January 2017 ISMP Report: FDA Database Has 524 Cases Of Liver Failure, Including 165 Deaths, And 1,058 Reports Of Severe Liver Injury
A January 24, 2017 article published by The New York Times, "Are New Drugs for Hepatitis C Safe? A Report Raises Concerns", sets the stage for and captures the essence of this emerging drug safety issue for a relatively new class of drugs:
The drugs covered in the new report include two blockbusters, Sovaldi and Harvoni, both made by Gilead Sciences and priced at $1,000 a pill, with billions of dollars in sales. Sovaldi was approved in 2013, and Harvoni in 2014. These drugs and other antivirals can cure the disease in 12 weeks in many patients.
Earlier drugs were less effective, had to be taken for much longer and had harsh side effects that left many patients unable to finish the course of therapy.
About 250,000 people took the newer drugs in 2015, the report said, at tremendous expense: $55,000 to $125,000 per patient. In those treated during the year ending June 30, 2016, the report identified 524 with liver failure, 165 of whom died. Of those with liver failure, 386 were from outside the United States. An additional 1,058 had severe liver injury, and in 761 the drugs appeared not to work.
But whether the drugs were to blame is not known. The problems were observed by doctors who suspected drugs were the cause, but that does not prove cause and effect. And details about the patients’ medical histories were not available....
Thomas J. Moore, a senior scientist at the Institute for Safe Medication Practices [(ISMP)] and an author of the report, said the study reflected a larger question about the drug approval process. Approval for the newer hepatitis C drugs was expedited because better treatments were so badly needed. But does the rush to market come at a price?
“Gosh, here is something that really qualifies as a breakthrough, and we have policies to get it into use as quickly as possible, which means we know less about it,” Mr. Moore said. “Benefits and side effects evolve over the long term, not over 12 weeks.”
The underlying report, "New Safety Issues for Hepatitis C Antivirals", appeared in the "ISMP QuarterWatch: January 25, 2017 — New data from 2016 Q2" publication.
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From that document, we learn that after the FDA identified the first new major safety problem linked to the nine new direct-acting antiviral drugs for hepatitis C -- namely, that treatment with the likes of Sovaldi and Harvoni opened the door to reactivation of hepatitis B -- the ISMP undertook this project.
Here are some of the details from the resulting full report on their research:
... [W]e searched the most recent 12 months of FAERS data for acute liver failure cases associated with these new drugs. Acute liver failure is a rare, dramatic, and catastrophic medical emergency that involves sudden damage to so much liver tissue that continued survival is at risk. While most organs are ultimately affected, one critical symptom is encephalopathy–a brain dysfunction that can involve psychiatric disturbances, motor problems, hyperventilation, and even coma.... [footnote omitted]
For the 12 months ending June 30, 2016, we identified 524 reported cases worldwide of liver failure in which one of the nine direct-acting antivirals was a primary or secondary suspect drug.... The 524 liver failure cases occurred more frequently in males (55%) and in patients with a median age of 61 years. In these reports, 165 cases (31.5%) had an outcome of death at the time the report was submitted. Overall, 90% of the reports were originated by health professionals, including 34 cases extracted from the medical literature with duplicate references excluded. Table 4 shows 55 cases involved liver transplants, but it was not clear whether the transplants were a treatment for liver failure, or whether the event might have occurred in a post-transplant population. These cases reflect the global reported adverse event experience, with 386 (73.7%) from outside the U.S.
And from the Executive Summary section of this January 2017 ISMP QuarterWatch publication, we get these additional facts about the liver failure cases associated with Sovaldi and Harvoni:
The 524 reported cases of liver failure included all the approved direct-acting antivirals as either primary or secondary suspect drugs, often in combination with each other or with ribavirin. Almost half the cases also included the hallmark symptom of liver failure, encephalopathy, which is a form of brain injury resulting in delirium, personality changes, suicidal behavior, sleep-wake reversal, and coma. Overall, 165 (31.5%) had died at the time of the report. While it was challenging to separate cases to which complications of hepatitis C might have contributed, 90% of the cases were submitted by healthcare professionals, who would be likely to understand the natural progression of the disease.
We will continue to monitor this new drug safety issue and are interested in hearing from or about any hepatitis C patients treated with Sovaldi or Harvoni who developed liver failure or were diagnosed liver injury, which might have been caused by these drugs.
In addition, we are interested in cases of hepatitis B reactivation in patients after using Solvaldi or Harvoni.
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