Pirfenex (pirfenidone) is an oral antifibrotic agent specifically indicated for the treatment of idiopathic pulmonary fibrosis (IPF). It is a disease-modifying therapy that works by targeting multiple pathways involved in the fibrotic process, thereby reducing the rate of decline in lung function. This medication represents a significant advancement in the management of this chronic, progressive, and ultimately fatal lung disease, offering a targeted approach to slow its relentless progression and help preserve patients’ quality of life.

Features

• Active Pharmaceutical Ingredient (API): Pirfenidone.
• Standard tablet strengths: 267 mg and 801 mg film-coated tablets.
• Mechanism of Action: Exerts antifibrotic, anti-inflammatory, and antioxidant effects by downregulating the production of growth factors and procollagens.
• Pharmacokinetics: Rapidly absorbed after oral administration, with peak plasma concentrations reached within 3 hours. Metabolized primarily in the liver via CYP1A2 and other enzymes.
• Bioavailability: Approximately 80% when taken with food.
• Half-life: Approximately 3 hours.
• Primary Excretion: Renal (mostly as metabolites).

Benefits

• Slows disease progression by significantly reducing the rate of decline in forced vital capacity (FVC), a key measure of lung function.
• Reduces the risk of all-cause mortality in patients with IPF.
• Helps to preserve exercise capacity and physical functioning over time.
• Provides a targeted therapeutic option that addresses the underlying fibrotic mechanisms of IPF.
• May decrease the frequency of acute exacerbations, which are associated with high mortality.

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. It is characterized by a progressive and irreversible decline in lung function due to scarring (fibrosis) of the lung tissue. Diagnosis must be confirmed by a specialist, typically through a combination of high-resolution computed tomography (HRCT) and, in some cases, histopathology from a lung biopsy, following established international guidelines. It is not indicated for other interstitial lung diseases (ILDs) unless specified by new clinical evidence and regulatory approval.

Dosage and direction

The dosage of Pirfenex must be titrated to the full maintenance dose to improve gastrointestinal tolerability.

• Weeks 1-14: Titration Period

  • Days 1-7: 267 mg (one 267 mg tablet) three times daily (total daily dose 801 mg).
  • Days 8-14: 534 mg (two 267 mg tablets) three times daily (total daily dose 1602 mg).
  • Day 15 onward (Maintenance Dose): 801 mg (one 801 mg tablet) three times daily (total daily dose 2403 mg).

• Administration:

  • Tablets must be swallowed whole with food to reduce the incidence of nausea and dizziness.
  • Doses should be taken at the same times each day, typically with breakfast, lunch, and dinner.
  • Dosage adjustments or interruption may be necessary based on tolerability and for patients with moderate or severe hepatic impairment. Dose reduction is required for patients taking strong CYP1A2 inhibitors.

Precautions

• Photosensitivity: Pirfenex causes photosensitivity reactions and phototoxicity. Patients must be advised to avoid direct sunlight, including sunlamps, and to use a high-protection (SPF 50+) sunscreen, wear protective clothing, and a hat when outdoors.
• Liver Function: Elevations in liver enzymes (ALT, AST, bilirubin) have been observed. Liver function tests (ALT, AST, and bilirubin) must 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 common. Taking the drug with food can mitigate these effects. Anti-emetic or anti-diarrheal agents may be considered.
• Dizziness and Fatigue: Patients should be cautioned about operating machinery or driving until they know how Pirfenex affects them.
• Weight Loss: Monitor patient weight; significant unintentional weight loss may require intervention.
• Smoking: Smoking can reduce the exposure to pirfenidone due to induction of CYP1A2 metabolism. Patients should be strongly advised to stop smoking.

Contraindications

Pirfenex is contraindicated in the following patient populations:

• Patients with a known hypersensitivity to pirfenidone or any of the excipients in the formulation.
• Patients with severe hepatic impairment (Child-Pugh Class C).
• Patients with severe renal impairment (CrCl <30 mL/min) or end-stage renal disease requiring dialysis.
• Concomitant use with fluvoxamine or other strong CYP1A2 inhibitors.
• History of angioedema related to pirfenidone use.

Possible side effect

The most common adverse reactions (incidence >5%) are:

• Gastrointestinal: Nausea, diarrhea, dyspepsia, vomiting, abdominal pain, gastroesophageal reflux disease, decreased appetite.
• Dermatological: Rash, photosensitivity reaction, pruritus.
• General: Fatigue, dizziness, headache, insomnia.
• Metabolic: Weight loss.
• Respiratory: Upper respiratory tract infection.

Serious but less common side effects can include:

• Significant elevation of liver enzymes and drug-induced liver injury.
• Severe photosensitivity reactions.
• Angioedema.

Drug interaction

Pirfenidone is primarily metabolized by CYP1A2, with minor contributions from other CYP isozymes. Key interactions include:

• Strong CYP1A2 Inhibitors (e.g., Fluvoxamine, Enoxacin): Contraindicated. Concomitant use significantly increases pirfenidone exposure and the risk of adverse effects.
• Moderate CYP1A2 Inhibitors (e.g., Ciprofloxacin, Amiodarone, Propafenone, Zileuton, Oral Contraceptives): Use with caution. A dose reduction of Pirfenex 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.
• Other Medicinal Products: Caution is advised with other drugs known to cause photosensitivity (e.g., tetracyclines, fluoroquinolones, sulfonamides, thiazides, St. John’s Wort) due to additive risk.

Missed dose

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

Overdose

• There is limited experience with pirfenidone overdose.
• Expected symptoms would be an exaggeration of known adverse effects, particularly nausea, vomiting, dizziness, and photosensitivity.
• There is no known specific antidote. Treatment should consist of general supportive measures, including monitoring of vital signs and observation of the patient’s clinical status.
• Gastric lavage may be considered if performed soon after ingestion. Due to rapid absorption, activated charcoal may only be effective if given within 1-2 hours of ingestion.
• Hemodialysis is unlikely to be effective due to the high protein binding of pirfenidone.

Storage

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

Disclaimer

This information is for educational purposes only 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 information provided is based on the product’s prescribing information but may not be exhaustive.

Reviews

“Initiated on Pirfenex 8 months ago following my IPF diagnosis. The titration period was rough with significant nausea, but since reaching the maintenance dose and being strict with taking it with meals, my symptoms are manageable. My most recent PFT showed my FVC has remained stable, which my pulmonologist is very pleased with. The photosensitivity is real—I got a rash after just 20 minutes in the garden without sunscreen. It’s a strict regimen, but for the chance to slow this disease down, it’s a commitment I’m willing to make.” – Patient M.K., 68

“As a pulmonologist specializing in ILDs, Pirfenidone is a cornerstone of my therapeutic arsenal for appropriate IPF patients. The clinical trial data for slowing FVC decline is robust. In practice, the key to success is meticulous patient education. I spend considerable time preparing patients for the GI side effects and, most importantly, drilling in the absolute necessity of sun protection. For patients who tolerate it, it can provide valuable years of stabilized lung function. It’s not a cure, but it’s a powerful tool for changing the trajectory of the disease.” – Dr. A. Sharma, MD