Pirfenex (pirfenidone) is an oral 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. This therapy is a critical option for physicians aiming to preserve lung function and improve long-term outcomes for appropriate patients.

Features

• Active Pharmaceutical Ingredient: Pirfenidone.
• Available Dosage Forms: Film-coated tablets (200 mg, 600 mg).
• Mechanism of Action: Exerts antifibrotic, anti-inflammatory, and antioxidant effects; believed to inhibit the synthesis of TGF-beta (Transforming Growth Factor-beta) and TNF-alpha (Tumor Necrosis Factor-alpha), key mediators of fibrosis.
• Bioavailability: Well-absorbed orally, with peak plasma concentrations achieved within 3 hours. Food significantly affects absorption.
• Half-life: Approximately 3 hours.
• Metabolism: Primarily hepatically metabolized via the CYP1A2 enzyme system, with minor contributions from other CYP isozymes.
• Excretion: Primarily renal (approximately 80%) as metabolites.

Benefits

• Slows Disease Progression: Clinically proven to reduce the rate of decline in lung function, as measured by forced vital capacity (FVC).
• Improves Progression-Free Survival: Demonstrated efficacy in increasing the time to disease progression or death in clinical trials.
• Reduces Risk of Acute Exacerbations: Associated with a lower incidence of these clinically significant and often fatal events.
• Preserves Exercise Tolerance: Helps maintain functional capacity and quality of life by mitigating the loss of lung function over time.
• Well-Established Safety Profile: Its safety and tolerability are well-characterized through extensive clinical trials and post-marketing surveillance.

Common use

Pirfenex is exclusively approved 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, and limited to the lungs. It is characterized by a progressive and irreversible decline in lung function. Diagnosis should be established according to international guidelines, which typically involve a multidisciplinary discussion (MDD) incorporating clinical, radiological (high-resolution computed tomography - HRCT), and, in some cases, histopathological data to confirm a usual interstitial pneumonia (UIP) pattern. It is not indicated for other interstitial lung diseases (ILDs) unless specifically supported by evidence.

Dosage and direction

• Initiation and Titration: Treatment must be initiated and monitored by a physician experienced in the diagnosis and management of IPF. The dosage is titrated to the full maintenance dose over a 14-day period to improve gastrointestinal tolerability:
  • Days 1-7: 267 mg (one 267 mg tablet) three times daily (801 mg/day).
  • Days 8-14: 534 mg (two 267 mg tablets or one 534 mg tablet) three times daily (1602 mg/day).
  • Day 15 onward: 801 mg (three 267 mg tablets or one 801 mg tablet) three times daily (2403 mg/day).
• Administration: Tablets must be taken with food to minimize the common side effect of nausea and to reduce peak plasma concentration-related adverse events like dizziness. Swallow the tablets whole; do not crush or break.
• 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.

Precautions

• Liver Function: Elevations in liver enzymes (ALT, AST, bilirubin) have been observed. Liver function tests (ALT, AST, and bilirubin) should be conducted prior to initiation of therapy, then monthly for the first 6 months, and every 3 months thereafter. Therapy should be interrupted or discontinued for significant elevations.
• Photosensitivity and Rash: Patients are at increased risk for photosensitivity reactions and rash. They must be advised to avoid direct sunlight (including sunlamps), to use a high-protection sunscreen (SPF 50+), and to wear protective clothing while outdoors throughout treatment and for some time after discontinuation.
• Gastrointestinal Disorders: Nausea, diarrhea, dyspepsia, vomiting, and gastroesophageal reflux disease are very common. These can often be managed by taking the medication with food, dose titration, and symptomatic treatment. Persistent symptoms may require dose reduction.
• Weight Loss: Patients should be monitored for weight loss. Underlying causes (e.g., nausea, diarrhea) should be investigated and managed.
• Dizziness and Fatigue: Patients should be cautioned about operating machinery or driving if they experience dizziness or significant fatigue.
• Smoking: Smoking can reduce the exposure to pirfenidone due to induction of the CYP1A2 enzyme. Smokers may have reduced efficacy. Patients should be advised to stop smoking before and during treatment.

Contraindications

Pirfenex is contraindicated in patients with:

• Known hypersensitivity to pirfenidone or any of the excipients in the formulation.
• Severe hepatic impairment (Child-Pugh Class C).
• Severe renal impairment (CrCl <30 mL/min) or end-stage renal disease requiring dialysis.
• Concomitant use of fluvoxamine or other strong inhibitors of CYP1A2 (e.g., enoxacin).
• Concomitant use of CYP1A2 inducers (e.g., rifampicin).

Possible side effect

The most frequently reported adverse reactions are gastrointestinal and skin-related.

• Very Common (≥1/10): Nausea, rash, fatigue, diarrhea, dyspepsia, abdominal pain (upper), vomiting, anorexia, photosensitivity reaction, headache, dizziness.
• Common (≥1/100 to <1/10): Weight decrease, gastroesophageal reflux disease, insomnia, pruritus, myalgia, arthralgia, hot flush, decreased appetite.
• Uncommon (≥1/1,000 to <1/100): Liver enzyme increased (ALT, AST), blood bilirubin increased, gamma-glutamyltransferase increased.
• Serious side effects include significant hepatotoxicity and severe photosensitivity reactions.

Drug interaction

Pirfenidone is primarily metabolized by CYP1A2, making it susceptible to numerous interactions.

• CYP1A2 Inhibitors (e.g., Fluvoxamine, Enoxacin): Contraindicated. Concomitant use significantly increases pirfenidone exposure, raising the risk of adverse effects.
• CYP1A2 Inducers (e.g., Rifampicin, Omeprazole, Smoking): May significantly decrease pirfenidone exposure, potentially reducing its efficacy. Avoid concomitant use. Smokers should be advised to quit.
• Other CYP1A2 Substrates (e.g., Theophylline, Caffeine, Tizanidine): Pirfenidone may inhibit the metabolism of these drugs, potentially increasing their plasma levels and risk of toxicity. Monitor closely.
• Ciprofloxacin (a moderate CYP1A2 inhibitor): Use with caution; may require dose reduction of Pirfenex.

Missed dose

If a dose is missed, it should be skipped, and the next dose should be taken at the regularly scheduled time. Do not take a double dose to make up for the missed one. Patients should be instructed to maintain their regular dosing schedule and not to compensate for any missed doses.

Overdose

There is limited experience with pirfenidone overdose. Reported symptoms are consistent with the known adverse reaction profile and may include severe nausea, vomiting, dizziness, drowsiness, and photosensitivity. There is no known specific antidote. Treatment should be supportive and symptomatic, including monitoring of vital signs and observation of the patient’s clinical status. Given its pharmacokinetics, dialysis is unlikely to be effective.

Storage

• Store below 30°C (86°F).
• Keep the tablets in the original blister pack to protect them from light and moisture.
• Keep out of the sight and reach of children.

Disclaimer

This information is for educational purposes for healthcare professionals and is not a substitute for the full Prescribing Information. The prescribing physician should be thoroughly familiar with the complete product label before initiating therapy. Dosage, administration, and monitoring must be individualized based on the patient’s clinical status, tolerability, and any concomitant medications. The ultimate decision for patient treatment resides with the healthcare provider.

Reviews

• “As a pulmonologist, Pirfenex has fundamentally changed our approach to IPF. It’s not a cure, but the ability to demonstrably slow FVC decline gives our patients more quality time. The titration schedule is key for managing initial GI side effects.” – Dr. A. Sharma, Pulmonologist
• “The real-world data continues to support the trial findings. The most challenging aspect is patient education on sun avoidance; it’s non-negotiable. In compliant patients, we see a meaningful alteration of the disease trajectory.” – Prof. L. Chen, Interstitial Lung Disease Unit
• “Managing my father’s IPF with Pirfenex has been a journey. The first few weeks were tough with nausea, but taking it with a full meal made a huge difference. Knowing it’s actively working to slow the disease provides us with crucial hope and a sense of control.” – Family Caregiver