Misdosing Ocaliva for Liver Disorder Can Be Fatal, FDA Says

September 21, 2017

The US Food and Drug Administration (FDA) today warned clinicians that excessive doses of obeticholic acid (Ocaliva, Intercept Pharmaceuticals) for patients with primary biliary cholangitis (PBC) can result in serious injury or death.

In addition, the drug may be linked to liver injury in patients with mild PBS who receive the correct dose.

The FDA approved obeticholic acid in May 2016 to treat adults with PBC in combination with ursodeoxycholic acid (UDCA) when the latter drug falls short therapeutically, or by itself when adults can't tolerate UDCA. PBC is a rare, progressive autoimmune disease that puts patients at risk for liver failure and death.

The recommended starting dose for obeticholic acid is 5 mg daily, according to the FDA-approved label. The maximum dose is 10 mg daily. However, when patients have moderate or severe liver impairment, clinicians should set the starting dose at 5 mg per week instead of 5 mg per day, and the dose should not exceed 10 mg twice a week. In addition, patients receiving the drug should be monitored for elevations in liver biochemical test results and the appearance of liver-related adverse events, such as abdominal swelling and jaundice. Clinicians should weigh the risks vs benefits of continuing treatment if patients experience clinically significant adverse events.

The problem, the FDA said in a news release, is that some clinicians are prescribing 5 mg per day of obeticholic acid right off the bat for patients with moderate or severe liver impairment.

Accordingly, clinicians should determine their patient's baseline liver function before ordering obeticholic acid and, depending on the results, set the dose at the recommended level, the agency said. In addition, clinicians should monitor patients frequently to see whether liver impairment progresses. If it reaches the moderate or severe level during the course of treatment, the dosing frequency should be reduced to once or twice a week. If outright liver injury is suspected, clinicians should discontinue obeticholic acid and weigh the pros and cons of resuming treatment once the patient's condition has stabilized.

Nineteen deaths connected to the use of obeticholic acid have been filed with the FDA Adverse Event Reporting System (FAERS) since the drug's approval. In eight of those cases, the cause of death was described ― the worsening of PBC in seven, and cardiovascular disease in one. In seven of those eight cases, the patients had moderate to severe liver impairment but received 5 mg of obeticholic per day.

FAERS also received reports of 11 cases in which patients developed serious liver injury; three of those patients died (those deaths were counted in the 19 identified in FAERS). In six of these cases, patients were receiving a daily dose 5 mg of obeticholic acid, even though they had moderate to severe liver impairment at baseline.

More information about today's announcement is available on the FDA website.

To report any problems with obeticholic acid, contact MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm; with postage-paid FDA form 3500, available at https://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.

Follow Robert Lowes on Twitter @LowesRobert


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