Pirfenidone

BRAND NAMES

Esbriet: Esbriet (pirfenidone) is a prescription drug used to treat persons with a lung illness known as idiopathic pulmonary fibrosis. It is available in capsules with strength of 267 mg and tablets with dosage ranges of 267 mg and 801 mg.

MECHANISM OF ACTION

Pirfenidone reduces the synthesis of TGF-β1, a cytokine associated with idiopathic pulmonary fibrosis. Pirfenidone suppresses TGF-β1 and prevents the development of human lung fibroblasts into myofibroblasts, reducing collagen synthesis and extracellular matrix creation.

Pirfenidone suppresses pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, IFN-γ, and PDGF. Pirfenidone has been shown in animal models to increase the production of anti-inflammatory IL-10 and reduce the formation of numerous inflammatory cells, such as lymphocytes, macrophages, and neutrophils. Pirfenidone decreased the inflow of inflammatory cells in animal models while improving bleomycin-induced pulmonary vascular permeability. Several in vitro investigations demonstrate that pirfenidone exerts antioxidant effects by scavenging reactive oxygen species (ROS) and decreasing lipid peroxidation, minimizing cellular damage in IPF.

PHARMACOKINETICS

Absorption

After a single oral dosage of 801 mg pirfenidone (as three 267 mg capsules), the Tmax varied from 30 minutes to four hours.

Distribution

The average apparent oral volume of distribution is 59 to 71 L. Pirfenidone is not abundantly disseminated into tissues.

Metabolism

According to in vitro studies, CYP1A2 mediates around 70-80% of pirfenidone metabolism, with modest contributions from CYP2C9, 2C19, 2D6, and 2E1. Following oral administration of pirfenidone, four metabolites were found. In vitro, findings indicate that metabolites are not predicted to be pharmacologically active at reported metabolite concentrations. Pirfenidone's exact metabolic routes have yet to be thoroughly characterized; however, one process involves CYP1A2-mediated 5-hydroxylation and subsequent oxidation to create 5-carboxy pirfenidone. In humans, only pirfenidone and 5-carboxypirfenidone are found in considerable amounts in plasma. The mean metabolism-to-parent ratio was between 0.6 and 0.7.

Elimination

Within 24 hours, over 80% of the pirfenidone dosage is eliminated primarily in the urine. The 5-carboxy metabolite excreted about 99.6% of the recovered pirfenidone dosage. Less than 1% of the dosage was excreted as the unaltered parent drug, whereas less than 0.1% was excreted as various metabolites. In healthy people, the average terminal half-life is about three hours.

DOSAGE AND ADMINISTRATION

The amount of medication you take depends on its strength. The number of daily dosages, intervals between doses, and duration of pharmaceutical use are also determined by the medical condition for which you are taking it.

In connection with oral dosage forms (capsules or tablets): 

For idiopathic pulmonary fibrosis: 

Adults: Take 267 mg three times daily for Days 1 through 7. From Day 8 to Day 14, take 534 mg three times daily. Take 801 mg three times a day after Day 15. Depending on how well it works, your doctor might need to adjust your dose. However, the daily allowance is frequently set at 2403 mg. 

Kids: Your physician must determine the right dosage and usage.

CONTRAINDICATIONS

• Hypersensitivity to any of the excipients or the active ingredient.

• Severe hepatic impairment or end-stage liver disease 

• Severe renal impairment or end-stage renal disease needing dialysis 

• History of angioedema with pirfenidone

• Concomitant usage of fluvoxamine 

DRUG INTERACTIONS

Using this drug with any of the following medications is typically not advised, although it may be necessary in some instances.

• Abametapir
• Capmatinib
• Carbamazepine
• Ciprofloxacin
• Enoxacin
• Fluvoxamine
• Interferon Alfa-2b
• Mexiletine
• Peginterferon Alfa-2b
• Viloxazine

SIDE EFFECTS

The common side effects of pirfenidone include

• Diarrhoea
• itching or skin rash
• nausea
• painful or difficult urination
• red, irritated eyes
• change in taste
• dizziness
• sneezing
• stuffy or runny nose
• trouble sleeping
• weight loss
• unusual bleeding or bruising
• unusual tiredness or weakness

TOXICITY

There is minimal clinical experience with pirfenidone overdosage. A maximum tolerable pirfenidone dosage of 4005 mg per day was achieved when five 267 mg capsules were delivered three times daily to healthy adult volunteers throughout a 12-day dose escalation period. Overdosage should be treated with supportive and symptomatic treatment, which includes monitoring vital signs and assessing the patient's clinical state.