title: Pharmacogenomics and tailored polypharmacy: an 80-year-old lady with rosuvastatin-associated rhabdomyolysis and maprotiline-related Ogilvie's syndrome .
abstract: What is known and objectives: Multiple adverse drug reactions (ADRs) are expected, and thus should be prevented in the elderly comorbid patient on polypharmacy. Rosuvastatin is commonly prescribed for the treatment and prevention of atherosclerotic diseases, and in rare cases, is associated with rhabdomyolysis. Maprotiline is a tetracyclic antidepressant, infrequently used in the United States, but seemingly more broadly in European countries. Acute colonic pseudo-obstruction (Ogilvie's syndrome) caused by maprotiline has thus far, to our knowledge, not yet been described in the literature.
  
  
  METHODS
  We present a unique case of synchronous rhabdomyolysis and Ogilvie's syndrome in an 80-year-old lung cancer survivor following a recent ischemic stroke for which she was prescribed clopidogrel and rosuvastatin for secondary prevention, and maprotiline for post-stroke, new-onset insomnia and anxiety. The ADRs resolved on removal of the offending agents and initiation of conservative treatment. Retrospective pharmacogenetic testing of the patient's drug-metabolizing enzymes and transporters was performed to guide further management and prevent future potential drug interactions and ADRs. What is novel and conclusions: This is an interesting, albeit unfortunate, complex case that depicts the risk of rare adverse effects to medications and their potential relationship to pharmacogenetics. The impact of anticholinergic side effects of antidepressants on gastrointestinal motility, risk of myopathies with statins, increased susceptibility to ADRs caused by drug-drug interactions, and the utility of pharmacogenomic testing are discussed. The question whether commercially available pharmacogenomic tools are relevant for everyday use to direct patient care and reduce harmful drug-drug interactions is addressed and warrants further research. .
authors.forename: Katherina B
authors.initials: KB
authors.lastname: Sreter
authors.forename: Blazenka
authors.initials: B
authors.lastname: Barisic
authors.forename: Sanja
authors.initials: S
authors.lastname: Popovic-Grle
mesh_terms: D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000493:pharmacokinetics; D003112:Colonic Pseudo-Obstruction / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics / Q000378:metabolism; D008376:Maprotiline / Q000009:adverse effects* / Q000493:pharmacokinetics; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D019338:Polypharmacy; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics; D012307:Risk Factors; D000068718:Rosuvastatin Calcium / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D018687:Antidepressive Agents, Second-Generation; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; C503999:SLCO1B1 protein, human; D008376:Maprotiline; D000068718:Rosuvastatin Calcium; D003577:Cytochrome P-450 Enzyme System