title: Uncommon serum creatine phosphokinase and lactic dehydrogenase increase during diosmin therapy: two case reports.
abstract: BACKGROUND
  Short-term administration of diosmin is usually considered safe, with only minor side effects (stomach and abdominal pain, diarrhea, dermatological disorders, and headache) occasionally observed. Within a 4-year period, a general practitioner noticed 17 cases of mild, diosmin-induced side effects, two of which showed particular interest.
  
  
  METHODS
  Case 1: A 55-year-old Caucasian woman presented with chronic leg venous insufficiency. She was prescribed diosmin 450 mg twice a day. After 5 days of therapy, she developed pain in the legs (myalgia), and diosmin therapy was suspended. She made a spontaneous attempt of drug rechallenge and her leg pain reappeared. Thus, she underwent blood analysis, which showed elevation of creatine phosphokinase levels. Creatine phosphokinase values normalized only after prolonged discontinuation of the therapy. Case 2: A 79-year-old Caucasian man, who was diagnosed with acute hemorrhoidal syndrome. After 21 days of continuous diosmin treatment, increased levels of serum lactic dehydrogenase were detected. In both cases a comprehensive analysis of all possible causes for enzyme elevation was made.
  
  
  CONCLUSIONS
  A feasible hypothesis to explain these rare effects could be that exaggerated adrenergic activity occurred on microcirculation, leading to an excessive peripheral vasoconstriction and subsequent ischemic damage. An individual predisposition is strongly suggested. A concurrence of events was probably responsible for the elevation of nonspecific tissue necrosis markers. Physicians and patients must be aware of these rare, but possible, adverse drug reactions.
authors.forename: Giulia
authors.initials: G
authors.lastname: Milano
authors.forename: Silvia
authors.initials: S
authors.lastname: Leone
authors.forename: Carmen
authors.initials: C
authors.lastname: Fucile
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Zuccoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Stimamiglio
authors.forename: Antonietta
authors.initials: A
authors.lastname: Martelli
authors.affiliation: Department of Internal Medicine, Clinical Pharmacology and Toxicology Unit, University of Genoa, Viale Benedetto XV 2, Genoa I-16132, Italy. francesca.mattioli@unige.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mattioli
mesh_terms: D000368:Aged; D003402:Creatine Kinase / Q000097:blood*; D004145:Diosmin / Q000009:adverse effects*; D005260:Female; D006484:Hemorrhoids / Q000188:drug therapy*; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000139:chemically induced*; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014689:Venous Insufficiency / Q000188:drug therapy*
chemical_list: D004145:Diosmin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase