Three widely prescribed medicines have been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC), the cancer research branch of the World Health Organization. The drugs are hydrochlorothiazide, a common blood pressure medicine; voriconazole, an antifungal drug; and tacrolimus, which is given to organ transplant patients to prevent rejection.

The findings are part of Volume 137 of the IARC Monographs, prepared after a group of international experts met in Lyon, France, in November 2024 to review existing research on these drugs.

All three have now been placed in Group 1, IARC’s highest category of certainty, alongside substances such as tobacco smoke and asbestos. However, this does not mean these medicines pose the same level of cancer risk as tobacco or asbestos. It means the evidence that they can cause cancer in humans is strong and consistent, not that the size of the risk is the same.

The report states that the evaluation for each drug is “based on sufficient evidence for cancer in humans”, the strongest category of proof IARC uses.

The IARC review examined the evidence for each drug separately and linked each to specific types of cancer.

Hydrochlorothiazide is one of the most commonly used drugs to treat high blood pressure, taken either on its own or combined with other medicines. The IARC panel found sufficient evidence that it causes squamous cell skin cancer and lip cancer.

Studies from Europe and the United States showed what the report calls a “consistent, moderate, and precise elevated risk, with evidence of a dose–response effect across study designs and across populations who are at variable risk of skin cancer.” It noted that the risk increased with longer use, a pattern researchers regard as strong evidence of a real effect rather than coincidence.

Hydrochlorothiazide can make the skin more sensitive to sunlight, a mechanism researchers believe contributes to the increased risk of skin cancer among long-term users.

Voriconazole is used to treat serious fungal infections, particularly in people who have received organ transplants and have weak immunity. The IARC review concluded that “voriconazole causes squamous cell carcinoma of the skin” in humans.

The evidence was also supported by laboratory findings. The review noted that voriconazole, when combined with exposure to sunlight, was linked to cancer-related changes in human skin cells, supporting the human data.

Tacrolimus is given to transplant patients to stop their bodies from rejecting new organs, and is also used in cases of bone marrow transplants to prevent complications. The IARC panel found that “tacrolimus causes non-Hodgkin lymphoma and post-transplant lymphoproliferative disease”, a condition involving uncontrolled growth of immune cells that can develop after transplantation because of long-term immune suppression. “Positive associations have been observed between tacrolimus and leukaemia and squamous cell carcinoma of the skin,” the report also noted, along with supporting evidence from animal studies.

Despite these findings, IARC emphasised that its evaluations are intended to identify cancer hazards, not to determine whether the medicines should or should not be used.

The report noted that hydrochlorothiazide is on the WHO Model List of Essential Medicines for the treatment of hypertension, heart failure and oedema. It also made clear that its evaluations are a scientific assessment of cancer hazard alone, based on the Monographs programme’s focus on hazard identification, not a weighing of risks against benefits or a recommendation on prescribing.

The report notes that its Monograph evaluations are “only one part of the body of information” used by national and international authorities when making regulatory and public health decisions. It does not make recommendations on what action to take, since options vary by country and depend on national priorities.

The report also provides context on how widely the medicines are used.

Newer blood pressure medicines are gradually replacing hydrochlorothiazide, though it remains common because of how widespread hypertension is worldwide.

Voriconazole use is higher in high-income countries than in middle-income countries.

Tacrolimus use in a country tends to rise and fall with its number of organ transplants. In cream form, the drug also serves as a second-line treatment for atopic dermatitis and vitiligo, used as an alternative to corticosteroid creams.

The report added that people may also come into contact with these three substances through the environment or their occupation, but that such exposure is expected to be “magnitudes lower than that from medications.”