OCALIVA SIDE EFFECTS
- Generic Name: obeticholic acid tablets
- Brand Name: Ocaliva
- Drug Class: Farnesoid X Receptor Agonists
SIDE EFFECTS
The following clinically significant adverse reactions are described elsewhere in labeling:
- Hepatic Decompensation and Failure in PBC Patients with Cirrhosis
- Severe Pruritus
- Reduction in HDL-C
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 clinical 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. 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 1.
Table 1: 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 % |
OCALIVA Titrationc N=70 % |
Placebo N=73 % |
| Pruritusd | 70 | 56 | 38 |
| Fatiguee | 25 | 19 | 15 |
| Abdominal pain and discomfortf | 10 | 19 | 14 |
| Rashg | 10 | 7 | 8 |
| Arthralgia | 10 | 6 | 4 |
| Oropharyngeal pain | 8 | 7 | 1 |
| Dizzinessh | 7 | 7 | 5 |
| Constipation | 7 | 7 | 5 |
| Peripheral Edema | 7 | 3 | 3 |
| Palpitations | 7 | 3 | 1 |
| Pyrexia | 7 | 0 | 1 |
| Thyroid function abnormalityi | 4 | 6 | 3 |
| Eczema | 3 | 6 | 0 |
| 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, rash pruritic. e Includes fatigue, tiredness, asthenia. f Includes abdominal pain upper, abdominal pain, abdominal discomfort, abdominal pain lower, abdominal tenderness, 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. |
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Hepatic Adverse Reactions
In Trial 1, the following serious or otherwise clinically significant hepatic 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.
Pruritus
Approximately 60% of patients had a history of pruritus upon enrollment in Trial 1. Treatment-emergent pruritus, including all the terms described in Table 1, 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.
Postmarketing Experience
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.
Hepatobiliary Disorders: liver failure, new onset cirrhosis, increased direct and total bilirubin, new or worsening of jaundice.
SRC: NLM .