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NEIGHBOURING MELANOMAS AND DYSPLASTIC NEVUS DEVELOPING SIMULTANEOUSLY AFTER CANDESARTAN INTAKE: NITROSAMINE
11Onkoderma - Clinic for Dermatology, Venereology and Dermatologic Surgery, Sofia, Bulgaria; 2Department of Dermatology and Venereology, Medical Institute of Ministry of Interior, Sofia, Bulgaria.
Abstract:
Although the problem with nitrosamines and their connection to the generation of skin cancer deepens, it is also thoroughly, carefully, and obligingly neglected. The probable reason for this is in all likelihood the lack of a solution or way out of this situation at the regulatory level. There is almost no sartan (on the European market/certain countries) after taking which the development of single or multiple melanomas, as well as melanomas in combination with single/multiple keratinocyte tumors, is not observed. But also, skin tumors (again melanomas) in combination with up to two other tumors - simultaneously or subsequently. These cases are immediately reported to the regional regulatory units, but unfortunately to no avail. Valsartan, irbesartan, olmesartan, and now candesartan is the main "suspect medications" for the development of melanomas, regardless of the dilemma: 1) whether the available nitrosamine remains responsible (for melanoma) as a mono/poly-contaminant (as availability or at a certain dose) or 2) is the generic substance itself also partly to blame? The literature data on the subject are contradictory, but does not exclude the involvement of any of these units in the generation and progression of melanomas. The lack of official results of possible checks for the presence (of nitrosamines) after the side effect reports were submitted to regulatory bodies further deepened the doubts of the clinicians, supporting the possible pathogenetic role of not only nitrosamines as a key link regarding the development of skin cancer. In practice, permissive regimes for the availability of carcinogens/mutagens in minimum permissible amounts, have been established? It is unclear whether this should be interpreted as a powerlessness of the regulatory authorities in the face of powerful pharmaceutical concerns? Or is it rather a lull before the start of general regulatory changes and a forthcoming "shifting of the layers"? The paradox also arises from the fact that many contaminated batches are quickly, quietly withdrawn from the market, despite being declared harmless or dangerous only for animals. We report on a patient who developed thin melanoma and neighbouring melanoma in situ after receiving candesartan, treated via one step melanoma surgery within one surgical session with a complete surgical margin of 2 cm. In parallel with the mentioned, a dysplastic nevus was observed clinically and confirmed dermatoscopically in the area of left scapula, for which surgical treatment is planned. Based on the currently available literature data, a thorough analysis of the role of nitrosamines, as a possible powerful pathogenetic factor for the occurrence and progression of melanomas, was made. The possible role of the generic substance as a cofactor in the carcinogenesis of skin cancer is also discussed.
Insights
The use of certain blood pressure medications, specifically sartans, is increasingly linked to skin cancer, particularly melanoma. Regulatory oversight and the exact role of nitrosamine contamination versus the drug substance itself require urgent clarification.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Growing concern exists regarding nitrosamine contamination in sartan medications and its potential link to skin cancer development.
- Numerous sartan-containing drugs available on the European market have been associated with cases of melanoma and keratinocyte tumors.
- Regulatory bodies have received reports of these adverse events, but a clear resolution or regulatory action remains insufficient.
Purpose of the Study:
- To analyze the potential role of nitrosamines as a pathogenetic factor in the occurrence and progression of melanomas.
- To discuss the possible involvement of the generic sartan substance itself as a cofactor in skin cancer carcinogenesis.
- To highlight the current regulatory challenges and ambiguities surrounding contaminated sartan medications.
Main Methods:
- Review of existing literature data on nitrosamine contamination in sartans and their association with skin cancer.
- Analysis of reported adverse events linking sartan use to melanoma and other skin tumors.
- Case report of a patient developing melanoma after candesartan treatment.
Main Results:
- Valsartan, irbesartan, olmesartan, and candesartan are identified as primary suspect medications for melanoma development.
- The exact contribution of nitrosamine contaminants versus the generic drug substance to carcinogenesis is still debated.
- A patient developed thin melanoma and melanoma in situ after candesartan use, with a concurrent dysplastic nevus noted.
Conclusions:
- Nitrosamines are a potential significant pathogenetic factor in melanoma development and progression.
- The role of the generic drug substance as a cofactor in skin carcinogenesis warrants further investigation.
- There is a critical need for enhanced regulatory scrutiny and action regarding nitrosamine contamination in pharmaceuticals.
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