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Adverse Reaction Management

Esbriet® (pirfenidone) provides flexible dosing to help manage adverse events (AEs)2

Individual 267 mg tablets allow for tailored dose modification to help manage potential AEs

Dose modification, interruption, or discontinuation may be appropriate to help manage side effects.

Elevated liver enzymes2

Monitoring  
  • ALT, AST and bilirubin levels should be measured prior to the initiation of therapy, monthly for the first 6 months, every 3 months thereafter, and as clinically indicated
  • Patients should be instructed to report symptoms of liver disease (eg, dark urine or jaundice) to their physician. Measure liver function tests promptly in patients who report symptoms
Enzyme level Dose modification
  • ALT and/or AST >3x but ≤ 5x ULN without symptoms or hyperbilirubinemia
  • Discontinue any confounding medications, exclude other causes, and monitor patient closely
  • Repeat liver function tests as clinically indicated
  • The full dosage of Esbriet may be maintained, if clinically appropriate, or reduced or interrupted
  • Dosing can be retitrated to full dosage as tolerated
  • ALT and/or AST >3x but ≤5x with symptoms or  hyperbilirubinemia or ALT and or AST >5x ULN regardless of symptoms of hyperbilirubinemia
  • Permanently discontinue Esbriet and do not rechallenge

ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal.

Reinitiating treatment following treatment interruptions

  • Patients who miss 14 or more days of Esbriet should reinitiate treatment by repeating the initial 2-week titration regimen
  • For a treatment interruption of fewer than 14 days, the dosage taken prior to the interruption can be resumed

Esbriet offers strategies to help patients manage AEs

Under physician guidance, patients may manage some AEs with everyday strategies and resources.

Photosensitivity reaction or rash2 GI disorders2
Patients should
  • Avoid or minimize exposure to sunlight (including sunlamps)
  • Always use broad spectrum (UVA/UVB) sunscreen with SPF 50 or higher
  • Wear a hat and clothing that protect against sun exposure
  • Avoid concomitant medications known to cause photosensitivity
  • Report symptoms of photosensitivity reaction or rash to their physician
Patients should
  • Always take Esbriet with meals
  • Report persistent GI events to their physician

Dosage reduction, interruption, or discontinuation may be necessary in some cases of GI AEs, photosensitivity reaction, or rash.2

Dose reduction or interruption for photosensitivity reaction occurred in 3.9% of patients with Esbriet vs 0.2% with placebo, and dose reduction or interruption for GI events occurred in 18.5% with placebo.2

In a post hoc analysis evaluating Esbriet dose adjustments for all AEs during three phase 3 trials pooled at 12 months23*

Dose reductions in 3 out of 5 patients were temporary

  • 59% of patients who had dose reductions with Esbriet were temporary (n=283/479 with dose reductions overall; 623 total patients) vs 71% with placebo (n=319/449 with dose reductions overall; 624 total patients)

Median cumulative days of dose reduction: 38 days (IQR: 9–103) with Esbriet vs 29 days (range: 7–95) with placebo
 Median cumulative days of dose interruption for Esbriet was 14 (IQR: 3–29) vs 4 (IQR: 1–13) for placebo

*Dose adjustments included dose reductions and dose interruptions. Dose reductions and interruptions were analyzed using descriptive statistics. A dose reduction was defined as any decrease to an Esbriet dose lower than 2403 mg/day after the first 2 weeks of treatment (excluding a zero dose), as reported by the patient. This reduction was temporary if the Esbriet dose was then increased back to 2403 mg/day. A dose interruption was defined as any reported dosing gap to a zero dose of Esbriet after the first 2 weeks of dose titration. Dose reductions or interruptions had no prespecified duration and could be temporary or permanent.

Side Effects

Some people may experience side effects when taking Esbriet

Learn more
NEXT: Safety & tolerability

Important Safety Information and Indication

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.

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with the use of Esbriet in the post-marketing setting. If signs or symptoms of SCAR occur, interrupt Esbriet treatment until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, permanently discontinue Esbriet.

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, decreased appetite, dyspepsia, dizziness, vomiting, 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 Legacy Pharma at 1-800-727-7151.

Please see full Prescribing Information for additional Important Safety Information.

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    • Data on file. Legacy Pharma Inc. SEZC 2022.

      Data on file. Legacy Pharma Inc. SEZC 2022.

    • Esbriet Prescribing Information. Legacy Pharma Inc. SEZC

      Esbriet Prescribing Information. Legacy Pharma Inc. SEZC

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