This DGI pertains to the interaction between the CYP2D6 gene and tramadol. Tramadol (brand name Ultram) is used to treat moderate to severe pain. It belongs to a class of drugs known as opioids. It works by activating the brain to produce a response of pain relief. Extensive literature and FDA warning labels indicate patients with genetically reduced CYP2D6 function demonstrate lower systemic exposure to the active metabolite of tramadol than do patients with normal CYP2D6 function.
The CYP2D6 gene encodes an enzyme that is involved in the metabolism of tramadol. There are different CYP2D6 gene versions, or variants, and each has a different effect on how well tramadol works in the body. The version termed ‘poor metabolizer’ does not produce a functional CYP2D6 enzyme to metabolize tramadol, due to an individual carrying NO functional alleles. The version termed ‘normal metabolizer’ results in a functional CYP2D6 enzyme. Patients who carry at least ONE reduced function and ONE nonfunctional allele are termed ‘intermediate metabolizer’. Studies have shown patients carrying more than TWO copies of functional alleles are termed ‘ultrarapid metabolizer’ and may be at increased risk for toxicity and adverse drug events while taking a standard dose of tramadol.
Genotyping for CYP2D6 was performed within a high complexity, certified DNA laboratory at Vanderbilt University Medical Center that is in full compliance with all guidelines established by the government as regulated by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement act of 1988. This validated clinical Laboratory Developed Test is carried out with strict adherence to protocols outlined by the College of American Pathology. The performance of the assay is closely monitored and the accuracy of the results is determined to be >99%.
The Pharmacogenetics of Tramadol.
Lassen D, Damkier P, Brosen K, Clin Pharmacokinet. 2015 Aug, 54 (8): 825-36
OBJECTIVE: Tramadol hydrochloride is used worldwide as an analgesic drug with a unique dual function. The metabolic enzymes cytochrome P450 (CYP) 3A4, CYP2B6, and CYP2D6 and the various transporters [adenosine triphosphate-binding cassette B1/multidrug resistance 1/P-glycoprotein, organic cation transporter 1, serotonin transporter (SERT), norepinephrine transporter (NET)] and receptor genes (opioid receptor μ 1 gene) give possible genetic differences that might affect the pharmacokinetics and/or pharmacodynamics of tramadol. Therefore, the aim of this review is to present a systematic walkthrough of all possible genetic factors involved in the pharmacology of tramadol.
METHODS: A systematic literature search was conducted in PubMed and EMBASE involving all metabolic enzymes, drug transporters and receptors, as well as SERT and NET that are involved in the pharmacokinetics and pharmacodynamics of tramadol. An additional search on population pharmacokinetics with genetic factors as covariates was performed separately.
RESULTS: A total of 56 studies (45 cohort and case-control studies, three case reports, six in vitro studies, and two animal studies) were included.
CONCLUSIONS: In this systematic review, the current knowledge on all possible genetic factors that might influence the metabolism or clinical efficacy of tramadol has been collected and summarized. Only the effect of CYP2D6 polymorphisms on the metabolism of tramadol and the consequent effect on pain relief has been thoroughly studied and sufficiently established as clinically relevant.