Drug interaction between dabrafenib and immunosuppressive drugs: about one case

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Abstract

Melanoma is a major public health problem. In recent years, it has been shown that melanoma can be characterized by specific oncogenes mutations such as the BRAF mutation, leading to the development of new therapeutic drugs. Dabrafenib is an inhibitor of BRAF, approved as a first-line treatment of metastatic or unresectable stage 3 or 4 melanoma with the BRAF mutation. Few studies have evaluated the drug interaction potential of dabrafenib. This molecule is an enzyme inducer that increases the synthesis of drug-metabolizing enzymes, including CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and UGT enzymes. Accordingly, the plasma concentrations of drugs metabolized by these enzymes are decreased. The decrease in plasma concentrations may cause a reduction or even loss of the clinical effect of these drugs. Many drugs metabolized by these enzymes may be affected, especially midazolam, warfarin, or rifampicin. However, interactions with immunosuppressants have not been described. Everolimus and tacrolimus are two immunosuppressive drugs metabolized by CYP3A4. We report a case of drug interaction between dabrafenib and immunosuppressive drugs (everolimus, tacrolimus), observed in a transplanted heart patient, requiring dosage adjustment of its immunosuppressive treatment to avoid graft rejection.

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