Background and importance Voriconazole is the primary treatment for invasive pulmonary aspergillosis. Antifungal nebulisation has advantages, but there are no commercial antifungal pharmaceutical presentations for nebulisation.
Aim and objectives To physicochemically characterise a compounded voriconazole solution for nebulisation and to describe its use in a cohort of patients.
Material and methods Voriconazole solution for nebulisation was prepared in the Pharmacy Department. Accord, Kern and Normon vials were used.
Clinical data from patients treated with nebulised voriconazole in our hospital were retrospectively collected.
Voriconazole concentration in plasma was determined using high-performance liquid chromatography.
Results Voriconazole vials containing 200 mg of powder for solution for infusion were diluted with sterile water for injection (19 mL). The solutions were adequate for nebulisation (pH 4.97, 7 and 5; osmolarity 359, 503 and 313 mOsm/kg, respectively). Syringes containing 40 mg/4 mL were dispensed.
Ten patients received nebulised voriconazole, 9 adults and 1 child; median age was 35 years (minimum 5 and maximum 69 years), all men. Five patients had cystic fibrosis and 8 had undergone lung transplantation (LT) 7 (0–84) months ago. 6 patients had respiratory distress and 2 were colonised. Treatment was started on the hospital floor (5), intensive care unit (3) or outpatient department (2).
Fungi detected were Aspergillus spp (5) (A. flavus (4)), Scedosporium spp (4) and Purpureocilium spp (1).
Treatment was started due to lack of response to systemic treatment (4), toxicity (4), avoiding drug-drug interactions (2), post-LT prophylaxis (1) and booster oral voriconazole effect (1).
Doses (40 mg for adults, 10 mg for children) were administered every 12–24 hours (2–3 days in the case of colonisation) during a median of 130 (26–911) days.
Three patients died, 3 fungal infections resolved, 2 had colonisation without exacerbations, there was one case of voriconazole resistance and the patient using voriconazole as prophylaxis had a successful evolution.
No adverse events were reported, only mild pruritus in a patient with a history of allergy (treatment withdrawal was not required).
There were 11 voriconazole plasma measurements for 6 patients. Voriconazole was only detected in 2 patients receiving oral voriconazole.
Conclusion and relevance The characteristics of the compounded voriconazole solution are adequate for nebulisation.
Compounded voriconazole solution is well tolerated and it is not absorbed into the systemic circulation.
Nebulised voriconazol could be an interesting therapeutic option to treat pulmonary infections and/or colonisations.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.