Several dozen patients taking certain drugs for hepatitis C have experienced liver problems – some leading to liver failure and death – prompting the Food and Drug Administration to issue a warning against their off-label use in patients with poor liver health.
On Wednesday, the FDA said that 63 cases of worsening liver function known as liver decompensation were reported to its Adverse Event Reporting System, or FAERS, or found in medical literature. The FAERS collects reports of potential side effects from healthcare professionals, though the side effects may or may not be connected to particular drugs. The drugs included in the Wednesday warning were AbbVie’s Mavyret (glecaprevir/pibrentasvir), Merck & Co.’s Zepatier (elbasvir/grazoprevir) and Gilead Sciences’ Vosevi (sofosbuvir/velpatasvir/voxilaprevir).
The agency added that most of the patients had moderate to severe liver impairment and should not have been prescribed those three drugs, as they are not indicated for patients with those conditions. Legally, doctors are free to prescribe drugs off-label within the constraints of medical ethics and insurance coverage, though manufacturers cannot market their drugs for uses outside their FDA-approved labels.
Given that the reported cases came from FAERS and the literature, there may be many additional cases as well, based on the estimated 72,000 patients who received the drugs last year, the FDA said. Symptoms resolved in most patients after they stopped the medicine.
Collectively, the three drugs belong to a class known as direct-acting antivirals, or DAAs, which are designed to inhibit nonstructural proteins that the hepatitis C virus depends upon for replication.
In the context of compensated liver disease, they are “incredibly safe and effective,” wrote Dr. Kristen Marks, an infectious disease specialist at NewYork-Presbyterian Hospital, in an email. The important take-home point, she wrote, is early testing and treatment, as there are simple and reliable tests that can determine which patients can be safely given the drugs – a category into which the vast majority of HCV patients fall.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
“In certain situations where these medications are the only drug options for potential cure, and liver transplant is not feasible, providers would weigh the risks and benefits of off-label use in the context of the particular patient and their goals of care,” she wrote. “For patients with cirrhosis and evidence of liver decompensation who have other options, options that do not contain a protease inhibitor medication should be chosen.”
Dr. Susanna Naggie, an infectious disease specialist at Duke University who has taken part in clinical trials of various DAAs, including the ones included in the FDA warning, concurred.
“Providers must be diligent to ensure they are adequately staging patients for liver fibrosis and liver disease severity before choosing a DAA regimen,” she wrote.
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