Skin cancer risk with hydrochlorothiazide

Hydrochlorothiazide diuretics cause serious adverse effect (nonmelanoma skin cancer)
Abdelwahab Ward, BS Pharm, PharmD

FDA alert!

Hydrochlorothiazide adverse reactions and warnings (July 2018)! ã…¡ Hydrochlorothiazide use is associated with a substantially increased risk of nonmelanoma skin cancer (NMSC), especially squamous cell carcinoma (SCC).

Previous studies found modest increases in risk for cutaneous squamous cell carcinoma (SCC) among patients using photosensitizing medications, and in particular; "thiazide diuretics". A danish case-control study including over 8000 patients with SCC and 172,000 controls found that, compared with nonusers, high users of hydrochlorothiazide had 2 to 7 fold increased risk of cutaneous SCC, with a clear dose-response effect. Although additional studies controlling for known risk factors for SCC (as; sun exposure, phototype, smoking) are still needed, education on sun avoidance and sun protection may be appropriate for patients taking thiazide diuretics!

Important points

Patients will ask the pharmacist if they should stop hydrochlorothiazide based on new labeling that points out increased skin cancer risk.

  • Growing evidence suggests a link between hydrochlorothiazide and nonmelanoma skin cancer, mostly squamous cell carcinoma.
  • Photosensitivity with hydrochlorothiazide may play a role.
  • Help patients put this in perspective.

Explain that an FDA study suggests about 1 additional case of squamous cell carcinoma for every 16,000 patients taking hydrochlorothiazide per year. Dose and duration seem to matter.

  • For patients taking about 25 mg/day for 5.5 years, risk is about 1 in 6,700 patients per year. But educate that risk of nonmelanoma skin cancer increases with age, fair skin tone, sun exposure, etc, regardless of medication use.
  • Emphasize the big picture treating hypertension reduces risk of stroke and other cardiovascular events. Reassure most patients it's okay to continue hydrochlorothiazide.
  • Don't automatically advise switching to a different diuretic (chlorthalidone, etc), they have limited data on skin cancer risk.
  • If needed, weigh other first-line antihypertensives like ACEIs, ARBs, or calcium channel blockers. For example, consider one of these BP medications instead in patients with a history of skin cancer.
  • Reinforce sun protection measures (sunscreen, etc). Remind patients to do regular skin checks and not to forget the ears, lips, and neck. Refer patients who have new, changing, or bleeding spots.

References

  1. Adalsteinsson JA, Muzumdar S, Waldman R, et al. Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study. J Am Acad Dermatol. 2021;84(3):669-675.
  2. FDA. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-label-changes-hydrochlorothiazide-describe-small-risk-non-melanoma-skin-cancer.
  3. Pedersen SA, Gaist D, Schmidt SAJ, Hölmich LR, Friis S, Pottegård A. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol. 2018;78(4):673-681.e9.
Abdelwahab Ward, BS Pharm, PharmD