Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs

Abstract

AIMSThe risk of hypoglycaemia with tramadol (TRM) is not well described. Our aim was to analyze spontaneous reports of hypoglycaemia registered in the French Pharmacovigilance database and to compare these data with two other step-2 analgesic drugs. METHODSCases of hypoglycaemia associated with TRM, dextropropoxyphene (DXP) and codeine (COD) recorded between 1997 and November 2010 in the French pharmacovigilance database were compared. RESULTSSeventy-two cases of hypoglycaemia associated with DXP and 43 with TRM were retained for evaluation (the single case reported with COD was not further considered). Most patients were elderly people with no significant difference in age between DXP-and TRM-treated patients (71.2 Ϯ 21 vs. 69.4 Ϯ 22.5 years). Hypoglycaemia occurred after a median of 4 and 5 days with DXP and TRM treatment, respectively. The mean lowest serum glucose concentration was 2.1 Ϯ 0.9 mmol l -1 in the DXP group compared with 2.5 Ϯ 1 mmol l -1 in the TRM group (P = 0.072). At least, one risk factor of hypoglycaemia was found in most patients, with no significant difference between groups (58.3% in the DXP group and 58.1% in the TRM group). In particular, 31.9% patients from the DXP group had diabetes compared with 41.8 % from the TRM group (P = 0.28) and 18% of DXP patients had renal insufficiency compared with 16.3% of TRM patients (P = 0.8). CONCLUSIONSOur study confirms that TRM is associated with the occurrence of hypoglycaemia in elderly or predisposed patients, with characteristics similar to those previously reported with DXP. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Whereas dextropropoxyphene (DXP) has been recognized as a possible cause of hypoglycaemia, only isolated reports have described a similar adverse effect with tramadol (TRM).• To the best of our knowledge, there is no large study comparing the occurrence of hypoglycaemia in patients treated with these step 2 analgesics. WHAT THIS STUDY ADDS• The aim of this study was to describe spontaneous reports of hypoglycaemia associated with TRM and to compare these data with that of DXP-induced hypoglycaemia.• The results show that the characteristics of hypoglycaemia in tramadol users are very similar to those described with DXP, with old age, diabetes and renal insufficiency as the main risk factors.• Physicians and patients should be warned of this potential adverse effect.

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

“…7 An in-depth analysis of spontaneous reports from a French pharmacovigilance database identified 43 tramadolassociated hypoglycemia cases between 1997 and 2010. 8 Most of these events occurred soon after initiation of tramadol therapy (77% within 10 days of treatment) and were more frequent in the elderly. Overall, our findings corroborate these signals because the increased risk seemed to be limited to the first 30 days of use and remained statistically significant in patients with no history of treated diabetes.…”

“…This was done to assess whether the risk varies with timing of treatment initiation, an analysis motivated by the pharmacovigilance study that signaled a rapid onset of tramadol-induced hypoglycemia (ie, within 10 days). 8 Thus, in a secondary analysis, tramadol use was further classified according to timing of the first prescription in the year before the index date (ie, first prescription ≤30 days and >30 days before index date). The reference category for all analyses consisted of codeine use.…”

Tramadol Induced Hypoglycemia Masquerading as a Seizure Disorder

“…Possible role of Tramadol in induction of recurrent hypoglycemia was considered because of its chemical structure being similar to another older non-steroidal analgesic 'propoxyphen' known to cause hypoglycemia [3][4][5][6]. Moreover, total remission of hypoglycemia and seizures following withdrawal of Tramadol and other anticonvulsants established the diagnosis of Tramadol induced hypoglycemia in this patient.…”

A Case Report of Toxicity to an Opioid Analgesic

“…10 Moreover, a few cases of hypoglycemia induced by selective serotonin re-uptake inhibitors (SSRI's) have been reported. 11 Tramadol should be avoided with alcohol, CNS depressants and other opioids. Treatment should be focused on adequate ventilation.…”