Obecol is indicated for the treatment of primary biliary cholangitis (PBC) in combination with Ursodeoxycholic Acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA, cholestatic liver disease & non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH).
Dosage & Administration
The recommended starting dosage of Obeticholic Acid is 5 mg orally once daily in adult patients who have not achieved an adequate biochemical response to an appropriate dosage of Ursodeoxycholic Acid (UDCA) for at least 1 year or are intolerant to UDCA.
If an adequate reduction in alkaline phosphatase (ALP) and/or total bilirubin has not been achieved after 3 months of Obeticholic Acid 5 mg once daily, and the patient is tolerating Obeticholic Acid, increase the dosage of Obeticholic Acid to 10 mg once daily.
The maximum recommended dosage of Obeticholic Acid is 10 mg once daily.
Management of Patients with Intolerable Pruritus on Obeticholic Acid
For patients with intolerable pruritus on Obeticholic Acid, consider one or more of the following:
? Add an antihistamine or bile acid binding resin
? Reduce the dosage of Obeticholic Acid 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 Obeticholic Acid dosing for up to 2 weeks followed by restarting at a reduced dosage
Increase the dosage of Obeticholic Acid to 10 mg once daily, as tolerated, to achieve optimal response. Consider discontinuing Obeticholic Acid treatment in patients who continue to experience persistent, intolerable pruritus.
Use in Specific Populations
Use in Pregnancy and Lactation
The limited available human data on the use of Obeticholic Acid during pregnancy are not sufficient to inform a drug-associated risk. There is no information on the presence of Obeticholic Acid in human milk, the effects on the breast-fed infant or the effects on milk production.
No dosage adjustment is recommended in elderly patient less than 65 years of age.
Safety and efficacy have not been established in patients younger than 18 years.
Use in Patients with Impaired Renal and Hepatic Function
Obeticholic Acid has not been studied in patients with moderate and severe renal impairment (estimated glomerular filtration rate [eGFR] less than 60 ml/min/1.73 m2). In the population
pharmacokinetic analysis, an eGFR greater than 50 ml/min/1.73 m2 did not have a meaningful effect on the pharmacokinetics of Obeticholic Acid and its conjugated metabolites.
Obeticholic Acid is metabolized in the liver. Plasma exposure to Obeticholic Acid and its active conjugates, increases significantly in patients with moderate to severe hepatic impairment (Child-Pugh Classes B and C).The recommended starting dosage of Obeticholic Acid for moderate (Child-Pugh Class B) and severe (Child-Pugh Class C) hepatic impairment is 5 mg once weekly. If an adequate reduction in ALP and/or total bilirubin has not been achieved after 3 months of Obeticholic Acid 5 mg once weekly, and the patient is tolerating the drug, increase the dosage of Obeticholic Acid to 5 mg twice weekly (at least three days apart) and subsequently to 10 mg twice weekly (at least three days apart) depending on response and tolerability.
The following clinically significant reactions are described:
• Liver-Related Adverse Reactions
• Severe Pruritus
• Reduction in high density lipoprotein-cholesterol (HDL-C)
Special monitoring is essential for the patient with such type of problems.