title: Exposure to sennoside-digoxin interaction and risk of digoxin toxicity: a population-based nested case-control study.
abstract: OBJECTIVE
  Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity.
  
  
  RESULTS
  This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94).
  
  
  CONCLUSIONS
  The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China. wmt@mail.ndmctsgh.edu.tw
authors.forename: Meng-Ting
authors.initials: MT
authors.lastname: Wang
authors.forename: I-Hsun
authors.initials: IH
authors.lastname: Li
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Lee
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Huang
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.forename: Agnes L F
authors.initials: AL
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000880:Anthraquinones / Q000009:adverse effects*; D016022:Case-Control Studies; D003248:Constipation / Q000150:complications / Q000188:drug therapy; D004077:Digoxin / Q000009:adverse effects*; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012676:Senna Extract; D000081226:Sennosides
chemical_list: D000880:Anthraquinones; D000081226:Sennosides; D004077:Digoxin; D012676:Senna Extract