Esbriet

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each capsule contains 267 mg pirfenidone. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL form 
 
Hard capsule (capsule). 
 
Two piece capsules with a white to off-white opaque body and white to off-white opaque cap 
imprinted with “PFD 267 mg” in brown ink and containing a white to pale yellow powder. 
 
 
4. Clinical particulars 
 
4.1 Therapeutic indications 
 
Esbriet is indicated in adults for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF). 
 
4.2 Posology and method of administration 
 
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 nine capsules 
per day over a 14-day period as follows: 
 
● Days 1 to 7: one capsule, three times a day (801 mg/day)  
● Days 8 to 14: two capsules, three times a day (1602 mg/day)  
● Day 15 onward: three capsules, three times a day (2403 mg/day)  
 
The recommended maintenance daily dose of Esbriet is three 267 mg capsules 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 1-2 capsules (267 mg – 534 mg) two to three 
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 one to two weeks to allow symptoms to 
resolve.  



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Photosensitivity reaction or rash:  Patients who experience a mild to moderate photosensitivity 
reaction or rash should be reminded to use a sunblock daily and to avoid exposure to the sun (see 
section 4.4). The dose of pirfenidone may be reduced to 3 capsules/day (1 capsule 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 capsules 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). 
 
4.3 Contraindications 
 
● Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
● History of angioedema with pirfenidone (see section 4.4). 
● Concomitant use of fluvoxamine (see section 4.5). 
● Severe hepatic impairment or end stage liver disease (see sections 4.2 and 4.4). 
● Severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis (see 
 sections 4.2 and 5.2). 
 
4.4 Special warnings and precautions for use 
 
Hepatic function 
 
Elevations in ALT and AST >3 × upper limit of normal (ULN) have been reported in patients 
receiving therapy with Esbriet. Rarely these have been associated with concomitant elevations in total 
serum bilirubin. Liver function tests (ALT, AST and bilirubin) should be conducted prior to the 
initiation of treatment with Esbriet, and subsequently at monthly intervals for the first 6 months and 
then every 3 months thereafter (see section 4.8). In the event of significant elevation of liver 
aminotransferases the dose of Esbriet should be adjusted or treatment discontinued according to the 



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guidelines listed below. For patients with confirmed elevations in ALT, AST or bilirubin during 
treatment, the following dose adjustments may be necessary.  
 
Recommendations in case of ALT/AST elevations 
If a patient exhibits an aminotransferase elevation to >3 to ≤5 x ULN after starting Esbriet therapy, 
confounding medicinal products should be discontinued, other causes excluded, and the patient 
monitored closely. If clinically appropriate the dose of Esbriet should be reduced or interrupted. Once 
liver function tests are within normal limits Esbriet may be re-escalated to the recommended daily 
dose if tolerated.  
 
If a patient exhibits an aminotransferase elevation to ≤5 x ULN accompanied by symptoms or 
hyperbilirubinaemia, Esbriet should be discontinued and the patient should not be rechallenged. 
 
If a patient exhibits an aminotransferase elevation to >5 x ULN, Esbriet should be discontinued and 
the patient should not be rechallenged. 
 
Hepatic impairment 
In subjects with moderate hepatic impairment (i.e. Child-Pugh Class B), pirfenidone exposure was 
increased by 60%. Esbriet should be used with caution in patients with pre-existing mild to moderate 
hepatic impairment (i.e. Child-Pugh Class A and B) given the potential for increased pirfenidone 
exposure. Patients should be monitored closely for signs of toxicity especially if they are 
concomitantly taking a known CYP1A2 inhibitor (see sections 4.5 and 5.2). Esbriet has not been 
studied in individuals with severe hepatic impairment and Esbriet must not be used in patients with 
severe hepatic impairment (see section 4.3). 
 
Photosensitivity reaction and rash 
 
Exposure to direct sunlight (including sunlamps) should be avoided or minimised during treatment 
with Esbriet. Patients should be instructed to use a sunblock daily, to wear clothing that protects 
against sun exposure, and to avoid other medicinal products known to cause photosensitivity. Patients 
should be instructed to report symptoms of photosensitivity reaction or rash to their physician. Severe 
photosensitivity reactions are uncommon. Dose adjustments or temporary treatment discontinuation 
may be necessary in mild to severe cases of photosensitivity reaction or rash (see section 4.2). 
 
Angioedema/Anaphylaxis 
 
Reports of angioedema (some serious) such as swelling of the face, lips and/or tongue which may be 
associated with difficulty breathing or wheezing have been received in association with use of Esbriet 
in the post-marketing setting. Reports of anaphylactic reactions have also been received. Therefore, 
patients who develop signs or symptoms of angioedema or severe allergic reactions following 
administration of Esbriet should immediately discontinue treatment. Patients with angioedema or 
severe allergic reactions should be managed according to standard of care. Esbriet must not be used in 
patients with a history of angioedema or hypersensitivity due to Esbriet (see section 4.3). 
 
Dizziness 
 
Dizziness has been reported in patients taking Esbriet. Therefore, patients should know how they react 
to this medicinal product before they engage in activities requiring mental alertness or coordination 
(see section 4.7). In clinical studies, most patients who experienced dizziness had a single event, and 
most events resolved, with a median duration of 22 days. If dizziness does not improve or if it worsens 
in severity, dose adjustment or even discontinuation of Esbriet may be warranted. 
 
Fatigue 
 
Fatigue has been reported in patients taking Esbriet. Therefore, patients should know how they react to 
this medicinal product before they engage in activities requiring mental alertness or coordination (see 
section 4.7). 
 



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Weight loss 
 
Weight loss has been reported in patients treated with Esbriet (see section 4.8). Physicians should 
monitor patient’s weight, and when appropriate encourage increased caloric intake if weight loss is 
considered to be of clinical significance. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Approximately 70–80% of pirfenidone is metabolised via CYP1A2 with minor contributions from 
other CYP isoenzymes including CYP2C9, 2C19, 2D6, and 2E1.  
 
Consumption of grapefruit juice is associated with inhibition of CYP1A2 and should be avoided 
during treatment with pirfenidone.  
 
Fluvoxamine and inhibitors of CYP1A2 
 
In a Phase 1 study, the co-administration of Esbriet and fluvoxamine (a strong inhibitor of CYP1A2 
with inhibitory effects on other CYP isoenzymes [CYP2C9, 2C19, and 2D6]) resulted in a 4-fold 
increase in exposure to pirfenidone in non-smokers.  
 
Esbriet is contraindicated in patients with concomitant use of fluvoxamine (see section 4.3).  
Fluvoxamine should be discontinued prior to the initiation of Esbriet therapy and avoided during 
Esbriet therapy due to the reduced clearance of pirfenidone. Other therapies that are inhibitors of both 
CYP1A2 and one or more other CYP isoenzymes involved in the metabolism of pirfenidone 
(e.g. CYP2C9, 2C19, and 2D6) should be avoided during pirfenidone treatment. 
 
In vitro and in vivo extrapolations indicate that strong and selective inhibitors of CYP1A2 (e.g. 
enoxacin) have the potential to increase the exposure to pirfenidone by approximately 2 to 4-fold.  If 
concomitant use of Esbriet with a strong and selective inhibitor of CYP1A2 cannot be avoided, the 
dose of pirfenidone should be reduced to 801 mg daily (one capsule, three times a day). Patients 
should be closely monitored for emergence of adverse reactions associated with Esbriet therapy. 
Discontinue Esbriet if necessary (see sections 4.2 and 4.4). 
 
Co-administration of Esbriet and 750 mg of ciprofloxacin (a moderate inhibitor of CYP1A2) increased 
the exposure to pirfenidone by 81%. If ciprofloxacin at the dose of 750 mg two times a day cannot be 
avoided, the dose of pirfenidone should be reduced to 1602 mg daily (two capsules, three times a day). 
Esbriet should be used with caution when ciprofloxacin is used at a dose of 250 mg or 500 mg once or 
two times a day.  
 
Esbriet should be used with caution in patients treated with other moderate inhibitors of CYP1A2 (e.g. 
amiodarone, propafenone).  
 
Special care should also be exercised if CYP1A2 inhibitors are being used concomitantly with potent 
inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone such as 
CYP2C9 (e.g. amiodarone, fluconazole), 2C19 (e.g. chloramphenicol) and 2D6 (e.g. fluoxetine, 
paroxetine). 
 
Cigarette smoking and inducers of CYP1A2 
 
A Phase 1 interaction study evaluated the effect of cigarette smoking (CYP1A2 inducer) on the 
pharmacokinetics of pirfenidone. The exposure to pirfenidone in smokers was 50% of that observed in 
non-smokers. Smoking has the potential to induce hepatic enzyme production and thus increase 
medicinal product clearance and decrease exposure. Concomitant use of strong inducers of CYP1A2 
including smoking should be avoided during Esbriet therapy based on the observed relationship 
between cigarette smoking and its potential to induce CYP1A2. Patients should be encouraged to 
discontinue use of strong inducers of CYP1A2 and to stop smoking before and during treatment with 
pirfenidone.  
 
In the case of moderate inducers of CYP1A2 (e.g. omeprazole), concomitant use may theoretically 
result in a lowering of pirfenidone plasma levels. 



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Co-administration of medicinal products that act as potent inducers of both CYP1A2 and the other 
CYP isoenzymes involved in the metabolism of pirfenidone (e.g. rifampicin) may result in significant 
lowering of pirfenidone plasma levels. These medicinal products should be avoided whenever 
possible. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no data from the use of Esbriet 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 (≥1,000 mg/kg/day) rats exhibited prolongation of gestation and reduction in foetal 
viability.  
As a precautionary measure, it is preferable to avoid the use of Esbriet during pregnancy. 
 
Breast-feeding 
 
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 (see section 5.3). A 
risk to the breastfed infant cannot be excluded.   
 
A decision must be made whether to discontinue breast-feeding or to discontinue from Esbriet therapy, 
taking into account the benefit of breast-feeding for the child and the benefit of Esbriet therapy for the 
mother. 
 
Fertility 
 
No adverse effects on fertility were observed in preclinical studies (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Esbriet may cause dizziness and fatigue, which could have a moderate influence on the ability to drive 
or use machines, therefore patients should exercise caution when driving or operating machinery if 
they experience these symptoms. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most frequently reported adverse reactions during clinical study experience with Esbriet at a dose 
of 2,403 mg/day compared to placebo, respectively, were nausea (32.4% versus 12.2%), rash (26.2% 
versus 7.7%), diarrhoea (18.8% versus 14.4%), fatigue (18.5% versus 10.4%), dyspepsia (16.1% 
versus 5.0%), anorexia (11.4% versus 3.5%), headache (10.1% versus 7.7%), and photosensitivity 
reaction (9.3% versus 1.1%).  
 
Tabulated list of adverse reactions 
The safety of Esbriet has been evaluated in clinical studies including 1,650 volunteers and patients. 
More than 170 patients have been investigated in open studies for more than five years and some for 
up to 10 years. 
 
Table 1 shows the adverse reactions reported at a frequency of ≥2% in 623 patients receiving Esbriet 
at the recommended dose of 2,403 mg/day in three pooled pivotal Phase 3 studies. Adverse reactions 
from post-marketing experience are also listed in Table 1. Adverse reactions are listed by System 
Organ Class (SOC) and within each frequency grouping [Very common (≥1/10), common (≥1/100 to 
<1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), not known (cannot be 
estimated from the available data)] the adverse reactions are presented in order of decreasing 
seriousness. 



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Table 1 Adverse reactions by SOC and MedDRA frequency 
Infections and infestations 
Common Upper respiratory tract infection; urinary tract infection 
Blood and lymphatic system disorders 
Rare Agranulocytosis1 
Immune system disorders 
Uncommon Angioedema1 
Not known Anaphylaxis1 
Metabolism and nutrition disorders 
Very Common Anorexia 
Common Weight decreased; decreased appetite 
Psychiatric disorders 
Common Insomnia 
Nervous system disorders 
Very Common Headache 
Common Dizziness; somnolence; dysgeusia; lethargy 
Vascular disorders 
Common Hot flush 
Respiratory, thoracic and mediastinal disorders 
Common Dyspnoea; cough; productive cough 
Gastrointestinal disorders 
Very Common Dyspepsia; nausea; diarrhoea 
Common Gastroesophageal reflux disease; vomiting; abdominal distension; abdominal 

discomfort; abdominal pain; abdominal pain upper; stomach discomfort; 
gastritis; constipation; flatulence 

Hepatobiliary disorders 
Common ALT increased; AST increased; gamma glutamyl transferase increased 
Rare Total serum bilirubin increased in combination with increases of ALT and 

AST1 
Skin and subcutaneous tissue disorders 
Very Common Photosensitivity reaction; rash  
Common Pruritus; erythema; dry skin; rash erythematous; rash macular; rash pruritic 
Musculoskeletal and connective tissue disorders 
Common Myalgia; arthralgia  
General disorders and administration site conditions 
Very Common Fatigue 
Common Asthenia; non-cardiac chest pain 
Injury poisoning and procedural complications 
Common Sunburn 

1. Identified through post-marketing surveillance 
 



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Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, other immunosuppressants, ATC code:  L04AX05 
 
The mechanism of action of pirfenidone has not been fully established. However, existing data suggest 
that pirfenidone exerts both antifibrotic and anti-inflammatory properties in a variety of in vitro 
systems and animal models of pulmonary fibrosis (bleomycin- and transplant-induced fibrosis). 
 
IPF is a chronic fibrotic and inflammatory pulmonary disease affected by the synthesis and release of 
pro-inflammatory cytokines including tumour necrosis factor-alpha (TNF-α) and interleukin-1-beta 
(IL-1β) and pirfenidone has been shown to reduce the accumulation of inflammatory cells in response 
to various stimuli.  
 
Pirfenidone attenuates fibroblast proliferation, production of fibrosis-associated proteins and 
cytokines, and the increased biosynthesis and accumulation of extracellular matrix in response to 
cytokine growth factors such as, transforming growth factor-beta (TGF-β) and platelet-derived growth 
factor (PDGF). 
 
Clinical efficacy 
 
The clinical efficacy of Esbriet has been studied in four Phase 3, multicentre, randomised, 
double-blind, placebo-controlled studies in patients with IPF. Three of the Phase 3 studies (PIPF-004, 
PIPF-006, and PIPF-016) were multinational, and one (SP3) was conducted in Japan.  
 
PIPF-004 and PIPF-006 compared treatment with Esbriet 2403 mg/day to placebo. The studies were 
nearly identical in design, with few exceptions including an intermediate dose group (1,197 mg/day) in 
PIPF-004. In both studies, treatment was administered three times daily for a minimum of 72 weeks. 
The primary endpoint in both studies was the change from Baseline to Week 72 in percent predicted 
Forced Vital Capacity (FVC). 
 
In study PIPF-004, the decline of percent predicted FVC from Baseline at Week 72 of treatment was 
significantly reduced in patients receiving Esbriet (N=174) compared with patients receiving placebo 
(N=174; p=0.001, rank ANCOVA). Treatment with Esbriet also significantly reduced the decline of 
percent predicted FVC from Baseline at Weeks 24 (p=0.014), 36 (p<0.001), 48 (p<0.001), and 
60 (p<0.001). At Week 72, a decline from baseline in percent predicted FVC of ≥10% (a threshold 
indicative of the risk of mortality in IPF) was seen in 20% of patients receiving Esbriet compared to 
35% receiving placebo (Table 2).  
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


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Table 2 Categorical assessment of change from Baseline to Week 72 
in percent predicted FVC in study PIPF-004 

 

Pirfenidone  
2,403 mg/day 

(N = 174) 
Placebo 

(N = 174) 
Decline of ≥10% or death or lung transplant 35 (20%) 60 (34%) 
Decline of less than 10% 97 (56%) 90 (52%) 
No decline (FVC change >0%) 42 (24%) 24 (14%) 

 
Although there was no difference between patients receiving Esbriet compared to placebo in change 
from Baseline to Week 72 of distance walked during a six minute walk test (6MWT) by the 
prespecified rank ANCOVA, in an ad hoc analysis, 37% of patients receiving Esbriet showed a 
decline of ≥50 m in 6MWT distance, compared to 47% of patients receiving placebo in PIPF-004. 
 
In study PIPF-006, treatment with Esbriet (N=171) did not reduce the decline of percent predicted 
FVC from Baseline at Week 72 compared with placebo (N=173; p=0.501). However, treatment with 
Esbriet reduced the decline of percent predicted FVC from Baseline at Weeks 24 (p<0.001), 
36 (p=0.011), and 48 (p=0.005). At Week 72, a decline in FVC of ≥10% was seen in 23% of patients 
receiving Esbriet and 27% receiving placebo (Table 3).  
 

Table 3 Categorical assessment of change from Baseline to Week 72 
in percent predicted FVC in study PIPF-006 

 

Pirfenidone  
2,403 mg/day 

(N = 171) 
Placebo 

(N = 173) 
Decline of ≥10% or death or lung transplant 39 (23%) 46 (27%) 
Decline of less than 10% 88 (52%) 89 (51%) 
No decline (FVC change >0%) 44 (26%) 38 (22%) 

 
The decline in 6MWT distance from Baseline to Week 72 was significantly reduced compared with 
placebo in study PIPF-006 (p<0.001, rank ANCOVA). Additionally, in an ad hoc analysis, 33% of 
patients receiving Esbriet showed a decline of ≥50 m in 6MWT distance, compared to 47% of patients 
receiving placebo in PIPF-006. 
 
In a pooled analysis of survival in PIPF-004 and PIPF-006 the mortality rate with Esbriet 2403 mg/day 
group was 7.8% compared with 9.8% with placebo (HR 0.77 [95% CI, 0.47–1.28]).  
 
PIPF-016 compared treatment with Esbriet 2,403 mg/day to placebo. Treatment was administered 
three times daily for 52 weeks. The primary endpoint was the change from Baseline to Week 52 in 
percent predicted FVC. In a total of 555 patients, the median baseline percent predicted FVC and 
%DLCO were 68% (range: 48–91%) and 42% (range: 27–170%), respectively. Two percent of patients 
had percent predicted FVC below 50% and 21% of patients had a percent predicted DLCO below 35% 
at Baseline. 
 
In study PIPF-016, the decline of percent predicted FVC from Baseline at Week 52 of treatment was 
significantly reduced in patients receiving Esbriet (N=278) compared with patients receiving placebo 
(N=277; p<0.000001, rank ANCOVA). Treatment with Esbriet also significantly reduced the decline 
of percent predicted FVC from Baseline at Weeks 13 (p<0.000001), 26 (p<0.000001), and 39 
(p=0.000002). At Week 52, a decline from Baseline in percent predicted FVC of ≥10% or death was 
seen in 17% of patients receiving Esbriet compared to 32% receiving placebo (Table 4). 
 



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Table 4 Categorical assessment of change from Baseline to Week 52 
in percent predicted FVC in study PIPF-016 

 

Pirfenidone  
2,403 mg/day 

(N = 278) 
Placebo 

(N = 277) 
Decline of ≥10% or death 46 (17%) 88 (32%) 
Decline of less than 10% 169 (61%) 162 (58%) 
No decline (FVC change >0%) 63 (23%) 27 (10%) 

 
The decline in distance walked during a 6MWT from Baseline to Week 52 was significantly reduced 
in patients receiving Esbriet compared with patients receiving placebo in PIPF-016 (p=0.036, rank 
ANCOVA); 26% of patients receiving Esbriet showed a decline of ≥50 m in 6MWT distance 
compared to 36% of patients receiving placebo. 
 
In a pre-specified pooled analysis of studies PIPF-016, PIPF-004, and PIPF-006 at Month 12, all-cause 
mortality was significantly lower in Esbriet 2403 mg/day group (3.5%, 22 of 623 patients) compared 
with placebo (6.7%, 42 of 624 patients), resulting in a 48% reduction in the risk of all-cause mortality 
within the first 12 months (HR 0.52 [95% CI, 0.31–0.87], p=0.0107, log-rank test).  
 
The study (SP3) in Japanese patients compared pirfenidone 1800 mg/day (comparable to 2403 mg/day 
in the US and European populations of PIPF-004/006 on a weight-normalised basis) with placebo 
(N=110, N=109, respectively). Treatment with pirfenidone significantly reduced mean decline in vital 
capacity (VC) at Week 52 (the primary endpoint) compared with placebo (-0.09±0.02 l versus 
-0.16±0.02 l respectively, p=0.042). 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Esbriet in all subsets of the paediatric population in IPF (see section 4.2 for information on paediatric 
use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Administration of Esbriet capsules with food results in a large reduction in Cmax (by 50%) and a 
smaller effect on AUC, compared to the fasted state. Following oral administration of a single dose of 
801 mg to healthy older adult volunteers (50-66 years of age) in the fed state, the rate of pirfenidone 
absorption slowed, while the AUC in the fed state was approximately 80-85% of the AUC observed in 
the fasted state. Bioequivalence was demonstrated in the fasted state when comparing the 801 mg 
tablet to three 267 mg capsules. In the fed state, the 801 mg tablet met bioequivalence criteria based on 
the AUC measurements compared to the capsules, while the 90% confidence intervals for Cmax 
(108.26% - 125.60%) slightly exceeded the upper bound of standard bioequivalence limit (90% CI:  
80.00% - 125.00%). The effect of food on pirfenidone oral AUC was consistent between the tablet and 
capsule formulations. Compared to the fasted state, administration of either formulation with food 
reduced pirfenidone Cmax, with Esbriet tablet reducing the Cmax slightly less (by 40%) than Esbriet 
capsules (by 50%). A reduced incidence of adverse events (nausea and dizziness) was observed in fed 
subjects when compared to the fasted group. Therefore, it is recommended that Esbriet be 
administered with food to reduce the incidence of nausea and dizziness.  
 
The absolute bioavailability of pirfenidone has not been determined in humans. 
 
Distribution 
 
Pirfenidone binds to human plasma proteins, primarily to serum albumin. The overall mean binding 
ranged from 50% to 58% at concentrations observed in clinical studies (1 to 100 μg/ml). Mean 
apparent oral steady-state volume of distribution is approximately 70 l, indicating that pirfenidone 
distribution to tissues is modest. 



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Biotransformation 
 
Approximately 70–80% of pirfenidone is metabolised via CYP1A2 with minor contributions from 
other CYP isoenzymes including CYP2C9, 2C19, 2D6, and 2E1. In vitro data indicate some 
pharmacologically relevant activity of the major metabolite (5-carboxy-pirfenidone) at concentrations 
in excess of peak plasma concentrations in IPF patients. This may become clinically relevant in 
patients with moderate renal impairment where plasma exposure to 5-carboxy-pirfenidone is 
increased. 
 
Elimination 
 
The oral clearance of pirfenidone appears modestly saturable. In a multiple-dose, dose-ranging study 
in healthy older adults administered doses ranging from 267 mg to 1,335 mg three times a day, the 
mean clearance decreased by approximately 25% above a dose of 801 mg three times a day. Following 
single dose administration of pirfenidone in healthy older adults, the mean apparent terminal 
elimination half-life was approximately 2.4 hours. Approximately 80% of an orally administered dose 
of pirfenidone is cleared in the urine within 24 hours of dosing. The majority of pirfenidone is 
excreted as the 5-carboxy-pirfenidone metabolite (>95% of that recovered), with less than 1% of 
pirfenidone excreted unchanged in urine. 
 
Special populations 
 
Hepatic impairment 
The pharmacokinetics of pirfenidone and the 5-carboxy-pirfenidone metabolite were compared in 
subjects with moderate hepatic impairment (Child-Pugh Class B) and in subjects with normal hepatic 
function. Results showed that there was a mean increase of 60% in pirfenidone exposure after a single 
dose of 801 mg pirfenidone (3 x 267 mg capsule) in patients with moderate hepatic impairment. 
Pirfenidone should be used with caution in patients with mild to moderate hepatic impairment and 
patients should be monitored closely for signs of toxicity especially if they are concomitantly taking a 
known CYP1A2 inhibitor (see sections 4.2 and 4.4). Esbriet is contraindicated in severe hepatic 
impairment and end stage liver disease (see sections 4.2 and 4.3). 
 
Renal impairment 
 
No clinically relevant differences in the pharmacokinetics of pirfenidone were observed in subjects 
with mild to severe renal impairment compared with subjects with normal renal function. The parent 
substance is predominantly metabolised to 5-carboxy-pirfenidone.  The mean (SD) AUC0-∞ of 5-
carboxy-pirfenidone was significantly higher in the moderate (p = 0.009) and severe (p < 0.0001) renal 
impairment groups than in the group with normal renal function. ; 100 (26.3) mg•h/L and 168 (67.4) 
mg•h/L compared to 28.7 (4.99) mg•h/L respectively. 
 

Renal 
Impairment 

Group 

 
Statistics 

AUC0-∞ (mg•hr/L) 

Pirfenidone 5-Carboxy-Pirfenidone 

Normal Mean (SD) 42.6 (17.9) 28.7 (4.99) 
n = 6 Median (25th–75th) 42.0 (33.1–55.6) 30.8 (24.1–32.1) 
Mild Mean (SD) 59.1 (21.5) 49.3

a 
(14.6) 

n = 6 Median (25th–75th) 51.6 (43.7–80.3) 43.0 (38.8–56.8) 
Moderate Mean (SD) 63.5 (19.5) 100

b 
(26.3) 

n = 6 Median (25th–75th) 66.7 (47.7–76.7) 96.3 (75.2–123) 
Severe Mean (SD) 46.7 (10.9) 168

c 
(67.4) 

n = 6 Median (25th–75th) 49.4 (40.7–55.8) 150 (123–248) 
 
AUC0-∞  = area under the concentration-time curve from time zero to infinity. 
a p-value versus Normal = 1.00 (pair-wise comparison with Bonferroni) 
b p-value versus Normal = 0.009 (pair-wise comparison with Bonferroni) 
c p-value versus Normal < 0.0001 (pair-wise comparison with Bonferroni)  



12 

 
Exposure to 5-carboxy-pirfenidone increases 3.5 fold or more in patients with moderate renal 
impairment. Clinically relevant pharmacodynamic activity of the metabolite in patients with moderate 
renal impairment cannot be excluded. No dose adjustment is required in patients with mild renal 
impairment who are receiving pirfenidone.  Pirfenidone should be used with caution in patients with 
moderate renal impairment.  The use of pirfenidone is contraindicated in patients with severe renal 
impairment (CrCl <30ml/min) or end stage renal disease requiring dialysis (see sections 4.2 and 4.3). 
 
Population pharmacokinetic analyses from 4 studies in healthy subjects or subjects with renal 
impairment and one study in patients with IPF showed no clinically relevant effect of age, gender or 
body size on the pharmacokinetics of pirfenidone.  
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. 
 
In repeated dose toxicity studies increases in liver weight were observed in mice, rats and dogs; this 
was often accompanied by hepatic centrilobular hypertrophy. Reversibility was observed after 
cessation of treatment. An increased incidence of liver tumours was observed in carcinogenicity 
studies conducted in rats and mice. These hepatic findings are consistent with an induction of hepatic 
microsomal enzymes, an effect which has not been observed in patients receiving Esbriet. These 
findings are not considered relevant to humans.  
 
A statistically significant increase in uterine tumours was observed in female rats administered 
1,500 mg/kg/day, 37 times the human dose of 2,403 mg/day. The results of mechanistic studies 
indicate that the occurrence of uterine tumours is probably related to a chronic dopamine-mediated sex 
hormone imbalance involving a species specific endocrine mechanism in the rat which is not present 
in humans. 
 
Reproductive toxicology studies demonstrated no adverse effects on male and female fertility or 
postnatal development of offspring in rats and there was no evidence of teratogenicity in rats 
(1,000 mg/kg/day) or rabbits (300 mg/kg/day). 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 (≥450 mg/kg/day) rats exhibited a prolongation of oestrous cycle and a 
high incidence of irregular cycles. At high doses (≥1,000 mg/kg/day) rats exhibited a prolongation of 
gestation and reduction in fetal viability. Studies in lactating rats indicate that pirfenidone and/or its 
metabolites are excreted in milk with the potential for accumulation of pirfenidone and/or its 
metabolites in milk. 
 
Pirfenidone showed no indication of mutagenic or genotoxic activity in a standard battery of tests and 
when tested under UV exposure was not mutagenic. When tested under UV exposure pirfenidone was 
positive in a photoclastogenic assay in Chinese hamster lung cells. 
 
Phototoxicity and irritation were noted in guinea pigs after oral administration of pirfenidone and with 
exposure to UVA/UVB light. The severity of phototoxic lesions was minimised by application of 
sunscreen.   
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule content 
 
Microcrystalline cellulose  
Croscarmellose sodium 
Povidone  
Magnesium stearate 
 



13 

Capsule shell 
 
Titanium dioxide (E171) 
Gelatin 
 
Printing Inks 
 
Brown S-1-16530 or 03A2 inks containing:  
Shellac  
Iron oxide black (E172) 
Iron oxide red (E172) 
Iron oxide yellow (E172) 
Propylene glycol 
Ammonium hydroxide 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years for blisters. 
3 years for bottles. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container  
 
Pack sizes 
 
2-week treatment initiation pack 
7 x PVC/PE/PCTFE aluminium foil blister strips, each containing 3 capsules (for the Week 1 dosing), 
packaged together with 7 x PVC/PE/PCTFE aluminium foil blister strips, each  containing 6 capsules 
(for the Week 2 dosing).  Each pack contains a total of 63 capsules. 
 
4-week treatment maintenance pack 
14 x PVC/PE/PCTFE aluminium foil blister strips each containing 18 capsules (2-day supply). There 
are 14 x 18 capsules in PVC/PE/PCTFE aluminium foil perforated blister strips for a total of 
252 capsules per pack. 
 
250 ml white HDPE bottle with child-resistant closure containing 270 capsules. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 



14 

8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/001 
EU/1/11/667/002 
EU/1/11/667/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 February 2011 
Date of latest renewal: 08 September 2015 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


15 

 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
Esbriet 534 mg film-coated tablets 
Esbriet 801 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 267 mg pirfenidone. 
Each film-coated tablet contains 534 mg pirfenidone. 
Each film-coated tablet contains 801 mg pirfenidone. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Esbriet 267 mg film-coated tablets are yellow, oval, approximately 1.3 x 0.6. cm biconvex film-coated 
tablets, debossed with “PFD”.  
Esbriet 534 mg film-coated tablets are orange, oval, approximately 1.6 x 0.8 cm biconvex film-coated 
tablets, debossed with “PFD”.  
Esbriet 801 mg film-coated tablets are brown, oval, approximately 2 x 0.9 cm biconvex film-coated 
tablets, debossed with “PFD”.  
 
 
4. Clinical particulars 
 
4.1 Therapeutic indications 
 
Esbriet is indicated in adults for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF). 
 
4.2 Posology and method of administration 
 
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. 



16 

 
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). 
 
4.3 Contraindications 
 
● Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
● History of angioedema with pirfenidone (see section 4.4). 
● Concomitant use of fluvoxamine (see section 4.5). 
● Severe hepatic impairment or end stage liver disease (see sections 4.2 and 4.4). 
● Severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis (see 
 sections 4.2 and 5.2). 
 



17 

4.4 Special warnings and precautions for use 
 
Hepatic function 
 
Elevations in ALT and AST >3 × upper limit of normal (ULN) have been reported in patients 
receiving therapy with Esbriet. Rarely these have been associated with concomitant elevations in total 
serum bilirubin. Liver function tests (ALT, AST and bilirubin) should be conducted prior to the 
initiation of treatment with Esbriet, and subsequently at monthly intervals for the first 6 months and 
then every 3 months thereafter (see section 4.8). In the event of significant elevation of liver 
aminotransferases the dose of Esbriet should be adjusted or treatment discontinued according to the 
guidelines listed below. For patients with confirmed elevations in ALT, AST or bilirubin during 
treatment, the following dose adjustments may be necessary.  
 
Recommendations in case of ALT/AST elevations 
If a patient exhibits an aminotransferase elevation to >3 to ≤5 x ULN after starting Esbriet therapy, 
confounding medicinal products should be discontinued, other causes excluded, and the patient 
monitored closely. If clinically appropriate the dose of Esbriet should be reduced or interrupted. Once 
liver function tests are within normal limits Esbriet may be re-escalated to the recommended daily 
dose if tolerated.  
 
If a patient exhibits an aminotransferase elevation to ≤5 x ULN accompanied by symptoms or 
hyperbilirubinaemia, Esbriet should be discontinued and the patient should not be rechallenged. 
 
If a patient exhibits an aminotransferase elevation to >5 x ULN, Esbriet should be discontinued and 
the patient should not be rechallenged. 
 
Hepatic impairment 
In subjects with moderate hepatic impairment (i.e. Child-Pugh Class B), pirfenidone exposure was 
increased by 60%. Esbriet should be used with caution in patients with pre-existing mild to moderate 
hepatic impairment (i.e. Child-Pugh Class A and B) given the potential for increased pirfenidone 
exposure. Patients should be monitored closely for signs of toxicity especially if they are 
concomitantly taking a known CYP1A2 inhibitor (see sections 4.5 and 5.2). Esbriet has not been 
studied in individuals with severe hepatic impairment and Esbriet must not be used in patients with 
severe hepatic impairment (see section 4.3). 
 
Photosensitivity reaction and rash 
 
Exposure to direct sunlight (including sunlamps) should be avoided or minimised during treatment 
with Esbriet. Patients should be instructed to use a sunblock daily, to wear clothing that protects 
against sun exposure, and to avoid other medicinal products known to cause photosensitivity. Patients 
should be instructed to report symptoms of photosensitivity reaction or rash to their physician. Severe 
photosensitivity reactions are uncommon. Dose adjustments or temporary treatment discontinuation 
may be necessary in mild to severe cases of photosensitivity reaction or rash (see section 4.2). 
 
Angioedema/Anaphylaxis 
 
Reports of angioedema (some serious) such as swelling of the face, lips and/or tongue which may be 
associated with difficulty breathing or wheezing have been received in association with use of Esbriet 
in the post-marketing setting. Reports of anaphylactic reactions have also been received. Therefore, 
patients who develop signs or symptoms of angioedema or severe allergic reactions following 
administration of Esbriet should immediately discontinue treatment. Patients with angioedema or 
severe allergic reactions should be managed according to standard of care. Esbriet must not be used in 
patients with a history of angioedema or hypersensitivity due to Esbriet (see section 4.3). 
 
Dizziness 
 
Dizziness has been reported in patients taking Esbriet. Therefore, patients should know how they react 
to this medicinal product before they engage in activities requiring mental alertness or coordination 
(see section 4.7). In clinical studies, most patients who experienced dizziness had a single event, and 



18 

most events resolved, with a median duration of 22 days. If dizziness does not improve or if it worsens 
in severity, dose adjustment or even discontinuation of Esbriet may be warranted. 
 
Fatigue 
 
Fatigue has been reported in patients taking Esbriet. Therefore, patients should know how they react to 
this medicinal product before they engage in activities requiring mental alertness or coordination (see 
section 4.7). 
 
Weight loss 
 
Weight loss has been reported in patients treated with Esbriet (see section 4.8). Physicians should 
monitor patient’s weight, and when appropriate encourage increased caloric intake if weight loss is 
considered to be of clinical significance. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Approximately 70–80% of pirfenidone is metabolised via CYP1A2 with minor contributions from 
other CYP isoenzymes including CYP2C9, 2C19, 2D6, and 2E1.  
 
Consumption of grapefruit juice is associated with inhibition of CYP1A2 and should be avoided 
during treatment with pirfenidone.  
 
Fluvoxamine and inhibitors of CYP1A2 
 
In a Phase 1 study, the co-administration of Esbriet and fluvoxamine (a strong inhibitor of CYP1A2 
with inhibitory effects on other CYP isoenzymes [CYP2C9, 2C19, and 2D6]) resulted in a 4-fold 
increase in exposure to pirfenidone in non-smokers.  
 
Esbriet is contraindicated in patients with concomitant use of fluvoxamine (see section 4.3).  
Fluvoxamine should be discontinued prior to the initiation of Esbriet therapy and avoided during 
Esbriet therapy due to the reduced clearance of pirfenidone. Other therapies that are inhibitors of both 
CYP1A2 and one or more other CYP isoenzymes involved in the metabolism of pirfenidone 
(e.g. CYP2C9, 2C19, and 2D6) should be avoided during pirfenidone treatment. 
 
In vitro and in vivo extrapolations indicate that strong and selective inhibitors of CYP1A2 (e.g. 
enoxacin) have the potential to increase the exposure to pirfenidone by approximately 2 to 4-fold.  If 
concomitant use of Esbriet with a strong and selective inhibitor of CYP1A2 cannot be avoided, the 
dose of pirfenidone should be reduced to 801 mg daily (267 mg, three times a day). Patients should be 
closely monitored for emergence of adverse reactions associated with Esbriet therapy. Discontinue 
Esbriet if necessary (see sections 4.2 and 4.4). 
 
Co-administration of Esbriet and 750 mg of ciprofloxacin (a moderate inhibitor of CYP1A2) increased 
the exposure to pirfenidone by 81%. If ciprofloxacin at the dose of 750 mg two times a day cannot be 
avoided, the dose of pirfenidone should be reduced to 1602 mg daily (534 mg, three times a day). 
Esbriet should be used with caution when ciprofloxacin is used at a dose of 250 mg or 500 mg once or 
two times a day.  
 
Esbriet should be used with caution in patients treated with other moderate inhibitors of CYP1A2 (e.g. 
amiodarone, propafenone).  
 
Special care should also be exercised if CYP1A2 inhibitors are being used concomitantly with potent 
inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone such as 
CYP2C9 (e.g. amiodarone, fluconazole), 2C19 (e.g. chloramphenicol) and 2D6 (e.g. fluoxetine, 
paroxetine). 
 
Cigarette smoking and inducers of CYP1A2 
 
A Phase 1 interaction study evaluated the effect of cigarette smoking (CYP1A2 inducer) on the 
pharmacokinetics of pirfenidone. The exposure to pirfenidone in smokers was 50% of that observed in 



19 

non-smokers. Smoking has the potential to induce hepatic enzyme production and thus increase 
medicinal product clearance and decrease exposure. Concomitant use of strong inducers of CYP1A2 
including smoking should be avoided during Esbriet therapy based on the observed relationship 
between cigarette smoking and its potential to induce CYP1A2. Patients should be encouraged to 
discontinue use of strong inducers of CYP1A2 and to stop smoking before and during treatment with 
pirfenidone.  
 
In the case of moderate inducers of CYP1A2 (e.g. omeprazole), concomitant use may theoretically 
result in a lowering of pirfenidone plasma levels. 
 
Co-administration of medicinal products that act as potent inducers of both CYP1A2 and the other 
CYP isoenzymes involved in the metabolism of pirfenidone (e.g. rifampicin) may result in significant 
lowering of pirfenidone plasma levels. These medicinal products should be avoided whenever 
possible. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no data from the use of Esbriet 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 (≥1,000 mg/kg/day) rats exhibited prolongation of gestation and reduction in foetal 
viability.  
As a precautionary measure, it is preferable to avoid the use of Esbriet during pregnancy. 
 
Breast-feeding 
 
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 (see section 5.3). A 
risk to the breastfed infant cannot be excluded.   
 
A decision must be made whether to discontinue breast-feeding or to discontinue from Esbriet therapy, 
taking into account the benefit of breast-feeding for the child and the benefit of Esbriet therapy for the 
mother. 
 
Fertility 
 
No adverse effects on fertility were observed in preclinical studies (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Esbriet may cause dizziness and fatigue, which could have a moderate influence on the ability to drive 
or use machines, therefore patients should exercise caution when driving or operating machinery if 
they experience these symptoms.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most frequently reported adverse reactions during clinical study experience with Esbriet at a dose 
of 2,403 mg/day compared to placebo, respectively, were nausea (32.4% versus 12.2%), rash (26.2% 
versus 7.7%), diarrhoea (18.8% versus 14.4%), fatigue (18.5% versus 10.4%), dyspepsia (16.1% 
versus 5.0%), anorexia (11.4% versus 3.5%), headache (10.1% versus 7.7%), and photosensitivity 
reaction (9.3% versus 1.1%).  
 



20 

Tabulated list of adverse reactions 
The safety of Esbriet has been evaluated in clinical studies including 1,650 volunteers and patients. 
More than 170 patients have been investigated in open studies for more than five years and some for 
up to 10 years. 
 
Table 1 shows the adverse reactions reported at a frequency of ≥2% in 623 patients receiving Esbriet 
at the recommended dose of 2,403 mg/day in three pooled pivotal Phase 3 studies. Adverse reactions 
from post-marketing experience are also listed in Table 1. Adverse reactions are listed by System 
Organ Class (SOC) and within each frequency grouping [Very common (≥1/10), common (≥1/100 to 
<1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), not known (cannot be 
estimated from the available data)] the adverse reactions are presented in order of decreasing 
seriousness. 
 

Table 1 Adverse reactions by SOC and MedDRA frequency 
Infections and infestations 
Common Upper respiratory tract infection; urinary tract infection 
Blood and lymphatic system disorders 
Rare Agranulocytosis1 
Immune system disorders 
Uncommon Angioedema1 
Not known Anaphylaxis1 
Metabolism and nutrition disorders 
Very Common Anorexia 
Common Weight decreased; decreased appetite 
Psychiatric disorders 
Common Insomnia 
Nervous system disorders 
Very Common Headache 
Common Dizziness; somnolence; dysgeusia; lethargy 
Vascular disorders 
Common Hot flush 
Respiratory, thoracic and mediastinal disorders 
Common Dyspnoea; cough; productive cough 
Gastrointestinal disorders 
Very Common Dyspepsia; nausea; diarrhoea 
Common Gastroesophageal reflux disease; vomiting; abdominal distension; abdominal 

discomfort; abdominal pain; abdominal pain upper; stomach discomfort; 
gastritis; constipation; flatulence 

Hepatobiliary disorders 
Common ALT increased; AST increased; gamma glutamyl transferase increased 
Rare Total serum bilirubin increased in combination with increases of ALT and 

AST1 
Skin and subcutaneous tissue disorders 
Very Common Photosensitivity reaction; rash  
Common Pruritus; erythema; dry skin; rash erythematous; rash macular; rash pruritic 
Musculoskeletal and connective tissue disorders 
Common Myalgia; arthralgia  



21 

Table 1 Adverse reactions by SOC and MedDRA frequency 
General disorders and administration site conditions 
Very Common Fatigue 
Common Asthenia; non-cardiac chest pain 
Injury poisoning and procedural complications 
Common Sunburn 

1. Identified through post-marketing surveillance 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, other immunosuppressants, ATC code:  L04AX05 
 
The mechanism of action of pirfenidone has not been fully established. However, existing data suggest 
that pirfenidone exerts both antifibrotic and anti-inflammatory properties in a variety of in vitro 
systems and animal models of pulmonary fibrosis (bleomycin- and transplant-induced fibrosis). 
 
IPF is a chronic fibrotic and inflammatory pulmonary disease affected by the synthesis and release of 
pro-inflammatory cytokines including tumour necrosis factor-alpha (TNF-α) and interleukin-1-beta 
(IL-1β) and pirfenidone has been shown to reduce the accumulation of inflammatory cells in response 
to various stimuli.  
 
Pirfenidone attenuates fibroblast proliferation, production of fibrosis-associated proteins and 
cytokines, and the increased biosynthesis and accumulation of extracellular matrix in response to 
cytokine growth factors such as, transforming growth factor-beta (TGF-β) and platelet-derived growth 
factor (PDGF). 
 
Clinical efficacy 
 
The clinical efficacy of Esbriet has been studied in four Phase 3, multicentre, randomised, 
double-blind, placebo-controlled studies in patients with IPF. Three of the Phase 3 studies (PIPF-004, 
PIPF-006, and PIPF-016) were multinational, and one (SP3) was conducted in Japan.  
 
PIPF-004 and PIPF-006 compared treatment with Esbriet 2403 mg/day to placebo. The studies were 
nearly identical in design, with few exceptions including an intermediate dose group (1,197 mg/day) in 
PIPF-004. In both studies, treatment was administered three times daily for a minimum of 72 weeks. 
The primary endpoint in both studies was the change from Baseline to Week 72 in percent predicted 
Forced Vital Capacity (FVC). 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


22 

In study PIPF-004, the decline of percent predicted FVC from Baseline at Week 72 of treatment was 
significantly reduced in patients receiving Esbriet (N=174) compared with patients receiving placebo 
(N=174; p=0.001, rank ANCOVA). Treatment with Esbriet also significantly reduced the decline of 
percent predicted FVC from Baseline at Weeks 24 (p=0.014), 36 (p<0.001), 48 (p<0.001), and 
60 (p<0.001). At Week 72, a decline from baseline in percent predicted FVC of ≥10% (a threshold 
indicative of the risk of mortality in IPF) was seen in 20% of patients receiving Esbriet compared to 
35% receiving placebo (Table 2).  
 

Table 2 Categorical assessment of change from Baseline to Week 72 
in percent predicted FVC in study PIPF-004 

 

Pirfenidone  
2,403 mg/day 

(N = 174) 
Placebo 

(N = 174) 
Decline of ≥10% or death or lung transplant 35 (20%) 60 (34%) 
Decline of less than 10% 97 (56%) 90 (52%) 
No decline (FVC change >0%) 42 (24%) 24 (14%) 

 
Although there was no difference between patients receiving Esbriet compared to placebo in change 
from Baseline to Week 72 of distance walked during a six minute walk test (6MWT) by the 
prespecified rank ANCOVA, in an ad hoc analysis, 37% of patients receiving Esbriet showed a 
decline of ≥50 m in 6MWT distance, compared to 47% of patients receiving placebo in PIPF-004. 
 
In study PIPF-006, treatment with Esbriet (N=171) did not reduce the decline of percent predicted 
FVC from Baseline at Week 72 compared with placebo (N=173; p=0.501). However, treatment with 
Esbriet reduced the decline of percent predicted FVC from Baseline at Weeks 24 (p<0.001), 
36 (p=0.011), and 48 (p=0.005). At Week 72, a decline in FVC of ≥10% was seen in 23% of patients 
receiving Esbriet and 27% receiving placebo (Table 3).  
 

Table 3 Categorical assessment of change from Baseline to Week 72 
in percent predicted FVC in study PIPF-006 

 

Pirfenidone  
2,403 mg/day 

(N = 171) 
Placebo 

(N = 173) 
Decline of ≥10% or death or lung transplant 39 (23%) 46 (27%) 
Decline of less than 10% 88 (52%) 89 (51%) 
No decline (FVC change >0%) 44 (26%) 38 (22%) 

 
The decline in 6MWT distance from Baseline to Week 72 was significantly reduced compared with 
placebo in study PIPF-006 (p<0.001, rank ANCOVA). Additionally, in an ad hoc analysis, 33% of 
patients receiving Esbriet showed a decline of ≥50 m in 6MWT distance, compared to 47% of patients 
receiving placebo in PIPF-006. 
 
In a pooled analysis of survival in PIPF-004 and PIPF-006 the mortality rate with Esbriet 2403 mg/day 
group was 7.8% compared with 9.8% with placebo (HR 0.77 [95% CI, 0.47–1.28]).  
 
PIPF-016 compared treatment with Esbriet 2,403 mg/day to placebo. Treatment was administered 
three times daily for 52 weeks. The primary endpoint was the change from Baseline to Week 52 in 
percent predicted FVC. In a total of 555 patients, the median baseline percent predicted FVC and 
%DLCO were 68% (range: 48–91%) and 42% (range: 27–170%), respectively. Two percent of patients 
had percent predicted FVC below 50% and 21% of patients had a percent predicted DLCO below 35% 
at Baseline. 
 
In study PIPF-016, the decline of percent predicted FVC from Baseline at Week 52 of treatment was 
significantly reduced in patients receiving Esbriet (N=278) compared with patients receiving placebo 
(N=277; p<0.000001, rank ANCOVA). Treatment with Esbriet also significantly reduced the decline 
of percent predicted FVC from Baseline at Weeks 13 (p<0.000001), 26 (p<0.000001), and 39 



23 

(p=0.000002). At Week 52, a decline from Baseline in percent predicted FVC of ≥10% or death was 
seen in 17% of patients receiving Esbriet compared to 32% receiving placebo (Table 4). 
 

Table 4 Categorical assessment of change from Baseline to Week 52 
in percent predicted FVC in study PIPF-016 

 

Pirfenidone  
2,403 mg/day 

(N = 278) 
Placebo 

(N = 277) 
Decline of ≥10% or death 46 (17%) 88 (32%) 
Decline of less than 10% 169 (61%) 162 (58%) 
No decline (FVC change >0%) 63 (23%) 27 (10%) 

 
The decline in distance walked during a 6MWT from Baseline to Week 52 was significantly reduced 
in patients receiving Esbriet compared with patients receiving placebo in PIPF-016 (p=0.036, rank 
ANCOVA); 26% of patients receiving Esbriet showed a decline of ≥50 m in 6MWT distance 
compared to 36% of patients receiving placebo. 
 
In a pre-specified pooled analysis of studies PIPF-016, PIPF-004, and PIPF-006 at Month 12, all-cause 
mortality was significantly lower in Esbriet 2403 mg/day group (3.5%, 22 of 623 patients) compared 
with placebo (6.7%, 42 of 624 patients), resulting in a 48% reduction in the risk of all-cause mortality 
within the first 12 months (HR 0.52 [95% CI, 0.31–0.87], p=0.0107, log-rank test).  
 
The study (SP3) in Japanese patients compared pirfenidone 1800 mg/day (comparable to 2403 mg/day 
in the US and European populations of PIPF-004/006 on a weight-normalised basis) with placebo 
(N=110, N=109, respectively). Treatment with pirfenidone significantly reduced mean decline in vital 
capacity (VC) at Week 52 (the primary endpoint) compared with placebo (-0.09±0.02 l versus 
-0.16±0.02 l respectively, p=0.042). 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Esbriet in all subsets of the paediatric population in IPF (see section 4.2 for information on paediatric 
use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Administration of Esbriet capsules with food results in a large reduction in Cmax (by 50%) and a 
smaller effect on AUC, compared to the fasted state. Following oral administration of a single dose of 
801 mg to healthy older adult volunteers (50-66 years of age) in the fed state, the rate of pirfenidone 
absorption slowed, while the AUC in the fed state was approximately 80-85% of the AUC observed in 
the fasted state. Bioequivalence was demonstrated in the fasted state when comparing the 801 mg 
tablet to three 267 mg capsules. In the fed state, the 801 mg tablet met bioequivalence criteria based on 
the AUC measurements compared to the capsules, while the 90% confidence intervals for Cmax 
(108.26% - 125.60%) slightly exceeded the upper bound of standard bioequivalence limit (90% CI:  
80.00% - 125.00%). The effect of food on pirfenidone oral AUC was consistent between the tablet and 
capsule formulations. Compared to the fasted state, administration of either formulation with food 
reduced pirfenidone Cmax, with Esbriet tablet reducing the Cmax slightly less (by 40%) than Esbriet 
capsules (by 50%). A reduced incidence of adverse events (nausea and dizziness) was observed in fed 
subjects when compared to the fasted group. Therefore, it is recommended that Esbriet be 
administered with food to reduce the incidence of nausea and dizziness.  
 
The absolute bioavailability of pirfenidone has not been determined in humans. 
 



24 

Distribution 
 
Pirfenidone binds to human plasma proteins, primarily to serum albumin. The overall mean binding 
ranged from 50% to 58% at concentrations observed in clinical studies (1 to 100 μg/ml). Mean 
apparent oral steady-state volume of distribution is approximately 70 l, indicating that pirfenidone 
distribution to tissues is modest. 
 
Biotransformation 
 
Approximately 70–80% of pirfenidone is metabolised via CYP1A2 with minor contributions from 
other CYP isoenzymes including CYP2C9, 2C19, 2D6, and 2E1. In vitro data  indicate some 
pharmacologically relevant activity of the major metabolite (5-carboxy-pirfenidone) at concentrations  
in excess of peak plasma concentrations in IPF patients. This may become clinically relevant in 
patients with moderate renal impairment where plasma exposure to 5-carboxy-pirfenidone is increased  
 
Elimination  
 
The oral clearance of pirfenidone appears modestly saturable. In a multiple-dose, dose-ranging study 
in healthy older adults administered doses ranging from 267 mg to 1,335 mg three times a day, the 
mean clearance decreased by approximately 25% above a dose of 801 mg three times a day. Following 
single dose administration of pirfenidone in healthy older adults, the mean apparent terminal 
elimination half-life was approximately 2.4 hours. Approximately 80% of an orally administered dose 
of pirfenidone is cleared in the urine within 24 hours of dosing. The majority of pirfenidone is 
excreted as the 5-carboxy-pirfenidone metabolite (>95% of that recovered), with less than 1% of 
pirfenidone excreted unchanged in urine. 
 
Special populations 
 
Hepatic impairment 
The pharmacokinetics of pirfenidone and the 5-carboxy-pirfenidone metabolite were compared in 
subjects with moderate hepatic impairment (Child-Pugh Class B) and in subjects with normal hepatic 
function. Results showed that there was a mean increase of 60% in pirfenidone exposure after a single 
dose of 801 mg pirfenidone (3 x 267 mg capsule) in patients with moderate hepatic impairment. 
Pirfenidone should be used with caution in patients with mild to moderate hepatic impairment and 
patients should be monitored closely for signs of toxicity especially if they are concomitantly taking a 
known CYP1A2 inhibitor (see sections 4.2 and 4.4). Esbriet is contraindicated in severe hepatic 
impairment and end stage liver disease (see sections 4.2 and 4.3). 
 
Renal impairment 
 
No clinically relevant differences in the pharmacokinetics of pirfenidone were observed in subjects 
with mild to severe renal impairment compared with subjects with normal renal function. The parent 
substance is predominantly metabolised to 5-carboxy-pirfenidone.  The mean (SD) AUC0-∞ of 5-
carboxy-pirfenidone was significantly higher in the moderate (p = 0.009) and severe (p < 0.0001) renal 
impairment groups than in the group with normal renal function; 100 (26.3) mg•h/L and 168 (67.4) 
mg•h/L compared to 28.7 (4.99) mg•h/L respectively.  
 



25 

Renal 
Impairment 

Group 

 
Statistics 

AUC0-∞ (mg•hr/L) 

Pirfenidone 5-Carboxy-Pirfenidone 

Normal Mean (SD) 42.6 (17.9) 28.7 (4.99) 
n = 6 Median (25th–75th) 42.0 (33.1–55.6) 30.8 (24.1–32.1) 
Mild Mean (SD) 59.1 (21.5) 49.3

a 
(14.6) 

n = 6 Median (25th–75th) 51.6 (43.7–80.3) 43.0 (38.8–56.8) 
Moderate Mean (SD) 63.5 (19.5) 100

b 
(26.3) 

n = 6 Median (25th–75th) 66.7 (47.7–76.7) 96.3 (75.2–123) 
Severe Mean (SD) 46.7 (10.9) 168

c 
(67.4) 

n = 6 Median (25th–75th) 49.4 (40.7–55.8) 150 (123–248) 
 
AUC0-∞  = area under the concentration-time curve from time zero to infinity. 
a p-value versus Normal = 1.00 (pair-wise comparison with Bonferroni) 
b p-value versus Normal = 0.009 (pair-wise comparison with Bonferroni) 
c p-value versus Normal < 0.0001 (pair-wise comparison with Bonferroni)  
 
Exposure to 5-carboxy-pirfenidone increases 3.5 fold or more in patients with moderate renal 
impairment. Clinically relevant pharmacodynamic activity of the metabolite in patients with moderate 
renal impairment cannot be excluded. No dose adjustment is required in patients with mild renal 
impairment who are receiving pirfenidone.  Pirfenidone should be used with caution in patients with 
moderate renal impairment.  The use of pirfenidone is contraindicated in patients with severe renal 
impairment (CrCl <30ml/min) or end stage renal disease requiring dialysis (see sections 4.2 and 4.3). 
 
Population pharmacokinetic analyses from 4 studies in healthy subjects or subjects with renal 
impairment and one study in patients with IPF showed no clinically relevant effect of age, gender or 
body size on the pharmacokinetics of pirfenidone.  
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. 
 
In repeated dose toxicity studies increases in liver weight were observed in mice, rats and dogs; this 
was often accompanied by hepatic centrilobular hypertrophy. Reversibility was observed after 
cessation of treatment. An increased incidence of liver tumours was observed in carcinogenicity 
studies conducted in rats and mice. These hepatic findings are consistent with an induction of hepatic 
microsomal enzymes, an effect which has not been observed in patients receiving Esbriet. These 
findings are not considered relevant to humans.  
 
A statistically significant increase in uterine tumours was observed in female rats administered 
1,500 mg/kg/day, 37 times the human dose of 2,403 mg/day. The results of mechanistic studies 
indicate that the occurrence of uterine tumours is probably related to a chronic dopamine-mediated sex 
hormone imbalance involving a species specific endocrine mechanism in the rat which is not present 
in humans. 
 
Reproductive toxicology studies demonstrated no adverse effects on male and female fertility or 
postnatal development of offspring in rats and there was no evidence of teratogenicity in rats 
(1,000 mg/kg/day) or rabbits (300 mg/kg/day). 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 (≥450 mg/kg/day) rats exhibited a prolongation of oestrous cycle and a 
high incidence of irregular cycles. At high doses (≥1,000 mg/kg/day) rats exhibited a prolongation of 
gestation and reduction in fetal viability. Studies in lactating rats indicate that pirfenidone and/or its 
metabolites are excreted in milk with the potential for accumulation of pirfenidone and/or its 
metabolites in milk. 
 



26 

Pirfenidone showed no indication of mutagenic or genotoxic activity in a standard battery of tests and 
when tested under UV exposure was not mutagenic. When tested under UV exposure pirfenidone was 
positive in a photoclastogenic assay in Chinese hamster lung cells. 
 
Phototoxicity and irritation were noted in guinea pigs after oral administration of pirfenidone and with 
exposure to UVA/UVB light. The severity of phototoxic lesions was minimised by application of 
sunscreen.   
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Microcrystalline cellulose 
Croscarmellose sodium 
Povidone K30 
Colloidal anhydrous silica 
Magnesium stearate 
 
Film coat  
 
Polyvinyl alcohol 
Titanium dioxide (E171) 
Macrogol 3350 
Talc 
267 mg tablet 
Iron oxide yellow (E172)  
534 mg tablet 
Iron oxide yellow (E172) 
Iron oxide red (E172)  
801 mg tablet 
Iron oxide red (E172)  
Iron oxide black (E172)  
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
267 mg tablet and 801 mg tablet 
3 years for blisters. 
4 years for bottles. 
 
534 mg tablet 
2 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container  
 
High-Density Polyethylene (HDPE) bottle with a child-resistant and tamper-evident screw cap 
Pack sizes 
 
267 mg film-coated tablets 
1 bottle containing 21 film-coated tablets 



27 

2 bottles each containing 21 film-coated tablets (42 film-coated tablets in total) 
1 bottle containing 42 film-coated tablets 
1 bottle containing 90 film-coated tablets 
2 bottles each containing 90 film-coated tablets (180 film-coated tablets in total) 
1 bottle containing 180 film-coated tablets 
 
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. 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/005 
EU/1/11/667/006 
EU/1/11/667/007 
EU/1/11/667/008 
EU/1/11/667/009 



28 

EU/1/11/667/010 
EU/1/11/667/011 
EU/1/11/667/012 
EU/1/11/667/013 
EU/1/11/667/014 
EU/1/11/667/015 
EU/1/11/667/016 
EU/1/11/667/017 
EU/1/11/667/018 
EU/1/11/667/019 
EU/1/11/667/020EU/1/11/667/021 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 February 2011 
Date of latest renewal: 08 September 2015 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
  AND USE  

 
C OTHER CONDITIONS AND REQUIREMENTS OF THE  
  MARKETING AUTHORISATION 

 
D CONDITIONS OR RESTRICTIONS WITH REGARD TO 
  THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
  PRODUCT 

 
 
 



30 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Roche Pharma AG 
Emil-Barell-Str. 1 
D-79639 Grenzach-Wyhlen 
Germany 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
● Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
● Risk Management Plan (RMP) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in  
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

● At the request of the European Medicines Agency; 
● Whenever the risk management system is modified, especially as the result of new information 
 being received that may lead to a significant change to the benefit/risk profile or as the result of 
 an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
● Additional risk minimisation measures   
 
The MAH must ensure that at launch all physicians who are expected to prescribe Esbriet are provided 
with a physician information pack containing the following: 
 

● Product information (SPC) 
● Physician information (safety checklists) 
● Patient information (PIL) 
 



31 

The safety checklist about Esbriet should contain the following key elements related to liver function 
and photosensitivity: 
 
Liver function 

● Esbriet is contraindicated in patients with severe hepatic impairment or end stage liver disease. 
● Elevations of serum transaminases can occur during treatment with Esbriet. 
● There is a need to monitor liver function tests prior to initiation of treatment with Esbriet and at 
 regular intervals thereafter. 
● Close monitoring is required of any patients who develop liver enzyme elevation with 
 appropriate dose adjustment or discontinuation. 

 
Photosensitivity 

● Patients should be informed that Esbriet is known to be associated with photosensitivity 
 reactions and that preventative measures have to be taken. 
● Patients are advised to avoid or reduce exposure to direct sunlight (including sunlamps). 
● Patients should be instructed to use a sunblock daily, to wear clothing that protects against sun 
 exposure, and to avoid other medications known to cause photosensitivity. 

 
The physician information should encourage the prescribers to report serious adverse reactions and 
clinically significant ADRs of special interest including: 
 

● Photosensitivity reactions and skin rashes 
● Abnormal liver function tests 
● Any other clinically significant ADRs based on the judgment of the prescriber 

 
 



32 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 



33 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
 



34 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON - BOTTLE 250 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg hard capsules  
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule  
 
270 capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use.  
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 



35 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
 OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
 APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/003 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esbriet  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
<2D barcode carrying the unique identifier included.> 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON –2-WEEK TREATMENT INITIATION PACK (7 X 3 CAPSULES AND 7 X 6 
CAPSULES CONFIGURATION) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg hard capsules  
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
Initiation Pack 
2-week treatment initiation pack (63 capsules): 
 
Week 1 – 21 capsules (7 blister strips, each with 3 capsules) 
Week 2 – 42 capsules (7 blister strips, each with 6 capsules) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use.  
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 



37 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esbriet  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
<2D barcode carrying the unique identifier included.> 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



38 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – 4-WEEK TREATMENT MAINTENANCE PACK CONTAINING 252 
CAPSULES (14 X 18 CAPSULES CONFIGURATION)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg hard capsules  
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule  
 
4-week treatment pack of 252 capsules   
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use.  
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 



39 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
 OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
 APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esbriet 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
<2D barcode carrying the unique identifier included.> 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



40 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL - BOTTLE 250 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg hard capsules  
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
270 capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use.  
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
 OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
 APPROPRIATE 
 
 



41 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/003 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



42 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTER STRIPS 
 
BLISTER STRIPS – 2-WEEK TREATMENT INITIATION PACK (7 X 3 CAPSULES AND 7 
X 6 CAPSULES CONFIGURATION)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg hard capsules  
 
Pirfenidone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
Week 1, Week 2 

   
 



43 

MINIMUM PARTICULARS TO APPEAR ON BLISTER STRIPS 
 
BLISTER STRIPS – 4-WEEK TREATMENT PACK OF 252 CAPSULES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg hard capsules  
 
Pirfenidone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH. 
 
 
3.        EXPIRY DATE 
 
EXP  
 
 
4.        BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 

   
 
 



44 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
21 tablets 
42 tablets)  
90 tablets 
180 tablets  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



45 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/005 21 tablets 
EU/1/11/667/006 42 tablets (2 x 21) 
EU/1/11/667/020 42 tablets 
EU/1/11/667/007 90 tablets 
EU/1/11/667/008 180 tablets (2 x 90) 
EU/1/11/667/021 180 tablets 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 267 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 



46 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 534 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 534 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
21 tablets 
90 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



47 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/009 21 tablets 
EU/1/11/667/010 90 tablets 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 534 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



48 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 801 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 801 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
90 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



49 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/011 90 tablets 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 801 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



50 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON Film-coated Tablets in Blisters  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
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) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



51 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/012 21 tablets 
EU/1/11/667/013 42 tablets (2 x 21) 
EU/1/11/667/014 84 tablets (4 x 21) 
EU/1/11/667/015 168 tablets (8 x 21) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 267 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
 
 



52 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON Film-coated Tablets in Blisters Multi Pack 63 – (INCLUDING BLUE BOX)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tabet 
 
Mutlipack: 63 (1 pack containing 1 blister of 21 and 1 pack containing 2 blisters of 21) film-
coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



53 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/016 63 tablets (21 + 42) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 267 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
 
 



54 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON Film-coated Tablets in Blisters Multi Pack 252 – (INCLUDING BLUE BOX)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet  
 
Multipack containing 252 (3 packs each containing 4 blisters of 21) film-coated Tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



55 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/017 252 tablets (3x84) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 267 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
 
 



56 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON Film-coated tablets in Blisters  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 801 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 801 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet  
 
4 blisters each containing 21 film-coated tablets (84 in total) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



57 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/018 84 tablets (4x21) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 801 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



58 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON Film-coated tablets in Blisters 252 Multipack (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 801 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 801 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
Multipack containing 252 (3 packs each containing 4 blisters of 21) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



59 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/019 252 tablets (3x84) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 801 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



60 

 
PARTICULARS TO APPEAR ON THE OUTERPACKAGING 
 
LABEL – INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
21 film-coated tablets. Component of a multipack, can’t be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



61 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/016 63 tablets (21+42) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 267 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



62 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
LABEL – INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
42 film-coated tablets. Component of a multipack, can’t be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



63 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/016 63 tablets (21 + 42) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 267 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



64 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
LABEL – INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
84 film-coated tablets. Component of a multipack, can’t be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



65 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/017 252 tablets (3 x 84) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 267 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



66 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
LABEL – INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 801 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 801 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
84 film-coated tablets.  Component of a multipack, can’t be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



67 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/019 252 tablets (3 x 84) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
esbriet 801 mg tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



68 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL – BOTTLE 70 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
21 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



69 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/005 
EU/1/11/667/006 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



70 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL – BOTTLE 70 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
42 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



71 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/020 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



72 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL - BOTTLE 200 ML  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
90 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



73 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/007 
EU/1/11/667/008 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



74 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL - BOTTLE 200 ML  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 267 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
180 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



75 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/021 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



76 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL - BOTTLE 70 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 534 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 534 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
21 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



77 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/009 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



78 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL - BOTTLE 200 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 534 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 534 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
90 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



79 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/0010 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



80 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL - BOTTLE 200 ML 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 801 mg film-coated tablets 
 
Pirfenidone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 801 mg pirfenidone. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
90 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



81 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/667/011 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



82 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTER STRIPS 
 
BLISTER STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 267 mg film-coated tablets  
 
Pirfenidone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 
 

   

Mon. Tue. Wed. Thu. Fri. Sat. Sun. 



83 

MINIMUM PARTICULARS TO APPEAR ON BLISTER STRIPS 
 
BLISTER STRIPS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esbriet 801 mg film-coated tablets  
 
Pirfenidone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. OTHER 
 

   

Mon. Tue. Wed. Thu. Fri. Sat. Sun. 
 



84 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 



85 

Package leaflet: Information for the user 
Esbriet 267 mg hard capsules 

Pirfenidone 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
Keep this leaflet. You may need to read it again. 
● If you have any further questions, ask your doctor or pharmacist. 
● This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 
 even if their signs of illness are the same as yours. 
● If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
 effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Esbriet is and what it is used for 
2. What you need to know before you take Esbriet  
3. How to take Esbriet  
4. Possible side effects 
5 How to store Esbriet 
6. Contents of the pack and other information 
 
 
1 What Esbriet is and what it is used for  
 
Esbriet contains the active substance pirfenidone and it is used for the treatment of mild to moderate 
Idiopathic Pulmonary Fibrosis (IPF) in adults.  
 
IPF is a condition in which the tissues in your lungs become swollen and scarred over time, and as a 
result makes it difficult to breathe deeply. This makes it hard for your lungs to work properly. Esbriet 
helps to reduce scarring and swelling in the lungs, and helps you breathe better.  
 
 
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 experienced angioedema with pirfenidone, including symptoms such as 
 swelling of the face, lips and/or tongue which 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 end stage liver disease 
● if you have severe or end stage kidney disease requiring dialysis.  
 
If any of the above affects you, do not take Esbriet. If you are unsure ask your doctor or pharmacist. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Esbriet 
● You may become more sensitive to sunlight (photosensitivity reaction) when taking Esbriet. 
 Avoid the sun (including sunlamps) whilst taking Esbriet. Wear sunblock daily and cover your 
 arms, legs and head to reduce exposure to sunlight (see section 4: Possible side effects). 
● You should not take other medicines, such as tetracycline antibiotics (such as doxycycline), 
 which may make you more sensitive to sunlight.   
● You should tell your doctor if you suffer from kidney problems.   
● You should tell your doctor if you suffer from mild to moderate liver problems. 
● You should stop smoking before and during treatment with Esbriet. Cigarette smoking can 
 reduce the effect of Esbriet. 



86 

● Esbriet may cause dizziness and tiredness. Be careful if you have to take part in activities 
where  you have to be alert and co-ordinated.  
● Esbriet can cause weight loss. Your doctor will monitor your weight whilst you are taking this 
 medicine.  
 
You will need a blood test before you start taking Esbriet and at monthly intervals for the first 
6 months and then every 3 months thereafter whilst you are taking this medicine to check whether 
your liver is working properly. It is important that you have these regular blood tests for as long as you 
are taking Esbriet.  
 
Children and adolescents 
Do not give Esbriet to children and adolescents under the age of 18. 
 
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 change the effect 
of Esbriet. 
 
Medicines that may increase side effects of Esbriet: 
● enoxacin (a type of antibiotic) 
● ciprofloxacin (a type of antibiotic) 
● amiodarone (used to treat some types of heart disease) 
● propafenone (used to treat some types of heart disease) 
● fluvoxamine (used to treat depression and obsessive compulsive disorder (OCD)). 
 
Medicines that may reduce how well Esbriet works: 
● omeprazole (used in the treatment of conditions such as indigestion, gastroesophageal reflux 
 disease) 
● rifampicin (a type of antibiotic).  
 
Esbriet with food and drink 
Do not drink grapefruit juice whilst taking this medicine. Grapefruit may prevent Esbriet from 
working properly.  
 
Pregnancy and breast-feeding 
As a precautionary measure, it is preferable to avoid the use of Esbriet if you are pregnant, planning to 
become pregnant or think you might be pregnant as the potential risks to the unborn child are 
unknown. 
 
If you are breast-feeding or plan to breast-feed speak to your doctor or pharmacist before taking 
Esbriet. As it is unknown whether Esbriet passes into breast milk, your doctor will discuss the risks 
and benefits of taking this medicine while breast-feeding if you decide to do so. 
 
Driving and using machines 
Do not drive or use machines if you feel dizzy or tired after taking Esbriet.  
 
 
3 How to take Esbriet 
 
Treatment with Esbriet should be started and overseen by a specialist doctor experienced in the 
diagnosis and treatment of IPF. 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.   
 
Your medicine will usually be given to you in increasing doses as follows: 
● for the first 7 days take 1 capsule, 3 times a day with food (a total of 801 mg/day) 



87 

● from day 8 to 14 take 2 capsules, 3 times a day with food (a total of 1,602 mg/day)  
● from day 15 onwards (maintenance), take 3 capsules, 3 times a day with food (a total of 
2,403 mg/day).   
 
The recommended maintenance daily dose of Esbriet is 3 capsules three times a day with food, for a 
total of 2403 mg/day. 
 
Swallow the capsules whole with a drink of water, during or after a meal to reduce the risk of 
side effects such as nausea (feeling sick) and dizziness. If symptoms continue, see your doctor.  
 
Dose reduction due to side effects 
Your doctor may reduce your dose if you suffer from side effects such as, stomach problems, any skin 
reactions to sunlight or sun lamps, or significant changes to your liver enzymes.  
 
If you take more Esbriet than you should  
Contact your doctor, pharmacist or nearest hospital casualty department immediately if you have taken 
more capsules than you should, and take your medicine with you.  
 
If you forget to take Esbriet  
If you forget a dose, take it as soon as you remember. Do not take a double dose to make up for a 
forgotten dose. Each dose should be separated by at least 3 hours. Do not take more capsules each day 
than your prescribed daily dose. 
 
If you stop taking Esbriet 
In some situations, your doctor may advise you to stop taking Esbriet. If for any reason you have to 
stop taking Esbriet for more than 14 consecutive days, your doctor will restart your treatment with 
1 capsule 3 times a day, gradually increasing this to 3 capsules 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 tell your doctor immediately 
● If you experience swelling of the face, lips and/or tongue, itching, hives, difficulty breathing or 

wheezing, or feeling faint, which are signs of angioedema, a serious allergic reaction or 
anaphylaxis. 

● If you experience yellowing of the eyes or skin, or dark urine, potentially accompanied by 
itching of the skin, which are signs of abnormal liver function tests. These are rare side effects. 

 
Other side effects may include 
Talk to your doctor if you get any side effects. 
 
Very common side effects (may affect more than 1 in 10 people):  
● skin reactions after going out in the sun or using sunlamps 
● feeling sick (nausea) 
● tiredness  
● diarrhoea 
● indigestion or stomach upset 
● loss of appetite 
● headache.  
 
Common side effects (may affect up to 1 in 10 people): 
● infections of the throat or the airways going into the lungs and/or sinusitis   
● bladder infections  
● weight loss  
● difficulty sleeping  



88 

● dizziness  
● feeling sleepy 
● changes in taste 
● hot flushes  
● shortness of breath 
● cough  
● stomach problems such as acid reflux, vomiting, feeling bloated, abdominal pain and 
 discomfort, heart burn, feeling constipated and passing wind 
● blood tests may show increased levels of liver enzymes  
● skin problems such as itchy skin, skin redness or red skin, dry skin, skin rash  
● muscle pain, aching joints/joint pains  
● feeling weak or feeling low in energy  
● chest pain  
● sunburn. 
 
Rare side effects (may affect up to 1 in 1,000 people): 
● blood tests may show decrease in white blood cells. 
 
Reporting of side effects  
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via 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. How to store 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 bottle label, blister and carton 
after EXP. The expiry date refers to the last day of that month.  
 
Do not store this medicine above 30ºC. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Esbriet contains  
The active substance is pirfenidone. Each capsule contains 267 mg of pirfenidone.  
The other ingredients are: 
● Capsule filling: microcrystalline cellulose, croscarmellose sodium, povidone, magnesium 
 stearate 
● Capsule shell: gelatin, titanium dioxide (E171) 
● Capsule brown printing ink: shellac, iron oxide black (E172), iron oxide red (E172), iron 
oxide yellow (E172), propylene glycol, ammonium hydroxide 
 
What Esbriet looks like and contents of the pack 
Esbriet hard capsules (capsules) have a white to off-white opaque body and a white to off-white 
opaque cap with ‘PFD 267 mg’ printed in brown ink. The capsules contain a white to pale yellow 
powder.  
 
Your medicine is provided in either a 2-week treatment initiation pack, a 4-week treatment pack or in 
a bottle.  
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


89 

The 2-week treatment initiation pack contains a total of 63 capsules. There are 7 blister strips with 3 
capsules per strip (1 capsule per pocket for Week 1) and 7 blister strips with 6 capsules per strip (2 
capsules per pocket for Week 2). 
 
The 4-week treatment pack contains a total of 252 capsules. There are 14 x 2-day blister strips each 
containing 18 capsules (3 capsules per pocket). 
 
The blisters strips in the 2-week treatment initiation pack and 4-week treatment maintenance pack are 
each marked with the following symbols as a reminder to take a dose three times a day: 

 (sunrise; morning dose)  (sun; daytime dose) and (moon; evening dose). 
 
The bottle pack contains 270 capsules.  
 
Not all pack sizes may be 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 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A.  
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva  
UAB “Roche Lietuva”  
Tel: +370 5 2546799 
  

България  
Рош България ЕООД  
Тел: +359 2 818 44 44  
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. o.  
Tel: +420 - 2 20382111 
 

Magyarország 
Roche (Magyarország) Kft.  
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s  
Tlf: +45 - 36 39 99 99 
 

Malta 
(See Ireland)  
 
 

Deutschland 
Roche Pharma AG  
Tel: +49 (0) 7624 140 
 

Nederland 
Roche Nederland B.V.  
Tel: +31 (0) 348 438050 
 



90 

Eesti 
Roche Eesti OÜ  
Tel: + 372 - 6 177 380  
 

Norge 
Roche Norge AS  
Tlf: +47 - 22 78 90 00 
 

Ελλάδα  
Roche (Hellas) A.E.  
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH  
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A.  
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o.  
Tel: +48 - 22 345 18 88 
 

France 
Roche  
Tél: +33 (0) 1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda  
Tel: +351 - 21 425 70 00 
 

Hrvatska 
Roche d.o.o.  
Tel: +385 1 4722 333 
 

România  
Roche România S.R.L.  
Tel: +40 21 206 47 01 

Ireland 
Roche Products (Ireland) Ltd.  
Tel: +353 (0) 1 469 0700  
 

Slovenija 
Roche farmacevtska družba d.o.o.  
Tel: +386 - 1 360 26 00 

Ísland 
Roche a/s  
c/o Icepharma hf  
Sími: +354 540 8000 
 

Slovenská republika 
Roche Slovensko, s.r.o.  
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A.  
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy  
Puh/Tel: +358 (0) 10 554 500 
 

Κύπρος  
Γ.Α.Σταμάτης & Σια Λτδ.  
Τηλ: +357 - 22 76 62 76  
 

Sverige 
Roche AB  
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA  
Tel: +371 - 6 7039831 
 

United Kingdom 
Roche Products Ltd.  
Tel: +44 (0) 1707 366000 
 

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
There are also links to other websites about rare diseases and treatments. 

 

http://www.ema.europa.eu/


91 

Package leaflet: Information for the user 
Esbriet 267 mg film-coated tablets 
Esbriet 534 mg film-coated tablets 
Esbriet 801 mg film-coated tablets 

Pirfenidone 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
Keep this leaflet. You may need to read it again. 
● If you have any further questions, ask your doctor or pharmacist. 
● This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 
 even if their signs of illness are the same as yours. 
● If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
 effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Esbriet is and what it is used for 
2. What you need to know before you take Esbriet  
3. How to take Esbriet  
4. Possible side effects 
5 How to store Esbriet 
6. Contents of the pack and other information 
 
 
1 What Esbriet is and what it is used for  
 
Esbriet contains the active substance pirfenidone and it is used for the treatment of mild to moderate 
Idiopathic Pulmonary Fibrosis (IPF) in adults.  
 
IPF is a condition in which the tissues in your lungs become swollen and scarred over time, and as a 
result makes it difficult to breathe deeply. This makes it hard for your lungs to work properly. Esbriet 
helps to reduce scarring and swelling in the lungs, and helps you breathe better.  
 
 
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 experienced angioedema with pirfenidone, including symptoms such as 
 swelling of the face, lips and/or tongue which 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 end stage liver disease 
● if you have severe or end stage kidney disease requiring dialysis.  
 
If any of the above affects you, do not take Esbriet. If you are unsure ask your doctor or pharmacist. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Esbriet 
● You may become more sensitive to sunlight (photosensitivity reaction) when taking Esbriet. 
 Avoid the sun (including sunlamps) whilst taking Esbriet. Wear sunblock daily and cover your 
 arms, legs and head to reduce exposure to sunlight (see section 4: Possible side effects). 
● You should not take other medicines, such as tetracycline antibiotics (such as doxycycline), 
 which may make you more sensitive to sunlight.   
● You should tell your doctor if you suffer from kidney problems 
● You should tell your doctor if you suffer from mild to moderate liver problems. 



92 

● You should stop smoking before and during treatment with Esbriet. Cigarette smoking can 
 reduce the effect of Esbriet. 
● Esbriet may cause dizziness and tiredness. Be careful if you have to take part in activities where 
 you have to be alert and co-ordinated.  
● Esbriet can cause weight loss. Your doctor will monitor your weight whilst you are taking this 
 medicine.  
 
You will need a blood test before you start taking Esbriet and at monthly intervals for the first 
6 months and then every 3 months thereafter whilst you are taking this medicine to check whether 
your liver is working properly. It is important that you have these regular blood tests for as long as you 
are taking Esbriet.  
 
Children and adolescents 
Do not give Esbriet to children and adolescents under the age of 18. 
 
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 change the effect 
of Esbriet. 
 
Medicines that may increase side effects of Esbriet: 
● enoxacin (a type of antibiotic) 
● ciprofloxacin (a type of antibiotic) 
● amiodarone (used to treat some types of heart disease) 
● propafenone (used to treat some types of heart disease) 
● fluvoxamine (used to treat depression and obsessive compulsive disorder (OCD)). 
 
Medicines that may reduce how well Esbriet works: 
● omeprazole (used in the treatment of conditions such as indigestion, gastroesophageal reflux 
 disease) 
● rifampicin (a type of antibiotic).  
 
Esbriet with food and drink 
Do not drink grapefruit juice whilst taking this medicine. Grapefruit may prevent Esbriet from 
working properly.  
 
Pregnancy and breast-feeding 
As a precautionary measure, it is preferable to avoid the use of Esbriet if you are pregnant, planning to 
become pregnant, or think you might be pregnant as the potential risks to the unborn child are 
unknown. 
 
If you are breast-feeding or plan to breast-feed speak to your doctor or pharmacist before taking 
Esbriet. As it is unknown whether Esbriet passes into breast milk, your doctor will discuss the risks 
and benefits of taking this medicine while breast-feeding if you decide to do so. 
 
Driving and using machines 
Do not drive or use machines if you feel dizzy or tired after taking Esbriet.  
 
 
3 How to take Esbriet 
 
Treatment with Esbriet should be started and overseen by a specialist doctor experienced in the 
diagnosis and treatment of IPF. 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.   
  



93 

Your medicine will usually be given to you in increasing doses 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) 
● from day 8 to 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 onwards (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 daily dose of Esbriet is 801 mg (3 yellow tablets or 1 brown tablet) 
three times a day with food, for a total of 2403 mg/day. 
 
Swallow the tablets whole with a drink of water, during or after a meal to reduce the risk of 
side effects such as nausea (feeling sick) and dizziness. If symptoms continue, see your doctor.  
 
Dose reduction due to side effects 
Your doctor may reduce your dose if you suffer from side effects such as, stomach problems, any skin 
reactions to sunlight or sun lamps, or significant changes to your liver enzymes.  
 
If you take more Esbriet than you should  
Contact your doctor, pharmacist or nearest hospital casualty department immediately if you have taken 
more tablets than you should, and take your medicine with you.  
 
If you forget to take Esbriet  
If you forget a dose, take it as soon as you remember. Do not take a double dose to make up for a 
forgotten dose. Each dose should be separated by at least 3 hours. Do not take more tablets each day 
than your prescribed daily dose. 
 
If you stop taking Esbriet 
In some situations, your doctor may advise you to stop taking Esbriet. If for any reason you have to 
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, gradually increasing this to a dose of 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 tell your doctor immediately 
● If you experience swelling of the face, lips and/or tongue, itching, hives, difficulty breathing or 

wheezing, or feeling faint, which are signs of angioedema, a serious allergic reaction or 
anaphylaxis.  

● If you experience yellowing of the eyes or skin, or dark urine, potentially accompanied by 
itching of the skin, which are signs of abnormal liver function tests. These are rare side effects. 

 
Other side effects may include 
Talk to your doctor if you get any side effects. 
 
Very common side effects (may affect more than 1 in 10 people):  
● skin reactions after going out in the sun or using sunlamps 
● feeling sick (nausea) 
● tiredness  
● diarrhoea 
● indigestion or stomach upset 
● loss of appetite 
● headache.  
 



94 

Common side effects (may affect up to 1 in 10 people): 
● infections of the throat or the airways going into the lungs and/or sinusitis   
● bladder infections  
● weight loss  
● difficulty sleeping  
● dizziness  
● feeling sleepy 
● changes in taste 
● hot flushes  
● shortness of breath 
● cough  
● stomach problems such as acid reflux, vomiting, feeling bloated, abdominal pain and 
 discomfort, heart burn, feeling constipated and passing wind 
● blood tests may show increased levels of liver enzymes  
● skin problems such as itchy skin, skin redness or red skin, dry skin, skin rash  
● muscle pain, aching joints/joint pains  
● feeling weak or feeling low in energy  
● chest pain  
● sunburn. 
 
Rare side effects (may affect up to 1 in 1,000 people): 
● blood tests may show decrease in white blood cells. 
 
Reporting of side effects  
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via 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. How to store 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 bottle label, blister  and carton 
after EXP. The expiry date refers to the last day of that month.  
 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Esbriet contains  
 
267 mg tablet 
The active substance is pirfenidone. Each film-coated tablet contains 267 mg of pirfenidone.  
The other ingredients are: microcrystalline cellulose, croscarmellose sodium, povidone K30, colloidal 
anhydrous silica, magnesium stearate  
The film coat consists of: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, iron oxide 
yellow (E172) 
 
534 mg tablet 
The active substance is pirfenidone. Each film-coated tablet contains 534 mg of pirfenidone.  
The other ingredients are: microcrystalline cellulose, croscarmellose sodium, povidone K30, colloidal 
anhydrous silica, magnesium stearate  

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


95 

The film coat consists of: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, iron oxide 
yellow (E172) and iron oxide red (E172) 
 
801 mg tablet 
The active substance is pirfenidone. Each film-coated tablet contains 801 mg of pirfenidone.  
The other ingredients are: microcrystalline cellulose, croscarmellose sodium, povidone K30, colloidal 
anhydrous silica, magnesium stearate  
The film coat consists of: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, iron oxide 
red (E172) and iron oxide black (E172) 
 
What Esbriet looks like and contents of the pack 
 
267 mg tablet 
Esbriet 267 mg film-coated tablets are yellow, oval, biconvex film-coated tablets, debossed with 
“PFD”. 
The bottle packs contain one bottle containing 21 tablets, two bottles each containing 21 tablets (42 
tablets in total), one bottle containing 42 tablets, one bottle containing 90 tablets,  two bottles each 
containing 90 tablets (180 tablets in total) or one bottle containing 180 tablets.  
The blister packs contain 21, 42, 84 or 168 film-coated tablets and the multipacks contain 63 (2-week 
treatment initiation pack 21+42) or 252 (continuation pack 3x84) film-coated tablets.  
 
The 267 mg blisters strips containing 63 film-coated tablets are each marked with the following 
symbols and abbreviated names of the day as a reminder to take a dose three times a day: 

 (sunrise; morning dose)  (sun; daytime dose) and (moon; evening dose). 

Mon. Tue. Wed. Thu. Fri. Sat. Sun. 
 
534 mg tablet 
Esbriet 534 mg film-coated tablets are orange, oval, biconvex film-coated tablets, debossed with 
“PFD”. 
The bottle packs contain either one bottle containing 21 tablets or one bottle containing 90 tablets.  
 
801 mg tablet 
Esbriet 801 mg film-coated tablets are brown, oval, biconvex film-coated tablets, debossed with 
“PFD”. 
The bottle pack contains one bottle containing 90 tablets.  
The blisters pack contains 84 film-coated tablets and the multipack contains 252 (continuation pack 
3x84) film-coated tablets.  
 
The 801 mg blisters strips are each marked with the following symbols and abbreviated names of the 
day as a reminder to take a dose three times a day: 

 (sunrise; morning dose)  (sun; daytime dose) and (moon; evening dose). 

Mon. Tue. Wed. Thu. Fri. Sat. Sun. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 



96 

 
Manufacturer 
 
Roche Pharma AG 
Emil-Barell-Str. 1 
D-79639 Grenzach- Wyhlen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A.  
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva  
UAB “Roche Lietuva”  
Tel: +370 5 2546799 
  

България  
Рош България ЕООД  
Тел: +359 2 818 44 44  
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. o.  
Tel: +420 - 2 20382111 
 

Magyarország 
Roche (Magyarország) Kft.  
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s  
Tlf: +45 - 36 39 99 99 
 

Malta 
(See Ireland)  
 
 

Deutschland 
Roche Pharma AG  
Tel: +49 (0) 7624 140 
 

Nederland 
Roche Nederland B.V.  
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ  
Tel: + 372 - 6 177 380  
 

Norge 
Roche Norge AS  
Tlf: +47 - 22 78 90 00 
 

Ελλάδα  
Roche (Hellas) A.E.  
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH  
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A.  
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o.  
Tel: +48 - 22 345 18 88 
 

France 
Roche  
Tél: +33 (0) 1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda  
Tel: +351 - 21 425 70 00 
 

Hrvatska 
Roche d.o.o.  
Tel: +385 1 4722 333 
 

România  
Roche România S.R.L.  
Tel: +40 21 206 47 01 



97 

Ireland 
Roche Products (Ireland) Ltd.  
Tel: +353 (0) 1 469 0700  
 

Slovenija 
Roche farmacevtska družba d.o.o.  
Tel: +386 - 1 360 26 00 

Ísland 
Roche a/s  
c/o Icepharma hf  
Sími: +354 540 8000 
 

Slovenská republika 
Roche Slovensko, s.r.o.  
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A.  
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy  
Puh/Tel: +358 (0) 10 554 500 
 

Κύπρος  
Γ.Α.Σταμάτης & Σια Λτδ.  
Τηλ: +357 - 22 76 62 76  
 

Sverige 
Roche AB  
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA  
Tel: +371 - 6 7039831 
 

United Kingdom 
Roche Products Ltd.  
Tel: +44 (0) 1707 366000 
 

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
There are also links to other websites about rare diseases and treatments. 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET