posaconazole
Brand: Noxafil
TDM Required Prototype: voriconazole
Drug Class: triazole antifungal
Drug Family: antifungal
Subclass: extended-spectrum triazole
Organ Systems: infectious-disease
Mechanism of Action
Inhibits fungal CYP51; extended spectrum over voriconazole includes Mucorales (important for mucormycosis prophylaxis and treatment); used primarily for prophylaxis in high-risk immunocompromised patients.
fungal CYP51 (14-alpha-demethylase)
Indications
- invasive aspergillosis prophylaxis (high-risk patients: AML remission induction, GVHD)
- mucormycosis (prophylaxis and salvage therapy)
- oropharyngeal candidiasis (refractory or in immunocompromised)
- antifungal prophylaxis during allogeneic HSCT
Contraindications
- posaconazole hypersensitivity
- concurrent simvastatin, lovastatin, ergotamine, pimozide, quinidine, sirolimus (unless sirolimus dose monitored)
Adverse Effects
Common
- nausea
- vomiting
- diarrhea
- headache
Serious
- hepatotoxicity
- QTc prolongation
- drug interactions via CYP3A4 and P-gp inhibition
- adrenal insufficiency (rare)
Pharmacokinetics (ADME)
| Absorption | oral suspension: highly food/fat dependent — must be taken with a full meal or nutritional supplement; delayed-release tablets: not food dependent; IV: complete |
| Distribution | large Vd; extensive tissue distribution |
| Metabolism | primarily by glucuronidation (UGT); minimal CYP involvement as substrate; but potent CYP3A4 and P-gp inhibitor |
| Excretion | fecal (77%); renal (13%) |
| Half-life | 35 hours (delayed-release tablets) |
| Onset | 3–5 hours |
| Peak | 3–6 hours |
| Duration | 24 hours (once-daily delayed-release or IV) |
| Protein Binding | >98% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| tacrolimus/cyclosporine | CYP3A4 inhibition increases levels; reduce doses and monitor TDM | major |
| sirolimus | combined CYP3A4/P-gp inhibition markedly elevates sirolimus | major |
| QTc-prolonging drugs | additive QTc prolongation | major |
Nursing Considerations
- The oral suspension must be taken with a full fatty meal or liquid nutritional supplement — inadequate absorption with the suspension is a major clinical pitfall.
- Preferred formulation is the delayed-release tablet or IV solution (not food-dependent, more reliable absorption).
- Monitor LFTs weekly during the first month; monitor ECG at baseline and periodically.
- Posaconazole is critical for mucormycosis prophylaxis — counsel immunocompromised patients on the importance of adherence.
Clinical Pearls
- Posaconazole is the only triazole with activity against Mucorales (Mucor, Rhizopus species), making it unique for mucormycosis prophylaxis; isavuconazole is the only other option for Mucorales among the azoles.
- The delayed-release tablet formulation achieves more reliable exposure than the oral suspension, especially in patients with poor oral intake; this formulation switch dramatically improved clinical outcomes.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.