Must-read: another adverse effect associated with tramadol
February 9, 2015, 9:54 pm
Tramadol and Hypoglycemia: One More Thing to Worry About. Nelson LS, Juurlink DN. JAMA Intern Med 2015 Feb 1;175(2):194-5
Hypoglycemia associated with use of tramadol has been noted previously in scattered case reports, after both overdose and therapeutic ingestion, involving patients with and without diabetes. In this month’s issue of JAMA Internal Medicine, Fournier et al. presented a large case-control study comparing patients started on tramadol for pain with similar patients started on codeine. They found that the tramadol patients had a significantly increased risk of hospitalization for hypoglycemia, especially in the first month after the drug was started.
True, the hypoglycemia cases were rare, with an incidence of 7 per 10,000 per year. However, as Lewis Nelson (@LNelsonMD) and David Juurlink (@DavidJuurlink) point out in this superb editorial accompanying the article, there are a number of other significant adverse effects associated with this problematic drug. The editorial is a must-read short summary of tramadol pharmacology and toxicology.
They start by noting:
” . . . the expectation that analgesics can significantly reduce or abolish pain is often overly optimistic and can lead to the progressive use of higher doses of stronger analgesics without a reasonable benchmark for success or failure. . . . Nonpharmacologic approaches such as physical therapy, meditation, exercise, and weight loss are harder to implement than medication because they are time consuming, labor intensive, and often not covered by insurance, even though each is supported by evidence of safety and effectiveness in elected patients.”
They then go on to make the following crucial points about tramadol:
- tramadol works through 2 different mechanisms:
- a metabolite (O-desmedthyltramadol[M1]) binds to μ opioid receptors; and
- tramadol inhibits reuptake of serotonin and norepinephrine
- the metabolism of tramadol to M1 is via CYP2D6, an enzyme with extremely variable activity
- because of the variable metabolism, “Giving a known dose of tramadol is tantamount to giving an unknown dose of opioid”
- despite earlier beliefs, tramadol is neither safe nor non-addictive
- significant adverse effects associated with tramadol include serotonin syndrome, drug-drug interactions, and respiratory depression
This short editorial is a must-read.