Popular pain medications carry a high risk of hypoglycemia.
Since its approval in 1995, the opioid tramadol (sold under the names Conzip and Ultram) has become widely prescribed for the treatment of osteoarthritis and other painful conditions, in part because of its lower risk of some side effects and lower potential for abuse than other opioids. It has become a popular drug. It is currently one of the top five most prescribed opioids in the country and one of the top 60 most prescribed medications.
However, as tramadol’s popularity has grown, so have reports of side effects in its users. In a new paper published Aug. 28, 2019, in the journal Scientific Reports, researchers from the Skaggs School of Pharmacy at the University of California, San Diego, and colleagues found that patients taking tramadol are at increased risk of developing hypoglycemia, or abnormally low blood glucose levels.
The research team, led by lead author Dr. Ruben Abagyan (Pharmacy), analyzed more than 12 million reports from the FDA Adverse Event Reporting System (FAERS) and Adverse Event Reporting System (AERS) databases. The study period covered January 2004 through March 2019.
The impetus was the recent surge in the popularity and prescribing of tramadol, says lead author Tigran Makunts, PharmD, of Abergeen Laboratories. “We wanted to study the side effects of tramadol based on objective data, but we encountered dangerous, unreported, and unexpected hypoglycemia.
Known side effects associated with tramadol include dizziness, nausea, headache and constipation – common side effects of opioids. More serious but rare side effects include serotonin syndrome and an increased risk of seizures. The link to hypoglycemia is relatively recent, but has long been hypothesized based on case studies and experiments in animal models.
Hypoglycemia is often associated with treatment of diabetes, but can also occur in people without diabetes. Untreated hypoglycemia can lead to serious complications such as neurocognitive impairment, vision loss, increased risk of falls, and decreased quality of life.
The researchers also looked at other commonly prescribed opioids and non-opioid drugs with similar effects, such as serotonin-noradrenaline reuptake inhibitors (Cymbalta, Effexor XR) and NMDA receptor inhibitors (Ketamine, Memantine). Tramadol alone presented a significant risk of patients developing hypoglycemia. In fact, the risk of hypoglycemia with tramadol was 10 times higher than with virtually all other opioids. The only drug that was as effective was methadone, the most commonly used opioid to reduce addiction to heroin and other opioids, as well as to aid in smoking cessation.
This study highlights the link between tramadol and hypoglycemia, but large randomized controlled clinical trials are needed to clearly establish causality.
The message received is to alert physicians to the possibility of hypoglycemia (and/or hyperinsulinemia), especially if the patient has a predisposition to diabetes, says Abagyan. This is especially important if tramadol or methadone is widely and frequently used chronically.”
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