Esbriet (pirfenidone) is an oral antifibrotic medication specifically indicated for the treatment of idiopathic pulmonary fibrosis (IPF). It is a disease-modifying agent that targets the underlying pathological processes of IPF, namely inflammation and fibrosis. By interfering with key profibrotic and proinflammatory pathways, Esbriet has been demonstrated in multiple large-scale, phase III clinical trials to significantly reduce the rate of decline in lung function. This therapy represents a cornerstone in the pharmacological management of IPF, offering a means to preserve functional capacity and potentially extend time to disease progression for appropriate patients.

Features

• Active Ingredient: Pirfenidone
• Pharmacologic Class: Antifibrotic agent
• Available Dosage Forms: Film-coated tablets (267 mg and 801 mg)
• Standard Dosing: Titrated to a maintenance dose of 801 mg taken three times daily (TID), with food, for a total daily dose of 2403 mg
• Mechanism of Action: Exerts antifibrotic, anti-inflammatory, and antioxidant effects; believed to downregulate the production of growth factors and procollagens, inhibiting the proliferation of fibroblasts and the deposition of extracellular matrix

Benefits

• Slows Disease Progression: Clinically proven to significantly reduce the annual rate of decline in forced vital capacity (FVC), a key measure of lung function and a predictor of mortality in IPF.
• Improves Progression-Free Survival: Extends the time to a composite endpoint of disease progression (absolute decline in FVC ≥10%, or death).
• Reduces Risk of Mortality: Pooled analysis of phase III trial data (CAPACITY and ASCEND) demonstrated a significant reduction in the risk of all-cause mortality at one year compared to placebo.
• Preserves Functional Capacity: By slowing the loss of lung function, patients may maintain a greater level of daily activity and exercise tolerance for a longer period.
• Well-Established Efficacy and Safety Profile: Supported by one of the largest bodies of clinical evidence among IPF therapies, with long-term extension studies confirming sustained benefits.

Common use

Esbriet is exclusively indicated for the treatment of idiopathic pulmonary fibrosis (IPF). IPF is a chronic, progressive, and ultimately fatal lung disease characterized by the scarring (fibrosis) of lung tissue, which leads to a progressive and irreversible loss of lung function. The diagnosis of IPF should be established by a multidisciplinary team experienced in interstitial lung diseases, following appropriate high-resolution computed tomography (HRCT) and, in some cases, histopathological evaluation. Esbriet is not indicated for the treatment of any other interstitial lung disease or condition.

Dosage and direction

Esbriet must be titrated to the full maintenance dose over a 14-day period to improve gastrointestinal tolerability. It is imperative that the capsules are swallowed whole and never crushed, split, or chewed. Esbriet must be taken with food to reduce the likelihood of nausea and dizziness.

• Days 1-7: 267 mg (one capsule) three times daily (TID). Total daily dose: 801 mg.
• Days 8-14: 534 mg (two 267 mg capsules or one 801 mg capsule) three times daily (TID). Total daily dose: 1602 mg.
• Day 15 onward (Maintenance Dose): 801 mg (three 267 mg capsules or one 801 mg capsule) three times daily (TID). Total daily dose: 2403 mg.

Dosage modifications or interruption are required for management of adverse reactions, such as gastrointestinal symptoms, photosensitivity reaction, or rash, and in patients with hepatic impairment. Dose reduction is not required for patients with mild to moderate renal impairment (eGFR 30-89 mL/min); use is not recommended in patients with severe renal impairment (eGFR <30 mL/min) or end-stage renal disease requiring dialysis.

Precautions

• Photosensitivity and Phototoxicity: Esbriet can cause serious skin reactions, including severe sunburn, rash, and blistering, after even short periods of sun exposure. Patients must be advised to avoid direct sunlight, including sunlamps, and to use a high-protection (SPF 50 or higher) sunscreen and wear protective clothing (e.g., long sleeves, hat) when outdoors.
• Liver Enzyme Elevations: ALT, AST, and bilirubin elevations have been observed. Liver function tests (ALT, AST, and bilirubin) should be conducted prior to initiating therapy, then monthly for the first 6 months, and every 3 months thereafter. Dosage modification or discontinuation is required for significant elevations.
• Gastrointestinal Events: Nausea, diarrhea, dyspepsia, vomiting, and gastroesophageal reflux disease (GERD) are common. Taking Esbriet with food is essential. Antacids or antiemetics may be used for symptomatic management; dose reduction or interruption may be necessary for persistent symptoms.
• Dizziness and Fatigue: Patients should be cautioned about operating machinery or driving until they know how Esbriet affects them, as it may cause dizziness and fatigue.
• Weight Loss: Clinically significant weight loss has been observed. Patient weight should be monitored regularly.

Contraindications

Esbriet is contraindicated in patients with a known hypersensitivity to pirfenidone or any of the excipients in the formulation. Its use is also contraindicated in combination with fluvoxamine or other strong inhibitors of CYP1A2, due to the risk of significantly increased pirfenidone exposure and subsequent toxicity.

Possible side effect

The most frequently reported adverse reactions (incidence ≥10% and greater than placebo) are:

• Gastrointestinal: Nausea, diarrhea, dyspepsia, vomiting, abdominal pain, gastroesophageal reflux disease (GERD), decreased appetite
• Dermatological: Rash, photosensitivity reaction, pruritus
• General: Fatigue, dizziness, headache
• Insomnia
• Upper respiratory tract infection
• Sinusitis
• Arthralgia
• Weight decrease

Serious but less common side effects include severe liver injury and severe photosensitivity reactions.

Drug interaction

Esbriet is primarily metabolized by the cytochrome P450 isoenzyme CYP1A2, with minor contributions from other CYP isoenzymes. This makes it susceptible to numerous drug interactions.

• Strong CYP1A2 Inhibitors (e.g., Fluvoxamine, Enoxacin): CONTRAINDICATED. Concomitant use will markedly increase pirfenidone plasma exposure.
• Moderate CYP1A2 Inhibitors (e.g., Ciprofloxacin, Amiodarone, Propafenone): Use with caution. A dose reduction of Esbriet may be required.
• CYP1A2 Inducers (e.g., Tobacco Smoking, Omeprazole, Rifampin): May decrease pirfenidone exposure, potentially reducing its efficacy. Patients should be advised to stop smoking. Smokers may require a higher dose, though this is not recommended due to a lack of established safety data.
• Drugs that Cause Dizziness or Drowsiness (e.g., Benzodiazepines, Opioids, Alcohol): Additive CNS effects may occur.
• Other Drugs that Prolong QT Interval: Pirfenidone may cause mild QT prolongation; use with caution with other QT-prolonging drugs.

Missed dose

If a dose is missed, it should be skipped if the next dose is due within 3 hours. The patient should then resume the normal dosing schedule with the next dose. Do not double the next dose to make up for a missed dose.

Overdose

There is limited experience with overdose in humans. Single doses up to 4005 mg and multiple doses up to 3000 mg daily for up to 7 days have been administered in clinical trials with an increase in adverse reactions but no life-threatening effects. Based on animal data, massive overdose may manifest as CNS depression (drowsiness, lethargy) and liver enzyme elevations. In case of suspected overdose, general supportive measures should be instituted, including monitoring of vital signs and observation of the patient’s clinical status. There is no specific antidote for pirfenidone overdose. Hemodialysis is unlikely to be effective due to the high protein binding of pirfenidone.

Storage

Store Esbriet capsules at room temperature, between 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Keep the bottle tightly closed in the original container to protect from light and moisture. Keep out of the reach of children and pets.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting or stopping any medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has been compiled from various sources believed to be accurate and reliable, however, no warranty is made to its accuracy. The prescribing physician should be consulted for full and current prescribing information.

Reviews

Clinical evidence for Esbriet is derived from robust, randomized, double-blind, placebo-controlled Phase III trials (CAPACITY 004, CAPACITY 006, and ASCEND) and their long-term extension studies (RECAP).

• CAPACITY/ASCEND Pooled Analysis: Demonstrated a statistically significant 48% reduction in the risk of all-cause mortality over 52 weeks (p=0.01) compared to placebo.
• FVC Decline: In the ASCEND trial, 23% of patients on Esbriet had a decline of ≥10% in FVC or death, compared to 35% in the placebo group (p=0.001). The mean change in FVC was -235 mL for the Esbriet group versus -428 mL for the placebo group.
• 6-Minute Walk Distance (6MWD): A significantly smaller decline in 6MWD was observed in patients treated with Esbriet compared to placebo. Expert consensus guidelines, such as those from the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT), conditionally recommend the use of pirfenidone for the treatment of IPF based on this high-quality evidence.