Ocaliva (obeticholic acid) is used to treat a rare disease called primary biliary cholangitis (PBC), which causes excess bile in the liver that can result in hepatic failure and death.
The US Food and Drug Administration (FDA) issued a warning about Ocaliva last week stating that, based on reports submitted to its Adverse Event Reporting System (FAERS), 19 people taking the drug have died since it was approved last May.
The Agency linked the incidents to incorrect dosing, pointing out that “seven of these eight cases described patients with moderate to severe decreased liver function who received Ocaliva 5mg daily, instead of a dose no greater than 10mg twice weekly as recommended in the label prescribing information for patients with this extend of decreased liver function.”
The FDA also said it had received report of 11 cases of serious liver injury, six of which involved patients were receiving Ocaliva 5mg daily, instead of the recommended limit of 10mg twice weekly.
It advised patients with new or worsening severe skin itching to seek medical assistance.
‘Non causal relationship’
Intercept spokesperson Christopher Frates agreed that prescribers had not followed correct dosing instructions for patients with moderate to severe liver damage, however told us the firm had not identified a causal relationship between the higher than recommended dosing and patient harm.
Rather, it has been shown that hepatic impairment increases systemic and hepatic concentrations of Ocaliva, he said.
“In PBC clinical trials, a dose-response relationship was observed for the occurrence of liver-related adverse reactions with Ocaliva. Consequently, the current US package insert recommends a longer dosing interval for PBC patients with moderate to severe hepatic impairment,” said Frates.
Frates told us all materials on the on-label education for prescribers contain the full and complete information, however the company has proactively reviewed and reinforced educational activities.
In the US and Europe, the firm has audited existing materials to identify opportunities ways it can increase the prominence of information about dose requirements for patients.
In addition, the company is reinforcing the labelled prescribing recommendations, and its medical team will re-train distributing pharmacies.
The firm is also reviewing its business rules for patient support service staff, in order to identify potential excessive dosing at the point of initial prescriptions, Frates told us.