ESBRIET 801 mg FILM-COATED TABLETS

2. What you need to know before you take Esbriet

Do not take Esbriet

• if you are allergic to pirfenidone or any of the other ingredients of this medicine (listed in section 6)
• if you have previously had angioedema with pirfenidone, including symptoms such as swelling of the face, lips and/or tongue that may be associated with difficulty breathing or wheezing
• if you are taking a medicine called fluvoxamine (used to treat depression and obsessive-compulsive disorder [OCD])
• if you have severe or terminal liver disease
• if you have severe or terminal kidney disease that requires dialysis.

If any of the above applies to you, do not take Esbriet. If you are unsure, consult your doctor or pharmacist.

Warnings and precautions

Consult your doctor or pharmacist before starting Esbriet

• You may have increased sensitivity to sunlight (photosensitivity reaction) when taking Esbriet. Avoid sun exposure (also UVA lamps) while taking Esbriet. Use a daily sunscreen and cover your arms, legs, and head to reduce sun exposure (see section 4: Possible side effects).
• Do not take other medicines, such as tetracycline antibiotics (e.g., doxycycline), that may increase your sensitivity to sunlight.
• You should inform your doctor if you have kidney problems.
• You should inform your doctor if you have mild to moderate liver problems.
• You should avoid smoking before and during treatment with Esbriet. Smoking may reduce the effect of Esbriet.
• Esbriet may cause dizziness and fatigue. Be careful if you need to perform activities that require attention and coordination.
• Esbriet may cause weight loss. Your doctor will monitor your weight while you are taking this medicine.
• Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in association with Esbriet treatment. Stop taking Esbriet and seek immediate medical attention if you notice any of the symptoms related to these severe skin reactions described in section 4.

Esbriet may cause serious liver problems. Some cases have been fatal. You will need to have a blood test before starting Esbriet, once a month for the first 6 months, and then every 3 months while taking this medicine, to check your liver function. It is essential that you have these blood tests periodically throughout the time you are taking Esbriet.

Children and adolescents

Do not give Esbriet to children and adolescents under 18 years of age.

Other medicines and Esbriet

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

This is especially important if you are taking the following medicines, as they may alter the effect of Esbriet.

The following medicines may increase the side effects of Esbriet:

• enoxacin (a type of antibiotic)
• ciprofloxacin (a type of antibiotic)
• amiodarone (used to treat certain types of heart conditions)
• propafenone (used to treat certain types of heart conditions)
• fluvoxamine (used to treat depression and obsessive-compulsive disorder [OCD]).

The following medicines may reduce the effectiveness of Esbriet:

• omeprazole (used to treat disorders such as indigestion, gastroesophageal reflux disease)
• rifampicin (a type of antibiotic).

Taking Esbriet with food and drinks

Do not drink grapefruit juice while taking this medicine. Grapefruit juice may make Esbriet not work properly.

Pregnancy and breastfeeding

As a precautionary measure, it is preferable to avoid the use of Esbriet if you are pregnant, planning to become pregnant, or think you may be pregnant, as the potential risks to the fetus are not known.

If you are breastfeeding or planning to breastfeed, consult your doctor or pharmacist before taking Esbriet. Since it is not known whether Esbriet is excreted in breast milk, your doctor will explain the risks and benefits of taking this medicine during breastfeeding if you decide to do so.

Driving and using machines

Do not drive or operate machinery if you feel dizzy or tired after taking Esbriet.

Esbriet contains sodium

Esbriet contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".

3. How to take Esbriet

Treatment with Esbriet should be initiated and supervised by specialist doctors with experience in the diagnosis and treatment of IPF.

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

Normally, you will be given this medicine by gradually increasing the dose as follows:

• for the first 7 days, take a dose of 267 mg (1 yellow tablet), 3 times a day with food (a total of 801 mg/day)
• between days 8 and 14, take a dose of 534 mg (2 yellow tablets or 1 orange tablet), 3 times a day with food (a total of 1,602 mg/day)
• from day 15 (maintenance), take a dose of 801 mg (3 yellow tablets or 1 brown tablet), 3 times a day with food (a total of 2,403 mg/day).

The recommended maintenance dose of Esbriet is 801 mg (3 yellow tablets or 1 brown tablet) three times a day with food, a total of 2,403 mg/day.

Swallow the tablets whole with water, during or after a meal to reduce the risk of side effects such as nausea (feeling sick) and dizziness. If symptoms persist, consult your doctor.

Dose reduction due to side effects

Your doctor may decide to reduce the dose if you experience side effects such as stomach problems, skin reactions to sunlight or UVA lamps, or significant changes in liver enzymes.

If you take more Esbriet than you should

Go to your doctor, pharmacist, or the nearest hospital emergency department immediately if you take more tablets than you should, and take your medicine with you.

If you forget to take Esbriet

If you forget to take a dose, take it as soon as you remember. Do not take a double dose to make up for forgotten doses. Each dose should be separated by an interval of at least 3 hours. Do not take more tablets per day than your prescribed daily dose.

If you stop taking Esbriet

In certain situations, your doctor will advise you to stop taking Esbriet. If for any reason you stop taking Esbriet for more than 14 consecutive days, your doctor will restart your treatment with a dose of 267 mg 3 times a day and gradually increase it to 801 mg 3 times a day.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Esbriet and seek immediate medical attention if you notice any of the following symptoms or signs:

? Swelling of the face, lips, or tongue, itching, hives, difficulty breathing or wheezing, or feeling faint, which are signs of angioedema, a severe allergic reaction or anaphylaxis.

? Yellowing of the eyes or skin or dark urine, and possibly accompanied by itching of the skin, pain in the upper right side of the abdomen, loss of appetite, bleeding or bruising more easily than normal, or feeling tired. These could be signs of abnormal liver function and may indicate liver damage, which is a rare side effect of Esbriet.

? Red patches without relief, or circular spots on the trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome or toxic epidermal necrolysis).

? Widespread rash, high body temperature, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).

Other possible side effects are

If you experience any side effect, consult your doctor.

Very common side effects(may affect more than 1 in 10 people):

• infections of the throat or respiratory tract that reach the lungs and/or sinusitis
• feeling sick (nausea)
• stomach problems, such as acid reflux, vomiting, and constipation
• diarrhea
• indigestion or stomach heaviness
• weight loss
• decreased appetite
• difficulty sleeping
• fatigue
• dizziness
• headache
• difficulty breathing
• cough
• joint pain

Common side effects(may affect up to 1 in 10 people):

• bladder infections
• drowsiness
• altered taste
• hot flashes
• stomach problems, such as feeling heavy, pain, and discomfort in the abdomen, heartburn, and flatulence
• blood tests may indicate increased liver enzymes
• skin reactions after sun exposure or use of UVA lamps
• skin problems such as itching, irritation, or redness, dryness, rash
• muscle pain
• weakness or lack of energy
• chest pain
• sunburn.

Uncommon side effects(may affect up to 1 in 100 people):

• Low sodium levels in the blood. This can cause headache, dizziness, confusion, weakness, muscle cramps, or nausea and vomiting.
• blood test results may show decreased white blood cell count.

Reporting of side effects

If you experience any side effect, consult your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Esbriet

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label of the bottle, on the blister, and on the carton after EXP. The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Esbriet Composition

267 mgtablets

The active ingredient is pirfenidone. Each film-coated tablet contains 267 mg of pirfenidone.

The other ingredients are: microcrystalline cellulose, sodium croscarmellose (see section 2 "Esbriet contains sodium"), povidone K30, anhydrous colloidal silica, magnesium stearate.

The film coating consists of: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, yellow iron oxide (E172).

534 mgtablets

The active ingredient is pirfenidone. Each film-coated tablet contains 534 mg of pirfenidone.

The other ingredients are: microcrystalline cellulose, sodium croscarmellose (see section 2 "Esbriet contains sodium"), povidone K30, anhydrous colloidal silica, magnesium stearate.

The film coating consists of: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, yellow iron oxide (E172) and red iron oxide (E172).

801 mgtablets

The active ingredient is pirfenidone. Each film-coated tablet contains 801 mg of pirfenidone.

The other ingredients are: microcrystalline cellulose, sodium croscarmellose (see section 2 "Esbriet contains sodium"), povidone K30, anhydrous colloidal silica, magnesium stearate.

The film coating consists of: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172) and black iron oxide (E172).

Product Appearance and Package Contents

267 mgtablets

Esbriet 267 mg film-coated tablets are yellow, oval, biconvex, film-coated tablets with the inscription "PFD".

The bottle packs contain a bottle with 90 tablets, or two bottles with 90 tablets each (180 tablets in total).

The blister packs contain 21, 42, 84 or 168 film-coated tablets and the multipacks contain 63 film-coated tablets (2-week starter treatment 21 + 42) or 252 film-coated tablets (maintenance pack 3x84).

534 mgtablets

Esbriet 534 mg film-coated tablets are orange, oval, biconvex, film-coated tablets with the inscription "PFD".

The bottle packs contain a bottle with 21 tablets or a bottle with 90 tablets.

801 mgtablets

Esbriet 801 mg film-coated tablets are brown, oval, biconvex, film-coated tablets with the inscription "PFD".

The bottle pack contains a bottle with 90 tablets.

The blister packs contain 84 film-coated tablets and the multipack contains 252 film-coated tablets (maintenance pack 3x84).

Each of the 801 mg tablet blister strips is marked with the following symbols and abbreviations, as a reminder to take a dose three times a day:

(dawn; morning dose) (sun; afternoon dose) and (moon; night dose).

LU, MA, MI, JU, VI, SA, DO

It is possible that only some pack sizes are marketed.

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Str. 1

D-79639 Grenzach-Wyhlen

Germany

You can request more information about this medicinal product by contacting the local representative of the marketing authorisation holder:

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

There are also links to other websites on rare diseases and orphan medicines.