Pulfibro 534-MG Tablet

Pulfibro is indicated in adults for the treatment of mild to moderate Idiopathic Pulmonary Fibrosis (IPF).

Pirfenidone is a novel agent with anti-inflammatory, antioxidant, and anti-fibrotic properties. It may improve lung function and reduce the number of acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF). The precise mechanism of action of pirfenidone and its specific molecular targets have yet to be elucidated. One vital anti-fibrotic mechanism involves the suppression of TGF-β1 (transforming growth factor-β1), a key cytokine involved in fibrogenesis and extracellular matrix production. There is also evidence to suggest that pirfenidone has the ability to downregulate the expression of potent pro-inflammatory cytokines including TNF-α, interleukin-1, and interferon-gamma. In animal models, pirfenidone can inhibit both the influx of inflammatory cells and the increased pulmonary vascular permeability induced by bleomycin.

Route of administration: Pirfenidone is administered orally with food.

Adults: Upon initiating treatment, the dose should be titrated to the recommended daily dose of nine 267 mg tablets or three 801 mg tablet per day over a 14-days period as follows:

• Days 1 to 7: One 267 mg tablet administered three times a day (801 mg/day)
• Days 8 to 14: Two 267 mg tablets administered three times a day (1602 mg/day)
• Day 15 onward: Three 267 mg tablets or one 801 mg tablet administered three times a day (2403 mg/day)

The recommended daily dose of Pirfenidone for patients with IPF is three 267 mg tablets or one 801 mg three times a day with food for a total of 2403 mg/day. Doses above 2403 mg/day are not recommended for any patient. Patients who miss 14 consecutive days or more of Pirfenidone treatment should re-initiate therapy by undergoing the initial 2-week titration regimen up to the recommended daily dose. For treatment interruption of less than 14 consecutive days, the dose can be resumed at the previous recommended daily dose without titration.

Dose adjustments and other considerations for safe use: Gastrointestinal events: In patients who experience intolerance to therapy due to gastrointestinal side effects, patients should be reminded to take the medicinal product with food. If symptoms persist Pirfenidone may be reduced to 1-2 tablets (267 mg-534 mg) 2-3 times/day with food with re-escalation to the recommended daily dose as tolerated. If symptoms continue, patients may be instructed to interrupt treatment for 1 to 2 weeks to allow symptoms to resolve.

Photosensitivity reaction or rash: Patients who experience a mild to moderate photosensitivity reaction or rash should be reminded of the instruction to use a sunblock daily and to avoid sun exposure. The dose of Pirfenidone may be reduced to three 267 mg tablets/day (one 267 mg tablet three times a day). If the rash persists after 7 days, Pirfenidone should be discontinued for 15 days, with re-escalation to the recommended daily dose in the same manner as the dose escalation period. Patients who experience severe photosensitivity reaction or rash should be instructed to interrupt the dose and to seek medical advice. Once the rash has resolved, Pirfenidone may be re-introduced and re-escalated up to the recommended daily dose at the discretion of the physician.

Hepatic function: In the event of significant elevation of alanine and/or aspartate aminotransferases (ALT/AST) with or without bilirubin elevation, the dose of Pirfenidone should be adjusted or treatment discontinued according to the guidelines.

With medicine: Moderate (e.g., ciprofloxacin) and strong inhibitors of CYP1A2 (e.g., fluvoxamine) increase the systemic exposure of Pulfibro and may alter the adverse reaction profile of Pulfibro. Discontinue fluvoxamine prior to administration of Pulfibro or reduce to 267 mg three times a day. Consider dosage reduction with use of ciprofloxacin.

With food and others: None. A reduced incidence of adverse reactions was observed in the fed group when compared to the fasted group.

Hypersensitivity to the active substance or to any of the excipients, concomitant use of fluvoxamine, severe hepatic impairment or end stage liver disease, severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis.

Common: nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, anorexia, gastroesophageal reflux disease, sinusitis, insomnia, weight decrease, and arthralgia.

Rare: photosensitivity reaction, decreased appetite, pruritus, asthenia, dysgeusia, and non-cardiac chest pain.

Pregnancy: There are no data from the use of Pirfenidone in pregnant women. In animals’ placental transfer of pirfenidone and/or its metabolites occurs with the potential for accumulation of pirfenidone and/or its metabolites in amniotic fluid. At high doses (1000 mg/kg/day) rats exhibited prolongation of gestation and reduction in fetal viability. As a precautionary measure, it is preferable to avoid the use of Pirfenidone during pregnancy.

Lactation: It is unknown whether pirfenidone or its metabolites are excreted in human milk. Available pharmacokinetic data in animals have shown excretion of pirfenidone and/or its metabolites in milk with the potential for accumulation of pirfenidone and/or its metabolites in milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue from Pirfenidone therapy, taking into account the benefit of breast-feeding for the child and the benefit of Pirfenidone therapy for the mother.

Fertility: Pirfenidone had no effects on fertility and reproductive performance in rats at dosages up to 1000 mg/kg/day (approximately 3 times the MRDD in adults on mg/m2 basis)

• Elevated liver enzymes: ALT, AST, and bilirubin elevations have occurred with Pulfibro. Monitor ALT, AST, and bilirubin before and during treatment. Temporary dosage reductions or discontinuations may be required.
• Photosensitivity and rash: Photosensitivity and rash have been noted with Pulfibro. Avoid exposure to sunlight and sunlamps. Wear sunscreen and protective clothing daily. Temporary dosage reductions or discontinuations may be required.
• Gastrointestinal disorders: Nausea, vomiting, diarrhea, dyspepsia, gastroesophageal reflux disease, and
  abdominal pain have occurred with Pulfibro. Temporary dosage reductions or discontinuations may be required.

Use in Children & Adolescents: It is not known if Pulfibro is safe and effective in children & adolescents.

Hepatic Impairment: Monitor for adverse reactions and consider dosage modification or discontinuation of Pulfibro as needed. Pulfibro is not recommended for use in patients with severe hepatic impairment.

Renal Impairment: Monitor for adverse reactions and consider dosage modification or discontinuation of Pulfibro as needed. Pulfibro is not recommended for use in patients with end-stage renal disease on dialysis.

Smokers: Decreased exposure has been noted in smokers which may alter the efficacy profile of Pulfibro.

There is limited clinical experience with overdose. Multiple doses of Pulfibro up to a dose of 4806 mg/day were administered as six 267 mg tablets three times daily to healthy adult volunteers over a 12-day dose escalation period. Adverse reactions were mild, transient, and consistent with the most frequently reported adverse reactions for Pulfibro.

Immunosuppressant

Store in a cool & dry place. Protect from light & moisture. Keep all medicine out of reach of children.