These highlights do not include all the information needed to use OCALIVA® safely and effectively. See full prescribing information for OCALIVA.
OCALIVA® (obeticholic acid) tablets, for oral use
Initial U.S. Approval: 2016
WARNING: HEPATIC DECOMPENSATION AND FAILURE IN INCORRECTLY DOSED PBC PATIENTS WITH CHILD-PUGH CLASS B OR C OR DECOMPENSATED CIRRHOSIS
See full prescribing information for complete boxed warning
In postmarketing reports, hepatic decompensation and failure, in some cases fatal, have been reported in patients with primary biliary cholangitis (PBC) with decompensated cirrhosis or Child-Pugh Class B or C hepatic impairment when OCALIVA was dosed more frequently than recommended. (5.1)
The recommended starting dosage of OCALIVA is 5 mg once weekly for patients with Child-Pugh Class B or C hepatic impairment or a prior decompensation event. (2.2)
RECENT MAJOR CHANGES
Boxed Warning 01/2018
Dosage and Administration (2.1, 2.2, 2.3, 2.4) 01/2018
Warnings and Precautions (5.1, 5.2, 5.3) 01/2018
INDICATIONS AND USAGE
OCALIVA, a farnesoid X receptor (FXR) agonist, 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.
This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (1)
DOSAGE AND ADMINISTRATION
Important Dosage and Administration Instructions (2.1)
Prior to starting OCALIVA in patients with suspected cirrhosis, use the nomogram to calculate Child-Pugh classification (A, B, or C) and determine the appropriate starting dosage.
Parameter Points Scored for Observed Findings
1 point 2 points 3 points
Encephalopathy grade None 1 or 2 3 or 4
Ascites Absent Slight Moderate
Serum bilirubin (mg/dL) < 2 2 to 3 > 3
Serum albumin (g/dL) > 3.5 2.8 to 3.5 < 2.8
International Normalized Ratio (INR) < 1.7 1.7 to 2.3 > 2.3
Child-Pugh Class is obtained by adding the points from all 5 parameters to derive a total score, which can range from 5 to 15 points.
Total Score: 5-6 points =A, 7-9 points =B, 10-15 points =C
Routinely monitor patients during OCALIVA treatment for biochemical response, tolerability, progression of PBC disease, and re-evaluate Child-Pugh classification to determine if dosage adjustment is needed.
Reduce the dosing frequency from once daily to once weekly as appropriate for patients who progress to advanced disease (i.e., from Child-Pugh Class A to Child-Pugh Class B or C).
Recommended Dosage Regimen (2.2)
The recommended starting dosage and titration regimen of OCALIVA, for patients who have not achieved an adequate biochemical response to an appropriate dosage of UDCA for at least 1 year or who are intolerant to UDCA, is dependent on disease stage.
Staging/ Classification Non-Cirrhotic or Compensated Child-Pugh Class A Child-Pugh Class B or C or Patients with a Prior Decompensation Eventa
Starting OCALIVA Dosage for first 3 months 5 mg once daily 5 mg once weekly
OCALIVA Dosage Titration after first 3 months, for patients who have not achieved an adequate reduction in ALP and/or total bilirubin and who are tolerating OCALIVAb 10 mg once daily 5 mg twice weekly (at least 3 days apart)
Titrate to 10 mg twice weekly (at least 3 days apart) based on response and tolerability
Maximum OCALIVA Dosage 10 mg once daily 10 mg twice weekly (at least 3 days apart)
aGastroesophageal variceal bleeding, new or worsening jaundice, spontaneous bacterial peritonitis, etc.
bPrior to dosage adjustment, re-calculate the Child-Pugh classification. (2.1)
Monitoring for Safety, Treatment Discontinuation (2.3)
Routinely monitor all patients for progression of PBC disease.
Reduce the dosing frequency for patients who progress from Child-Pugh Class A to Child-Pugh Class B or C. (2.2)
Closely monitor patients at an increased risk of hepatic decompensation.
Interrupt treatment in patients with laboratory or clinical evidence of worsening liver function indicating risk of decompensation, and monitor liver function.
Consider discontinuing OCALIVA in patients who experience clinically significant liver-related adverse reactions.
Management of Patients with Intolerable Pruritus
See full prescribing information for management options. (2.4)
Administration Instructions (2.5)
Take with or without food.
For patients taking bile acid binding resins, take OCALIVA at least 4 hours before or 4 hours after taking a bile acid binding resin, or at as great an interval as possible. (7.1)
DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg, 10 mg (3)
Patients with complete biliary obstruction (4)
WARNINGS AND PRECAUTIONS
Hepatic Decompensation and Failure in Incorrectly Dosed PBC Patients with Child-Pugh Class B or C or Decompensated Cirrhosis: Routinely monitor patients for progression of PBC disease, including liver-related complications, with laboratory and clinical assessments. Dosage adjustment, interruption, or discontinuation may be required. Discontinue in patients who develop complete biliary obstruction. (2.3, 4, 5.1)
Severe Pruritus: Management strategies include the addition of bile acid binding resins or antihistamines; OCALIVA dosage reduction and/or temporary dosing interruption. (2.4, 5.3)
Reduction in HDL-C: Monitor for changes in serum lipid levels during treatment. (5.4)
Most common adverse reactions (≥ 5%) are: pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Warfarin: Potential for decreased INR; monitor INR and adjust the dosage of warfarin, as needed, to maintain the target INR range. (7.2)
CYP1A2 Substrates with Narrow Therapeutic Index (e.g., theophylline and tizanidine): Potential for increased exposure to CYP1A2 substrates; monitor drug concentrations of CYP1A2 substrates with narrow therapeutic index. (7.3)
Inhibitors of Bile Salt Efflux Pump (e.g., cyclosporine): Avoid use. If concomitant use is necessary, monitor serum transaminases and bilirubin. (7.4)
USE IN SPECIFIC POPULATIONS
Hepatic Impairment: Dosage adjustment is required in patients with Child-Pugh-Class B and C or a prior decompensation event. (2.2, 8.6)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.