Popular pain medication associated with greater risk of hypoglycemia

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Since its approval in 1995, the opioid tramadol (marketed as ConZip and Ultram) has become a widely prescribed remedy for osteoarthritis and other painful indications, in part because it presents a lesser risk for some side effects and has a lower abuse potential when compared to other opioids. It is currently ranked among the top five prescribed opioids and top 60 prescribed medications in the country.

But as has grown in popularity so too have documented cases of adverse effects among its users. In a new paper, published August 28, 2019 by Scientific Reports, researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego show that patients who take tramadol are at greater risk for developing , or abnormally .

The research team, led by senior author Ruben Abagyan, Ph.D., professor of pharmacy, analyzed more than 12 million reports from the FDA Adverse Effect Reporting System (FAERS) and Adverse Event Reporting System (AERS) databases, which chronicle voluntary reports of adverse effects while taking a medication. The period studied ranged from January 2004 to March 2019.

"The impetus was the recent dramatic surge in tramadol popularity and prescriptions," said first author Tigran Makunts, PharmD, a researcher in Abagyan's lab. "We wanted to have an objective data-driven look at its adverse effects and bumped into a dangerous, unlisted and unexpected hypoglycemia."

Recognized adverse drug reactions associated with tramadol include dizziness, nausea, headaches and constipation—all common of opioids. More serious but rarer include serotonin syndrome and increased seizure risk. The link to hypoglycemia is relatively new, though it had been previously suggested by and animal model testing.

Hypoglycemia is often related to the treatment of diabetes, but can also occur in persons without diabetes. Untreated, hypoglycemia can lead to serious complications of its own, such as neurocognitive dysfunction, , greater risk of falls and loss of quality of life.

The researchers also looked at other widely prescribed opioids and similar acting, non-opioid medications, such serotonin and norepinephrine reuptake inhibitors (Cymbalta, Effexor XR) and NMDA receptors (ketamine and memantine). Only tramadol produced a significant risk of developing hypoglycemia in patients. In fact, there was a 10-fold greater risk of hypoglycemia using tramadol than virtually every other opioid. The only other drug identified with comparable effect was methadone, an opioid most commonly used to help persons reduce or quit addictions to heroin or other opiates.

While this study underscores an association between tramadol and hypoglycemia, a large, randomized, controlled clinical trial would be needed to definitively establish causality.

"The takeaway message is to warn physicians about the likelihood of low blood sugar (and/or high insulin content), in particular if the patient is predisposed to diabetes," said Abagyan, "and to motivate research about the unique molecular mechanism leading to that side effect. It is particularly important for tramadol or methadone that are used widely and, often, chronically."

Explore further

Tramadol associated with increased risk of hospitalization for hypoglycemia

More information: Scientific Reports (2019). www.nature.com/articles/s41598-019-48955-y
Journal information: Scientific Reports

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User comments

Aug 28, 2019
I took some tramadol when in hospital, and spent one tedious day hallucinating pictures on the ceiling. No mention of that side effects. And no - it wasn't fun.

Aug 28, 2019
I need to tell you that all pills have side effects that could be worse than hypoglycemic being low. I have been using Tramadol for a couple of months now for Cervical Radiculopathy and very painful nerve pain that starts from the neck to the shoulder, down the arm, to the hand and my thumb and forefinger, and pain radiates from my neck to my ear. Since this Opiod Crisis, I don't even have enough pills for a month. I have to nurture my pills, only being able to take 1 a day. Tramadol has really been very helpful when I take it. I am not addicted to it, but I would really like to be able to take 2 a day. Since our country is trying to get rid of this wonderful pain pill, I don't know what I will do. Gabapentin does not work for me. Please don't ad more hype to getting rid of Tramadol.

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