This New Medical Research Was Published Just Before "Black-Box Warning" About Lower Limb Amputations Added To Drug Labels
In the final week of July 2017, the FDA issued a notification that it had approved a revised drug label for Invokana and Invokamet, as well as a revised Medication Guide for these two diabetes drugs from Janssen Pharmaceuticals. This label change was previewed in a May 2017 FDA Drug Safety Communication about an increased risk of leg and foot amputations. For more information on this recent development, see this earlier article: "Invokana - Amputation Side Effect Gets "Black-Box Warning" On Revised Drug Label Issued In July 2017".
Just before this Invokamet / Invokana label change was finally done, The Lancet Diabetes & Endocrinology medical journal published this Correspondence item on July 18, 2017, "SGTL2 inhibitors and amputations in the US FDA Adverse Event Reporting System".
From that item, we get these two excerpts:
- In summary, this pharmacovigilance analysis confirms that use of canagliflozin, but not dapagliflozin or empagliflozin, might be associated with an increased risk of amputations. However, [the US Food and Drug Administration (FDA) adverse event Reporting System (FAERS)] data analysis has important limitations because there is no definite causal link between drug exposure and adverse event.... [footnote omitted]
- Most of the available reports (57 [86%] of [66 SGLT2 inhibitor-associated amputations]) listed canagliflozin as a suspect or concomitant drug. Average and detailed report information is provided in the appendix. On average, patients were aged about 60 years, and most were men. In 57 (89%) of 64 cases (two reports could not be retrieved for detailed analysis), an SGLT2 inhibitor was the primary suspect and average treatment duration was about 1·5 years. Based on indications, 11% of patients had diabetic foot or wounds, but concomitant adverse events included wound, necrosis, gangrene, or ischaemia in 14 cases, and osteomyelitis or other infections in 15 cases. Cumulatively, in 23 (36%) of 64 cases there was at least one of such features of diabetic foot syndrome. The most common level of amputation was the toe, but there were 13 above-ankle leg or limb amputations, two multiple amputations, one hand amputation, and three fatal cases.
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In early August 2017 an article with some additional contextual information, "FDA Reports Further Support for Canagliflozin-Amputation Link", was published on the Medscape website (free registration required). From that article we get the following points:
Among 66 reports of SGLT2-inhibitor–associated amputations, 57 (86%) involved canagliflozin. Moreover, two-thirds of those reports were among people with no discernible risk factors for amputation, "which, worryingly, points to an unpredictable effect of the drug," [Gian Paolo Fadini, MD, PhD, of the division of metabolic diseases, department of medicine, University of Padova, Italy] told Medscape Medical News....
Thus far, the FDA has not extended the label warning about amputations to other drugs in the class [e.g., Jardiance (empagliflozin) and Farxiga (dapagliflozin)], although the European Medicines Agency (EMA) has, pending further investigation.
"Our data are the first to confirm the warning originated from CANVAS and tends to suggest this is not a class effect," Dr Fadini told Medscape Medical News.
We are currently investigating possible drug injury cases against the responsible drug company, Janssen Pharmaceuticals, where a patient who used Invokana or Invokamet had to have a lower limb amputation.
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