What are the side effects of posaconazole?

Posaconazole Side Effects

Posaconazole is generally well tolerated, but it can cause several important side effects including gastrointestinal disturbances, liver toxicity, QTc prolongation, and significant drug interactions that require monitoring and potential dose adjustments. 1, 2

Common Side Effects

• Gastrointestinal effects:
  • Diarrhea
  • Nausea
  • Vomiting
  • Fever
  • Headache
  • Cough 2

Serious Side Effects

Hepatic Effects

• Liver toxicity (primarily mild but can be severe)
• Elevated liver enzymes
• Abnormal liver function test values
• In rare cases, severe liver problems that may lead to death, especially in patients with serious underlying medical conditions 1, 2

Cardiovascular Effects

• QTc interval prolongation
• Arrhythmias
• Heart rhythm problems 1, 2

Electrolyte Abnormalities

• Low potassium levels (hypokalemia)
• Changes in body salt (electrolyte) levels 1, 2

Drug Interactions

• Significant interactions with:
  • Cyclosporine and tacrolimus: Increased blood levels that can cause serious kidney or brain side effects
  • Midazolam: Increased blood levels leading to prolonged sedation
  • CYP3A4 substrates: Posaconazole inhibits CYP3A4 enzymes, potentially increasing plasma concentrations of other medications 1, 2

Monitoring Recommendations

1. Therapeutic Drug Monitoring (TDM):

   • Recommended for patients on posaconazole therapy
   • Particularly important with the delayed-release tablets that may achieve high drug concentrations
   • Very high serum concentrations (≥3000 ng/mL) are associated with increased adverse drug reactions 3

2. Laboratory Monitoring:

   • Regular liver function tests
   • Electrolyte levels, particularly potassium
   • Blood levels of cyclosporine or tacrolimus if co-administered

3. ECG Monitoring:

   • Particularly in patients taking other QTc-prolonging medications
   • Caution when combined with fluoroquinolones, macrolides, ondansetron, and certain chemotherapies 1

Formulation-Specific Considerations

• Delayed-release tablets: May have higher serum levels and potentially more toxicities than the oral suspension 1
• Oral suspension: Requires administration with food to maximize absorption 1

Special Populations

• Renal impairment: No dosage adjustments required for patients with varying degrees of renal disease, including those on hemodialysis 4

Risk Factors for Increased Toxicity

• Concomitant use of other QTc-prolonging medications
• Pre-existing liver dysfunction
• Higher posaconazole serum concentrations
• Drug interactions affecting CYP3A4 pathway

Clinical Pearls

• Report diarrhea or vomiting to healthcare providers immediately 2
• Avoid concomitant use with drugs that interact with CYP3A4 when possible
• Unlike voriconazole, posaconazole is not associated with visual disturbances, photosensitivity reactions, or fluoride-related periostitis 1
• Long-term posaconazole treatment has been shown to have a favorable safety profile without increasing the risk of adverse events 5

Remember that posaconazole's toxicity profile is generally more favorable than some other triazoles, but careful monitoring remains essential, especially when used at higher doses or for prolonged periods.