FDA WARNS OF RISK OF SERIOUS LIVER INJURY AND DEATH IN CERTAIN PATIENTS IF OBETICHOLIC ACID IS INCORRECTLY DOSED

September 27, 2017

Here's an important alert for patients taking obeticholic acid (OCALIVA), which was approved by the Food and Drug Administration (FDA) in May 2016 to treat a rare chronic liver disease known as primary biliary cholangitis.

On September 21, the FDA warned that for some patients with moderate-to-severe decreases in liver function, taking a higher-than-approved dose of obeticholic acid may result in an increased risk of serious liver injury and death.[1]

The approved starting dose of obeticholic acid is 5 milligrams (mg) once daily in patients with normal or mildly decreased liver function. In patients with moderately or severely decreased liver function, however, the approved starting dose is 5 mg once weekly, which can be increased to a maximum dose of 10 mg twice weekly over time.

The FDA based its alert on reports of serious liver injury and death in patients with moderate or severe decreases in liver function who were incorrectly given obeticholic acid at a dose of 5 mg once daily, well above the approved maximum dose for such patients of 10 mg twice weekly.

The agency therefore recommended that doctors check the liver function of all patients before starting treatment with obeticholic acid, and "frequently" thereafter, and to follow the approved dosing regimen based on patients' liver function.

Of note, the lower dosing regimen for patients with moderately or severely reduced liver function already was in the drug’s FDA-approved label and should have been followed by the affected patients' doctors.[2] It is therefore questionable whether the FDA's safety communication on its own will result in safer prescribing without further actions by the agency, such as a monitored prescribing program.

It also should be noted that five cases of reported serious liver injury associated with obeticholic acid use occurred in patients with no or only mild decreases in liver function prior to starting the drug and who were given the FDA-approved dose of 5 mg once daily. At least two of these patients experienced improvement upon stopping the drug. Although it is difficult to determine whether obeticholic acid was, in fact, responsible for these patients' liver injuries, such reports raise concern that obeticholic acid, even at the FDA-approved dose, may cause serious liver injury in patients without a history of significantly impaired liver function.

What You Can Do

If you have primary biliary cholangitis, your health care provider should test your liver function before you start taking obeticholic acid and frequently thereafter. In addition, you should be alert for symptoms of possible liver toxicity even if you have normal or mildly decreased liver function.

Contact your health care provider if you experience new or worsening skin itching. You also should contact your health care provider immediately if you experience any of the following symptoms:

• New or worsening fatigue
• Diarrhea
• Weight loss
• Abdominal pain
• Decreased appetite
• Nausea and vomiting
• Change in behavior or confusion
• Vague symptoms such as anxiety or unease
• Abdominal swelling
• Yellow eyes or skin
• Bloody stools

To see the FDA’s safety alert, visit the following link: https://www.fda.gov/Drugs/DrugSafety/ucm576656.htm.

References

[1] Food and Drug Administration. FDA drug safety communication: FDA warns about serious liver injury with Ocaliva (obeticholic acid) for rare chronic liver disease. September 21, 2017. https://www.fda.gov/Drugs/DrugSafety/ucm576656.htm. Accessed September 21, 2017.

[2] Intercept Pharmaceuticals, Inc. Label: obeticholic acid (OCALIVA). May 2017. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=cdfbe0cd-eb15-45a1-ac17-531bcda21aec&type=pdf&name=cdfbe0cd-eb15-45a1-ac17-531bcda21aec. Accessed September 21, 2017.