ESBRIET SIDE EFFECTS
- Generic Name: pirfenidone capsules
- Brand Name: Esbriet
- Drug Class: Transforming Growth Factor Inhibitors
SIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Liver Enzyme Elevations and Drug-Induced Liver Injury
- Photosensitivity Reaction or Rash
- Gastrointestinal Disorders
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.
The safety of pirfenidone has been evaluated in more than 1400 subjects with over 170 subjects exposed to pirfenidone for more than 5 years in clinical trials.
ESBRIET was studied in 3 randomized, double-blind, placebo-controlled trials (Studies 1, 2, and 3) in which a total of 623 patients received 2403 mg/day of ESBRIET and 624 patients received placebo. Subjects ages ranged from 40 to 80 years (mean age of 67 years). Most patients were male (74%) and Caucasian (95%). The mean duration of exposure to ESBRIET was 62 weeks (range: 2 to 118 weeks) in these 3 trials.
At the recommended dosage of 2403 mg/day, 14.6% of patients on ESBRIET compared to 9.6% on placebo permanently discontinued treatment because of an adverse event. The most common (>1%) adverse reactions leading to discontinuation were rash and nausea. The most common (>3%) adverse reactions leading to dosage reduction or interruption were rash, nausea, diarrhea, and photosensitivity reaction.
The most common adverse reactions with an incidence of ≥10% and more frequent in the ESBRIET than placebo treatment group are listed in Table 1.
Table 1: Adverse Reactions Occurring in ≥10% of ESBRIET-Treated Patients and More Commonly Than Placebo in Studies 1, 2, and 3
| Adverse Reaction | % of Patients (0 to 118 Weeks) | |
| ESBRIET 2403 mg/day (N = 623) |
Placebo (N = 624) |
|
| Nausea | 36% | 16% |
| Rash | 30% | 10% |
| Abdominal Pain* | 24% | 15% |
| Upper Respiratory Tract Infection | 27% | 25% |
| Diarrhea | 26% | 20% |
| Fatigue | 26% | 19% |
| Headache | 22% | 19% |
| Dyspepsia | 19% | 7% |
| Dizziness | 18% | 11% |
| Vomiting | 13% | 6% |
| Anorexia | 13% | 5% |
| Gastro-esophageal Reflux Disease | 11% | 7% |
| Sinusitis | 11% | 10% |
| Insomnia | 10% | 7% |
| Weight Decreased | 10% | 5% |
| Arthralgia | 10% | 7% |
| *Includes abdominal pain, upper abdominal pain, abdominal distension, and stomach discomfort. | ||
Adverse reactions occurring in ≥5 to <10% of ESBRIET-treated patients and more commonly than placebo are photosensitivity reaction (9% vs. 1%), decreased appetite (8% vs. 3%), pruritus (8% vs. 5%), asthenia (6% vs. 4%), dysgeusia (6% vs. 2%), and non-cardiac chest pain (5% vs. 4%).
Postmarketing Experience
In addition to adverse reactions identified from clinical trials the following adverse reactions have been identified during post-approval use of pirfenidone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.
Blood And Lymphatic System Disorders
Agranulocytosis
Immune System Disorders
Angioedema
Hepatobiliary Disorders
Drug-induced liver injury
SRC: NLM .