title: Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology.
abstract: OBJECTIVE
  To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia.
  
  
  METHODS
  Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology).
  
  
  METHODS
  Healthcare claims data from the IMS Lifelink database in the United States.
  
  
  METHODS
  Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5α reductase inhibitor (5ARI) between January 2001 and June 2011 after a minimum of six months' enrolment.
  
  
  METHODS
  Hypotension requiring admission to hospital. Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted.
  
  
  RESULTS
  Among 383,567 new users of study drugs (tamsulosin 297,596; 5ARI 85,971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10,000 person years) than for 5ARIs (31.3 events per 10,000 person years) or all accrued person time (29.1 events per 10,000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis.
  
  
  CONCLUSIONS
  We observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the "first dose phenomenon" with tamsulosin.
authors.affiliation: Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Department of Epidemiology, Silver Spring, MD, USA.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Bird
authors.forename: Joseph A C
authors.initials: JA
authors.lastname: Delaney
authors.forename: James M
authors.initials: JM
authors.lastname: Brophy
authors.forename: Mahyar
authors.initials: M
authors.lastname: Etminan
authors.forename: Sean C
authors.initials: SC
authors.lastname: Skeldon
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Hartzema
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000453:epidemiology*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D012189:Retrospective Studies; D018570:Risk Assessment; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D000077409:Tamsulosin; D014481:United States
chemical_list: D058891:5-alpha Reductase Inhibitors; D058668:Adrenergic alpha-1 Receptor Antagonists; D013449:Sulfonamides; D000077409:Tamsulosin