September 2019
Ampath | ampath.co.za
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
📌 For further clinical advice or assistance with testing, contact your local Ampath pathologist.