title: Dose-reducing H2 receptor antagonists in the presence of low glomerular filtration rate: a systematic review of the evidence.
abstract: BACKGROUND
  While it is recommended that H2 receptor antagonists (H2RAs) be dose reduced in the presence of low glomerular filtration rate (GFR), in practice such adjustments often do not occur. We reviewed the evidence for this recommendation.
  
  
  METHODS
  We searched multiple medical reference databases for relevant cohort studies and randomized clinical trials. Studies that enrolled five or more participants with low GFR who also received at least one unadjusted dose of an H2RA, and who were compared with controls were included. Data were abstracted on study and participant characteristics and drug-related adverse effects. Pharmacokinetic measures were pooled using meta-analysis.
  
  
  RESULTS
  A total of 22 articles were included, comprising 19 unique cohort studies. With declining GFR, there was a significant increase in the area under the curve (AUC) and elimination half-life (t(1/2)) of the serum drug concentration of H2RAs (P < 0.001). Compared with a GFR >80 ml/min/1.73 m2, drug AUC increased by 200% when the GFR was 30 ml/min/1.73 m2, and by 300% when the GFR was 20 ml/min/1.73 m2. In hospitalized patients with low GFR, reducing the interval dose of intravenous H2RA was associated with fewer adverse reactions. The gastro-protective effects of H2RAs were similar with reduced and unadjusted doses.
  
  
  CONCLUSIONS
  Reducing the dose of H2RAs in persons with low GFR will decrease drug expenditure and may prevent adverse events, without a change in efficacy. Quality assurance programmes, which improve deficiencies in H2RAs prescribing, appear justified.
authors.affiliation: Division of Nephrology, University of Western Ontario, London, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Manlucu
authors.forename: M
authors.initials: M
authors.lastname: Tonelli
authors.forename: J G
authors.initials: JG
authors.lastname: Ray
authors.forename: A
authors.initials: A
authors.lastname: Papaioannou
authors.forename: G
authors.initials: G
authors.lastname: Youssef
authors.forename: H R
authors.initials: HR
authors.lastname: Thiessen-Philbrook
authors.forename: A
authors.initials: A
authors.lastname: Holbrook
authors.forename: A X
authors.initials: AX
authors.lastname: Garg
mesh_terms: D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D010437:Peptic Ulcer / Q000188:drug therapy / Q000378:metabolism; D012307:Risk Factors
chemical_list: D006635:Histamine H2 Antagonists