What is Voriconazole?
Voriconazole is a broad-spectrum, second-generation triazole antifungal medication [1.6.5]. It is used to treat serious, invasive fungal infections that are often seen in immunocompromised patients [1.6.3]. Approved by the FDA in 2002, it is effective against a wide range of pathogens, including Aspergillus species, Candida species, Scedosporium, and Fusarium [1.6.1, 1.6.3]. Its mechanism of action involves inhibiting the fungal cytochrome P450-dependent enzyme 14-alpha-lanosterol demethylation. This disruption in ergosterol synthesis, an essential component of the fungal cell membrane, ultimately leads to fungal cell death [1.6.1, 1.6.6]. Voriconazole is available in both intravenous (IV) and oral formulations, providing flexibility in treatment [1.6.5].
Is Voriconazole a Hazardous Drug?
Yes, voriconazole is classified as a hazardous drug. This designation is based on evidence of carcinogenicity and reproductive toxicity. Several major health and safety organizations have listed voriconazole due to its inherent risks.
NIOSH and IARC Classifications
The National Institute for Occupational Safety and Health (NIOSH) includes voriconazole on its list of hazardous drugs in healthcare settings [1.2.1]. Drugs on this list meet at least one of the following criteria: carcinogenicity, teratogenicity or other developmental toxicity, reproductive toxicity, organ toxicity at low doses, genotoxicity, or structure and toxicity profiles that mimic existing hazardous drugs [1.2.3].
Reinforcing this classification, in November 2024, the International Agency for Research on Cancer (IARC), part of the World Health Organization (WHO), evaluated voriconazole and classified it as Group 1, "carcinogenic to humans" [1.2.2]. This evaluation was based on sufficient evidence of cancer in humans [1.2.2]. Safety data sheets for voriconazole also identify it as suspected of causing cancer (Carcinogenicity Category 2) and damaging fertility or the unborn child (Reproductive Toxicity Category 1B/2) [1.3.3, 1.8.5].
Risks for Patients
While effective, voriconazole carries a significant side effect profile for patients. The risks must be carefully weighed against the benefits, especially for life-threatening fungal infections.
Common and Serious Side Effects:
- Visual Disturbances: This is one of the most common side effects, affecting up to 30% of patients. It can include blurred vision, changes in color perception, and photophobia (light sensitivity) [1.4.3, 1.9.2]. Driving at night is not recommended [1.4.4].
- Hepatotoxicity (Liver Damage): Elevations in liver function tests are common [1.9.5]. Serious hepatic reactions, including hepatitis, cholestasis, and fulminant hepatic failure, have been reported. Liver function should be monitored before and during treatment [1.4.3].
- Skin Reactions and Cancer Risk: Photosensitivity (increased sensitivity to sunlight) is a major concern [1.4.3]. Patients must use high-SPF sunscreen and wear protective clothing [1.4.4]. Long-term use is associated with an increased risk of developing skin cancers, particularly squamous cell carcinoma (SCC) [1.6.5, 1.9.3].
- Embryo-Fetal Toxicity: Voriconazole can cause fetal harm and is classified as FDA Pregnancy Category D [1.2.5, 1.8.1]. It is associated with teratogenicity, embryotoxicity, and embryomortality in animal studies [1.8.1, 1.8.2]. Effective contraception is required for women of childbearing potential during treatment [1.8.4].
- Cardiovascular Effects: The drug has been associated with prolongation of the QT interval on an electrocardiogram, which can lead to life-threatening heart rhythms like Torsade de pointes [1.4.3, 1.9.5].
- Neurological Effects: Hallucinations, confusion, dizziness, and headache are possible side effects [1.4.3, 1.4.6].
Risks for Healthcare Workers and Safe Handling
Because of its hazardous classification, healthcare workers who handle voriconazole are at risk of occupational exposure. This can occur through inhalation of dust from tablets or powder, skin contact, or accidental ingestion. The primary risks are related to its reproductive toxicity and carcinogenicity [1.2.3, 1.5.4].
USP General Chapter <800> provides standards for the safe handling of hazardous drugs. Facilities that handle voriconazole must adhere to these guidelines, which include:
- Personal Protective Equipment (PPE): When handling voriconazole, especially when compounding or crushing tablets, appropriate PPE is required. This includes double gloves, a non-permeable gown, and respiratory protection (e.g., N95 respirator) to avoid inhaling dust [1.5.1, 1.5.3]. Eye protection should also be worn [1.5.1].
- Engineering Controls: The drug should be handled in a controlled environment, such as a biological safety cabinet or compounding aseptic containment isolator, to minimize airborne particles [1.5.1].
- Spill Management: Spills should be cleaned immediately by trained personnel wearing full PPE. The area must be decontaminated according to established protocols [1.5.1].
- Disposal: All waste contaminated with voriconazole, including used PPE and administration equipment, must be disposed of as hazardous waste in clearly labeled, sealed containers [1.5.1].
Comparison of Antifungal Alternatives
When considering treatment, physicians may evaluate alternatives to voriconazole, especially if a patient has contraindications or is at high risk for adverse effects. Other major antifungal classes include other azoles, echinocandins, and polyenes.
| Drug/Class | Key Advantages | Key Disadvantages | Primary Use vs. Voriconazole |
|---|---|---|---|
| Posaconazole | Generally better tolerated with fewer CNS side effects; also covers Mucorales [1.7.4]. Non-inferior mortality rates in studies [1.7.2]. | Potential for GI side effects and mineralocorticoid excess [1.7.4]. | A primary alternative for invasive aspergillosis with a better safety profile [1.7.5]. |
| Isavuconazole | Broader spectrum including Mucorales; more favorable safety profile regarding QT prolongation; fewer drug interactions [1.7.4]. | Higher cost; cross-resistance with voriconazole-resistant Aspergillus is possible [1.7.3, 1.7.4]. | A primary alternative for invasive aspergillosis, often preferred for its better tolerability [1.7.3]. |
| Echinocandins (e.g., Caspofungin, Micafungin) | Excellent safety profile; fewer drug interactions. | Primarily fungistatic against Aspergillus; limited CNS penetration; IV only. | Often used for invasive candidiasis; less preferred for primary aspergillosis treatment compared to azoles [1.7.1, 1.7.4]. |
| Amphotericin B | Broadest spectrum of activity; fungicidal. | Significant toxicity, particularly nephrotoxicity (kidney damage) and infusion-related reactions [1.6.1]. | Historically a standard of care, now often reserved for severe cases or when azoles are contraindicated due to its toxicity [1.6.5]. |
Conclusion
Voriconazole is unequivocally a hazardous drug, a fact underscored by its classification as a Group 1 carcinogen by IARC and its inclusion on the NIOSH hazardous drug list [1.2.1, 1.2.2]. Its potency against life-threatening fungal infections makes it an invaluable tool in medicine, but its use demands a careful assessment of risks for patients, including potential for liver damage, skin cancer, and fetal harm [1.4.3, 1.6.5, 1.8.1]. For healthcare workers, the risks of occupational exposure necessitate strict adherence to safe handling protocols as outlined by USP <800> [1.5.1]. The availability of alternatives like posaconazole and isavuconazole, which may offer similar efficacy with improved safety profiles, provides important options in the management of invasive fungal diseases [1.7.2, 1.7.3].
Authoritative Link: NIOSH List of Hazardous Drugs in Healthcare Settings
