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Esbriet (pirfenidone) offers established safety built on multiple clinical studies 2

Safety data were obtained from 1247 patients in 3 randomized, controlled trials

Photosensitivity and GI events

*Includes abdominal pain, upper abdominal pain, abdominal distension, and stomach discomfort.

  • The most common adverse reactions (>1%) leading to discontinuation were rash and nausea
  • The most common AEs (>3%) leading to dosage reduction or interruption were rash, nausea, diarrhea, and photosensitivity reaction
  • Serious AEs, including elevated liver enzymes and drug-induced liver injury, photosensitivity reactions, and gastrointestinal (GI) disorders, have been reported with Esbriet
Clinical trial safety tiles

Tolerability with Esbriet

SOME AEs WITH ESBRIET WERE MILD TO MODERATE, OCCURRED EARLY, AND DECREASED OVER TIME 2

The first dermatologic AE tended to occur within the first 2 to 3 months of treatment and GI and nausea AEs during the peri-titration period. 19

PHOTOSENSITIVITY REACTIONS AND GI EVENTS TYPICALLY OCCURRED IN THE FIRST 3 TO 6 MONTHS OF TREATMENT AND INFREQUENTLY LED TO DISCONTINUATION 1,2

Esbriet® (pirfenidone) tolerability chart
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  • The majority of photosensitivity reactions occurred in the first 6 months of treatment 2
  • Incidence was 9% with Esbriet vs 1% with placebo 2
  • Median time to first photosensitivity AE was 90 (IQR: 48.0–149.0) days 19,20†
  • <1% discontinuation due to photosensitivity with Esbriet 1

IQR=interquartile range.
Median time to first AE of interest.

Gastro Icon
  • Most GI AEs occurred in the first 3 months of treatment and decreased over time 2
  • Median time to first GI AE was 14 (IQR: 5.0–40.0) days 19,20†
  • Discontinuation due to GI events was 2.2% with Esbriet vs 1% with placebo 2

Flexible dosing (dose modification, interruptions, discontinuations) with Esbriet 267 mg may help manage potential AEs like GI events and photosensitivity reactions. 2  See Adverse Event Management for more on managing AEs


Long-term, open-label, phase 3 extension study

Follow-up safety data available for up to 6.7 years 21

  • In a long-term, open-label extension of the phase 3 studies, 1058 patients with IPF were exposed to Esbriet (2403 mg/day) for a median of 88 weeks/1.7 years (range: >0 to 349 weeks/6.7 years) with the primary objective of obtaining additional safety data for Esbriet 2403 mg/day
  • 40.4% (n=427) completed the study, with an overall discontinuation rate of 59.2% (n=626)
    • The most frequent adverse drug reactions were nausea (21.6%), diarrhea (12.3%), and rash (11.6%)
    • The most common treatment-emergent serious adverse events were IPF (21.7%) and pneumonia (8.5%)
    • 42% (n=444) discontinued due to treatment-emergent adverse events, including 16.8% (n=178) who discontinued due to IPF§
  • Care should be exercised when interpreting open-label results due to the inability to minimize bias. The data represented are not designed to establish the long-term safety or tolerability profile for Esbriet

Adverse drug reactions are defined as AEs judged by the investigator as possibly or probably related to pirfenidone.
§Treatment-emergent AEs are defined as all events that occurred from the first dose of pirfenidone through 28 days after the last dose in the long-term, open-label, phase 3 extension study.

Indication

Esbriet® (pirfenidone) is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

Important Safety Information

Elevated liver enzymes and drug-induced liver injury (DILI): DILI has been observed with Esbriet. In the postmarketing period, non-serious and serious cases of DILI, including severe liver injury with fatal outcome, have been reported. Patients treated with Esbriet had a higher incidence of ALT and/or AST elevations of ≥3x ULN (3.7%) compared with placebo patients (0.8%). Increases in ALT and AST ≥3x ULN were reversible with dose modification or treatment discontinuation.

Conduct liver function tests (ALT, AST, and bilirubin) prior to the initiation of therapy with Esbriet, monthly for the first 6 months, every 3 months thereafter, and as clinically indicated. Measure liver function promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Dosage modification or interruption may be necessary for liver enzyme elevations.

Photosensitivity reaction or rash: Patients treated with Esbriet had a higher incidence of photosensitivity reactions (9%) vs placebo (1%). Patients should avoid or minimize exposure to sunlight and sunlamps, regularly use sunscreen (SPF 50 or higher), wear clothing that protects against sun exposure, and avoid concomitant medications that cause photosensitivity. Dosage reduction or discontinuation may be necessary.

Gastrointestinal (GI) disorders: Patients treated with Esbriet had a higher incidence of nausea, diarrhea, dyspepsia, vomiting, gastroesophageal reflux disease (GERD), and abdominal pain. GI events required dose reduction or interruption in 18.5% of 2403 mg/day Esbriet-treated patients, compared with 5.8% of placebo patients; 2.2% of 2403 mg/day Esbriet-treated patients discontinued treatment due to a GI event, vs 1.0% of placebo patients. The most common (>2%) GI events leading to dosage reduction or interruption were nausea, diarrhea, vomiting, and dyspepsia. Dosage modification may be necessary.

Adverse reactions: The most common adverse reactions (≥10%) were nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, anorexia, GERD, sinusitis, insomnia, weight decreased, and arthralgia.

Drug Interactions:

CYP1A2 inhibitors: Concomitant use of Esbriet and strong CYP1A2 inhibitors (e.g., fluvoxamine) is not recommended, as CYP1A2 inhibitors increase systemic exposure of Esbriet. If discontinuation of the CYP1A2 inhibitor prior to starting Esbriet is not possible, dosage reduction of Esbriet is recommended. Monitor for adverse reactions and consider discontinuation of Esbriet.

Concomitant use of ciprofloxacin (a moderate CYP1A2 inhibitor) at the dosage of 750 mg BID and Esbriet are not recommended. If this dose of ciprofloxacin cannot be avoided, dosage reductions of Esbriet are recommended, and patients should be monitored.

Moderate or strong inhibitors of both CYP1A2 and other CYP isoenzymes involved in the metabolism of Esbriet should be avoided during treatment.

CYP1A2 inducers: Concomitant use of Esbriet and strong CYP1A2 inducers should be avoided, as CYP1A2 inducers may decrease the exposure and efficacy of Esbriet.

Specific Populations:

Mild to moderate hepatic impairment: Esbriet should be used with caution in patients with Child Pugh Class A and B. Monitor for adverse reactions and consider dosage modification or discontinuation of Esbriet as needed.

Severe hepatic impairment: Esbriet is not recommended for patients with Child Pugh Class C. Esbriet has not been studied in this patient population.

Mild (CLcr 50–80 mL/min), moderate (CLcr 30–50 mL/min), or severe (CLcr<30 mL/min) renal impairment: Esbriet should be used with caution. Monitor for adverse reactions and consider dosage modification or discontinuation of Esbriet as needed.

End-stage renal disease requiring dialysis: Esbriet is not recommended. Esbriet has not been studied in this patient population.

Smokers: Smoking causes decreased exposure to Esbriet which may affect efficacy. Instruct patients to stop smoking prior to treatment and to avoid smoking when on Esbriet.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch or to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information.

    • Data on file. Genentech, Inc. 2020.

      Data on file. Genentech, Inc. 2020.

    • Esbriet Prescribing Information. Genentech, Inc. July 2019.

      Esbriet Prescribing Information. Genentech, Inc. July 2019.

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