Important Dosage and Administration Instructions

Prior to the initiation of OCALIVA, healthcare providers should determine whether the patient has decompensated cirrhosis (e.g., Child-Pugh Class B or C), has had a prior decompensation event, or has compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) because OCALIVA is contraindicated in these patients [see Contraindications (4), Warnings and Precautions (5.1)].

Recommended Dosage Regimen

The recommended dosage of OCALIVA for PBC patients without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, who have not achieved an adequate biochemical response to an appropriate dosage of UDCA for at least 1 year or are intolerant to UDCA [see Clinical Studies (14)] follows below:

• Start with a dosage of 5 mg once daily for the first 3 months.
• After the first 3 months, for patients who have not achieved an adequate reduction in ALP and/or total bilirubin and who are tolerating OCALIVA, increase to a maximum dosage of 10 mg once daily.

Monitoring to Assess Safety, Need for OCALIVA Discontinuation

Routinely monitor patients during OCALIVA treatment for biochemical response, tolerability, and progression of PBC. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation, have compensated cirrhosis and develop evidence of portal hypertension, experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction [see Contraindications (4), Warnings and Precautions (5.1)].

Management of Patients with Intolerable Pruritus on OCALIVA

For patients with intolerable pruritus on OCALIVA, consider one or more of the following management strategies:

• Add an antihistamine or bile acid binding resin [see Dosage and Administration (2.5), Clinical Studies (14)].
• Reduce the dosage of OCALIVA to:
  • 5 mg every other day, for patients intolerant to 5 mg once daily.
  • 5 mg once daily, for patients intolerant to 10 mg once daily.
• Temporarily interrupt OCALIVA dosing for up to 2 weeks. Restart at a reduced dosage.

For patients whose dosage is reduced or interrupted, titrate the dosage based on biochemical response and tolerability [see Dosage and Administration (2.2)].

Consider discontinuing OCALIVA treatment in patients who continue to experience persistent, intolerable pruritus despite management strategies [see Warnings and Precautions (5.2)].

Administration Instructions

• Take OCALIVA with or without food.
• For patients taking a bile acid binding resin, take OCALIVA at least 4 hours before or 4 hours after taking the bile acid binding resin, or at as great an interval as possible [see Drug Interactions (7.1), Clinical Studies (14)].