Dutch care providers and patients were confronted in October 2018 by a nationwide warning about a “slightly increased” risk of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) when using hydrochlorothiazide. Although there was no need to actively invite regular users of the drug for consultation, it was recommended to inform them about this association at regular follow-up appointments. If patients had SCC or BCC or were at increased risk thereof, their use of hydrochlorothiazide would need to be reviewed. This rather vague advice was based on two Danish case-control studies which found positive associations between hydrochlorothiazide and SCC (after >5.5 years of 12.5 mg daily) or BCC (after >11 years of 12.5 mg daily). The effects found are, however, too small to warrant immediate discontinuation of hydrochlorothiazide, especially for patients using sufficient protection against sunlight. These findings are of little or no consequence for the balance between the safety and effectiveness of hydrochlorothiazide in the treatment of hypertension.
- Research has found a limited association between the development of squamous cell carcinoma (SCC) of the skin and the use of at least 12.5 mg hydrochlorothiazide a day over a period of at least 5.5 years.
- Another limited association was found between the development of basal cell carcinoma (BCC) of the skin and the use of at least 12.5 mg of hydrochlorothiazide a day over a period of at least 11 years.
- These associations between hydrochlorothiazide and skin cancer have been found in the Danish population, in studies that did not taken exposure to UV radiation, skin type or smoking status into account, factors which are also associated with skin cancer.
- Despite the limited associations with skin cancer that were found, the balance between the effectiveness and safety of hydrochlorothiazide for the treatment of hypertension remains positive.
- The effect of discontinuing hydrochlorothiazide on the secondary prevention of SCC and BCC in patients who already have these forms of skin cancer is unknown.
- Patients who have previously had a form of skin cancer, and patients using medication that has photosensitising effects should – just like anybody – be informed about sensible tanning, and should monitor any changes in skin abnormalities.
- Nederlands Huisartsen Genootschap. Waarschuwing medicijnen met hydrochlorothiazidehydrochloorthiazide 2018 [Available from: https://www.nhg.org/actueel/nieuws/waarschuwing-medicijnen-met-hydrochloorthiazide.
- Nederlands Huisartsen Genootschap. Cardiovasculair risicomanagement (Tweede herziening) 2012 [Available from: https://www.nhg.org/standaarden/volledig/cardiovasculair-risicomanagement#Begrippen.
- Pottegard A, Hallas J, Olesen M, Svendsen MT, Habel LA, Friedman GD, et al. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med. 2017;282(4):322-31.
- Pedersen SA, Gaist D, Schmidt SAJ, Holmich LR, Friis S, Pottegard A. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol. 2018;78(4):673-81 e9.
- Monteiro AF, Rato M, Martins C. Drug-induced photosensitivity: Photoallergic and phototoxic reactions. Clin Dermatol. 2016;34(5):571-81.
- Nederlands Huisartsen Genootschap. NHG-Standaard Verdachte huidafwijkingen 2017 [Available from: https://www.nhg.org/standaarden/samenvatting/verdachte-huidafwijkingen.
- Nederlandse Vereniging voor Dermatologie en Venereologie. Evidence-based Richtlijn Basaalcelcarcinoom (modulaire update 2015) 2015 [Available from: http://www.nvdv.nl/wp-content/uploads/2014/08/20160725-eindversie-richtlijn-BCC-2015.pdf.
- MDCalc. Charlson Comorbidity Index (CCI) 2019 [Available from: https://www.mdcalc.com/charlson-comorbidity-index-cci.
- Grobbee DE, Bijl D. Het patiënt-controle-onderzoek. Gebu 1999;33(12):127-134.
- Nederlandse Vereniging voor Dermatologie en Venereologie. Richtlijn Plaveiselcelcarcinoom van de huid 2018 [Available from: https://www.nvmka.nl/sites/www.nvmka.nl/files/Richtlijn%20Plaveiselcelcarcinoom%20van%20de%20huid%202018.pdf.
- Zorginstituut Nederland. Farmacotherapeutisch Kompas 2019 [Available from: https://www.farmacotherapeutischkompas.nl/bladeren/preparaatteksten/h/hydrochloorthiazide#waarschuwingen-en-voorzorgen.
The literature refers to the Dutch text