Why Monitor Voriconazole Levels?
Voriconazole is the drug of choice for treating invasive aspergillosis, and is also used against infections caused by Fusarium species.
Patients at high risk for invasive fungal infections include:
- Immunocompromised individuals
- Those with haematological malignancies
- Stem cell transplant recipients
Advantages of voriconazole:
- Broad antifungal spectrum (including mould activity)
- Oral formulation available
- Suitable for prolonged treatment and secondary prophylaxis
Challenges with Voriconazole Dosing
Voriconazole has:
- A narrow therapeutic index
- High inter- and intra-patient variability in drug levels
- Complex PK/PD (pharmacokinetics/pharmacodynamics)
Factors contributing to variability in levels include:
- Genetic polymorphisms in CYP2C19 (e.g. fast or slow metabolism)
- Drug interactions with other medications
- Variable gastrointestinal absorption
Toxicity increases significantly at trough levels ≥6 mg/L
Trough levels of 1–5.5 mg/L are generally required for efficacy
In severe infections, a target trough level of 2–6 mg/L is recommended
Role of CYP2C19 Genotyping
CYP2C19 mutations affect voriconazole metabolism:
- Slow metabolisers → risk of toxicity
- Fast metabolisers → risk of subtherapeutic levels
Genetic testing is available at Ampath
- Mnemonic: CYP19
Consider pharmacogenetic testing if clinical response is suboptimal or toxicity is suspected.
When to Monitor Voriconazole Levels
Therapeutic drug monitoring (TDM) is indicated in the following situations:
- Patient has a poor clinical response
- Toxicity is suspected (e.g. neurotoxicity or visual disturbances)
- Treatment of life-threatening fungal infections such as invasive aspergillosis
- Concurrent use of interacting medications
- Haematopoietic stem cell transplant recipients, both for treatment and prophylaxis
- Paediatric patients, due to rapid drug elimination and high variability in levels
Sample Collection Guidelines
Timing:
- Collect a serum trough level sample (30 minutes before the next dose)
- Initial test: 2–5 days after starting treatment
- Repeat test: After 1 week to ensure therapeutic range is maintained
Ongoing Monitoring:
- Continue monitoring until a steady-state therapeutic level is achieved
- Repeat if:
- Clinical condition changes
- Concomitant medications are introduced or changed
- Toxicity is suspected