IARC classifies three essential medicines as carcinogenic; doctors urge continued treatment

Three medicines that millions of people take every day—for high blood pressure, serious fungal infections, and to prevent rejection of transplanted organs—have just been placed in the same cancer risk category as tobacco and asbestos. The International Agency for Research on Cancer, the World Health Organisation's specialized cancer research arm, classified hydrochlorothiazide, voriconazole, and tacrolimus as Group 1 carcinogens in Volume 137 of its Monographs, following a review by 22 scientists from 13 countries, including Indian toxicologist G.B. Jena. The findings expand on conclusions first published in The Lancet Oncology last November. All three drugs appear on the WHO Model List of Essential Medicines and are prescribed to millions worldwide.

But here is what matters most: doctors across the medical establishment are united in saying patients should not stop taking these medicines. The distinction between what IARC does and what it does not do is crucial. The agency identifies hazards—agents capable of causing cancer under some circumstances. It does not measure actual risk at the doses people are prescribed. It does not weigh the benefits of treatment against potential harms. Those calculations belong to drug regulators and treating physicians, who must consider clinical evidence, dosage, duration, and the patient's underlying condition. Stopping any of these three medicines can be immediately life-threatening. Untreated high blood pressure leads to heart attack, stroke, kidney failure, and premature death. Voriconazole treats severe fungal infections in people with weakened immune systems; interrupting therapy can be fatal. Tacrolimus prevents organ rejection; missing even a few doses can trigger acute rejection and irreversible damage to a transplanted kidney or liver.

The three medicines entered this category for different reasons. Hydrochlorothiazide, the cheapest and most widely available blood pressure drug, causes squamous cell carcinoma of the skin and lip cancer, particularly after high cumulative doses over long periods. The mechanism involves phototoxicity: the drug makes skin more sensitive to ultraviolet radiation, increasing DNA damage after repeated sun exposure. Evidence comes largely from epidemiological studies in Denmark and the United States. Voriconazole, another photosensitizing agent, has been linked to squamous cell carcinoma of the skin, especially in transplant recipients on prolonged treatment, again through heightened UV sensitivity. Tacrolimus works differently. Rather than increasing photosensitivity, it suppresses the immune system to prevent organ rejection. That same immune suppression may allow abnormal cells or virus-infected cells to multiply unchecked. IARC found sufficient evidence linking tacrolimus to non-Hodgkin lymphoma and post-transplant lymphoproliferative disorder, with limited evidence for leukaemia and skin cancer.

In India, all three medicines are routinely prescribed. Hydrochlorothiazide remains the inexpensive backbone of hypertension management, often combined with other blood pressure drugs. Voriconazole is used extensively in tertiary hospitals for invasive fungal infections in immunocompromised patients. Tacrolimus forms the foundation of immunosuppressive therapy after kidney, liver, and other solid-organ transplants. The number of patients taking these drugs has grown steadily as hypertension rates rise, transplant programs expand, and invasive fungal diseases gain recognition. Dr. Kabir Sardana, Director Professor and Head of Dermatology at Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, said the IARC findings reinforce concerns already recognized in clinical practice. Hydrochlorothiazide carries particular risk in rural areas, the North-East, hilly and coastal regions, and among outdoor workers like farmers exposed to high ultraviolet radiation. Voriconazole warrants careful use because it is sometimes prescribed beyond approved indications, including for fungal skin infections caused by Trichophyton indotineae. Sardana noted that India faces significant challenges with irrational prescribing, over-the-counter availability, and poor adherence to ethical prescribing practices.

The medical response is not to abandon these medicines but to prescribe them more carefully and monitor patients more closely. Patients taking hydrochlorothiazide or voriconazole should minimize ultraviolet exposure, use broad-spectrum sunscreen, wear protective clothing outdoors, and undergo periodic skin examinations, especially during prolonged treatment. Transplant recipients on tacrolimus are already routinely monitored for skin cancers and lymphoproliferative disorders as part of long-term follow-up. Doctors emphasize that medicines should be prescribed only when clearly indicated, at the lowest effective dose, for the appropriate duration, with patients counseled about potential adverse effects and the need for follow-up. The IARC classification is likely to stimulate further research into identifying high-risk patients, understanding biological mechanisms, and exploring whether alternatives might be preferable for some individuals. As Sardana put it, the new evaluation should 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.