Noxafil (Posaconazole)

Posaconazole is an antifungal agent used to manage serious fungal diseases, particularly in high‑risk patient groups.

• Invasive aspergillosis: helps control infection and improve survival in patients with compromised immunity.
• Prophylaxis of fungal infections: prevents invasive candidiasis and aspergillosis in patients undergoing hematopoietic stem‑cell transplantation.
• Refractory candidiasis: provides an oral treatment option when first‑line agents are ineffective.
• Chronic pulmonary aspergillosis: reduces fungal burden and stabilises lung function.
• Empirical therapy for febrile neutropenia: adds coverage against yeasts and molds when fever persists despite broad‑spectrum antibiotics.

• Posaconazole inhibits the fungal enzyme lanosterol 14α‑demethylase, a cytochrome P450‑dependent protein essential for converting lanosterol to ergosterol. By blocking ergosterol synthesis, the drug disrupts fungal cell membrane integrity, leading to increased permeability and ultimately cell death. This mechanism provides broad activity against yeasts and molds, including Aspergillus and Candida species.

Adverse reactions to posaconazole vary in frequency and severity.

Common Side Effects

• Nausea: mild to moderate stomach upset.
• Diarrhea: loose stools, often transient.
• Headache: mild, intermittent.
• Elevated liver enzymes: mild increases in ALT/AST.
• Fatigue: general tiredness.
• Abdominal pain: cramping or discomfort.

Serious or Rare Side Effects

• Hepatotoxicity: significant liver injury, jaundice or elevated bilirubin.
• QT prolongation: cardiac rhythm disturbance that may predispose to arrhythmia.
• Severe hypersensitivity: rash, angioedema, or anaphylaxis.
• Visual disturbances: blurred vision or photophobia.
• Thromboembolic events: rare clot formation.
• Acute pancreatitis: sudden abdominal pain with elevated enzymes.

Posaconazole requires careful monitoring in several clinical situations.

• Liver function: assess baseline enzymes and monitor periodically.
• Cardiac risk: evaluate QT interval in patients with known arrhythmias or electrolyte abnormalities.
• Drug interactions: review concomitant medications that affect CYP3A4.
• Pregnancy and lactation: avoid use unless benefits outweigh potential risks.
• Renal impairment: adjust therapy based on clinical response, as no dose reduction is required.
• Store at below 25°C: keep in the original container, protect from moisture and direct sunlight.

Posaconazole interacts with several medicines through CYP3A4 inhibition and other pathways.

Major Interactions (Avoid)

• Rifampicin: markedly reduces posaconazole exposure, compromising efficacy.
• St. John’s wort: strong CYP3A4 inducer that lowers posaconazole levels.
• Certain anti‑arrhythmics (e.g., amiodarone): may increase risk of QT prolongation.

Moderate Interactions (Monitor Closely)

• Statins metabolised by CYP3A4 (e.g., simvastatin): may require dose adjustment.
• Proton pump inhibitors: can reduce absorption of the oral suspension.
• Midazolam: increased sedation due to CYP3A4 inhibition.