title: Quinine induced simvastatin toxicity through cytochrome inhibition - a case report.
abstract: Nocturnal leg cramps are painful, involuntary muscle contractions commonly seen in elderly. While mostly harmless, they can severely impair quality of life and often disrupt sleep. Adverse drug effects may be responsible for a fraction of nocturnal leg cramps but often go unrecognized, resulting in additional prescribing intended to deal with adverse effects that might be better addressed by reduction, substitution, or discontinuation of the offending agent.
  
  
  
  An 87 year old female presented as outpatient in family medicine with nocturnal leg cramps which had been present for five years and increasingly burdened her quality of life. She had been using quinine 200 mg once daily for symptomatic relief but the cramps kept returning with increasing intensity. During clinical examination we found neither structural nor neurological or metabolic disorders that explained her symptoms. When doing a medication analysis, we found that she was taking a statin together with quinine. Quinine is a cytochrome P450 isoenzyme 3A4 inhibitor, the very enzyme which is involved in the metabolism of most statins. Therefore the use of both substances simultaneously increases blood levels of the statin thereby increasing the risk of side effects including symptomatic myopathy and myalgia. After discontinuing both medications, the patient was, and remained, symptom free.
  
  
  
  This case report describes a possible medication interaction that has rarely been noted in literature.
authors.affiliation: Institute of General Practice and Family Medicine Bonn, University Clinic Bonn, Siegmund-Freud Str. 25, 53127, Bonn, Germany. johannes.just@ukb.uni-bonn.de.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Just
authors.affiliation: Institute of General Practice and Family Medicine Bonn, University Clinic Bonn, Siegmund-Freud Str. 25, 53127, Bonn, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Weckbecker
authors.affiliation: Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany.
authors.forename: Katja S
authors.initials: KS
authors.lastname: Just
mesh_terms: D000369:Aged, 80 and over; D003580:Cytochromes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009120:Muscle Cramp / Q000188:drug therapy* / Q000378:metabolism; D011788:Quality of Life; D011803:Quinine / Q000008:administration & dosage / Q000009:adverse effects*; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D003580:Cytochromes; D011803:Quinine; D019821:Simvastatin
keywords: Adverse drug event; Adverse drug reaction; Aged 80, and over; Cytochrome P-450 Enzyme System; Drug interaction; Geriatrics