OCALIVA- obeticholic acid tablet, film coated
Intercept Pharmaceuticals Inc
WARNING: HEPATIC DECOMPENSATION AND FAILURE IN INCORRECTLY DOSED PBC PATIENTS WITH CHILD-PUGH CLASS B OR C OR DECOMPENSATED CIRRHOSIS
- 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 [see Warnings and Precautions (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 [see Dosage and Administration (2.2)].
OCALIVA® 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) [see Clinical Studies (14)]. 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.
- Prior to the initiation of OCALIVA in patients with suspected cirrhosis, use the nomogram (see Table 1) to calculate the patient’s score to determine their Child-Pugh classification (A, B, or C) and determine the appropriate starting dosage (see Table 2) [see Dosage and Administration (2.2), Warnings and Precautions (5.1)].
|Parameter||Points Scored for Observed Findings|
|1 point||2 points||3 points|
|Encephalopathy grade||None||1 or 2||3 or 4|
|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.Child-Pugh Class A: 5 to 6 pointsChild-Pugh Class B: 7 to 9 pointsChild-Pugh Class C: 10 to 15 points|
- 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) [see Dosage and Administration (2.2)].
The recommended starting dose and titration dosage 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 are intolerant to UDCA [see Clinical Studies (14)] is dependent upon disease stage, as shown in Table 2:
- Non-cirrhotic patients or compensated cirrhotic patients with no or mild hepatic impairment (Child-Pugh Class A) are dosed once daily.
- Cirrhotic patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) or patients who have previously experienced a decompensation event are dosed initially once weekly and not more than twice weekly.
|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 [see Clinical Pharmacology (12.2), Clinical Studies (14)]||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 [see Use in Specific Populations (8.6)]|
|Maximum OCALIVA Dosage||10 mg once daily||10 mg twice weekly (at least 3 days apart)|
|a Gastroesophageal variceal bleeding, new or worsening jaundice, spontaneous bacterial peritonitis, etc.b Prior to dosage adjustment, re-calculate the Child-Pugh classification [see Dosage and Administration (2.1)].|
Routinely monitor patients during OCALIVA treatment for progression of PBC disease with laboratory and clinical assessments to determine whether dosage adjustment is needed. Reduce the dosing frequency for patients who progress from Child-Pugh Class A to Child-Pugh Class B or C (see Table 2 above). Close monitoring is recommended for patients at an increased risk of hepatic decompensation, including those with laboratory evidence of worsening liver function (i.e., total bilirubin, INR, albumin) and/or progression to cirrhosis [see Warnings and Precautions (5.1)].
Interrupt treatment with OCALIVA in patients with laboratory or clinical evidence of worsening liver function indicating risk of decompensation, and monitor the patient’s liver function.
If the patient’s condition returns to baseline, weigh the potential risks and benefits of restarting OCALIVA treatment. If OCALIVA is re-initiated, use the recommended starting dosage with adjustment for Child-Pugh classification [see Dosage and Administration (2.2)].
Consider discontinuing OCALIVA in patients who have experienced clinically significant liver-related adverse reactions.
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