Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | JAMA Network
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Original Investigation
February 2015

Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain

Author Affiliations
  • 1Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
  • 2Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  • 3Department of Oncology, McGill University, Montreal, Quebec, Canada
  • 4Laboratoire de Pharmacologie Médicale et Clinique, Equipe de Phamacoepidémiologie Institut National de la Santé et de la Recherche Médicale U1027, Faculté de Médecine, Université Paul Sabatier, Toulouse, France
  • 5Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Information sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
JAMA Intern Med. 2015;175(2):186-193. doi:10.1001/jamainternmed.2014.6512

Importance  Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia.

Objective  To assess whether tramadol use, when compared with codeine use, is associated with an increased risk of hospitalization for hypoglycemia.

Design, Setting, and Participants  A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Cohort and case-crossover analyses were also conducted to assess consistency of the results.

Main Outcomes and Measures  Cases of hospitalization for hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated comparing use of tramadol with codeine. A cohort analysis, with high-dimensional propensity score–adjusted hazard ratios (HRs) and 95% CIs, was performed comparing tramadol with codeine in the first 30 days after treatment initiation. Finally, a case-crossover analysis was also performed, in which exposure to tramadol in a 30-day risk period immediately before the hospitalization for hypoglycemia was compared with 11 consecutive 30-day control periods. Odds ratios and 95% CIs were estimated using conditional logistic regression analysis.

Results  The cohort included 334 034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11 019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 [95% CI, 1.09-2.10]), particularly elevated in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the cohort (HR, 3.60 [95% CI, 1.56-8.34]) and case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]).

Conclusions and Relevance  The initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.