@article {978, title = {Potential interactions between complementary/alternative products and conventional medicines in a Medicare population.}, journal = {Ann Pharmacother}, volume = {41}, year = {2007}, month = {2007 Oct}, pages = {1617-24}, abstract = {

BACKGROUND: Despite the high prevalence of complementary and alternative medicine (CAM) product use among the elderly, little is known about the extent of concurrent CAM-conventional medicine use and the potential for adverse reactions.

OBJECTIVE: To determine the prevalence of CAM product use concurrent with conventional medications, prescription and nonprescription, in a Medicare population and assess the risk for adverse interactions.

METHODS: Retrospective analysis was performed on Cardiovascular Health Study interview data from 1994, 1995, 1997, and 1999. The prevalence of concurrent combinations of CAM products and conventional drugs was tabulated. The adverse interaction risks were categorized as unknown, theoretical, and significant.

RESULTS: Of 5052 participants, the median age was 75, 60.2\% were female, 16.6\% were African American, and 83.4\% were white. The percent using CAM products during the 4 time periods was 6.3\%, 6.7\%, 12.8\%, and 15.1\%. The percent using both CAM products and conventional drugs was 6.0\%, 6.2\%, 11.7\%, and 14.4\%. Of these, 294 (5.8\%) individuals took combinations considered to have a significant risk for an adverse interaction. Combinations with risk were observed on 393 separate interviews. Most (379) involved a risk of bleeding due to use of ginkgo, garlic, or ginseng together with aspirin, warfarin, ticlopidine, or pentoxifylline. An additional 786 observations of combinations were considered to have some, albeit theoretical or uncertain, risk for an adverse interaction.

CONCLUSIONS: Concurrent use of CAM products and conventional medicines in a Medicare population was found to be common. Research to define the risks of combining ginkgo and garlic supplements with aspirin should be of high priority.

}, keywords = {Aged, Complementary Therapies, Drug Interactions, Drug-Related Side Effects and Adverse Reactions, Female, Hemorrhage, Herb-Drug Interactions, Humans, Male, Medicare, Pharmaceutical Preparations, Phytotherapy, Plant Extracts, Plant Preparations, Retrospective Studies, Risk Factors, Washington}, issn = {1542-6270}, doi = {10.1345/aph.1K221}, author = {Elmer, Gary W and Lafferty, William E and Tyree, Patrick T and Lind, Bonnie K} } @article {6565, title = {Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 Apr 15}, pages = {1957-63}, abstract = {

The study of genetic influences on drug response and efficacy ({\textquoteright}pharmacogenetics{\textquoteright}) has existed for over 50 years. Yet, we still lack a complete picture of how genetic variation, both common and rare, affects each individual{\textquoteright}s responses to medications. Exome sequencing is a promising alternative method for pharmacogenetic discovery as it provides information on both common and rare variation in large numbers of individuals. Using exome data from 2203 AA and 4300 Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a survey of coding variation within 12 Cytochrome P450 (CYP) genes that are collectively responsible for catalyzing nearly 75\% of all known Phase I drug oxidation reactions. In addition to identifying many polymorphisms with known pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles across the 12 CYP genes of interest. These alleles include many with diverse functional effects such as premature stop codons, aberrant splicesites and mutations at conserved active site residues. Our analysis considering both novel, predicted functional alleles as well as known, actionable CYP alleles reveals that rare, deleterious variation contributes markedly to the overall burden of pharmacogenetic alleles within the populations considered, and that the contribution of rare variation to this burden is over three times greater in AA individuals as compared with Caucasians. While most of these impactful alleles are individually rare, 7.6-11.7\% of individuals interrogated in the study carry at least one newly described potentially deleterious alleles in a major drug-metabolizing CYP.

}, keywords = {Cytochrome P-450 Enzyme System, Databases, Genetic, European Continental Ancestry Group, Exome, Humans, Pharmaceutical Preparations, Pharmacogenetics, Polymorphism, Genetic}, issn = {1460-2083}, doi = {10.1093/hmg/ddt588}, author = {Gordon, Adam S and Tabor, Holly K and Johnson, Andrew D and Snively, Beverly M and Assimes, Themistocles L and Auer, Paul L and Ioannidis, John P A and Peters, Ulrike and Robinson, Jennifer G and Sucheston, Lara E and Wang, Danxin and Sotoodehnia, Nona and Rotter, Jerome I and Psaty, Bruce M and Jackson, Rebecca D and Herrington, David M and O{\textquoteright}Donnell, Christopher J and Reiner, Alexander P and Rich, Stephen S and Rieder, Mark J and Bamshad, Michael J and Nickerson, Deborah A} }