Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The most commonly reported adverse reactions were pruritus (63%) and fatigue (22%). The most common adverse reaction leading to discontinuation was pruritus. The majority of pruritus occurred within the first month of treatment and tended to resolve over time with continued dosing.

Tabulated list of adverse reactions
The adverse reactions reported with OCALIVA are listed in the table below by MedDRA system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).

Table 1. Frequency of adverse reactions in PBC patients

System organ class               Very common              Common                       Not known Endocrine disorders                                       Thyroid function abnormality
Nervous system disorders                                  Dizziness
Cardiac disorders                                         Palpitations Respiratory, thoracic and                                 Oropharyngeal pain mediastinal disorders
Gastrointestinal disorders       Abdominal pain and       Constipation discomfort
Hepatobiliary disorders                                                                Hepatic failure, Blood bilirubin increased,
Jaundice, Hepatic cirrhosis
Skin and subcutaneous tissue Pruritus                     Eczema, Rash disorders
Musculoskeletal and                                       Arthralgia connective tissue disorders
General disorders and          Fatigue                    Oedema         peripheral, administration site conditions                            Pyrexia

Description of selected adverse reactions

Discontinuation of treatment
Adverse reactions leading to discontinuation of treatment were 1% (pruritus) in the obeticholic acid titration arm and 11% (pruritus and fatigue) in the obeticholic acid 10 mg arm.

Pruritus

Approximately 60% of patients had a history of pruritus upon enrollment in the phase III study.
Treatment-emergent pruritus generally started within the first month following the initiation of treatment.
Relative to patients who started on 10 mg once daily in the OCALIVA 10 mg arm, patients in the OCALIVA titration arm had a lower incidence of pruritus (70% and 56% respectively) and a lower discontinuation rate due to pruritus (10% and 1%, respectively).

The percentages of patients who required interventions (i.e., dose adjustments, treatment interruptions, or initiation of antihistamines or bile acid binding resins) were 41% in the OCALIVA 10 mg arm, 34% in the OCALIVA titration group, and 19% in the placebo group.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il and additionally emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com