Esbriet (Pirfenidone)

What Is Esbriet and What Is It Used For?

Esbriet (pirfenidone) is an antifibrotic medication prescribed for the treatment of idiopathic pulmonary fibrosis (IPF) in adults. It helps slow the scarring process in the lungs, preserving breathing capacity and slowing disease progression.

Esbriet contains the active substance pirfenidone, which belongs to a class of medications known as antifibrotic agents. It was approved by the European Medicines Agency (EMA) in 2011 and by the U.S. Food and Drug Administration (FDA) in 2014 for the treatment of IPF, making it one of the first medications specifically developed for this condition.

Idiopathic pulmonary fibrosis is a chronic, progressive disease in which the lung tissue gradually becomes thickened, stiff, and scarred (fibrotic). The term "idiopathic" means the cause of the fibrosis is unknown. As the scarring worsens, it becomes increasingly difficult to take deep breaths, and the lungs become less efficient at delivering oxygen to the bloodstream. IPF primarily affects adults over the age of 50 and is more common in men than in women.

While pirfenidone does not cure IPF or reverse existing lung damage, clinical trials have demonstrated that it can significantly slow the rate of decline in lung function. The landmark ASCEND trial (Assessment of Pirfenidone to Confirm Efficacy and Safety in IPF) and the earlier CAPACITY trials showed that pirfenidone reduces the decline in forced vital capacity (FVC), a key measure of lung function, and may improve progression-free survival compared to placebo.

The exact mechanism by which pirfenidone works is not fully understood, but research suggests it has three main properties: anti-fibrotic (reduces the formation of scar tissue), anti-inflammatory (reduces lung inflammation), and antioxidant (protects cells from damage caused by reactive oxygen species). Together, these actions help slow the progressive scarring that characterizes IPF.

What Should You Know Before Taking Esbriet?

Before starting Esbriet, your doctor must evaluate your liver and kidney function, review all your current medications, and discuss the risks of sun sensitivity. Several medical conditions and drug interactions can make Esbriet unsafe or require dose adjustments.

It is essential that your prescribing physician has a complete picture of your medical history, current medications, and lifestyle before initiating treatment with Esbriet. Certain conditions absolutely prevent the use of this medication, while others require careful monitoring and possible dose adjustments.

Contraindications

You must not take Esbriet in the following situations:

• Allergy to pirfenidone or any of the other ingredients in the tablets (including microcrystalline cellulose, croscarmellose sodium, povidone K30, colloidal anhydrous silica, magnesium stearate, and film-coating components)
• Previous angioedema with pirfenidone – symptoms include swelling of the face, lips, and/or tongue, which may be associated with difficulty breathing or wheezing
• Concurrent use of fluvoxamine – this antidepressant (used for depression and obsessive-compulsive disorder) is a potent CYP1A2 inhibitor that dramatically increases pirfenidone blood levels, creating a risk of serious toxicity
• Severe liver disease or end-stage liver disease – the liver is responsible for metabolizing pirfenidone, and impaired liver function can lead to dangerous drug accumulation
• Severe kidney disease or end-stage kidney disease requiring dialysis – impaired renal clearance affects drug elimination

Warnings and Precautions

Discuss the following with your doctor before and during treatment with Esbriet:

Photosensitivity (sun sensitivity): Pirfenidone significantly increases your skin's sensitivity to ultraviolet radiation. You may develop severe sunburn, blisters, or rashes even after brief sun exposure. Use broad-spectrum sunscreen (SPF 50 or higher) every day, wear protective clothing covering your arms, legs, and head, and avoid direct sunlight and sunlamps. Do not take tetracycline antibiotics (such as doxycycline) concurrently, as these can further increase photosensitivity.

Liver function: Esbriet can cause serious liver problems, and some cases have been life-threatening. You will need blood tests to check liver function before starting treatment, then monthly for the first six months, and every three months thereafter for the duration of treatment. If liver enzyme levels rise significantly, your doctor may reduce the dose or discontinue treatment.

Severe skin reactions: Rarely, pirfenidone has been associated with Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Stop taking Esbriet and seek immediate medical attention if you develop widespread skin rashes, blisters, mouth sores, or skin peeling, especially if accompanied by fever.

Kidney problems: If you have mild to moderate kidney impairment, tell your doctor, as dose adjustments may be necessary and more frequent monitoring may be required.

Smoking: Cigarette smoking induces CYP1A2 enzymes, which can reduce blood levels of pirfenidone and decrease its effectiveness. You should not smoke before or during treatment with Esbriet.

Dizziness and fatigue: Esbriet can cause dizziness and tiredness. Exercise caution when driving, operating machinery, or performing activities that require alertness and coordination.

Weight loss: Pirfenidone may cause weight loss. Your doctor will monitor your weight throughout treatment.

Pregnancy and Breastfeeding

As a precautionary measure, it is advisable to avoid using Esbriet if you are pregnant, planning to become pregnant, or think you may be pregnant, as the risks to the unborn child are unknown. There are no adequate clinical studies of pirfenidone in pregnant women. Animal studies have not provided sufficient data to fully characterize reproductive risks.

It is not known whether pirfenidone passes into breast milk. If you are breastfeeding or planning to breastfeed, discuss the risks and benefits with your doctor before taking Esbriet. Your healthcare provider will help weigh the benefits of treatment against any potential risk to the nursing infant.

Children and Adolescents

Esbriet should not be given to children and adolescents under 18 years of age. The safety and efficacy of pirfenidone in pediatric patients have not been established. IPF is almost exclusively an adult disease.

Sodium Content

Esbriet contains less than 1 mmol (23 mg) sodium per tablet, which means it is essentially sodium-free and is unlikely to affect patients on a sodium-restricted diet.

How Does Esbriet Interact with Other Drugs?

Esbriet (pirfenidone) is primarily metabolized by the CYP1A2 enzyme system in the liver. Drugs that inhibit CYP1A2 can increase pirfenidone levels and side effects, while CYP1A2 inducers can reduce its effectiveness. Several common medications have clinically significant interactions.

Pirfenidone is metabolized mainly by the cytochrome P450 enzyme CYP1A2, with minor contributions from other CYP enzymes including CYP2C9, CYP2C19, CYP2D6, and CYP2E1. Any medication that significantly affects CYP1A2 activity can alter pirfenidone blood levels, potentially leading to increased toxicity or reduced efficacy. Always inform your doctor about all medications you are taking, including over-the-counter drugs and herbal supplements.

Major Interactions (Avoid or Use with Extreme Caution)

Interactions That May Reduce Effectiveness

Other Notable Interactions

Amiodarone and propafenon: These cardiac medications can alter the effect of Esbriet. If you are taking either of these drugs for heart rhythm problems, your doctor should carefully evaluate the risks and benefits and may need to adjust your dose.

Grapefruit juice: You should not drink grapefruit juice while taking Esbriet. Grapefruit contains compounds that inhibit CYP enzymes involved in pirfenidone metabolism, potentially leading to increased drug levels and a higher risk of side effects.

Tetracycline antibiotics (e.g., doxycycline): While not a pharmacokinetic interaction, tetracyclines also cause photosensitivity. Taking them alongside pirfenidone can significantly increase the risk and severity of sun-related skin reactions.

What Is the Correct Dosage of Esbriet?

Esbriet is gradually increased over a 14-day titration period to minimize side effects. The target maintenance dose is 801 mg (three 267 mg tablets or one 801 mg tablet) taken three times daily with food, for a total of 2,403 mg per day.

Treatment with Esbriet must be initiated and supervised by a specialist physician experienced in the diagnosis and management of idiopathic pulmonary fibrosis. The dose is gradually increased over two weeks to allow your body to adjust to the medication and to reduce the likelihood of gastrointestinal and other side effects.

Adults – Standard Dose Titration

Swallow the tablets whole with a glass of water, during or after a meal. Taking Esbriet with food is important because it reduces the risk of nausea and dizziness. If symptoms persist despite taking the medication with food, contact your doctor.

Dose Reduction for Side Effects

Your doctor may reduce the dose if you experience certain side effects such as gastrointestinal problems (nausea, vomiting, diarrhea), skin reactions from sun exposure or sunlamps, or significant changes in liver enzyme levels. The dose can be temporarily reduced and then gradually increased back to the maintenance level once side effects resolve.

Children

Esbriet is not approved for use in children or adolescents under 18 years of age. IPF does not typically occur in the pediatric population, and safety and efficacy data in children are not available.

Elderly Patients

No dose adjustment is generally required in elderly patients based on age alone. However, elderly patients may be more susceptible to side effects, particularly gastrointestinal symptoms and dizziness. Close monitoring is recommended, and dose adjustments should be made based on tolerability and liver/kidney function.

Missed Dose

If you forget a dose, take it as soon as you remember. Do not take a double dose to make up for a missed one. There should be at least 3 hours between each dose. Do not take more tablets each day than your prescribed daily dose.

Overdose

If you have taken too many tablets, contact your doctor, pharmacist, or the nearest emergency department immediately and bring the medication with you. Overdose symptoms may include an intensification of the known side effects, particularly gastrointestinal distress. Treatment is supportive, as there is no specific antidote for pirfenidone.

What Are the Side Effects of Esbriet?

Like all medicines, Esbriet can cause side effects, although not everyone gets them. The most common side effects include nausea, fatigue, diarrhea, dizziness, and skin reactions from sun exposure. Serious but rare side effects include liver damage, severe allergic reactions, and serious skin conditions.

Side effects with pirfenidone tend to be most prominent during the initial dose titration period and often improve as your body adjusts to the medication. Taking Esbriet with food significantly reduces the incidence and severity of gastrointestinal side effects. If side effects are bothersome or persistent, your doctor can adjust the dose.

If you experience any side effects, including those not listed here, talk to your doctor or pharmacist. Reporting side effects helps regulatory authorities continuously monitor the benefit-risk profile of medications. In the United States, you can report side effects to the FDA MedWatch program; in the European Union, contact your national medicines agency; in the United Kingdom, use the MHRA Yellow Card scheme.

How Should You Store Esbriet?

Store Esbriet at room temperature, out of reach of children, and use before the expiration date on the packaging. No special storage conditions are required for this medication.

Keep this medicine out of the sight and reach of children. Store at room temperature – Esbriet does not require any special storage conditions such as refrigeration or protection from light.

Do not use this medicine after the expiry date printed on the bottle label, blister pack, and carton after "EXP." The expiry date refers to the last day of that month. Once opened, the bottle should be used within the timeframe indicated on the packaging.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help protect the environment and prevent accidental exposure.

What Does Esbriet Contain?

Esbriet tablets contain pirfenidone as the active ingredient, available in 267 mg (yellow), 534 mg (orange), and 801 mg (brown) film-coated tablets. The tablets are oval, biconvex, and imprinted with "PFD."

Each tablet strength contains pirfenidone along with the following inactive (excipient) ingredients:

Tablet core: Microcrystalline cellulose, croscarmellose sodium, povidone K30, colloidal anhydrous silica, and magnesium stearate.

267 mg tablet film coating: Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, and yellow iron oxide (E172). The 267 mg tablets are yellow, oval, biconvex, and imprinted with "PFD."

534 mg tablet film coating: Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, yellow iron oxide (E172), and red iron oxide (E172). The 534 mg tablets are orange, oval, biconvex, and imprinted with "PFD."

801 mg tablet film coating: Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172), and black iron oxide (E172). The 801 mg tablets are brown, oval, biconvex, and imprinted with "PFD."

The tablets are available in bottles and blister packs of various sizes. Not all pack sizes may be marketed in all countries. Blister strips for the 801 mg tablets are marked with symbols and abbreviated day names as a reminder to take the dose three times daily.