Is bendroflumethazide (thiazide diuretic) safe to use as an antihypertensive in an elderly patient with a history of multiple non-melanoma skin cancers and melanomas?

Bendroflumethazide Should Be Avoided in This Patient

Given this patient's history of multiple non-melanoma skin cancers and melanomas, bendroflumethazide—like all thiazide diuretics—should be avoided and an alternative antihypertensive class should be selected instead. 1

Evidence for Thiazide-Associated Skin Cancer Risk

All Thiazide Diuretics Increase Skin Cancer Risk

The evidence demonstrates that thiazide diuretics as a class are associated with increased risk across all skin cancer types 2:

• Squamous cell carcinoma: 35% increased risk (pooled adjusted OR 1.35,95% CI 1.22-1.48) 2
• Basal cell carcinoma: 5% increased risk (pooled adjusted OR 1.05,95% CI 1.02-1.09) 2
• Malignant melanoma: 10% increased risk (pooled adjusted OR 1.10,95% CI 1.04-1.15) 2
• Lip cancer: 92% increased risk (pooled adjusted OR 1.92,95% CI 1.52-2.42) 2

Bendroflumethazide Is Not Exempt

While hydrochlorothiazide has been most extensively studied, the photosensitizing properties and skin cancer risk extend to the entire thiazide class, including bendroflumethiazide 3, 4. The 2016 British Hypertension Society guidelines acknowledge that patients already stable on bendroflumethiazide may continue it, but explicitly recommend thiazide-like diuretics (chlorthalidone or indapamide) over conventional thiazides like bendroflumethiazide for new initiations 1. This recommendation predates the full understanding of skin cancer risk but reinforces that bendroflumethiazide is not a preferred agent.

Risk Magnitude in High-Risk Patients

For this elderly patient with multiple prior skin cancers, the baseline risk is already substantially elevated 5, 6. Adding a thiazide would compound this risk:

• The absolute risk becomes clinically significant when baseline risk is high 2
• Patients over 50 years have the highest absolute risk despite lower relative risk 1
• Prior skin cancer history represents one of the strongest predictors of future skin cancer 5

Recommended Alternative Antihypertensive Classes

First-Line Alternatives for Elderly Patients

Based on current hypertension guidelines, the following are appropriate alternatives 1:

1. Calcium channel blockers (CCBs): Preferred first-line for patients >55 years 1

   • However, note that CCBs also show a modest increased skin cancer risk (pooled RR 1.14,95% CI 1.07-1.21) 7
   • This risk is substantially lower than with thiazides 7, 4

2. ACE inhibitors or ARBs: No association with skin cancer risk 7, 4

   • These show no increased risk across multiple meta-analyses 7, 4
   • Appropriate for combination therapy if monotherapy insufficient 1

3. Beta-blockers: Avoid as they show increased melanoma risk (pooled RR 1.21,95% CI 1.05-1.40) 7

Practical Algorithm for This Patient

Step 1: Initiate a CCB (recognizing modest skin cancer risk but substantially lower than thiazides) OR an ACE inhibitor/ARB (no skin cancer risk) 1, 7

Step 2: If blood pressure remains uncontrolled, combine CCB with ACE inhibitor or ARB 1

Step 3: If three drugs needed, add a thiazide-like diuretic (chlorthalidone or indapamide) only as a last resort, with explicit informed consent about skin cancer risk and mandatory dermatologic surveillance 1, 2

Step 4: Avoid beta-blockers given melanoma history 7

Critical Caveats

Surveillance Requirements

If any diuretic must eventually be used 5:

• Annual dermatologic examination is mandatory 5
• Monthly skin self-examination should be performed 5
• Sun protection measures must be rigorously implemented (avoid 10 AM-4 PM sun exposure, SPF ≥30, protective clothing, complete avoidance of tanning beds) 5

Conflicting Evidence Acknowledgment

Some studies suggest the thiazide-skin cancer association may be confounded by sun exposure and other factors 4, 8. However, the most recent and comprehensive meta-analysis (2022,30 studies, >10 million patients) demonstrates consistent associations across all skin cancer types with very low heterogeneity for hydrochlorothiazide and squamous cell carcinoma 2. In a patient with established high-risk skin cancer history, the precautionary principle mandates avoiding thiazides regardless of residual uncertainty about causation.

Existing Bendroflumethiazide Use

The guidelines state that patients already stable and well-controlled on bendroflumethiazide may continue it 1. However, this recommendation does not apply to patients with multiple prior skin cancers, where the risk-benefit calculation fundamentally changes 2.