Pirfenex (pirfenidone) is an orally administered antifibrotic agent specifically indicated for the treatment of idiopathic pulmonary fibrosis (IPF). It represents a cornerstone of pharmacological management for this chronic, progressive, and ultimately fatal lung disease. By targeting key pathways in the fibrotic cascade, Pirfenex modifies the disease course rather than merely addressing symptoms. Its efficacy in reducing the rate of forced vital capacity (FVC) decline has been substantiated in multiple large-scale, phase III clinical trials, offering a evidence-based therapeutic option for appropriate patients.

Features

• Active Pharmaceutical Ingredient: Pirfenidone.
• Available Dosage Forms: Film-coated tablets (200 mg, 600 mg) and hard capsules (267 mg).
• Mechanism of Action: Exerts antifibrotic, anti-inflammatory, and antioxidant effects. It is believed to downregulate the production of growth factors (e.g., TGF-β, TNF-α, PDGF) and procollagens I and III.
• Pharmacokinetics: Rapidly absorbed following oral administration, with a time to maximum concentration (Tmax) of approximately 0.5 to 4 hours. Bioavailability is greater than 80%. Extensive hepatic metabolism primarily via CYP1A2 isoenzymes.
• Half-life: The elimination half-life is approximately 2.5 to 3.5 hours in healthy volunteers.

Benefits

• Slows Disease Progression: Clinically proven to significantly reduce the rate of decline in forced vital capacity (FVC), a key predictor of mortality in IPF.
• Preserves Lung Function: Helps maintain functional lung tissue for a longer period, potentially delaying the need for supplemental oxygen and preserving quality of life.
• Improves Progression-Free Survival: Demonstrated efficacy in reducing the risk of disease progression, defined as a categorical decline in FVC or death.
• Evidence-Based Efficacy: Supported by a robust body of clinical evidence from international, randomized, double-blind, placebo-controlled trials (CAPACITY and ASCEND).
• Oral Administration: Convenient tablet or capsule formulation allows for treatment in an outpatient setting.

Common use

Pirfenex is exclusively indicated for the treatment of idiopathic pulmonary fibrosis (IPF). IPF is a specific type of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults. Diagnosis should be established according to international guidelines, which typically involve a multidisciplinary discussion (MDD) incorporating high-resolution computed tomography (HRCT) pattern and, in some cases, histopathology. It is not indicated for other interstitial lung diseases (ILDs) unless evidence specifically supports its use in a particular fibrosing ILD phenotype.

Dosage and direction

• Initial Titration: To improve gastrointestinal tolerability, the dosage must be titrated to the full maintenance dose over a 14-day period.
  • Days 1-7: 267 mg (one capsule) three times daily (801 mg/day).
  • Days 8-14: 534 mg (two capsules or one 600 mg tablet) three times daily (1602 mg/day).
• Maintenance Dose: From Day 15 onward: 801 mg (three capsules or one 600 mg tablet + one 200 mg tablet) three times daily with food, for a total daily dose of 2403 mg.
• Administration: Tablets and capsules must be swallowed whole with food to reduce the incidence and severity of nausea and dizziness.
• Dosage Modification: Dose reduction or temporary interruption is recommended for patients who experience significant adverse reactions (e.g., gastrointestinal intolerance, photosensitivity reaction, liver enzyme elevations). Consult the full prescribing information for specific guidance on management and re-titration.

Precautions

• Photosensitivity and Phototoxicity: Pirfenex can cause serious skin reactions following exposure to sunlight (including sunlamps). Patients must be advised to avoid direct sunlight, use a high-protection sunscreen (SPF 50+), and wear protective clothing while taking Pirfenex and for some time after discontinuation.
• Liver Enzyme Elevations: ALT, AST, and bilirubin elevations have been observed. Liver function tests (ALT, AST, and bilirubin) should be conducted prior to initiation, monthly for the first 6 months, and then every 3 months thereafter.
• Gastrointestinal Disorders: Nausea, diarrhea, dyspepsia, vomiting, and gastroesophageal reflux disease are very common. Administering the drug with food is essential to mitigate these effects.
• Dizziness and Fatigue: Patients should be cautioned about engaging in activities requiring mental alertness, such as driving or operating machinery, until they know how Pirfenex affects them.
• Weight Loss: Clinically significant weight loss has been reported. Patient weight should be monitored regularly.

Contraindications

Pirfenex is contraindicated in patients with:

• Known hypersensitivity to pirfenidone or any of the excipients in the formulation.
• Severe hepatic impairment or end-stage liver disease.
• Severe renal impairment (CrCl <30 mL/min) or end-stage renal disease requiring dialysis.
• Concomitant use of strong inhibitors of both CYP1A2 (e.g., fluvoxamine) and moderate inhibitors of CYP1A2 in combination with strong inhibitors of other CYP isoenzymes (e.g., CYP2C9, CYP2C19, CYP2D6, CYP3A4).

Possible side effect

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

• Very Common (≥1/10): Nausea, rash, fatigue, diarrhea, dyspepsia, photosensitivity reaction, abdominal pain, headache, dizziness, vomiting, anorexia, gastroesophageal reflux disease, insomnia, upper respiratory tract infection, sinusitis, arthralgia, weight decreased.
• Common (≥1/100 to <1/10): Pruritus, erythema, sunburn, asthenia, hot flush, decreased appetite.

Drug interaction

Pirfenidone is primarily metabolized by CYP1A2, with minor contributions from other CYP isoenzymes. Concomitant use requires careful management:

• Strong CYP1A2 Inhibitors (e.g., Fluvoxamine, Enoxacin): Contraindicated. Concomitant use significantly increases pirfenidone exposure.
• Moderate CYP1A2 Inhibitors (e.g., Ciprofloxacin, Amiodarone, Propafenone): Avoid concomitant use. If use is unavoidable, reduce Pirfenex dose to 267 mg TID (801 mg/day) during co-administration.
• CYP1A2 Inducers (e.g., Smoking, Omeprazole, Rifampicin): May decrease pirfenidone exposure, potentially reducing efficacy. Patients should be advised to stop smoking. Monitor for loss of efficacy with other inducers.
• Other Medicinal Products: Use with caution with other drugs known to cause photosensitivity or hepatotoxicity.

Missed dose

If a dose is missed, it should be skipped if the next dose is due within 3 hours. Do not take a double dose to make up for a missed one. Resume the normal dosing schedule with the next prescribed dose.

Overdose

• Symptoms: There is limited experience with overdose. Based on the drug’s profile, exaggerated adverse effects such as severe nausea, vomiting, dizziness, and photosensitivity are anticipated.
• Management: There is no specific antidote for pirfenidone overdose. Treatment should consist of supportive and symptomatic measures, including monitoring of vital signs and observation of the patient’s clinical status. Hemodialysis is unlikely to be effective due to the high protein binding of pirfenidone (~60%).

Storage

• Store below 30°C (86°F).
• Keep the blister strips in the outer carton to protect from light and moisture.
• Keep out of the sight and reach of children.

Disclaimer

This information is for educational purposes and 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 any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The full official prescribing information should be consulted before initiating therapy.

Reviews

“Pirfenex has been a pivotal addition to our therapeutic arsenal against IPF. In my practice, we have observed a notable stabilization in FVC decline in a significant proportion of patients who tolerate the therapy. The titration schedule is crucial for managing the initial gastrointestinal side effects. While not a cure, it provides a meaningful intervention to slow this devastating disease.” – Dr. A. Sharma, Pulmonologist.

“After my IPF diagnosis, starting on Pirfenex was a decision made with my doctor. The first two weeks were challenging with some nausea, but taking it with a full meal made a big difference. Now, over a year in, my breathing tests have been stable. The strict sun avoidance is a lifestyle change, but a small price to pay for potentially more time.” – Patient M., 68.

“The clinical trial data for pirfenidone is compelling and it remains a first-line pharmacologic therapy in all major international IPF guidelines. Its benefit in reducing functional decline is statistically significant and clinically meaningful. Vigilant monitoring for hepatotoxicity and patient education on photosensitivity are non-negotiable components of management.” – Prof. L. Chen, Respiratory Medicine.