Personalized Medicine
Richard B. Kim MD, FRCPC
Wolfe Medical research Chair in Pharmacogenomics
Professor of Medicine, Physiology & Pharmacology, and Oncology
Clinic phone number: 519-685-8500 ext 34340
Fax: 519-663-3090
Referrals must be from a physician (for inquiries and referral forms, call the number noted above or email: Jody.Murray@lhsc.on.ca).
In my personalized medicine clinic located at the London Health Sciences Centre (LHSC)-University Hospital (339 Windermere Road, London, Ontario, Canada), we assess patients on certain medications where genetic variation in their ability to breakdown (metabolize) or respond to drugs may be a reason for lack of drug efficacy or adverse drug response. When appropriate, we measure drug and drug metabolite levels using a latest generation liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. My clinic does not assess patients who have allergic drug reactions. My expertise is in pharmacogenomics and clinical pharmacology where emerging research insights are utilized to deliver personalized medicine-based care to our patients. Patients referred to my clinic will not incur any out-of-pocket expenses related to pharmacogenomic testing or drug level analysis. Currently, I see patients in relation to drugs noted below.
Cancer Therapy
5-FU and Capecitabine: These are important chemotherapy medications, often used for gastrointestinal cancer chemotherapy. However, we know genetic variation in a gene called DPYD can result in profoundly severe toxicity among patients prescribed even standard dose of 5-FU or capecitabine. Since 2014, our team has made a concerted effort to provide preemptive DPYD testing with a goal of providing the consultation and results usually within 1 week of referral, so that we can prevent potentially severe toxicity, without delaying treatment timelines. We have assessed well over 1,200 patients to date.
Tamoxifen: I started this clinic at the London Health Sciences Centre-University Hospital in March 2010. We believe this is the first clinic of its type in Canada to provide a real world referral/consultation support for patients at risk for suboptimal tamoxifen therapy for breast cancer, whether due to drug interactions or genetic variation in the metabolism of the drug. This is important in that breast cancer patients are prescribed a single dose of this medication (20 mg/day) and typically for 5 years (often 10 years). We carry out genotyping for CYP2D6 and also measure blood level of tamoxifen and its active metabolite endoxifen. I have assessed over 900 patients receiving tamoxifen in this clinic so far, and provide guidance to referring oncologists.
Immunosuppressive Medications
Azathioprine and 6-MP: Azathioprine is widely used in the setting of certain inflammatory conditions such as inflammatory bowel disease (Crohn’s disease and ulcerative colitis). 6-MP is also used in the setting of childhood leukemia therapy. In our clinic, we carry out TPMT genotype testing. This is a gene that is essential to the metabolism (breakdown) of azathioprine and 6-MP. We have recently incorporated a genetic marker in an HLA locus that can be predictive of the risk for azathioprine-induced pancreatitis.
Oral Anticoagulants
Warfarin: Since opening in September 2008, we have seen over 1000 patients and actively following over 250 patients on the blood thinning drug, warfarin (CoumadinTM) for the treatment of atrial fibrillation. When appropriate, we will test for genetic variation in two genes, CYP2C9 and VKORC1 for determining optimal starting dose of warfarin. Several physicians, including myself, are a part of this clinic.
Direct Oral Anticoagulants: For some patients, selecting the most appropriate dose of a DOAC can be complicated by drug interactions and clinical factors such as renal function and weight. More recently, we have been individualizing dose and selection of a new class of oral anticoagulants known as Direct Oral Anticoagulants (DOACs, also called Novel Oral Anticoagulants (NOACs)), such as dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) by utilizing our LC-MS/MS technology to measure blood level of DOACs, to be sure our patients are obtaining optimal benefit from these newer agents. Several physicians, including myself, are a part of this clinic.
Cardiovascular Medications
Statins: 10-15% of patients on a statin (cholesterol lowering drugs such as atorvastatin (Lipitor), simvastatin (Zocor), and rosuvastatin (Crestor), complain of muscle aches and weakness. In the vast majority of such patients, such symptoms do not lead to worsening of symptoms or result in actual muscle injury. However, in a small subset of such patients, recent data clearly show that patients who possess a commonly occurring genetic variation in a drug transporting protein called OATP1B1 (gene name SLCO1B1 (formerly known as OATP2 and OATP-C) that my group discovered in 2001, have a nearly 18-fold greater risk for statin-induced myopathy (muscle injury)). In this clinic, after the patient is assessed, a detailed report and recommendation to the referring physician are provided regarding SLCO1B1 genotype, statin level (when relevant), and recommended statin dosing or switching.
Clopidogrel (Plavix): Clopidogrel is prescribed to some patients who have had a recent heart attack, stroke, or after insertion of a stent in large blood vessels in the heart called coronary arteries. Clopidogrel is inactive. In the liver, clopidogrel is converted to the active form of the drug called H4 by a drug metabolizing enzyme called CYP2C19. Commonly occurring genetic differences in CYP2C19 can affect its activity and ability to break-down drugs such as clopidogrel. In my clinic, genotyping for CYP2C19 can be carried out to identify those who may benefit from clopidogrel as well as those who might be better suited for other antiplatelet drugs (such as ticagrelor or prasugrel).
CYP2D6 genotyping: This enzyme (CYP2D6), is involved in the metabolism of a large number of drugs in clinical use. Approximately 1 in 11 Canadians are deficient for this enzyme. This enzyme is also affected by drug-drug interactions, particularly by certain antidepressants.
PPI Medication Metabolism
Genetic variation in CYP2C19 can have a major impact to metabolism of the currently prescribed PPIs such as pantoprazole, lansoprazole, and omeprazole. Interestingly, there are patients who carry what is known as gain of function genetic variation in CYP2C19, often referred to as CYP2C19 rapid or ultrarapid metabolizer, who are at risk for suboptimal response to standard dose of PPIs.
