Another major side effect of Tramadol found, leading to hospitalization.

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Latest studies have shown that Tramadol causes severe Hypoglycaemia which can lead to one’s hospitalization.

Tramadol: is an opioid analgesic used for treating moderate to severe pain.

Hypoglycaemia: is a condition of low blood sugar, involving an abnormally diminished content of glucose in the blood. A variety of symptoms are seen with this condition, ranging from mild dysphoria to more serious situations like seizures, brain damage and death. Major problems arise when the supply of glucose to brain is inadequate, leading to impaired functioning.

As tramado is widely used for its pain relieving properties and seems to be less addicting, researchers from Jewish General Hospital in Montreal conducted a study to assess whether the increased hypoglycemic risk with the use of tramadol is serious enough to cause hospitalization of the patients.

Study:

Objective: to figure out whether tramadol is increasing the chances of hospitalization by causing severe hypoglycemia, on comparison with codeine.

Authors surveyed the UK database of all patients, newly treated with tramadol or codeine for non cancer pain between 1998 and 2012. 3334,034 patients were contained in the study, out of which 305,924 just started using codeine and 28,100 were the new users of tramadol.

Result of the study:  1105 patients ended up being hospitalized due to low blood glucose levels and 110 died from severe hypoglycemia during a 5 year follow up period.

The study showed that tramadol on comparison with codeine is responsible for increasing the risks of hospitalization for hypoglycemia. The study also showed that the patients were more prone to this risk in the first 30 days of using the drug, this relation was ascertained in case crossover and cohort analyses. The incidence of hospitalization for hypoglycemia with tramadol within first 30 days was seen to be 3.0% per 10,000 persons- month, whereas it was only 0.7/10,000 persons- month with codeine.

Tramadol overdose in a woman leading to hospitalization for hypoglycemia was also reported.

This shows that tramadol is responsible for 3 fold increase in risk of hospitalization for hypoglycemia.

“Although rare, tramadol induced hypoglycemia is a potential adverse drug event. The clinical significance of these novel findings require additional investigations.” authors.

According to co author Laurent Azoulay, assistant professor of oncology department at McGill University, Montreal,  patients with diabetes and taking glucose lowering agents are not the only ones at risk with tramadol but non diabetic patients are at an equal chance of suffering from severe low blood glucose by this drug.

But it is still unclear whether tramadol should not be used in patients taking glucose lowering drugs or it should be administered in such patients but with more care and caution.

Another surprising fact which was found in the study was that the risk of hypoglycemia with tramadol was higher in non diabetic patients.

Mechanism through which tramadol causes hypoglycemia: it is believed that the pharmacodynamic properties of the drug could be playing a role in causing hypoglycemia. Tramadol shows its actions or effects by activating the MOR and by inhibiting the central serotonin and nor epinephrine re uptake. Serotonin is seen to regulate the glucose levels in our body.

Animal studies: it was seen that in rats with streptozotocin 60mg/kg IV (a chemical that is toxic to the insulin producing beta cells of the mammalian pancreas) induced diabetes, tramadol depicted a dose dependent glucose lowering effect. This effect continued when these rats were exhausted of serotonin by using P- chlorophenylalanine, showing that the effect is serotonin independent or serotonin free. But when naloxone hydrochloride was used, these effects appeared to be weak.

Results of the animal study: after inducing diabetes in rats the test drug which was tramadol showed hypoglycemic activity when compared to the standard drug which was glimepiride.

According to Dr. Lewis Nelson, Professor in the department of emergency medicine at New York School of Medicine, tramadol is not a safe alternative to conventional narcotic pain relievers. He also stated that although the cases of hospitalization for hypoglycemia is less likely to be seen in this study, the actual rates of hypoglycemia caused by tramadol can be much more higher due to under recognition and under reporting. 

The writers suggest that hypoglycemia can prove a life threatening situation, so clinicians need to practice a lot of care and vigilance in patients taking tramadol or those who abuse it.

Time on tramadol when patients have low blood sugar:

<1 month… 82.26%

1-6 months… 3.23%

6-12 months… 0.00%

1-2 years… 9.68%

2-5 years… 1.61%

5-10 years… 3.23%

10+ years… 0.00%

Gender differences of having low blood sugar with tramadol: 

Female… 48.68%

Male… 51.32%

Severity of low blood sugar with tramadol:

Least… 0.00%

Moderate… 40%

Severe… 60.00%

Most severe… 0.00%

Age of people who have low blood sugar with tramadol:

0-1… 0.00%

2-9… 0.72%

10-19… 2.16%

20-29… 9.35%

30-39… 12.59%

40-49… 14.03%

50-59… 15.11%

60+… 46.04%

This study will help physicians better to compare the risks and benefits of tramadol before prescribing it to the patients. Before initiating the treatment with tramadol, physicians and patients need to see whether its benefits are actually overpowering its adverse effects. It is believed that tramadol’s adverse effects in majority of patients outweigh the benefits and the patients need to be educated about all the serious side effects of this drug, including hypoglycemic problems and how these conditions should be managed.

Reference:

  • JAMA internal medicine December 2014
  • US Pharmacist December  2014
  • Web Md
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