What is Esbriet (pirfenidone)?

What is Esbriet (Pirfenidone)?

Esbriet (pirfenidone) is an oral antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), which works by reducing fibroblast proliferation and collagen synthesis to slow disease progression and decline in lung function. 1

Mechanism of Action

Pirfenidone is a small molecule with pleiotropic effects that:

• Regulates profibrotic and proinflammatory cytokine cascades 1
• Reduces fibroblast proliferation in lung tissue 1
• Inhibits collagen synthesis in animal models of lung fibrosis 1
• Has anti-inflammatory and antioxidative properties 1

The exact mechanism of action in IPF treatment has not been fully established, but its antifibrotic properties appear to be the primary therapeutic benefit. 2

Clinical Efficacy

Pirfenidone has demonstrated significant benefits in clinical trials:

• Slows decline in lung function: Reduces the rate of forced vital capacity (FVC) decline by approximately 30% compared to placebo 1
• Improves progression-free survival: Reduces risk of disease progression by 30% (HR 0.70,95% CI 0.56-0.88) 1
• Mortality benefit: Shows favorable trends in reducing IPF-related mortality (HR 0.62,95% CI 0.35-1.13) and on-treatment mortality (HR 0.65,95% CI 0.36-1.16) 1

The CAPACITY trials and subsequent ASCEND trial provided the primary evidence for pirfenidone's efficacy, leading to its approval for mild to moderate IPF. 3

Formulation and Dosing

Pirfenidone is available as:

• Yellow film-coated tablets (267 mg)
• Brown film-coated tablets (801 mg)
• Yellow capsules (267 mg) 2, 4

The recommended maintenance dose is 2,403 mg/day, divided into three equal doses taken with food. Dosing is typically titrated over 14 days to minimize side effects:

• Days 1-7: 267 mg three times daily
• Days 8-14: 534 mg three times daily
• Day 15 onward: 801 mg three times daily 2

Common Side Effects

The most frequent adverse effects include:

• Gastrointestinal: Nausea, vomiting, dyspepsia, diarrhea, abdominal pain 2
• Skin-related: Photosensitivity reactions, rash 2
• Other: Fatigue, anorexia, weight loss, dizziness, insomnia 2

Important Precautions

Several important precautions should be observed:

1. Liver function monitoring: Regular liver enzyme tests are required (monthly for first 6 months, then every 3 months) 1
2. Sun protection: Patients must avoid sun exposure and use SPF 50 sunscreen due to photosensitivity 2
3. Smoking cessation: Smoking reduces pirfenidone's effectiveness and should be discontinued 2
4. Medication interactions: Avoid fluvoxamine (contraindicated) and use caution with omeprazole 1
5. Dose adjustments: May be needed for patients with hepatic or renal impairment 2

Clinical Recommendations

Current guidelines suggest that:

• Pirfenidone is recommended for patients with mild to moderate IPF (FVC >50% predicted and DLCO >35% predicted) 1
• Treatment should be initiated and supervised by physicians experienced in IPF management 1
• Shared decision-making is essential, considering the potential benefits against side effects and cost 1
• The optimal duration of therapy remains unknown 1

Limitations

Important limitations to consider:

• Not approved for severe IPF (limited evidence in this population) 1
• Not approved for pediatric patients 2
• Limited data in patients with severe hepatic or renal impairment 2
• Relatively high cost that may impact accessibility 1

Pirfenidone represents a significant advance in IPF treatment as one of the few medications shown to slow disease progression, though it is not curative and careful patient selection and monitoring remain essential.