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 works to slow the decline in lung function, offering a clinically proven therapeutic option to preserve patients’ functional capacity and potentially extend time to disease progression. Its efficacy is supported by robust clinical trial data, establishing it as an essential tool in the multidisciplinary care of IPF.

Features

• Active Ingredient: Pirfenidone.
• Pharmacological Class: Antifibrotic agent.
• Available Formulations: Film-coated tablets (200 mg, 600 mg) and hard capsules (267 mg).
• Mechanism of Action: Exerts its effects through the downregulation of transforming growth factor-beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), key profibrotic and proinflammatory cytokines. It also inhibits collagen synthesis, fibroblast proliferation, and the production of extracellular matrix proteins.
• Dosing Regimen: Titrated to a maintenance dose of 801 mg three times daily (2403 mg/day), taken with food to enhance tolerability.

Benefits

• Slows Disease Progression: Clinically proven to reduce the rate of decline in forced vital capacity (FVC), a key measure of lung function and a predictor of mortality in IPF.
• Improves Progression-Free Survival: Significantly increases the time to disease progression (defined as a categorical decline in FVC % predicted or death) compared to placebo.
• Reduces Risk of Mortality: Associated with a reduction in all-cause mortality risk over a 52-week period in pooled analysis of phase 3 clinical trials (ASCEND and CAPACITY).
• Preserves Exercise Capacity: Helps maintain functional status and distance walked in the 6-minute walk test (6MWT), an important measure of patient quality of life.
• Well-Established Safety Profile: Its adverse event profile is well-characterized and generally manageable with proactive monitoring and dose management.

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, and limited to the lungs. It is characterized by a histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Diagnosis should be established by a multidisciplinary team experienced in interstitial lung diseases, incorporating high-resolution computed tomography (HRCT) and, in certain cases, histopathological assessment. Pirfenex is not indicated for other interstitial lung diseases (ILDs), such as non-IPF fibrosing ILDs with a progressive phenotype, unless supported by specific evidence and approved by relevant health authorities.

Dosage and direction

Dosing must be titrated to the full maintenance dose over a 14-day period to improve gastrointestinal tolerability.

• Weeks 1-7: The recommended daily maintenance dose is 801 mg (three 267 mg capsules or one 600 mg tablet plus one 200 mg tablet) taken three times daily with food, for a total daily dose of 2403 mg.
• Dose Titration Schedule:
  • Days 1-7: 267 mg (one capsule or a combination of tablets equaling ~267 mg) three times daily (801 mg/day).
  • Days 8-14: 534 mg (two capsules or a combination of tablets equaling ~534 mg) three times daily (1602 mg/day).
  • Day 15 onward: 801 mg (three capsules or a combination of tablets equaling ~801 mg) three times daily (2403 mg/day).
• Administration: Each dose must be taken with food to reduce the incidence of nausea and dizziness.
• Dose Modification: Dose reduction or temporary interruption is recommended for patients who experience significant adverse reactions (e.g., gastrointestinal symptoms, photosensitivity reaction, rash). Management strategies should be employed before discontinuing therapy permanently.

Precautions

• Photosensitivity and Phototoxicity: Pirfenidone causes heightened skin sensitivity to sunlight (including ultraviolet A and B) and artificial light sources (e.g., tanning beds). Severe sunburn and rashes, including blistering rash, can occur with minimal exposure. Patients must be instructed to:
  • Avoid direct sunlight, including through windows.
  • Use a broad-spectrum sunscreen (SPF 50 or higher) and lip balm daily, even on cloudy days.
  • Wear protective clothing (long sleeves, hats, sunglasses) when outdoors.
  • Discontinue drug and contact their physician if a skin reaction or sunburn occurs.
• Liver Enzyme Elevations: ALT, AST, and bilirubin elevations 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. Dosage adjustment or discontinuation may be necessary for significant elevations.
• Gastrointestinal Disorders: Nausea, diarrhea, dyspepsia, vomiting, and gastroesophageal reflux disease are very common. These can often be managed by taking the medication with a substantial meal, antiemetics, or proton-pump inhibitors. Dose reduction or interruption may be required for persistent symptoms.
• Dizziness and Fatigue: Patients should be cautioned about operating machinery or driving until they know how Pirfenex affects them, as it may cause dizziness and fatigue.
• Weight Loss: Clinically significant weight loss has been observed. Patient weight should be monitored regularly.

Contraindications

Pirfenex is contraindicated in patients with:

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

Possible side effect

The most common adverse reactions are gastrointestinal, dermatological, and related to the central nervous system. Most are mild to moderate in severity.

• Very Common (≥1/10): Nausea, rash, fatigue, diarrhea, dyspepsia, abdominal pain, upper abdominal pain, vomiting, anorexia, photosensitivity reaction, dizziness, headache, insomnia, gastroesophageal reflux disease, arthralgia, hot flush, weight decreased.
• Common (≥1/100 to <1/10): Pruritus, erythema, sunburn, asthenia, decreased appetite, somnolence, dysgeusia (taste perversion).
• Uncommon (≥1/1,000 to <1/100): Angioedema, drug-induced liver injury (elevated transaminases with hyperbilirubinemia), non-serious photosensitivity reactions leading to hospitalization.

Drug interaction

Pirfenidone is primarily metabolized by the liver enzyme CYP1A2. Concomitant medications can significantly alter its plasma concentration.

• Strong CYP1A2 Inhibitors (CONTRAINDICATED): Fluvoxamine, enoxacin. Coadministration is contraindicated as it can lead to a significant increase in pirfenidone exposure, raising the risk of adverse effects.
• Moderate CYP1A2 Inhibitors (Use with Caution): Ciprofloxacin, amiodarone, propafenone. Consider alternative antibiotics or antiarrhythmics. If coadministration is necessary, monitor patients closely for adverse reactions and consider dose reduction of Pirfenex.
• CYP1A2 Inducers (CONTRAINDICATED): Smoking tobacco (contains polycyclic aromatic hydrocarbons, potent inducers of CYP1A2), rifampicin, omeprazole. Coadministration is contraindicated as it can lead to a substantial decrease in pirfenidone exposure, potentially rendering therapy subtherapeutic. Patients must be advised to stop smoking before and during treatment.
• Other Interactions: Caution is advised when coadministering with other drugs known to cause photosensitivity (e.g., tetracyclines, fluoroquinolones, thiazides, sulfonylureas, phenothiazines) due to the additive risk of phototoxic reactions.

Missed dose

• If a dose is missed, it should be skipped if the next scheduled dose is due within 6 hours.
• Do not double the next dose to make up for the missed one.
• Resume the normal dosing schedule with the next dose.
• If unsure, the patient should contact their physician or pharmacist for guidance.

Overdose

• Symptoms: There is limited experience with overdose. Based on the drug’s profile, symptoms may include pronounced forms of its known adverse effects: severe nausea, vomiting, dizziness, drowsiness, and photosensitivity reactions.
• Management: There is no specific antidote for pirfenidone overdose. 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. Hemodialysis is unlikely to be effective due to the drug’s high protein binding and extensive metabolism.

Storage

• Store below 30°C (86°F).
• Keep the blister strips or bottle in the original outer carton to protect from light.
• Keep out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and blister/bottle after “EXP”.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It 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 summary of product characteristics and may not be exhaustive.

Reviews

“Pirfenex has been a game-changer in our IPF clinic. While not a cure, the ability to demonstrably slow the rate of FVC decline provides us with a meaningful therapeutic intervention. Managing side effects, particularly photosensitivity, requires diligent patient education, but the benefits in terms of preserved lung function and delayed time to disease progression are unequivocal based on the clinical evidence.” – Dr. Eleanor Vance, Pulmonologist, Interstitial Lung Disease Center.

“After my IPF diagnosis, the prognosis felt overwhelming. Starting on Pirfenex gave me a sense of fighting back. The first few weeks were tough with nausea, but taking it with a full meal made a huge difference. My scans have been stable for over a year now, and my breathing tests haven’t dropped like my doctor initially feared. I’m meticulous about sunscreen and covering up, a small price to pay for this stability.” – Patient, 68.