Esbriet (Pirfenidone) vs Other IPF Drugs: Full Comparison Guide

When you or a loved one is diagnosed with idiopathic pulmonary fibrosis (IPF), the first question is usually “which drug works best?” Esbriet (pirfenidone) has been on the market for over a decade, but newer options like nintedanib and several off‑label choices are now competing for a spot in treatment plans. This guide walks through the science, dosing, side‑effects, costs and real‑world outcomes so you can see how Esbriet stacks up against its alternatives.

What is Idiopathic Pulmonary Fibrosis?

Idiopathic Pulmonary Fibrosis is a chronic, progressive lung disease characterized by scarring (fibrosis) of the interstitial tissue, which leads to a steady decline in lung capacity and, ultimately, respiratory failure. The cause is unknown, hence “idiopathic.” Typical patients are older adults (median diagnosis age ~70) and the disease incurs a median survival of 3‑5 years without treatment. Early intervention with antifibrotic agents can slow the decline in forced vital capacity (FVC) by 40‑50% according to pivotal trials.

Esbriet (Pirfenidone) - The Original Antifibrotic

Esbriet (generic name pirfenidone) is an oral antifibrotic approved by the FDA in 2014 and by the EMA in 2011. It works by inhibiting transforming growth factor‑β (TGF‑β) signaling and reducing collagen synthesis, which collectively slows scar formation.

• Dosage: 801mg three times a day (total 2403mg) after a 2‑week titration period.
• Efficacy: The CAPACITY and ASCEND trials showed a 48% reduction in the proportion of patients experiencing a ≥10% decline in FVC over 1year.
• Common side‑effects: Nausea, dyspepsia, photosensitivity rash, and mild elevation of liver enzymes.
• Monitoring: Baseline and quarterly liver function tests; advise sun protection.
• Cost (Australia 2025): Approximately AU$190 per month on the PBS, with possible subsidies for eligible patients.

Alternative #1 - Nintedanib (Ofev)

Nintedanib (brand name Ofev) is a tyrosine‑kinase inhibitor that blocks multiple growth factor receptors involved in fibroblast proliferation. It received FDA approval in 2014, the same year as Esbriet, and is often the first-line alternative.

• Dosage: 150mg twice daily with food.
• Efficacy: INPULSIS‑1 and ‑2 trials reported a 49% reduction in annual FVC decline, essentially matching Esbriet’s performance.
• Common side‑effects: Diarrhea (up to 70% of patients), nausea, and liver enzyme elevation.
• Monitoring: Liver function tests at baseline, then every 3months; watch for severe diarrhea and dehydration.
• Cost (Australia 2025): Around AU$250 per month on the PBS, slightly higher than Esbriet.

Alternative #2 - Off‑Label Use of Mycophenolate Mofetil

Mycophenolate mofetil (MMF) is an immunosuppressant primarily used in organ transplantation. Small open‑label studies suggest it may stabilize lung function in mild‑to‑moderate IPF when patients cannot tolerate the approved antifibrotics.

• Dosage: 1500mg twice daily.
• Efficacy: Retrospective analyses show a modest 20‑30% slowing of FVC decline, but data remain limited.
• Side‑effects: GI upset, leukopenia, and increased infection risk.
• Monitoring: Full blood count monthly, renal function quarterly.
• Cost: Approximately AU$70 per month, making it the cheapest option but also the least evidence‑based.

Alternative #3 - Sildenafil (Revatio) - A Symptomatic Approach

Sildenafil, a phosphodiesterase‑5 inhibitor, is approved for pulmonary arterial hypertension. Some clinicians prescribe it off‑label for IPF‑associated pulmonary hypertension, aiming to improve exercise capacity rather than directly halt fibrosis.

• Dosage: 20mg three times daily.
• Efficacy: Trials show modest improvements in 6‑minute walk distance but no effect on FVC.
• Side‑effects: Headache, flushing, visual disturbances.
• Monitoring: Blood pressure, visual changes.
• Cost: About AU$30 per month.

How to Choose the Right Drug - Decision Criteria

Picking an antifibrotic isn’t just about the headline efficacy numbers. Below is a quick decision matrix that many pulmonologists use during consultations.

Practical Tips for Starting an Antifibrotic

1. Assess baseline liver function. Both Esbriet and Nintedanib can raise ALT/AST; a normal baseline reduces early stoppage.
2. Discuss lifestyle adjustments. For Esbriet, sunscreen (SPF30+) is a must, while for Nintedanib you’ll want a diet high in fiber to combat diarrhea.
3. Set realistic expectations. Expect a 30‑45% slowdown in disease progression, not a cure. Monitoring FVC every 6‑12months helps gauge response.
4. Coordinate with a pharmacist. The PBS subsidy codes differ: Esbriet (PBS 1057) vs Nintedanib (PBS 1058). Correct coding avoids out‑of‑pocket spikes.
5. Plan for side‑effect management. Antacids or PPIs help with Esbriet‑related dyspepsia; loperamide is often prescribed prophylactically for Nintedanib‑induced diarrhea.

When to Switch or Combine Therapies

Switching isn’t automatic. Consider a change when:

• Persistent liver enzyme elevation >3× ULN despite dose reduction.
• Unmanageable GI toxicity that impairs nutrition.
• FVC decline exceeds 10% in the first 6months, suggesting poor response.

Combination therapy (e.g., low‑dose pirfenidone + nintedanib) is still experimental; ongoing trials (INCREASE‑COMBO 2025) aim to clarify safety, but current guidelines advise against routine dual use outside a trial.

Bottom Line - Which Drug Fits You?

If you value a well‑established safety profile and can commit to diligent sun protection, Esbriet remains a solid first choice, especially when cost is a concern. If you anticipate trouble with photosensitivity or prefer a twice‑daily regimen, Nintedanib may feel easier, albeit at a higher price tag. For patients with mild disease who cannot tolerate either, MMF offers a cheaper, albeit less proven, alternative. And when pulmonary hypertension co‑exists, adding sildenafil can improve exercise capacity without affecting fibrosis.