Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

Hepatic adverse events
Hepatic failure, sometimes fatal or resulting in liver transplant, has been reported with obeticholic acid treatment in PBC patients with either compensated or decompensated cirrhosis.

Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dose for that patient population; however, cases of hepatic decompensation and failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dose.

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. Hepatic adverse events have primarily been observed at doses higher than the maximum recommended dose of 10 mg once daily (see section 4.9).

All patients should be routinely monitored for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether obeticholic acid treatment discontinuation is needed. Patients at increased risk of hepatic decompensation, including those with elevated bilirubin levels, evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or severe intercurrent illness should be closely monitored to determine whether obeticholic acid treatment discontinuation is needed.

Treatment with obeticholic acid in patients with laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy), including progression to Child-Pugh Class B or C, should be permanently discontinued (see section 4.3).
Treatment with obeticholic acid should be interrupted during severe intercurrent illness or in patients who experience clinically significant hepatic adverse reactions and the patient’s liver function should be monitored. After resolution and if there is no laboratory or clinical evidence of hepatic decompensation, the potential risks and benefits of restarting obeticholic acid treatment should be considered.


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).

Excipients
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7   Effects on ability to drive and use machines

Obeticholic acid has no or negligible influence on the ability to drive and use machines.