Side effects

Problems with thiazides include:

• potassium depletion, hence caution when used in combination with digoxin
• impotence
• gout
• rashes
• photosensitivity, which the patient should be warned about, especially if they have an impending holiday. The effect may last for 3 months after stopping the drug. It may resemble actinic reticuloid syndrome. Other photosensitive effects include lichen planus and lupus erythematous
• risk of non-melanoma skin cancer, particularly in long-term use (1,2)
  • clinicians should advise patients taking hydrochlorothiazide-containing products of the cumulative, dose-dependent risk of non-melanoma skin cancer, particularly in long-term use, and the need to regularly check for (and report) any suspicious skin lesions or moles
  • UK population study found that cumulative hydrochlorothiazide doses >= 50,000 mg was associated with an increased risk of squamous cell carcinoma, basal cell carcinoma and lip cancer (overall number needed to harm was 804, 2463 and 200,000, respectively, but varied by age and sex)
    • cumulative hydrochlorothiazide exposure is much greater in those aged over 60 years with some evidence that absolute risk is also greater in men
    • counsel patients to limit exposure to sunlight and UV rays and to use adequate sun protection
  • counsel patients to limit exposure to sunlight and UV rays and to use adequate sun protection
• risk of melanoma (3)
  • Drucker et al conducted a population-based inception cohort study using linked administrative health data from Ontario, 1998-2017
    • noted an increased risk of melanoma associated with thiazide use (melanoma (adjusted HR 1.34, 95% CI 1.01-1.78)) where Hazard Ratio (HR) was defined per 1 Defined Annual Dose unit
    • also noted ncreasing thiazide exposure was associated with an increased rate of incident keratinocyte carcinoma adjusted hazard (HR) 1.08, 95% confidence interval [CI] 1.03-1.14), and advanced keratinocyte carcinoma (adjusted HR 1.07, 95% CI 0.93-1.23)
    • concluded that higher cumulative exposure to thiazides was associated with increased rates of incident skin cancer in people aged 66 years and olde
      
      
• hypercalcaemia
• aplastic anaemia
• impaired glucose tolerance, worsening diabetic control and new-onset diabetes mellitus have been reported with long-term thiazide treatment - however 'these findings should not limit the use of thiazides (4)'

Reference:

1. MHRA - Drug Safety Update November 2018. Hydrochlorothiazide: risk of non-melanoma skin cancer, particularly in long-term use.
2. Specialist Pharmacy Service (June 2020). Commentary: Association between hydrochlorthiazide exposure and different incident skin, lip and oral cavity cancers - A series of population-based nested case-control studies
3. Drucker AM et al. Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study. CMAJ Apr 2021, 193 (15) E508-E516; DOI: 10.1503/cmaj.201971
4. Prescriber (2001), 12 (18), 49-61.