Introduction: The management of patients with BRAF-mutated advanced melanoma who are undergoing targeted therapy with MEK inhibitors can be complicated by the co-administration of multiple medications, which can give rise to drug-drug interactions of clinical significance.
Covered areas: Our review presents a comprehensive analysis of the pharmacokinetic and pharmacodynamic interactions of the three approved for advanced melanoma MEK inhibitor drugs - binimetinib, cobimetinib, and trametinib. MEDLINE (PubMed) was utilized for the literature search, comprising clinical studies, observational studies, and preclinical research. The review discusses the impact of these interactions on efficacy and safety of the treatments and differentiates between interactions supported by pharmacokinetic or pharmacodynamic mechanisms, those encountered in clinical practice, and those observed in preclinical studies.
Expert opinion: Physicians should be aware about potential benefits, but also increased toxicity caused by drug interactions between MEK inhibitors and other drugs in the management of patients with metastatic melanoma.
Keywords: BRAF inhibitors; MEK inhibitors; pharmacodynamics; pharmacokinetics; side-effects; synergistic interactions.