Fluvoxamine (Luvox) – CYP2D6
Rationale
This drug gene interaction (DGI) pertains to the interaction between the CYP2D6 gene and fluvoxamine. Fluvoxamine (Luvox®) belongs to a class of drugs known as selective serotonin re-uptake inhibitors (SSRIs). SSRIs work by blocking the re-uptake of serotonin. The increase in serotonin levels has been linked to the management of depression, social anxiety disorder, obsessive-compulsive disorder, panic disorder, premenstrual dysphoric disorder, and post-traumatic stress disorder among other conditions. Extensive literature and FDA warning labels indicate patients with genetically reduced CYP2D6 function experience lower systemic exposure to the active metabolite of fluvoxamine and have an increased risk of side effects than patients with normal CYP2D6 protein function. Specific genetic differences in the CYP2D6 gene may require dose adjustments of fluvoxamine or an alternative medication in order to achieve therapeutic benefits or to avoid side effects.
Information presented on this page is based on evidence provided by the Clinical Pharmacogenomics Implementation Consortium (CPIC®). CPIC provides peer-reviewed, updated, evidence-based, and freely accessible guidelines for implementing pharmacogenomic results into actionable prescribing decisions for providers. CPIC guidelines include standardized terminology and a systematic grading of evidence and clinical recommendations published in a leading journal (Clinical Pharmacology and Therapeutics).
Genetic Variant Information
The CYP2D6 (sounds like “sip-2-dee-6”) gene encodes an enzyme that is involved in the metabolism of fluvoxamine. There are different CYP2D6 gene versions, or variants, and each has a different effect on how well fluvoxamine is metabolized in the body. Some variants result in a non-functioning or low-functioning CYP2D6 protein while other variants result in a normal-functioning CYP2D6 protein. A duplication of variants can lead to a hyper-active CYP2D6 protein. Different ‘metabolizer statuses’ are assigned to patients depending on their genetic information (genotype).
See chart below for a description of each metabolizer status and any implications for treatment.
|
CYP2D6 metabolizer status |
Prevalence of metabolizer status (% of patients) | Variants (genotype) |
Implication for fluvoxamine |
| Poor metabolizer | ~5-10% | An individual carrying ONLY no-function alleles | Greatly reduced metabolism of fluvoxamine when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects. |
| Intermediate metabolizer | ~2-11% | An individual carrying ONE decreased function allele and ONE no-function allele | Reduced metabolism of fluvoxamine when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects. |
| Normal metabolizer | ~77-92% | An individual carrying TWO normal function alleles OR TWO decreased function alleles OR ONE normal function with ONE no-function OR ONE normal function with ONE decreased function allele. | Normal metabolism of fluvoxamine. |
| Ultrarapid metabolizer | ~1-2% | An individual carrying duplications of functional alleles | No data available for fluvoxamine ultrarapid metabolizers. |
The patient’s reported genotype corresponds to a phenotype (i.e., metabolizer status). To see an interpretation table assigning metabolizer status by genetic variant, click here to visit CPIC and scroll down to click and download “CYP2D6_Diplotype_Phenotype_Table”.
Results Interpretation
Fluvoxamine is a medicine used to manage several different conditions and your genes can affect how well the drug works. CPIC updates guidelines on how to best use these genetic results to support patient care and has published its current recommendations here.
Quality of Results
Genotyping for CYP2D6 was performed within a 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%.
Supporting Evidence
This link will take you to the main page on the CPIC website relating to CYP2D6, CYP2C19 and SSRIs. On the site, you will find links to the main guideline publication and all supplementary information including a table that reports variant frequencies across different races/ethnic groups, a table that defines genetic variants, and a table that provides a phenotype interpretation (i.e. metabolizer status). Additionally, examples of point of care clinical decision support can be found at the bottom of the page.
Please note that additional drugs may have CYP2D6 interactions. For more information on drug-gene interactions, please use the search feature on the CPIC website.