Skip To Main Content
For Patients and Caregivers

A Differential Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) Is Crucial3,9,12

A Differential Diagnosis

HRCT graphic

ILD=interstitial lung disease; HRCT=high-resolution computed tomography; UIP=usual interstitial pneumonitis; MDD=multidisciplinary discussion; BAL=bronchoalveolar lavage.

Obtaining a precise diagnosis is important because management strategies and prognoses differ among forms of fibrotic interstitial lung diseases (ILDs)13

Learn more about diagnostic criteria for IPF issued by ATS/ERS/JRS/ALAT in 2018 at www.thoracic.org/statements

ATS=American Thoracic Society; ERS=European Respiratory Society; JRS=Japanese Respiratory Society; ALAT=Latin American Thoracic Association.

Identifying UIP From HRCT

Upon suspicion of IPF, an HRCT is an essential part of confirming diagnosis before evaluating treatment options11

IPF diagnosis flowchart

Image and labeling courtesy of David A. Lynch, MD.
Additional contributions from Felipe Martinez, MD

ATS GUIDELINES HRCT PATTERN CATEGORIES11

  UIP Probable UIP Indeterminate for UIP Alternative diagnosis*
Distribution Subpleural, basal predominance
  • Often heterogeneous†
 Subpleural, basal predominance
  • Often heterogeneous
  • Variable
  • Peribronchovascular
  • Perilymphatic
  • Upper or mid-lung
Features
  • Honeycombing with or without peripheral traction bronchiectasis or bronchiolectasis
  • GGO superimposed on a reticular pattern‡
  • Absence of alternative diagnostic features
  • Reticular pattern with peripheral traction bronchiectasis or bronchiolectasis 
  • May have mild GGO
  • Absence of alternative diagnostic features
 “Early UIP pattern”
  • Subtle reticulation
  • May have mild GGO or distortion
“Truly indeterminate”
  • CT features and/or fibrotic distribution that does not suggest specific etiology
  • Cysts
  • Marked mosaic attenuation/air trapping
  • Predominant GGO
  • Profuse micronodules
  • Centrilobular nodules
  • Nodules
  • Consolidation

GGO=ground-glass opacity. 
*List not comprehensive; see the 2018 ATS Guideline for additional features and associated diseases.
†Variants of distribution: occasionally diffuse, may be asymmetrical.
‡Mild GGO (not a dominant feature) and usually fibrotic. Small, ossified nodules in areas of fibrosis are seen in ~29% of patients with UIP.

Learn more about diagnostic criteria for IPF issued by ATS/ERS/JRS/ALAT in 2018 at www.thoracic.org/statements

ATS=American Thoracic Society; ERS=European Respiratory Society; JRS=Japanese Respiratory Society; ALAT=Latin American Thoracic Association.

Adverse Reaction Management

Esbriet offers strategies to help patients manage AEs. Under physician guidance, patients may manage some AEs with everyday strategies and resources.

Learn more
NEXT: Clinical results

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 Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information.

TOP

    • Data on file. Genentech, Inc. 2022.

      Data on file. Genentech, Inc. 2022.

    • Esbriet Prescribing Information. Genentech, Inc. February 2023.

      Esbriet Prescribing Information. Genentech, Inc. February 2023.

    • Behr J. The diagnosis and treatment of idiopathic pulmonary fibrosis. Dtsch Arztebl Int. 2013;110(51–52):875–881.

      Behr J. The diagnosis and treatment of idiopathic pulmonary fibrosis. Dtsch Arztebl Int. 2013;110(51–52):875–881.

    • Kreuter M, Bonella F, Wijsenbeek M, Maher TM, Spagnolo P. Pharmacological treatment of idiopathic pulmonary fibrosis: current approaches, unsolved issues, and future perspectives. Biomed Res Int. 2015;2015:329481. doi:10.1155/2015/329481

      Kreuter M, Bonella F, Wijsenbeek M, Maher TM, Spagnolo P. Pharmacological treatment of idiopathic pulmonary fibrosis: current approaches, unsolved issues, and future perspectives. Biomed Res Int. 2015;2015:329481. doi:10.1155/2015/329481

    • Zisberg A, Shadmi E, Gur-Yaish N, Tonkikh O, Sinoff G. Hospital-associated functional decline: the role of hospitalization processes beyond individual risk factors. J Am Geriatr Soc. 2015;63(1):55–62.

      Zisberg A, Shadmi E, Gur-Yaish N, Tonkikh O, Sinoff G. Hospital-associated functional decline: the role of hospitalization processes beyond individual risk factors. J Am Geriatr Soc. 2015;63(1):55–62.

    • Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431–440.

      Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431–440.

    • Padilla M. Idiopathic pulmonary fibrosis: the role of pathobiology in making a definitive diagnosis. Am J Manag Care. 2015;21(suppl 14):s276–s283.

      Padilla M. Idiopathic pulmonary fibrosis: the role of pathobiology in making a definitive diagnosis. Am J Manag Care. 2015;21(suppl 14):s276–s283.

    • Brown AW, Fischer CP, Shlobin OA, et al. Outcomes after hospitalization in idiopathic pulmonary fibrosis: a cohort study. Chest. 2015;147(1):173–179.

      Brown AW, Fischer CP, Shlobin OA, et al. Outcomes after hospitalization in idiopathic pulmonary fibrosis: a cohort study. Chest. 2015;147(1):173–179.

    • Raghu G, Collard HR, Egan JJ, et al; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.

      Raghu G, Collard HR, Egan JJ, et al; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.

    • Mortimer K, Hartmann N, Chan C, Norman H, Wallace L, Enger C. Characterizing idiopathic pulmonary fibrosis patients using US Medicare-advantage health plan claims data. BMC Pulm Med. 2019;19(1):11. doi:10.1186/s12890-018-0759-5

      Mortimer K, Hartmann N, Chan C, Norman H, Wallace L, Enger C. Characterizing idiopathic pulmonary fibrosis patients using US Medicare-advantage health plan claims data. BMC Pulm Med. 2019;19(1):11. doi:10.1186/s12890-018-0759-5

    • Raghu G, Remy-Jardin M, Myers JL, et al; ATS, ERS, JRS, and ALAT. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.

      Raghu G, Remy-Jardin M, Myers JL, et al; ATS, ERS, JRS, and ALAT. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68.

    • Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018;6(2):138-153.

      Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018;6(2):138-153.

    • Meyer KC. Diagnosis and management of interstitial lung disease. Transl Respir Med. 2014;2:4. doi:10.1186/2213-0802-2-4

      Meyer KC. Diagnosis and management of interstitial lung disease. Transl Respir Med. 2014;2:4. doi:10.1186/2213-0802-2-4

    • King TE Jr, Bradford WZ, Castro-Bernardini S, et al; for the ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis [published correction appears in N Engl J Med. 2014;371(12):1172]. N Engl J Med. 2014;370(22):2083–2092.

      King TE Jr, Bradford WZ, Castro-Bernardini S, et al; for the ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis [published correction appears in N Engl J Med. 2014;371(12):1172]. N Engl J Med. 2014;370(22):2083–2092.

    • Noble PW, Albera C, Bradford WZ, et al; for the CAPACITY Study Group. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760–1769.

      Noble PW, Albera C, Bradford WZ, et al; for the CAPACITY Study Group. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760–1769.

    • Raghu G, Rochwerg B, Zhang Y, et al; ATS, ERS, JRS, and ALAT. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline [published correction appears in Am J Respir Crit Care Med. 2015;192(5):644]. Am J Respir Crit Care Med. 2015;192(2):e3-e19.

      Raghu G, Rochwerg B, Zhang Y, et al; ATS, ERS, JRS, and ALAT. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline [published correction appears in Am J Respir Crit Care Med. 2015;192(5):644]. Am J Respir Crit Care Med. 2015;192(2):e3-e19.

    • du Bois RM, Weycker D, Albera C, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011;184(12):1382–1389.

      du Bois RM, Weycker D, Albera C, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011;184(12):1382–1389.

    • Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4): 830–836.

      Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4): 830–836.

    • Lancaster LH, de Andrade KJA, Zibrak JD, et al. Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis. Eur Respir Rev. 2017;26(146):170057.

      Lancaster LH, de Andrade KJA, Zibrak JD, et al. Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis. Eur Respir Rev. 2017;26(146):170057.

    • Mason WR, Nathan SD, Zibrak JD, et al. Time-to-event analysis of common adverse events with pirfenidone in patients with IPF—a pooled analysis of three phase III clinical trials. Am J Respir Crit Care Med. 2017;195:A6798.

      Mason WR, Nathan SD, Zibrak JD, et al. Time-to-event analysis of common adverse events with pirfenidone in patients with IPF—a pooled analysis of three phase III clinical trials. Am J Respir Crit Care Med. 2017;195:A6798.

    • Costabel U, Albera C, Lancaster LH, et al. An open-label study of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis (RECAP). Respiration. 2017;94(5):408-415.

      Costabel U, Albera C, Lancaster LH, et al. An open-label study of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis (RECAP). Respiration. 2017;94(5):408-415.

    • Glassberg MK, Nathan SD, Lin C-Y, et al. Cardiovascular risks, bleeding risks, and clinical events from 3 phase III trials of pirfenidone in patients with idiopathic pulmonary fibrosis. Adv Ther. 2019;36(10):2910-2926.

      Glassberg MK, Nathan SD, Lin C-Y, et al. Cardiovascular risks, bleeding risks, and clinical events from 3 phase III trials of pirfenidone in patients with idiopathic pulmonary fibrosis. Adv Ther. 2019;36(10):2910-2926.

    • Nathan SD, Lancaster LH, Albera C, et al. Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials. BMJ Open Respir Res. 2018;5(1):e000323. doi:10.1136/bmjresp-2018-000323

      Nathan SD, Lancaster LH, Albera C, et al. Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials. BMJ Open Respir Res. 2018;5(1):e000323. doi:10.1136/bmjresp-2018-000323