Posaconazole
NOXAFIL
Pronunciation: poe-sa-KON-a-zoel (NOX-a-fil)
What it isTriazole antifungal; prophylaxis in neutropenia and mucormycosis.
Why this oneThe broadest azole spectrum, covering Mucorales, which voriconazole does not.
What limits itA strong CYP3A4 inhibitor. The delayed-release tablet absorbs far better than the suspension and they are not interchangeable.
FDA-approved for
- fungal prophylaxis (2006)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Prophylaxis of invasive Aspergillus and Candida infections | Adults | 300 mg BID ×1 day (load) | 300 mg QD | 300 mg QD |
| Prophylaxis of invasive Aspergillus and Candida infections | Peds 13 to <18 yr, >40 kg | 300 mg BID ×1 day (load) | 300 mg QD | 300 mg QD |
Renal No dosage adjustment; monitor closely for breakthrough fungal infections in severe renal impairment
Hepatic Undefined
Not substitutable with the oral suspension / PowderMix formulations
Instructions
- Swallow whole; do not divide, crush, or chew
- Take with or without food
- Not substitutable with Noxafil Oral Suspension or PowderMix (different dosing)
Available strengths
- DR tab 100 mg
- susp 300 mg
- susp 40 mg/mL
- inj 18 mg/mL
- tab 100 mg
Contraindications
- Hypersensitivity to other azole antifungal agents
- Coadministration with sirolimus
- Coadministration with CYP3A4 substrates that prolong QT (pimozide, quinidine) — risk of TdP
- Coadministration with HMG-CoA reductase inhibitors primarily metabolized by CYP3A4
- Coadministration with ergot alkaloids
- Coadministration with venetoclax at initiation/ramp-up in CLL/SLL
Cautions
- Calcineurin-inhibitor (cyclosporine/tacrolimus) toxicity
- QTc prolongation / torsades de pointes
- Electrolyte disturbances (K+, Mg++, Ca++)
- Pseudoaldosteronism (hypertension, hypokalemia)
- Hepatic toxicity
- Prolonged midazolam sedation
- Vincristine neurotoxicity
Adverse reactions
- Diarrhea
- Nausea
- Fever
- Vomiting
- Headache
- Cough
- Hypokalemia
Pregnancy May cause fetal harm based on animal data (skeletal malformations)
Lactation No human data; present in rat milk
Cost
Generic entry2019
NO BOXED WARNINGS
Principal riskA strong CYP3A4 inhibitor; formulations are not interchangeable
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityHepatotoxicity and clinically important CYP/QT interactions; organ toxicity varies markedly by agent.