism of CYP3A4 Substrates.
Digoxin: Posaconazole may increase the serum concentration of Digoxin.
Dihydroergotamine: Posaconazole may increase the serum concentration of Dihydroergotamine.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Unknown dialysability. Dose as in normal renal function |
| CAV/VVHD | Not dialysed. Dose as in normal renal function |
Hepatic Dose :
No dose adjustment recommended.
If hepatotoxicity develops during treatment: Consider stopping the therapy.