From the Guidelines
Not all thiazide diuretics are associated with an increased risk of skin cancer, but hydrochlorothiazide has been linked to non-melanoma skin cancers like basal cell carcinoma and squamous cell carcinoma, as reported in a study published in 2022 1. The association between thiazide diuretics and skin cancer risk appears to be dose-dependent, with higher cumulative doses over time increasing risk.
- The mechanism is thought to involve the photosensitizing properties of thiazide diuretics, which can enhance UV damage to skin cells.
- Chlorthalidone, indapamide, and metolazone have less evidence linking them to skin cancer risk, as noted in guidelines published in 2018 1. For patients requiring thiazide therapy who are concerned about skin cancer risk, especially those with fair skin or history of skin cancer,
- considering alternative agents like chlorthalidone or
- implementing strict sun protection measures (sunscreen, protective clothing, limiting sun exposure) is advisable, as recommended in a study published in 2022 1. Regular skin examinations are also recommended for long-term thiazide users. The benefits of thiazide therapy for hypertension management should be weighed against these potential risks in individual patient care decisions, taking into account the latest evidence from 2022 1.
From the FDA Drug Label
Non-melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year. Information for Patients: Non-melanoma Skin Cancer: Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening
Not all thiazide diuretics have been directly associated with skin cancer in the provided drug labels. The labels only provide information about hydrochlorothiazide, which is associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC) in white patients taking large cumulative doses 2. It is unclear if this risk applies to all thiazide diuretics.
From the Research
Association Between Thiazide Diuretics and Skin Cancer
- The use of thiazide diuretics has been associated with an increased risk of skin cancers, including squamous cell carcinoma, basal cell carcinoma, and malignant melanoma 3, 4, 5.
- Hydrochlorothiazide, a specific type of thiazide diuretic, has been shown to have a significant association with squamous cell carcinoma 3, 6.
- However, not all thiazide diuretics may be associated with the same level of risk, with bendroflumethiazide and indapamide showing different associations with skin cancer types 6.
Specific Skin Cancer Types
- Squamous cell carcinoma: associated with an increased risk in users of thiazide diuretics, particularly hydrochlorothiazide 3, 4, 6.
- Basal cell carcinoma: associated with a marginally increased risk in users of thiazide diuretics, but the evidence is less consistent 3, 4, 5.
- Malignant melanoma: associated with an increased risk in users of thiazide diuretics, but the evidence is limited 4, 5.
Variations in Risk Across Different Populations
- The risk of skin cancer associated with thiazide diuretics may vary across different populations, with some studies suggesting a higher risk in Caucasian populations 7.
- A study in an Asian population found that the risk of skin cancer was not significantly increased with the use of hydrochlorothiazide compared to other antihypertensives 7.