Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile

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The most frequently reported adverse reactions during clinical study experience with Esbriet at a dose of 2,403 mg/day compared to placebo, respectively, were nausea (32.4% versus 12.2%), rash (26.2% versus 7.7%), diarrhoea (18.8% versus 14.4%), fatigue (18.5% versus 10.4%), dyspepsia (16.1% versus 5.0%), decreased appetite (20.7% versus 8.0%), headache (10.1% versus 7.7%), and photosensitivity reaction (9.3% versus 1.1%).

Tabulated list of adverse reactions
The safety of Esbriet has been evaluated in clinical studies including 1,650 volunteers and patients.
More than 170 patients have been investigated in open studies for more than five years and some for up to 10 years.

Table 1 shows the adverse reactions reported at a frequency of ≥2% in 623 patients receiving Esbriet at the recommended dose of 2,403 mg/day in three pooled pivotal Phase 3 studies. Adverse reactions from post-marketing experience are also listed in Table 1. Adverse reactions are listed by System Organ Class (SOC) and within each frequency grouping [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), not known (cannot be estimated from the available data)] the adverse reactions are presented in order of decreasing seriousness.

Table 1     Adverse reactions by SOC and MedDRA frequency
Infections and infestations
Very Common         Upper respiratory tract infection
Common              Urinary tract infection
Blood and lymphatic system disorders
Uncommon            Agranulocytosis1
Immune system disorders
Uncommon            Angioedema 1
Not known           Anaphylaxis1
Metabolism and nutrition disorders
Very Common         Weight decreased; decreased appetite
Uncommon            Hyponatraemia1
Psychiatric disorders
Very Common         Insomnia
Nervous system disorders
Very Common         Headache; dizziness
Common              Somnolence; dysgeusia; lethargy
Vascular disorders
Common              Hot flush
Respiratory, thoracic and mediastinal disorders
Very Common         Dyspnoea; cough
Common              Productive cough
Gastrointestinal disorders
Very Common         Dyspepsia; nausea; diarrhoea; gastroesophageal reflux disease; vomiting; constipation
Common              Abdominal distension; abdominal discomfort; abdominal pain; abdominal pain upper; stomach discomfort; gastritis; flatulence
Hepatobiliary disorders
Common              ALT increased; AST increased; gamma glutamyl transferase increased Uncommon            Total serum bilirubin increased in combination with increases of ALT and AST1; Drug-induced liver injury2
Table 1     Adverse reactions by SOC and MedDRA frequency
Skin and subcutaneous tissue disorders
Very Common        Rash
Common             Photosensitivity reaction; pruritus; erythema; dry skin; rash erythematous; rash macular; rash pruritic
Not Known          Stevens-Johnson syndrome1; toxic epidermal necrolysis1; drug reaction with eosinophilia and systemic symptoms (DRESS)1
Musculoskeletal and connective tissue disorders
Very Common        Arthralgia
Common             Myalgia
General disorders and administration site conditions
Very Common        Fatigue
Common             Asthenia; non-cardiac chest pain
Injury poisoning and procedural complications
Common             Sunburn
1.      Identified through post-marketing surveillance (see section 4.4) 2.      Cases of severe drug-induced liver injury, including reports with fatal outcome have been identified through post-marketing surveillance (see section 4.3, 4.4).

Description of selected adverse reactions

Decreased appetite
During the pivotal clinical trials, cases of decreased appetite were readily manageable and generally not associated with significant sequelae. Uncommonly, cases of decreased appetite were associated with significant weight loss and required medical intervention.

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