Published: 15 April 2019
Revised: 29 August 2023
Safety Information
Alert Communication
Hydrochlorothiazide: risk of non-melanoma skin cancer
15 April 2019
Products Affected
Information for consumers and caregivers
Information for healthcare professionals
Detailed Information
Further information
How to report adverse events
Description
Hydrochlorothiazide is a prescription medicine available in New Zealand in combination with other medicines, such as cilazapril, quinapril, losartan, or amiloride. These medicines are used to treat high blood pressure (hypertension) and build-up of excess fluid in the body (oedema).
Two studies from Denmark found an association between hydrochlorothiazide and non-melanoma skin cancer, specifically squamous cell carcinoma (SCC), squamous cell carcinoma of the lip, and basal cell carcinoma (BCC).
Products Affected
| Medicines | Trade Names/Products |
|---|---|
| Cilazapril and Hydrochlorothiazide tablets (5mg/12.5mg) | Apo-Cilazapril/Hydrochlorothiazide |
| Quinapril and Hydrochlorothiazide tablets (10mg/12.5mg and 20mg/12.5mg) | Accuretic |
| Losartan and Hydrochlorothiazide tablets (50mg/12.5mg) | Hyzaar, Arrow-Losartan & Hydrochlorothiazide |
| Amiloride and Hydrochlorothiazide tablets (5mg/50mg) | Moduretic |
Advice For Consumers and Caregivers
- A link between hydrochlorothiazide and non-melanoma skin cancer has been found in some patients who have taken hydrochlorothiazide-containing medicines long-term.
- Do not stop taking a hydrochlorothiazide-containing medicine unless instructed to by your doctor. The benefits of treating your condition (e.g. high blood pressure) outweigh the small risk of developing non-melanoma skin cancer.
- Non-melanoma skin cancer includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCCs and SCCs can be easily treated if they are found early.
- Hydrochlorothiazide can increase the sensitivity of your skin to sunlight and UV rays. Limit the amount of time you spend in the sun or artificially tanning, and make sure you wear sunscreen (SPF of 30 or higher on your skin and lips) and sun-protective clothing (eg, a wide brimmed hat, collared t-shirt, trousers or long legged shorts, and sunglasses) when outdoors. The sun is strongest from September through to April.
- Check your skin and lips regularly and talk to your doctor if you notice any new or changed spots, lumps, moles, or sores.
- More information about non-melanoma skin cancer, sun safety advice, and how to check for skin cancer is available at: https://www.healthnavigator.org.nz/health-a-z/s/skin-cancer/
Information for Healthcare Professionals
- Two recent case-control studies using Danish population data have found an increased risk of non-melanoma skin cancer (basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma of the lip) with exposure to hydrochlorothiazide. The risk increased with increasing cumulative dose (see Table 1
- Whilst the mechanism is unknown, hydrochlorothiazide has skin photosensitizing effects.
- Patients who are at higher risk of developing non-melanoma skin cancer (e.g. those with light-coloured skin, personal or family history of skin cancer, ongoing immunosuppressive therapy) should take protective measures in any case.
- Inform patients of this risk and advise them to limit their exposure to sunlight or to UV rays and to use adequate sun protection.
- Encourage patients taking a hydrochlorothiazide-containing medicine to check their skin and lips regularly and report any new or changed skin lesions or moles. Any suspicious skin lesions should be examined thoroughly.
- Thoroughly discuss the risks and benefits of hydrochlorothiazide treatment with patients who have experienced previous non-melanoma skin cancer, taking into consideration other treatment options.
- Report any suspected adverse reactions associated with hydrochlorothiazide-containing medicines to the Centre for Adverse Reactions Monitoring (CARM).
Detailed Information
The two Danish population based studies found the following increases in risk of non-melanoma skin cancer (Table 1).
Table 1: Summary of results from Pedersen et al and Pottegard et al1,2
| Type of non-melanoma skin cancer | Number of cases | Number of matched population controls | Adjusted odds ratios with ‘ever-use’ of hydrochlorothiazide (95% Confidence Interval) | Adjusted odds ratios with high cumulative use of hydrochlorothiazide (95% Confidence Interval) | Adjusted odds ratios with the highest cumulative use of hydrochlorothiazide (95% Confidence Interval) |
|---|---|---|---|---|---|
| BCC1 | 71,553 | 1,430,883 | 1.08 (1.05 -1.10) | 1.29 (1.23 – 1.35)a | 1.54 (1.38 – 1.71)b |
| SCC1 | 8,629 | 172,462 | 1.75 (1.66 -1.85) | 3.98 (3.68 – 4.31)a | 7.38 (6.32 – 8.60)b |
| SCC of the lip2 | 633 | 63,067 | 2.1 (1.7 – 2.6) | 3.9 (3.0 – 4.9)c | 7.7 (5.7 - 10.5)d |
a high cumulative use: ≥50,000 mg, equivalent to 12.5mg hydrochlorothiazide
taken daily for approximately 11 years or more.
b highest cumulative use: ≥200,000 mg, equivalent to 12.5mg hydrochlorothiazide
taken daily for approximately 44 years or more.
c high cumulative use: ≥25,000 mg, equivalent to 12.5mg hydrochlorothiazide
taken daily for approximately 5.5 years or more.
d highest cumulative use: ≥100,000 mg, equivalent to 12.5mg hydrochlorothiazide
taken daily for approximately 22 years or more.
The authors did not find a similar association for risk of BCC, SCC, or SCC of the lip with overall or cumulative use of other diuretics or other non-diuretic medicines used in the treatment of high blood pressure, including bendroflumethiazide, furosemide, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.
The incidence of BCC and SCC in New Zealand is currently unknown. Figures have been published in the past that show in some areas of the world the lifetime risk of developing a BCC is estimated to be 30 percent (3). Additionally, in Australia, which shares similar latitude to New Zealand, the annual incidence of cutaneous SCC has been approximated to be 1035 and 472 cases per 100,000 for men and women, respectively (4).
Based on the findings of these studies, Medsafe is working with sponsors of hydrochlorothiazide-containing products to update the data sheets to include information about the risk of non-melanoma skin cancer.
Further Information
The Medicines Adverse Reactions Committee (MARC) discussed hydrochlorothiazide and non-melanoma skin cancer at the 176th MARC meeting. The minutes of this meeting are available at: www.medsafe.govt.nz/profs/adverse/Minutes176.htm#3.2.1
Medsafe’s report on hydrochlorothiazide and non-melanoma skin cancer is available at: www.medsafe.govt.nz/committees/marc/Reports.asp
How to Report Adverse Events
| Phone | From your iPhone using the ADR online app |
| Online |
Submit a CARM report Prescribers can also submit a report using the online reporting tool available in patient management software. |
| Yellow Card | A completed Yellow card can be submitted to CARM via email, fax or mail |
| CARMReport@health.govt.nz |
Medsafe cannot give advice about an individual’s medical condition. If you
have any concerns about a medicine you are taking Medsafe encourages you
to talk to your healthcare professional.
References
- Pedersen SA, Gaist D, Schmidt SAJ, Holmich LR, Friis S, Pottegard A. 2018. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 78: 673-81 e9
- Pottegard A, Hallas J, Olesen M, Svendsen MT, Habel LA, Friedman GD, Friis S. 2017. Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med 282: 322-31
- Wu PA. 2018. Epidemiology, pathogenesis, and clinical features of basal cell carcinoma. In: UpToDate 9 July 2018. URL: www.uptodate.com/contents/epidemiology-pathogenesis-and-clinical-features-of-basal-cell-carcinoma (accessed 4 April 2019).
- Green A, Battistutta D, Hart V, Leslie D, Weedon D. 1996. Skin cancer in a subtropical Australian population: incidence and lack of association with occupation. The Nambour Study Group. Am J Epidemiol 144: 1034-40
