Libertek

1

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



2

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

Libertek 500 micrograms film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 500 micrograms of roflumilast.

Excipient with known effect:
Each film-coated tablet contains 188.72 mg lactose (as monohydrate).
For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

Yellow, D-shaped film-coated tablet of 9 mm, embossed with “D” on one side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Libertek is indicated for maintenance treatment of severe chronic obstructive pulmonary disease 
(COPD) (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult 
patients with a history of frequent exacerbations as add on to bronchodilator treatment.

4.2 Posology and method of administration

Posology
The recommended dose is 500 micrograms (one tablet) roflumilast once daily.

Libertek may need to be taken for several weeks to achieve its effect (see section 5.1). Libertek has been 
studied in clinical trials for up to one year.

Special populations

Elderly
No dose adjustment is necessary. 

Renal impairment 
No dose adjustment is necessary. 

Hepatic impairment 
The clinical data with Libertek in patients with mild hepatic impairment classified as Child-Pugh A are 
insufficient to recommend a dose adjustment (see section 5.2) and therefore Libertek should be used 
with caution in these patients.

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



3

Patients with moderate or severe hepatic impairment classified as Child-Pugh B or C must not take 
Libertek (see section 4.3).

Paediatric population 
There is no relevant use of Libertek in the paediatric population (under 18 years) in the indication 
COPD.

Method of administration
For oral use.
The tablet should be swallowed with water and taken at the same time every day. The tablet can be 
taken with or without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Moderate or severe hepatic impairment (Child-Pugh B or C).

4.4 Special warnings and precautions for use

All patients should be informed about the risks of Libertek and the precautions for safe use and should 
be given a patient card before starting Libertek.

Rescue medicinal products
Libertek is not indicated as rescue medicinal product for the relief of acute bronchospasms.

Weight decrease
In 1-year studies (M2-124, M2-125), a decrease of body weight occurred more frequently in patients 
treated with roflumilast compared to placebo-treated patients. After discontinuation of roflumilast, the 
majority of patients had regained body weight after 3 months. 
Body weight of underweight patients should be checked at each visit. Patients should be advised to 
check their body weight on a regular basis. In the event of an unexplained and clinically concerning 
weight decrease, the intake of roflumilast should be stopped and body weight should be further 
followed-up.

Special clinical conditions
Due to lack of relevant experience, treatment with roflumilast should not be initiated or existing 
treatment with roflumilast should be stopped in patients with severe immunological diseases (e.g. HIV 
infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy), severe 
acute infectious diseases, cancers (except basal cell carcinoma), or patients being treated with 
immunosuppressive medicinal products (i.e.: methotrexate, azathioprine, infliximab, etanercept, or oral 
corticosteroids to be taken long-term; except short-term systemic corticosteroids). Experience in patients 
with latent infections such as tuberculosis, viral hepatitis, herpes viral infection and herpes zoster is 
limited.
Patients with congestive heart failure (NYHA grades 3 and 4) have not been studied and therefore 
treatment of these patients is not recommended. 

Psychiatric disorders
Roflumilast is associated with an increased risk of psychiatric disorders such as insomnia, anxiety, 
nervousness and depression. Rare instances of suicidal ideation and behaviour, including suicide, have 
been observed in patients with or without history of depression, usually within the first weeks of 
treatment (see section 4.8). The risks and benefits of starting or continuing treatment with roflumilast
should be carefully assessed if patients report previous or existing psychiatric symptoms or if 
concomitant treatment with other medicinal products likely to cause psychiatric events is intended. 
Roflumilast is not recommended in patients with a history of depression associated with suicidal 
ideation or behaviour. Patients and caregivers should be instructed to notify the prescriber of any 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



4

changes in behaviour or mood and of any suicidal ideation. If patients suffered from new or worsening 
psychiatric symptoms, or suicidal ideation or suicidal attempt is identified, it is recommended to 
discontinue treatment with roflumilast.

Persistent intolerability
While adverse reactions like diarrhoea, nausea, abdominal pain and headache mainly occur within the 
first weeks of therapy and mostly resolve on continued treatment, roflumilast treatment should be 
reassessed in case of persistent intolerability. This might be the case in special populations that may 
have higher exposure, such as in black, non-smoking females (see section 5.2) or in patients 
concomitantly treated with CYP1A2/ 2C19/3A4 inhibitors (such as fluvoxamine and cimetidine) or the 
CYP1A2/3A4 inhibitor enoxacin (see section 4.5).

Body weight <60 kg
Treatment with roflumilast may lead to a higher risk of sleep disorders (mainly insomnia) in patients 
with a baseline body weight of <60 kg, due to a higher total PDE4 inhibitory activity found in these 
patients (see section 4.8).

Theophylline
There are no clinical data to support the concomitant treatment with theophylline for maintenance 
therapy. Therefore, the concomitant treatment with theophylline is not recommended.

Lactose
Libertek tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the 
Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

A major step in roflumilast metabolism is the N-oxidation of roflumilast to roflumilast N-oxide by 
CYP3A4 and CYP1A2. Both roflumilast and roflumilast N-oxide have intrinsic phosphodiesterase-4 
(PDE4) inhibitory activity. Therefore, following administration of roflumilast, the total PDE4 inhibition 
is considered to be the combined effect of both roflumilast and roflumilast N-oxide. Interaction studies 
with CYP1A2/3A4 inhibitor enoxacin and the CYP1A2/2C19/3A4 inhibitors cimetidine and 
fluvoxamine, resulted in increases of the total PDE4 inhibitory activity of 25%, 47% and 59%, 
respectively. The tested dose of fluvoxamine was 50 mg. A combination of roflumilast with these active 
substances might lead to an increase of exposure and persistent intolerability. In this case, roflumilast
treatment should be reassessed (see section 4.4).

Administration of the cytochrome P450 enzyme inducer rifampicin resulted in a reduction in total PDE4 
inhibitory activity by about 60%. Therefore, the use of strong cytochrome P450 enzyme inducers (e.g. 
phenobarbital, carbamazepine, phenytoin) may reduce the therapeutic efficacy of roflumilast. Thus, 
roflumilast treatment is not recommended in patients receiving strong cytochrome P450 enzyme 
inducers.

Clinical interaction studies with CYP3A4 inhibitors erythromycin and ketoconazole showed increases of 
9% of the total PDE4 inhibitory activity. Co-administration with theophylline resulted in an increase of 
8% of the total PDE4 inhibitory activity (see section 4.4). In an interaction study with an oral 
contraceptive containing gestodene and ethinyl oestradiol, the total PDE4 inhibitory activity was 
increased by 17%. No dose adjustment is necessary in patients receiving these active substances.

No interactions were observed with inhaled salbutamol, formoterol, budesonide and oral montelukast, 
digoxin, warfarin, sildenafil and midazolam. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



5

Co-administration with an antacid (combination of aluminium hydroxide and magnesium hydroxide) did 
not alter the absorption or pharmacokinetics of roflumilast or its N-oxide. 

4.6 Fertility, pregnancy and lactation

Women of childbearing potential 
Women of childbearing age should be advised to use an effective method of contraception during 
treatment. Roflumilast is not recommended in women of childbearing potential not using contraception.

Pregnancy
There are limited amount of data from the use of roflumilast in pregnant women.

Studies in animals have shown reproductive toxicity (see section 5.3). Roflumilast is not recommended 
during pregnancy.

Roflumilast has been demonstrated to cross the placenta in pregnant rats. 

Breastfeeding
Available pharmacokinetic data in animals have shown excretion of roflumilast or its metabolites in 
milk. A risk to the breastfed infant cannot be excluded. Roflumilast should not be used during 
breast-feeding. 

Fertility
In a human spermatogenesis study, roflumilast 500 micrograms had no effects on semen parameters or 
reproductive hormones during the 3-month treatment period and the following 3-month off-treatment 
period.

4.7 Effects on ability to drive and use machines

Libertek has no influence on the ability to drive and use machines. 

4.8 Undesirable effects

Summary of the safety profile
In clinical COPD studies, approximately 16% of patients experienced adverse reactions with roflumilast 
(compared to 5% in placebo). The most commonly reported adverse reactions were diarrhoea (5.9%), 
weight decreased (3.4%), nausea (2.9%), abdominal pain (1.9%) and headache (1.7%). The majority of 
these adverse reactions were mild or moderate. These adverse reactions mainly occurred within the first 
weeks of therapy and mostly resolved on continued treatment.

Tabulated list of adverse reactions
Within the following table, adverse reactions are ranked under the MedDRA frequency classification:

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); very rare (<1/10,000), not known (cannot be estimated from the available 
data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



6

Table 1. Adverse reactions with roflumilast in clinical COPD studies and post-marketing experience

Frequency

System 
Organ Class

Common Uncommon Rare

Immune system disorders Hypersensitivity Angioedema
Endocrine disorders Gynaecomastia
Metabolism and nutrition 
disorders

Weight decreased
Decreased 
appetite 

Psychiatric disorders Insomnia Anxiety Suicidal ideation and 
behaviour*
Depression 
Nervousness 
Panic attack

Nervous system disorders Headache Tremor 
Vertigo 
Dizziness

Dysgeusia

Cardiac disorders Palpitations
Respiratory, thoracic and 
mediastinal disorders

Respiratory tract 
infections (excluding 
Pneumonia)

Gastrointestinal disorders Diarrhoea
Nausea
Abdominal pain

Gastritis
Vomiting
Gastro-esophageal 
reflux disease
Dyspepsia

Haematochezia 
Constipation

Hepatobiliary disorders Gamma-GT increased
Aspartate 
aminotransferase (AST) 
increased

Skin and subcutaneous 
tissue disorders 

Rash Urticaria

Musculoskeletal and 
connective tissue disorders

Muscle spasms and 
weakness
Myalgia
Back pain

Blood creatine 
phosphokinase (CPK) 
increased

General disorders and 
administration site 
conditions

Malaise 
Asthenia
Fatigue

Description of selected adverse reactions
* In clinical studies and post-marketing experience, rare instances of suicidal ideation and behaviour,
including suicide, were reported. Patients and caregivers should be instructed to notify the prescriber of 
any suicidal ideation (see also section 4.4).

Other special populations
A higher incidence of sleep disorders (mainly insomnia) in patients ≥75 years or older was observed in 
Study RO-2455-404-RD for patients treated with roflumilast when compared to those treated with 
placebo (3.9% vs 2.3%). The incidence observed was also higher in patients less than 75 years old, 
treated with roflumilast when compared to those treated with placebo (3.1% vs 2.0%). 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



7

A higher incidence of sleep disorders (mainly insomnia) in patients with a baseline body weight <60 kg 
was observed in Study RO-2455-404-RD for patients treated with roflumilast when compared to those 
treated with placebo (6.0% vs 1.7%). The incidence was 2.5% vs 2.2% in patients with a baseline body 
weight ≥60 kg, treated with roflumilast when compared to those treated with placebo.

Concomitant treatment with long acting muscarinic antagonists (LAMA)
A higher incidence of weight decrease, decreased appetite, headache and depression was observed 
during Study RO-2455-404-RD in patients receiving concomitant roflumilast and long-acting 
muscarinic antagonists (LAMA) plus concomitant inhaled corticosteroids (ICS) and long acting B2
agonists (LABA) compared to those treated only with concomitant roflumilast, ICS and LABA. 
Difference of incidence between roflumilast and placebo was quantitatively greater with concomitant 
LAMA for weight decreased (7.2% vs 4.2%), decreased appetite (3.7% vs 2.0%), headache (2.4% vs 
1.1%) and depression (1.4% vs -0.3%).

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

Symptoms
In Phase I studies, the following symptoms were observed at an increased rate after single oral doses of 
2,500 micrograms and one single dose of 5,000 micrograms (ten times the recommended dose): 
headache, gastrointestinal disorders, dizziness, palpitations, light-headedness, clamminess and arterial 
hypotension. 

Management
In case of overdose, it is recommended that the appropriate supportive medical care is provided. Since 
roflumilast is highly protein bound, haemodialysis is not likely to be an efficient method of its removal. 
It is not known whether roflumilast is dialysable by peritoneal dialysis. 

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for obstructive 
airway diseases, ATC code: R03DX07

Mechanism of action
Roflumilast is a PDE4 inhibitor, a non-steroid, anti-inflammatory active substance designed to target 
both the systemic and pulmonary inflammation associated with COPD. The mechanism of action is the 
inhibition of PDE4, a major cyclic adenosine monophosphate (cAMP)-metabolizing enzyme found in 
structural and inflammatory cells important to the pathogenesis of COPD. Roflumilast targets the 
PDE4A, 4B and 4D splicing variants with similar potency in the nanomolar range. The affinity to the 
PDE4C splicing variants is 5 to 10-fold lower. This mechanism of action and the selectivity also apply 
to roflumilast N-oxide, which is the major active metabolite of roflumilast.  

Pharmacodynamic effects
Inhibition of PDE4 leads to elevated intracellular cAMP levels and mitigates COPD-related 
malfunctions of leukocytes, airway and pulmonary vascular smooth muscle cells, endothelial and airway 
epithelial cells and fibroblasts in experimental models. Upon in vitro stimulation of human neutrophils, 
monocytes, macrophages or lymphocytes, roflumilast and roflumilast N-oxide suppress the release of 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



8

inflammatory mediators e.g. leukotriene B4, reactive oxygen species, tumor necrosis factor α, 
interferon γ and granzyme B. 
In patients with COPD, roflumilast reduced sputum neutrophils. Furthermore, roflumilast attenuated 
influx of neutrophils and eosinophils into the airways of endotoxin challenged healthy volunteers. 

Clinical efficacy and safety
In two confirmative replicate one-year studies (M2-124 and M2-125) and two supplementary six-month 
studies (M2-127 and M2-128), a total number of 4,768 patients were randomized and treated of whom 
2,374 were treated with roflumilast. The design of the studies was parallel-group, double-blind and 
placebo-controlled. 

The one-year studies included patients with a history of severe to very severe COPD [FEV1 (forced 
expiratory volume in one second) ≤50% of predicted] associated with chronic bronchitis, with at least 
one documented exacerbation in the previous year and with symptoms at baseline as determined by 
cough and sputum score. Long-acting beta-agonists (LABAs) were allowed in the studies and were used 
in approximately 50% of the study population. Short-acting anticholinergics (SAMAs) were allowed for 
those patients not taking LABAs. Rescue medicinal products (salbutamol or albuterol) were allowed on 
an as-needed basis. The use of inhaled corticosteroids and theophylline was prohibited during the 
studies. Patients with no history of exacerbations were excluded.

In a pooled analysis of the one-year studies M2-124 and M2-125, roflumilast 500 micrograms once 
daily significantly improved lung function compared to placebo, on average by 48 ml 
(pre-bronchodilator FEV1, primary endpoint, p<0.0001), and by 55 ml (post-bronchodilator FEV1, 
p<0.0001). The improvement in lung function was apparent at the first visit after 4 weeks and was 
maintained up to one year (end of treatment period). The rate (per patient per year) of moderate 
exacerbations (requiring intervention with systemic glucocorticosteroids) or severe exacerbations 
(resulting in hospitalisation and/or leading to death) after 1 year was 1.142 with roflumilast and 1.374 
with placebo corresponding to a relative risk reduction of 16.9% (95%CI: 8.2% to 24.8%) (primary 
endpoint, p=0.0003). Effects were similar, independent of previous treatment with inhaled 
corticosteroids or underlying treatment with LABAs. In the subgroup of patients with history of 
frequent exacerbations (at least 2 exacerbations during the last year), the rate of exacerbations was 
1.526 with roflumilast and 1.941 with placebo corresponding to a relative risk reduction of 21.3% 
(95%CI: 7.5% to 33.1%). Roflumilast did not significantly reduce the rate of exacerbations compared 
with placebo in the subgroup of patients with moderate COPD.
The reduction of moderate or severe exacerbations with roflumilast and LABA compared to placebo 
and LABA was on average 21% (p=0.0011). The respective reduction in exacerbations seen in patients 
without concomitant LABAs was on average 15% (p=0.0387). The numbers of patients who died due to 
any reason were equal for those treated with placebo or roflumilast (42 deaths each group; 2.7% each 
group; pooled analysis). 

A total of 2,690 patients were included and randomized in two supportive 1-year studies (M2-111 and 
M2-112). In contrast to the two confirmative studies, a history of chronic bronchitis and of COPD 
exacerbations was not requested for patients’ inclusion. Inhaled corticosteroids were used in 809 (61%) 
of the roflumilast treated patients, whereas the use of LABAs and theophylline was prohibited. 
Roflumilast 500 micrograms once daily significantly improved lung function compared to placebo, on 
average by 51 ml (pre-bronchodilator FEV1, p<0.0001), and by 53 ml (post-bronchodilator FEV1, 
p<0.0001). The rate of exacerbations (as defined in the protocols) were not significantly reduced by
roflumilast in the individual studies (relative risk reduction: 13.5% in study M2-111 and 6.6% in study 
M2-112; p= not significant). Adverse events rates were independent of concomitant treatment with 
inhaled corticosteroids.

Two six-month supportive studies (M2-127 and M2-128) included patients with a history of COPD for 
at least 12 months prior to baseline. Both studies included moderate to severe patients with a 
non-reversible airway obstruction and a FEV1 of 40% to 70% of predicted. Roflumilast or placebo 
treatment was added to continuous treatment with a long-acting bronchodilator, in particular salmeterol 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



9

in study M2-127 or tiotropium in study M2-128. In the two six-month studies, pre-bronchodilator FEV1
was significantly improved by 49 ml (primary endpoint, p<0.0001) beyond the bronchodilator effect of 
concomitant treatment with salmeterol in study M2-127 and by 80 ml (primary endpoint, p<0.0001) 
incremental to concomitant treatment with tiotropium in study M2-128. 

Study RO-2455-404-RD was a one year study in COPD patients with a baseline (pre-bronchodilator) 
FEV1 <50% of predicted normal and a history of frequent exacerbations. The study assessed the effect 
of roflumilast on COPD exacerbation rate in patients treated with fixed combinations of LABA and 
inhaled corticosteroids, compared to placebo. A total of 1935 patients were randomised to double-blind 
medication and approximately 70% were also using a long-acting muscarinic antagonist (LAMA) 
through the course of the trial. The primary endpoint was reduction in rate of moderate or severe COPD 
exacerbations per patient per year. The rate of severe COPD exacerbations and changes in FEV1 were 
evaluated as key secondary endpoints.

Table 2. Summary of COPD exacerbation endpoints in Study RO-2455-404-RD

Exacerbation 
Category

Analysis 
model

Roflumilast

(N=969)
Rate (n)

Placebo
(N=966)
Rate (n)

Ratio Roflumilast/Placebo
2-Sided

p-value
Rate 
Ratio

Change
(%) 95% CI

Moderate or 
severe

Poisson 
regression

0.805 
(380)

0.927 
(432)

0.868 -13.2
0.753, 
1.002

0.0529

Moderate Poisson 
regression

0.574 
(287)

0.627 
(333)

0.914 -8.6
0.775, 
1.078

0.2875

Severe Negative 
binomial 

regression

0.239 
(151)

0.315 
(192) 0.757 -24.3

0.601, 
0.952

0.0175

There was a trend towards a reduction in moderate or severe exacerbations in subjects treated with 
roflumilast compared with placebo over 52 weeks, which did not achieve statistical significance (Table 
2). A pre-specified sensitivity analysis using the negative binomial regression model treatment showed a 
statistically significant difference of -14.2% (rate ratio: 0.86; 95% CI: 0.74 to 0.99).

The per-protocol Poisson regression analysis and the non-significant sensitivity to drop-out Poisson 
regression intention-to-treat analysis rate ratios were 0.81 (95% CI: 0.69 to 0.94) and 0.89 (95% CI: 
0.77 to 1.02), respectively.

Reductions were achieved in the subgroup of patients concomitantly treated with LAMA (rate ratio: 
0.88; 95% CI: 0.75 to 1.04) and in the subgroup not treated with LAMA (rate ratio: 0.83; 95% CI: 0.62 
to 1.12).

The rate of severe exacerbations was reduced in the overall patient group (rate ratio: 0.76; 95% CI: 
0.60 to 0.95) with a rate of 0.24 per patient/year compared to a rate of 0.32 per patient/year in patients 
treated with placebo. A similar reduction was achieved in the subgroup of patients concomitantly treated
with LAMA (rate ratio: 0.77; 95% CI: 0.60 to 0.99) and in the subgroup not treated with LAMA (rate 
ratio: 0.71; 95% CI: 0.42 to 1.20). 

Roflumilast improved lung function after 4 weeks (sustained over 52 weeks). Post-bronchodilator FEV1
increased for the roflumilast group by 52 mL (95% CI: 40, 65 mL) and decreased for the placebo group 
by 4 mL (95% CI:  -16, 9 mL). Post-bronchodilator FEV1 showed a clinically significant improvement 
in favour of Roflumilast by 56 mL over placebo (95% CI: 38, 73 mL).

Seventeen (1.8%) patients in the roflumilast group and 18 (1.9%) patients in the placebo group died 
during the double-blind treatment period due to any reason and 7 (0.7%) patients in each group due to a 
COPD exacerbation. The proportion of patients who experienced at least 1 adverse event during the 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



10

double-blind treatment period were 648 (66.9%) patients and 572 (59.2%) patients in the roflumilast 
and placebo groups, respectively. The observed adverse reactions for roflumilast in Study RO-2455-
404-RD were in line with those already included in section 4.8. 

More patients in the roflumilast group (27.6%) than placebo (19.8%) withdrew study medication due to 
any reason (risk ratio: 1.40; 95%CI: 1.19 to 1.65). The major reasons for trial discontinuation were 
withdrawal of consent and reported adverse events.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
roflumilast in all subsets of the paediatric population in chronic obstructive pulmonary disease (see 
section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Roflumilast is extensively metabolised in humans, with the formation of a major pharmacodynamically 
active metabolite, roflumilast N-oxide. Since both roflumilast and roflumilast N-oxide contribute to 
PDE4 inhibitory activity in vivo, pharmacokinetic considerations are based on total PDE4 inhibitory 
activity (i.e. total exposure to roflumilast and roflumilast N-oxide).

Absorption
The absolute bioavailability of roflumilast following a 500 micrograms oral dose is approximately 80%. 
Maximum plasma concentrations of roflumilast typically occur approximately one hour after dosing 
(ranging from 0.5 to 2 hours) in the fasted state. Maximum concentrations of the N-oxide metabolite are 
reached after about eight hours (ranging from 4 to 13 hours). Food intake does not affect the total PDE4 
inhibitory activity, but delays time to maximum concentration (tmax) of roflumilast by one hour and 
reduces Cmax by approximately 40%. However, Cmax and tmax of roflumilast N-oxide are unaffected.

Distribution
Plasma protein binding of roflumilast and its N-oxide metabolite is approximately 99% and 97%, 
respectively. Volume of distribution for single dose of 500 micrograms roflumilast is about 2.9 l/kg. 
Due to the physico-chemical properties, roflumilast is readily distributed to organs and tissues including 
fatty tissue of mice, hamster and rat. An early distribution phase with marked penetration into tissues is 
followed by a marked elimination phase out of fatty tissue most probably due to pronounced 
break-down of parent compound to roflumilast N-oxide. These studies in rats with radiolabeled 
roflumilast also indicate low penetration across the blood-brain barrier. There is no evidence for a 
specific accumulation or retention of roflumilast or its metabolites in organs and fatty tissue. 

Biotransformation
Roflumilast is extensively metabolised via Phase I (cytochrome P450) and Phase II (conjugation) 
reactions. The N-oxide metabolite is the major metabolite observed in the plasma of humans. The 
plasma AUC of the N-oxide metabolite on average is about 10-fold greater than the plasma AUC of 
roflumilast. Thus, the N-oxide metabolite is considered to be the main contributor to the total PDE4 
inhibitory activity in vivo. 

In vitro studies and clinical interaction studies suggest that the metabolism of roflumilast to its N-oxide 
metabolite is mediated by CYP1A2 and 3A4. Based on further in vitro results in human hepatic 
microsomes, therapeutic plasma concentrations of roflumilast and roflumilast N-oxide do not inhibit 
CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11. Therefore, there is a low 
probability of relevant interactions with substances metabolised by these P450 enzymes. In addition, in 
vitro studies demonstrated no induction of the CYP1A2, 2A6, 2C9, 2C19, or 3A4/5 and only a weak 
induction of CYP2B6 by roflumilast.

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



11

Elimination
The plasma clearance after short-term intravenous infusion of roflumilast is about 9.6 l/h. Following an 
oral dose, the median plasma effective half-life of roflumilast and its N-oxide metabolite are 
approximately 17 and 30 hours, respectively. Steady state plasma concentrations of roflumilast and its 
N-oxide metabolite are reached after approximately 4 days for roflumilast and 6 days for roflumilast 
N-oxide following once-daily dosing. Following intravenous or oral administration of radiolabeled 
roflumilast, about 20% of the radioactivity was recovered in the faeces and 70% in urine as inactive 
metabolites.

Linearity/Non-linearity
The pharmacokinetics of roflumilast and its N-oxide metabolite are dose-proportional over a range of 
doses from 250 micrograms to 1,000 micrograms.

Special populations
In older people, females and in non-Caucasians, total PDE4 inhibitory activity was increased. Total 
PDE4 inhibitory activity was slightly decreased in smokers. None of these changes were considered to 
be clinically meaningful. No dose adjustment is recommended in these patients. A combination of 
factors, such as in black, non-smoking females, might lead to an increase of exposure and persistent 
intolerability. In this case, roflumilast treatment should be reassessed (see section 4.4).

In study RO-2455-404-RD when compared with the overall population, the total PDE4 inhibitory 
activity determined from ex vivo unbound fractions was found to be 15% higher in patients ≥75 years of 
age, and 11% higher in patients with baseline body weight <60 kg (refer to section 4.4).

Renal impairment
Total PDE4 inhibitory activity decreased by 9% in patients with severe renal impairment (creatinine 
clearance 10-30 ml/min). No dose adjustment is necessary.

Hepatic impairment
The pharmacokinetics of roflumilast 250 micrograms once-daily was tested in 16 patients with mild to 
moderate hepatic impairment classified as Child-Pugh A and B. In these patients, the total PDE4 
inhibitory activity was increased by about 20% in patients with Child-Pugh A and about 90% in 
patients with Child-Pugh B. Simulations suggest dose proportionality between roflumilast 250 and 
500 micrograms in patients with mild and moderate hepatic impairment. Caution is necessary in 
Child-Pugh A patients (see section 4.2). Patients with moderate or severe hepatic impairment classified 
as Child-Pugh B or C should not take roflumilast (see section 4.3).

5.3 Preclinical safety data

There is no evidence for an immunotoxic, skin sensitising or phototoxic potential.

A slight reduction in male fertility was seen in conjunction with epididymal toxicity in rats. No 
epididymal toxicity or changes in semen parameters were present in any other rodent or non-rodent 
species including monkeys in spite of higher exposures. 

In one of two rat embryofetal development studies, a higher incidence of incomplete skull bone 
ossification was seen at a dose producing maternal toxicity. In one of three rat studies on fertility and 
embryofetal development, post-implantation losses were observed. Post-implantation losses were not 
seen in rabbits. Prolongation of gestation was seen in mice. 

The relevance of these findings to humans is unknown. 

Most relevant findings in safety pharmacology and toxicology studies occurred at higher doses and 
exposure than that intended for clinical use. These findings consisted mainly of gastrointestinal findings 
(i.e. vomiting, increased gastric secretion, gastric erosions, intestine inflammation) and cardiac findings 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



12

(i.e. focal haemorrhages, haemosiderin deposits and lympho-histiocytic cell infiltration in the right atria 
in dogs, and decreased blood pressure and increased heart rate in rats, guinea pigs and dogs).

Rodent-specific toxicity in the nasal mucosa was observed in repeat-dose toxicity and carcinogenicity 
studies. This effect seems to be due to an ADCP (4-Amino-3,5-dichloro-pyridine) N-oxide intermediate 
specifically formed in rodent olfactory mucosa, with special binding affinity in these species (i.e. mouse, 
rat and hamster).

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Core
Lactose monohydrate
Maize starch
Povidone (K90)
Magnesium stearate

Coating
Hypromellose 
Macrogol 4000
Titanium dioxide (E171)
Iron oxide yellow (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/PVDC aluminum blisters in packs of 10, 30, or 90 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

AstraZeneca AB
SE-151 85 Södertälje
Sweden

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



13

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/11/666/001-003

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 28 February 2011
Date of latest renewal: 24 April 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

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



14

ANNEX II

A. MANUFACTURER 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

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



15

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Takeda GmbH
Production Site Oranienburg
Lehnitzstrasse 70-98
D-16515 Oranienburg
Germany

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic Safety Update Reports 

The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided
for under Article 107c(7) of Directive 2001/83/EC and 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.

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted 
at the same time.

 Additional risk minimisation measures

The Marketing Authorisation Holder shall agree the content and format of the updated educational 
material with the national competent authority.

The Marketing Authorisation Holder (MAH) should ensure that all Healthcare Professionals who are 
expected to prescribe Libertek are provided with an updated Educational pack.

The educational pack should contain the following:

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



16

 Summary of Product Characteristics and Patient Information Leaflet for Libertek

 Educational material for the physician.

 Copies of the patient card to be given to patients or caregivers before they receive Libertek

The educational material for the prescriber should include information on the following key elements:

 The specific indication approved. 

 The fact that Libertek is not indicated for the treatment of COPD patients outside of the 
approved indication, nor for use in patients with asthma or alpha-1 antitrypsin deficiency.

 The need to inform patients about the risks of Libertek and the precautions for safe use
including:

 The risk of weight decrease in underweight patients and the need to monitor the body weight at 
each visit and to stop the treatment in the event of an unexplained and clinically concerning 
weight decrease. Patients should be advised to weigh themselves at regular intervals and record 
the weight in the patient card.

 The risk of psychiatric disorders such as insomnia, anxiety, depression in patients receiving 
Libertek and the potential risk of suicide. Rare instances of suicidal ideation and behaviour, 
including completed suicide, have been observed in patients with and without a history of 
depression, usually in the first weeks of treatment. Physicians should carefully assess the 
benefit risk balance of this treatment in patients with existing psychiatric symptoms or with 
history of depression. Libertek is not recommended in patients with a history of depression 
associated with suicidal ideation or behaviour. If patients suffer from new or worsening 
psychiatric symptoms, or suicidal ideation or suicidal attempt, it is recommended to discontinue 
treatment with Libertek.

 Patients and caregivers should be requested to report any changes in the patient`s behaviour or 
mood or suicidal ideation.

 The potential risk of malignant tumours and the lack of experience in patients with past history 
of cancer. Libertek should not be initiated or should be stopped in patients with cancers (except 
basal cell carcinoma).

 That increased exposure might occur in certain populations and increase the risk of persistent 
intolerability:

o Special populations who have increased PDE4 inhibition such as black non smoking 
females;

o Patients concomitantly treated with CYP1A2/2C19/3A4 inhibitors (such as 
fluvoxamine and cimetidine) or CYP1A2/3A4 inhibitors (such as enoxacin).

 The potential risk of infections: Libertek should not be initiated, or treatment should be stopped, 
in patients with severe acute infectious diseases. The limited experience in patients with latent 
infections such as tuberculosis, viral hepatitis or herpes infections. 

 The lack of experience in patients with HIV infection or active hepatitis, with severe 
immunological diseases (e.g..multiple sclerosis, lupus erythematosus, multifocal 
leukoencephalopathy) or treated with immunosuppressive therapy (other than short-term 
systemic corticosteroids) and that Libertek should not be initiated or should be stopped in these 
patients.

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



17

 The potential cardiac risk: Libertek has not been studied in patients in congestive heart failure 
(NYHA grade 3 and 4); hence, it is not recommended in this population.

 The limited or missing information in patients with liver impairment. Libertek is contraindicated 
in patients with moderate or severe liver impairment (Child-Pugh B or C). Clinical data are 
considered insufficient to recommend dose adjustment and caution should be observed in 
patients with mild liver impairment (Child-Pugh A). 

 The lack of clinical data to support the combination with theophylline and that such 
combination is not recommended.

Patient Card

The patient card should contain the following key elements:

That they should tell their doctor if they have a history of any of the following conditions 

 cancer

 insomnia, anxiety, depression, suicidal ideation or behaviour

 multiple sclerosis or SLE

 infection with tuberculosis, herpes, hepatitis, HIV

That patients or their caregivers should tell their doctor if the patient develops symptoms indicative of:

 insomnia, anxiety, depression, changes in behaviour or mood, suicidal ideation or behaviour

 severe infection

That patients should tell their doctor if they are taking any other medicines.

That Libertek may cause weight loss and patients should weigh themselves regularly and record their 
weight on the patient card.

The patient card should include an area where patients can record their weight and the date they 
weighed themselves and they should be asked to bring the patient card with them at each visit.

 Obligation to conduct post-authorisation measures

The MAH shall complete, within the stated timeframe, the below measures:

Description Due date

ANX 2.1 - The MAH commits to conduct a long-term comparative 

observational safety study. This study should be appropriate to compare 

the incidences of all-cause mortality, major cardiovascular events, new 

diagnosis of cancer, all-cause hospitalisation, hospitalisation related to 

respiratory disease, suicide or hospitalisation for suicide attempt, and new 

diagnosis of depression, tuberculosis or viral hepatitis B or C in 

roflumilast treated COPD patients compared with COPD patients not 

treated with roflumilast.

Interim Study 

Reports  - with each

PSUR

Final study report 

by 31/03/2021

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



18

ANNEX III

LABELLING AND PACKAGE LEAFLET

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



19

A. LABELLING

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



20

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON FOR BLISTER

1. NAME OF THE MEDICINAL PRODUCT

Libertek 500 micrograms film-coated tablets
roflumilast

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 500 micrograms roflumilast.

3. LIST OF EXCIPIENTS

Contains lactose. See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

10 film-coated tablets
30 film-coated tablets
90 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

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



21

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

AstraZeneca AB
SE-151 85 Södertälje
Sweden

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/11/666/001
EU/1/11/666/002
EU/1/11/666/003

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Libertek 500 micrograms

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



22

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTERS

1. NAME OF THE MEDICINAL PRODUCT

Libertek 500 micrograms tablets
roflumilast

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. OTHER

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



23

B. PACKAGE LEAFLET

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



24

Package leaflet: Information for the patient

Libertek 500 micrograms film-coated tablets 
Roflumilast

This medicine is subject to additional monitoring. This will allow quick identification of new safety 
information. You can help by reporting any side effects you may get. See the end of section 4 for how to 
report side effects.

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 Libertek is and what it is used for
2. What you need to know before you take Libertek
3. How to take Libertek
4. Possible side effects
5. How to store Libertek
6. Contents of the pack and other information

1 What Libertek is and what it is used for

Libertek contains the active substance roflumilast, which is an anti-inflammatory medicine called 
phosphodiesterase-4 inhibitor. Roflumilast reduces the activity of phosphodiesterase-4, a protein 
occurring naturally in body cells. When the activity of this protein is reduced, there is less inflammation 
in the lungs. This helps to stop narrowing of airways occurring in chronic obstructive pulmonary 
disease (COPD). Thus Libertek eases breathing problems.

Libertek is used for maintenance treatment of severe COPD in adults who in the past had frequent 
worsening of their COPD symptoms (so-called exacerbations) and who have chronic bronchitis. COPD 
is a chronic disease of the lungs that results in tightening of the airways (obstruction) and swelling and 
irritation of the walls of the small air passages (inflammation). This leads to symptoms such as 
coughing, wheezing, chest tightness or difficulty in breathing. Libertek is to be used in addition to 
bronchodilators.

2 What you need to know before you take Libertek

Do not take Libertek
- if you are allergic to roflumilast or any of the other ingredients of this medicine (listed in section 

6)
- if you have moderate or severe liver problems. 

Warnings and precautions
Talk to your doctor or pharmacist before taking Libertek

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



25

Sudden attack of breathlessness
Libertek is not intended for the treatment of a sudden attack of breathlessness (acute bronchospasms). In 
order to relieve a sudden attack of breathlessness it is very important that your doctor provides you with 
another medicine to be available to you at all times that can cope with such an attack. Libertek will not 
help you in this situation.

Body weight
You should check your body weight on a regular basis. Talk to your doctor if, while taking this 
medicine, you observe an unintentional loss of body weight (not related to a diet or exercise 
programme). 

Other diseases
Libertek is not recommended if you have one or more of the following diseases:
- severe immunological diseases such as HIV infection, multiple sclerosis (MS), lupus erythematosus 

(LE) or progressive multifocal leukoencephalopathy (PML)
- severe acute infectious diseases such as tuberculosis, or acute hepatitis 
- cancer (except basal-cell carcinoma, a slow-growing type of skin cancer) 
- or severe impairment of the heart function 
There is a lack of relevant experience with Libertek under these conditions. You should talk to your 
doctor, if you are diagnosed with any of these diseases. 

Experience is also limited in patients with a previous diagnosis of tuberculosis, viral hepatitis, herpes 
viral infection or herpes zoster. Please talk to your doctor if you have one of these diseases.

Symptoms you should be aware of
You may experience diarrhoea, nausea, abdominal pain or headache during the first weeks of treatment 
with Libertek. Talk to your doctor if these side effects do not resolve within the first weeks of treatment.

Libertek is not recommended in patients with a history of depression associated with suicidal thinking or 
behaviour. You may also experience sleeplessness, anxiety, nervousness, or depressive mood. Before 
starting treatment with Libertek, inform your doctor if you are suffering from any symptoms of this kind 
and of any additional medicines you may take since some of those could increase the probability of these 
side effects. You or your caregiver should also immediately inform your doctor of any changes in 
behaviour or mood and of any suicidal thoughts you may have.

Children and adolescents
Libertek should not be used by children and adolescents under 18 years of age.

Other medicines and Libertek
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, 
especially the following:
- a medicine containing theophylline (a medicine to treat respiratory diseases), or 
- a medicine used for treatment of immunological diseases, such as methotrexate, azathioprine, 
infliximab, etanercept, or oral corticosteroids to be taken long-term.
- a medicine containing fluvoxamine (a medicine to treat anxiety disorders and depression), enoxacin (a 
medicine to treat bacterial infections) or cimetidine (a medicine to treat stomach ulcers or heartburn).

The effect of Libertek may be reduced if taken together with rifampicin (an antibiotic medicine) or with 
phenobarbital, carbamazepine or phenytoin (medicines usually prescribed for the treatment of epilepsy). 
Ask your doctor for advice.

Libertek may be taken with other medicines used in the treatment of COPD such as inhaled or oral 
corticosteroids or bronchodilators. Do not stop taking these medicines or reduce their dose unless 
advised by your doctor.

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



26

Pregnancy and breast-feeding
Do not take Libertek if you are or plan to become pregnant, think you may be pregnant, or are 
breast-feeding. You should not become pregnant during treatment with this medicine and should use an 
effective method of contraception during therapy, because Libertek may be harmful for the unborn 
baby.

Driving and using machines
Libertek has no influence on the ability to drive and use machines.

Libertek contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine.

3 How to take Libertek

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure.

The recommended dose is one 500 micrograms tablet once daily.

Swallow the tablet with some water. You may take this medicine with or without food. Take the tablet
at the same time every day.

You may need to take Libertek for several weeks to achieve its beneficial effect.

If you take more Libertek than you should
If you have taken more tablets than you should, you may experience the following symptoms: headache, 
nausea, diarrhoea, dizziness, throbbing of your heart, light-headedness, clamminess and low blood 
pressure. Tell your doctor or pharmacist straight away. If possible take your medicine and this leaflet 
with you.

If you forget to take Libertek
If you forget to take a tablet at the usual time, take the tablet as soon as you remember on the same day. 
If on one day you have forgotten to take a tablet of Libertek, just carry on the next day with the next 
tablet as usual. Continue taking your medicine at the usual times. Do not take a double dose to make up 
for a forgotten dose. 

If you stop taking Libertek
It is important to continue taking Libertek for as long as prescribed by your doctor, even when you have 
no symptoms, in order to maintain control of your lung function.

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.

You may experience diarrhoea, nausea, stomach ache or headache during the first weeks of treatment 
with Libertek. Talk to your doctor if these side effects do not resolve within the first weeks of treatment.

Some side effects could be serious. In clinical studies and post-marketing experience, rare instances of 
suicidal thinking and behaviour (including suicide) were reported. Please notify your doctor immediately 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



27

of any suicidal thoughts you may have. You may also experience sleeplessness (common), anxiety 
(uncommon), nervousness (rare), panic attack (rare) or depressive mood (rare).

In uncommon cases allergic reactions may occur. Allergic reactions may affect the skin and in rare 
cases cause swelling of the eyelids, face, lips and tongue, possibly leading to difficulties in breathing
and/or a drop in blood pressure and accelerated heartbeat. In case of an allergic reaction, stop taking 
Libertek and contact your doctor immediately, or go immediately to the emergency department in the 
nearest hospital. Take all your medicines and this leaflet with you and provide full information of your 
current medications.

Other side effects include the following:

Common side effects (may affect up to 1 in 10 people)
- diarrhoea, nausea, stomach ache
- weight decrease, decreased appetite
- headache

Uncommon side effects (may affect up to 1 in 100 people)
- trembling, sensation of spinning head (vertigo), dizziness
- sensation of rapid or irregular heartbeat (palpitations)
- gastritis, vomiting
- reflux of stomach acid to the gullet (acid regurgitations), indigestion
- rash
- muscle pain, muscle weakness or cramps
- back pain
- feeling of weakness or tiredness, feeling unwell.

Rare side effects (may affect up to 1 in 1,000 people)
- male breast enlargement
- decreased sense of taste
- respiratory tract infections (excluding pneumonia)
- bloody stools, constipation
- elevation of liver or muscle enzymes (seen in blood tests)
- wheals (urticaria).

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 Libertek

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 carton and blister 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.

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



28

6. Contents of the pack and other information

What Libertek contains
- The active substance is roflumilast. Each film-coated tablet (tablet) contains 500 micrograms 

roflumilast.
- The other ingredients are:

- Core: lactose monohydrate, maize starch, povidone (K90), magnesium stearate, 
- Coating: hypromellose, Macrogol 4000, titanium dioxide (E171), and iron oxide yellow 

(E172).

What Libertek looks like and contents of the pack
Libertek 500 micrograms film-coated tablets are yellow, D-shaped film-coated tablets, embossed with 
'D' on one side.
Each pack contains 10, 30, or 90 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer
Takeda GmbH
Production site Oranienburg
Lehnitzstraße 70-98
16515 Oranienburg
Germany

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 24455000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 41 03 7080

Nederland
AstraZeneca BV
Tel: +31 79 363 2222

Eesti
AstraZeneca 
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



29

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
Laboratorio Beta, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska 
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland) Ltd
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777 

Italia
Simesa S.p.A.
Tel: +39 02 9801 1

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

United Kingdom
AstraZeneca UK Ltd
Tel: +44 1582 836 836

This leaflet was last approved in 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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