, to achieve optimal response.
Consider discontinuing treatment with obeticholic acid for patients who continue to experience persistent, intolerable pruritus.
Special populations
Patients with hepatic impairment
See table 1 for dose recommendations. Further, see sections 4.4 and 5.2.
Elderly (≥ 65 years)
Limited data exists in elderly patients. No dose adjustment is required for elderly patients (see section 5.2).
Patients with renal impairment
Limited data exists in patients with mild and moderate renal impairment and no data exists in severe renal impairment. No dose adjustment is required for patients with renal impairment (see section 5.2).
Paediatric population
There is no relevant use of obeticholic acid in the paediatric population in the treatment of primary biliary cholangitis (PBC).
Method of administration
The tablet should be taken orally with or without food.
For patients taking bile acid binding resins, obeticholic acid should be administered at least 4-6 hours before or 4-6 hours after taking a bile acid binding resin, or at as great an interval as possible (see section 4.5).
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
- Complete biliary obstruction.
4.4 Special warnings and precautions for use
Liver related adverse events
Elevations in alanine amino transferase (ALT) and aspartate aminotransferase (AST) have been observed in patients taking obeticholic acid. Clinical signs and symptoms of hepatic decompensation have also been observed. These events have occurred as early as within the first month of treatment. Liver-related adverse events have primarily been observed at doses higher than the maximum recommended dose of 10 mg once daily (see section 4.9). In the post marketing setting, serious liver injury and death have been reported with more frequent dosing of obeticholic acid than recommended in patients with moderate to severe decreases in liver function.
After initiation of therapy, all patients should be monitored for progression of PBC disease with laboratory and clinical assessment to determine whether dosage adjustment is needed. Patients at an increased risk of hepatic decompensation, including those with laboratory evidence of worsening liver function and /or progression to cirrhosis, should be monitored more closely. Dosing frequency should be reduced for patients who progress to advanced disease (i.e. from Child-Pugh Class A to Child-Pugh Class B or C) (see sections 4.2 and 5.2).
Severe pruritus
Severe pruritus was reported in 23% of patients treated with OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arms. The median time to onset of severe pruritus was 11, 158, and 75 days for patients in the OCALIVA 10 mg, OCALIVA titration, and placebo arms, respectively. Management strategies include the addition of bile acid binding resins or antihistamines, dose reduction, reduced dosing frequency, and/or temporary dose interruption (see sections 4.2 and 4.8).
4.5 Interaction with other medicinal products and other forms of interaction
Medicinal products that are affected by obeticholic acid
Warfarin
International normalised ratio (INR) is decreased following co-administration of warfarin and obeticholic acid. INR should be monitored and the dose of warfarin adjusted, if needed, to maintain the target INR range when co-administering obeticholic acid and warfari |
