The story so far: Three widely prescribed medicines used to treat high blood pressure, life-threatening fungal infections and organ transplant rejection have been classified as “carcinogenic to humans” (Group 1) by the International Agency for Research on Cancer (IARC), the World Health Organisation’s specialised cancer research agency.
The three drugs — hydrochlorothiazide, voriconazole and tacrolimus — feature on the WHO Model List of Essential Medicines and are prescribed to millions of people worldwide. Hydrochlorothiazide is commonly used to treat hypertension, voriconazole is an antifungal medicine used to manage serious invasive fungal infections, while tacrolimus is an immunosuppressant that prevents rejection of transplanted organs.
What do doctors say about this and what does IARC classification mean?
Doctors note that the classification identifies a cancer hazard and should not be interpreted to mean that patients should stop taking the medicines.
The findings appear in Volume 137 of the IARC Monographs, following an evaluation by an international Working Group comprising 22 scientists from 13 countries, including Indian toxicologist G.B. Jena. The detailed assessment expands on conclusions first published in The Lancet Oncology in November 2024.
The IARC’s Group 1 category is reserved for agents for which there is sufficient evidence that they can cause cancer in humans. Tobacco smoking, asbestos, alcohol and ultraviolet radiation are among the many agents already placed in this category. However, IARC classifies hazards, not risk.
A hazard means an agent is capable of causing cancer under some circumstances. It does not estimate the likelihood that cancer will occur in a person taking a medicine at the prescribed dose, nor does it weigh the benefits of treatment against the potential risks. Those decisions are made by drug regulators and treating physicians after considering clinical evidence, dosage, duration of treatment and the patient’s underlying illness.
Experts therefore caution that the classification should not trigger panic or prompt patients to discontinue medicines without consulting their doctors.
Why was the medicine classified?
According to IARC, there is sufficient evidence that hydrochlorothiazide causes squamous cell carcinoma of the skin and cancer of the lip. The conclusion is based largely on epidemiological studies from Denmark and the United States that found an increased occurrence of non-melanoma skin cancers among people receiving high cumulative doses of the medicine over prolonged periods.
Researchers believe the mechanism is related to phototoxicity. Hydrochlorothiazide makes the skin more sensitive to ultraviolet radiation, increasing the likelihood of DNA damage after repeated sun exposure.
Voriconazole, another photosensitising medicine, has also been linked to squamous cell carcinoma of the skin, particularly among transplant recipients receiving prolonged treatment. The risk again appears to be mediated by heightened sensitivity to ultraviolet light combined with long-term exposure.
Tacrolimus differs from the other two medicines. Rather than increasing photosensitivity, it suppresses the immune system to prevent rejection of transplanted organs. While this action is essential for transplant survival, reduced immune surveillance may allow abnormal cells or virus-infected cells to proliferate. IARC concluded there is sufficient evidence linking tacrolimus with non-Hodgkin lymphoma and post-transplant lymphoproliferative disorder, and limited evidence for leukaemia and skin cancer.
What other drugs and agents are classified by IARC
Besides these latest additions, the IARC list includes chemotherapy drugs such as cyclophosphamide, melphalan, chlorambucil, busulfan and etoposide, the breast cancer drug tamoxifen, and immunosuppressants such as azathioprine and cyclosporine.
While some of these medicines increase the risk of secondary cancers after prolonged use, they remain indispensable in treating cancers, preventing organ transplant rejection and managing severe autoimmune disorders.
IARC has classified several commonly encountered agents as Group 1 carcinogens, including tobacco smoking, alcoholic beverages, processed meat, asbestos, benzene, ultraviolet (UV) radiation from sunlight, diesel engine exhaust, and infections caused by human papillomavirus (HPV) and hepatitis B and C viruses.
Experts emphasise that the IARC Monographs are designed to identify whether an agent is capable of causing cancer under certain conditions and do not assess the magnitude of risk at normal levels of exposure or weigh that risk against the proven therapeutic or public health benefits. Consequently, patients should not stop prescribed medicines without consulting their treating physician.
What does this mean for India
The findings are particularly relevant because all three medicines are routinely prescribed in India. Hydrochlorothiazide remains an inexpensive and widely available option for managing hypertension, particularly in combination with other blood pressure-lowering medicines.
Voriconazole is used extensively in tertiary hospitals for invasive fungal infections in immunocompromised patients, while tacrolimus forms the backbone of immunosuppressive therapy after kidney, liver and other solid-organ transplants.
The number of patients receiving these medicines has grown steadily alongside increasing rates of hypertension, expanding transplant programmes and greater recognition of invasive fungal diseases.
Kabir Sardana, Director Professor and Head of the Department of Dermatology at Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, said the IARC findings reinforce concerns already recognised in clinical practice.
“The IARC classification is highly relevant, particularly in India,” he said. “Hydrochlorothiazide has long been recognised as carrying a risk, especially in rural areas, the North-East, hilly and coastal regions, and among outdoor workers such as farmers who are exposed to high levels of ultraviolet radiation.”
He said voriconazole also warrants careful use because it is sometimes prescribed beyond its approved indications, including for fungal skin infections caused by Trichophyton indotineae. “Doctors welcome measures to curb such inappropriate use. We cannot ignore these warnings in a country where irrational prescribing, over-the-counter availability, and poor adherence to ethical prescribing and dispensing practices remain significant challenges,” he said.
Should patients stop taking these medicines?
Doctors unanimously advise against discontinuing any of these medicines without medical consultation. In many cases, the consequences of stopping treatment can be immediate and life-threatening.
Untreated hypertension substantially increases the risk of heart attack, stroke, kidney failure and premature death. Likewise, voriconazole is often used to treat severe fungal infections in patients with weakened immunity, where delayed or interrupted therapy can prove fatal. Tacrolimus is indispensable after organ transplantation; missing even a few doses can trigger acute rejection and irreversible damage to the transplanted organ.
Instead, clinicians recommend appropriate risk-reduction strategies. Patients taking hydrochlorothiazide or voriconazole should minimise ultraviolet exposure, use broad-spectrum sunscreen, wear protective clothing when outdoors and undergo periodic skin examinations, especially if treatment is prolonged. Transplant recipients receiving tacrolimus are already routinely monitored for skin cancers and lymphoproliferative disorders as part of long-term follow-up.
Doctors say that the IARC decision also underscores the importance of rational prescribing. Medicines should be prescribed only when clearly indicated, at the lowest effective dose and for the appropriate duration, while patients should be counselled about potential adverse effects and the need for follow-up.
The classification is also likely to stimulate further research into identifying patients at highest risk, understanding the biological mechanisms involved and exploring whether alternative therapies may be preferable for some individuals.
“The new IARC evaluation should therefore be viewed as a reminder to prescribe carefully, monitor appropriately and counsel patients about preventive measures—not as a reason to abandon treatments whose clinical value continues to outweigh their potential risks,’’ said Dr. Kabir Sardana.
