ESBRIET Film-coated tablet Ref.[9677] Active ingredients: Pirfenidone

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

Posology

Adults

Upon initiating treatment, the dose should be titrated to the recommended daily dose of 2403 mg/day over a 14-day period as follows:

• Days 1 to 7: a dose of 267 mg administered three times a day (801 mg/day)
• Days 8 to 14: a dose of 534 mg administered three times a day (1602 mg/day)
• Day 15 onward: a dose of 801 mg administered three times a day (2403 mg/day)

The recommended maintenance daily dose of Esbriet is 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 (see section 4.9).

Patients who miss 14 consecutive days or more of Esbriet 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 undesirable effects, patients should be reminded to take the medicinal product with food. If symptoms persist, the dose of pirfenidone may be reduced to 267 mg – 534 mg, two to three times a day with food with re-escalation to the recommended daily dose as tolerated. If symptoms continue, patients may be instructed to interrupt treatment for one to two weeks to allow symptoms to resolve.

Photosensitivity reaction or rash

Patients who experience a mild to moderate photosensitivity reaction or rash should be reminded to use a sunblock daily and avoid exposure to the sun (see section 4.4). The dose of pirfenidone may be reduced to 801 mg each day (267 mg three times a day). If the rash persists after 7 days, Esbriet 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 (see section 4.4). Once the rash has resolved, Esbriet 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 listed in section 4.4.

Special populations

Elderly

No dose adjustment is necessary in patients 65 years and older (see section 5.2).

Hepatic impairment

No dose adjustment is necessary in patients with mild to moderate hepatic impairment (i.e. Child-Pugh Class A and B). However, since plasma levels of pirfenidone may be increased in some individuals with mild to moderate hepatic impairment, caution should be used with Esbriet treatment in this population. Esbriet therapy should not be used in patients with severe hepatic impairment or end stage liver disease (see section 4.3, 4.4 and 5.2).

Renal impairment

No dose adjustment is necessary in patients with mild renal impairment. Esbriet should be used with caution in patients with moderate (CrCl 30-50 ml/min) renal impairment. Esbriet therapy should not be used in patients with severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis (see sections 4.3 and 5.2).

Paediatric population

There is no relevant use of Esbriet in the paediatric population for the indication of IPF.

Method of administration

Esbriet is for oral use. The tablets are to be swallowed whole with water and taken with food to reduce the possibility of nausea and dizziness (see sections 4.8 and 5.2).

There is limited clinical experience with overdose. Multiple doses of pirfenidone up to a total dose of 4,806 mg/day were administered as six 267 mg capsules 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 pirfenidone.

In the event of a suspected overdose, supportive medical care should be provided including monitoring of vital signs and close observation of the clinical status of the patient.

267 mg tablet and 801 mg tablet:

3 years for blisters.
4 years for bottles.

534 mg tablet:

2 years.

This medicinal product does not require any special storage conditions.

High-Density Polyethylene (HDPE) bottle with a child-resistant and tamper-evident screw cap

Pack sizes

267 mg film-coated tablets:

1 bottle containing 90 film-coated tablets
2 bottles each containing 90 film-coated tablets (180 film-coated tablets in total)

534 mg film-coated tablets:

1 bottle containing 21 film-coated tablets
1 bottle containing 90 film-coated tablets

801 mg film-coated tablets:

1 bottle containing 90 film-coated tablets

PVC/Aclar (PCTFE) aluminium foil blister

Pack sizes

267 mg film-coated tablets:

1 blister containing 21 film-coated tablets (21 in total)
2 blisters each containing 21 film-coated tablets (42 in total)
4 blisters each containing 21 film-coated tablets (84 in total)
8 blisters each containing 21 Film-coated tablets (168 in total)

2-week treatment initiation pack: multipack containing 63 (1 pack containing 1 blister of 21 and 1 pack containing 2 blisters of 21) film-coated tablets

Continuation pack: multipack containing 252 (3 packs each containing 4 blisters of 21) film-coated tablets

801 mg film-coated tablets:

4 blisters each containing 21 film-coated tablets (84 in total)

Continuation pack: multipack containing 252 (3 packs each containing 4 blisters of 21) film-coated tablets

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.