Medical Editor: John P. Cunha, DO, FACOEP
Ocaliva (obeticholic acid) is a farnesoid X receptor (FXR) agonist 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. Common side effects of Ocaliva include:
- abdominal pain and discomfor
- mouth and throat pain, dizziness
- joint pain
- thyroid function abnormality
- swelling of the extremities
- palpitations, and
The recommended starting dosage of Ocaliva is 5 mg orally once daily in adults who have not achieved an adequate response to an appropriate dosage of UDCA for at least 1 year or are intolerant to UDCA. Ocaliva may interact with warfarin, bile acid binding resins, theophylline, and tizanidine. Tell your doctor all medications and supplements you use. Tell your doctor if you are pregnant before taking Ocaliva. It is unknown if it would affect a fetus. It is unknown if Ocaliva passes into breast milk or if it would affect a nursing infant. Consult your doctor before breastfeeding.
Our Ocaliva (obeticholic acid) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
The following clinically significant adverse reactions are described elsewhere in labeling:
- Hepatic Decompensation and Failure in Incorrectly Dosed PBC Patients with Child-Pugh Class B or C or Decompensated Cirrhosis [see WARNINGS AND PRECAUTIONS]
- Liver-Related Adverse Reactions [see WARNINGS AND PRECAUTIONS]
- Severe Pruritus [see WARNINGS AND PRECAUTIONS]
- Reduction in HDL-C [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
A total of 432 patients with PBC were studied in three double-blind placebo-controlled trials. Of these patients, 290 were treated with OCALIVA for at least 6 months, 232 were treated for at least 12 months, and 70 were treated for at least 2 years. There were 131 patients who received OCALIVA 10 mg once daily and 70 who received OCALIVA 5 mg once daily.
In Trial 1, 216 patients were randomized (1:1:1) to receive either:
- OCALIVA 10 mg once daily for the entire 12 months of the trial (n=73);
- OCALIVA titration (5 mg once daily for the initial 6 months, with the option to increase to 10 mg once daily for the last 6 months, in patients who were tolerating OCALIVA, but had ALP 1.67-times ULN or greater, and/or total bilirubin greater than ULN, or less than 15% ALP reduction) (n=70); or
- placebo (n=73).
During the trial, OCALIVA or placebo was administered in combination with UDCA in 93% of patients and as monotherapy in 7% of patients who were unable to tolerate UDCA. The overall discontinuation rate was 12% in the OCALIVA 10 mg arm, 10% in the OCALIVA titration arm, and 4% in the placebo arm.
The recommended starting dosage of OCALIVA is 5 mg orally once daily for 3 months with titration to 10 mg once daily based upon tolerability and response [see DOSAGE AND ADMINISTRATION]. Initiation of therapy with OCALIVA 10 mg once daily is not recommended due to an increased risk of pruritus.
The most common adverse reactions in Trial 1 occurring in at least 5% of patients in either OCALIVA treatment arm and at an incidence at least 1% higher than the placebo treatment arm are shown in Table 3.
Table 3: Most Common Adverse Reactions in Adult
Patients with PBC in Trial 1 by Treatment Arm with or without UDCAa
|Adverse Reactionb||OCALIVA 10 mg
N = 73 %
N = 70 %
N = 73 %
|Abdominal pain and discomfortf||10||19||14|
|Thyroid function abnormalityi||4||6||3|
|a In the trial there were 16 patients (7%) who
were intolerant and did not receive concomitant UDCA: 6 patients (8%) in the
OCALIVA 10 mg arm, 5 patients (7%) in the OCALIVA titration arm, and 5 patients
(7%) in the placebo arm.
b Occurring in greater than or equal to 5% of patients in either OCALIVA treatment arm and at an incidence greater than or equal to1% higher than in the placebo treatment arm.
c Patients randomized to OCALIVA titration received OCALIVA 5 mg once daily for the initial 6 month period. At Month 6, patients who were tolerating OCALIVA, but had an ALP 1.67-times ULN or greater, and/or total bilirubin greater than ULN, or less than 15% ALP reduction were eligible for titration from 5 mg once daily to 10 mg once daily for the final 6 months of the trial.
d Includes skin eruptions, prurigo, pruritus, pruritus generalized, eye pruritus, ear pruritus, anal pruritus, vulvovaginal pruritus, and rash pruritic.
e Includes fatigue, tiredness and asthenia.
f Includes abdominal pain upper, abdominal pain, abdominal discomfort, abdominal pain lower, abdominal tenderness, and gastrointestinal pain.
g Includes urticaria, rash, rash macular, rash papular, rash maculo-papular, heat rash, urticaria cholinergic.
h Includes dizziness, syncope, presyncope.
i Includes thyroxine free decreased, blood thyroid stimulating hormone increased, hypothyroidism.
Liver-Related Adverse Reactions
In Trial 1, the following serious or otherwise clinically significant liver-related adverse reactions were reported at the recommended dosage of OCALIVA: one patient in the OCALIVA 10 mg treatment arm experienced ascites; one patient in the OCALIVA titration treatment arm experienced two episodes of ascites and four episodes of hepatic encephalopathy; one patient in the placebo treatment arm experienced variceal bleeding.
Approximately 60% of patients had a history of pruritus upon enrollment in Trial 1. Treatment-emergent pruritus, including all the terms described in Table 3, generally started within the first month following the initiation of treatment with OCALIVA.
The incidence of pruritus was higher in patients who started on OCALIVA 10 mg once daily relative to the OCALIVA titration arm, 70% and 56%, respectively. Discontinuation rates due to pruritus were also higher in patients who started on OCALIVA 10 mg once daily relative to the OCALIVA titration arm, 10% and 1%, respectively.
The number of patients with pruritus who required an intervention (e.g., dosage adjustment, treatment interruption, or initiation of bile acid binding resin or antihistamine) was 30 of 51 patients (59%) in the OCALIVA 10 mg arm, 24 of 39 patients (62%) in the OCALIVA titration arm, and 14 of 28 patients (50%) in the placebo arm.
The following adverse reactions have been identified during post approval use of OCALIVA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure, particularly in PBC patients who have progressive liver disease.
Read the entire FDA prescribing information for Ocaliva (Obeticholic Acid Tablets)