1. PHARMACEUTICAL FORM Film-coated tablet (tablet). Yellow, O

DAXAS 500 micrograms film-coated tablets
Each tablet contains 500 micrograms of roflumilast.
1. PHARMACEUTICAL FORM
Film-coated tablet (tablet).
Yellow, O-shaped film-coated tablet, embossed with "D" on one side.
2. CLINICAL PARTICULARS
2.1 Therapeutic Indications
Daxas is Indicated as add-on therapy to long-acting bronchodilator(s) treatment for the
maintenance 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
2.2 Posology and method of administration Posology
The recommended dose Is one tablet of 500 mlcrograms roflumilast once daily.
Daxas may need to bo taken for several weeks to achieve its effect (see section 3.1). Daxas
has been studied in clinical trials for up to one year.
Special populations
Elderly (65 years and older)
No dose adjustment is necessary.
Renal impairment
No dose adjustment Is necessary,
Hepatic Impairment
The clinical data with Daxas In patients with mild hepatic impairment classified as Child-Pugh
A are insufficient to recommend a dose adjustment (see section 3.2) and therefore Dexas should
be used with caution in these patients.
Patients with moderate or severe hepatic Impairment classified as Child-Pugh B or C should
not take Daxas (see section 2.3),
Paediatric population
There is no relevant use of Daxas In the paediatric population (under l8 years).
Method of administration For oral use.
The tablet should be swallowed wlth water and taken at the same time every day. The tablet
can be taken with or without food.
2.3 Contraindications
Hypersensitivity to roflumilast or to any of the excipient. Moderate or severe hepatic
impairment (Child-Pugh B or C).
2.4 Special warnings and precautions for use Rescue medicinal products
Roflumilast is an anti-lnflammatory substance indicated for maintenance treatment of severe
COPD associated with chronic bronchitis In adult patients with a history of frequent
exacerbations as add on to bronchoditalor treatment. It is not indicated as rescue
medicinal product for the relief of acute bronchospasms.
All patients should be informed about the risk of Daxas and the precautions for safe use.
Weight decrease
In 1-year studies (M2-124, M2-125). a decrease of body weight occured more frequently In
patients treated with Daxas compared to placebo-treated patients. Alter discontinuation of
Daxas, 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 chock their body weight on a regular basis, in the event of an unexplained and
clinically concerning weight decrease, the intake of Daxas should be stopped end body
weight should be further followed- up.
Special clinical conditions
Due to lack of relevant experience, treatment with Daxas should not be initiated or existing
treatment with Daxas should be stopped in patients with severe Immu nological diseases (e.g.
HIV Infection, multiple sclerosis, lupus erythematosus, progressive multifocal
leukoencephalopathy), severe acute infectious disease, cancers (except basal cell carcinoma).
Or patients being treated with Immunosuppressive medicinal products (I.e.: methotrexate,
azathioprine, infliximab, etenarcept, or oral corticosteroid 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
Daxas is associated with an increased risk of psychiatric disorders such as insomnia, anxiety,
nervousness and depression. Rate instances of suicidal Idea- tion and behavior, including
completed suicide, have been observed in clinical trials (see section 2.8), Therefore, the risks
and benefits of starting or continuing treatment with Daxas 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. Patients should be
instructed to notify their presciber of any changes in behavior or mood and of any suicidal
ideation. Moreover, Daxas is not recommended in patient with a history of depression
associated with suicidal ideation ot behavior.
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, Daxas
treatment should be , reassessed in case of persistent intolerability. This might be the one
in special populations that may hava higher exposure, such as in black, non-smoking
females (see section 3.2) or in patients concomitantly treated with the CYP1A2 inhibitor
fluvoxamine or the dual CYP3A4/1A2 inhibitors enoxacin and cimetidine (see section
2.5).
Theophylline
There are no clinical date to support the concomitant treatment with theophylline for
maintenance therapy. Therefore, the concomitant treatment with theophylline Is not
recommanded.
Lactose
Daxas tablets contain lactose. Patients with rare hereditary problems of galactose
intolerance, the Lapp lactate deficiency or glucose-galactose malabsorption should not
take this medicinal product.
2.5 Interaction With other medicinal product 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 Noxide by CYP3A4 and CYP1A2.Both roflumilast and roflumilast N-oxide have intinsic
phospodiesterase 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. Clinical Interaction Studies with CYP3A4 inhibitors
erythromycin and ketoconazole showed increases of 9% of the total PDE4 inhibitory
activity (I.e. total exposure to roflumilast and roflumilast N-oxide Interaction studies with
CYP1A2 inhibitor fluvoxamlne, and the dual CYP3A4/1A2 inhibitors enoxacln and
cimetidine resulted in increases of the total PDE4 inhibitory activity of 59%, 25%, and
47%, respectively. A combination of Daxas wtlh these active substance might lead to an
increase of exposure and persistant intolerability, In this case, Daxas treatment should be
reassessed (see section special warnings and precautions for use). 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 inducers
(e.g. pjemobarbital, carbamazepine, phenytoin) may reduce the therapeutic efficacy of
roflumilast Co-administration with theophylline resulted in an increase of 8% of the total
PDE4 inhibitory activity (see section 2.4). In an interaction study with an oral contraceptive containing gastodene and ethinyl oestradiol, the total PDE4 inhibitory activity
was increased by 17%.
No interactions were observed with inhaled salbutamol, formeterol, budesonide and oral
montelukast, digoxin. warafarin, sildenfil and midazolam. 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.
2.6 Fertility, pregnancy and lactation Pregnancy
There are limited amount of data from the use of roflumilast in pregnant women.
Studies in animals have shown reproductive toxicity (sea section 3.3). Daxas is not
recommended during pregnancy and In woman of childbearing potential not using
concentraception.
Roflumilast hat been demonstrated to cross the placenta in pregnant rate.
Breastfeeding
Available pharmacokinetic data in animals have shown excretion of reflumilast or its
metabolites in milk, A risk to the sucking child cannot ba excluded. Daxas should not be
used during breast-feeding
Fertility
In a humah spermatogenesis study; roflumilast 500 micro- grams had no effects on semen
parameters or reproductive hormones during the 3-month treatment period and the
following 3-month off-tratment period.
2.7 Effects on ability to drive and use machines
Daxas has no Influence on the ability to drive and use machines.
2.8 Undesirable effects
In clinical COPD studies, approximately 16% of patients experienced adverse reactions
with roflumilast (compared to 6% in plasebo). 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.
Within the following table, adverse reactions are ranked under the MedDRA frequency
classification:
Very common (> 1/10); common (> 1/100 to <1/10); uncom- mon (>1/1000 to <1/100);
rare (>1/10,000 to <1/1,000); vary rare (<1/10.000), not known (cannot be estimated from
the available data).
Within each frequency grouping. adverse reactions ara presented in order of decreasing
seriousness.
Table 1. Adverse reactions with roflumilast In clinical COPD studies
Frequency
Syste,
Organ Class
Immune
system
disorders
Endocrine disorders
Metabolism
and
nutrition disorders
Psychiatric disorders
Common
Uncommon
Rare
Hypersensitivity
Gynecomastia
Weight decreased
Decreased appetite
Insomnia
Anxiety
Depression
Nervous
disorders
system
Cardiac disorder
Respiratory, thoracic,
and
medistinal
disorders
Gastrointestinal
disorders
Headache
Diarrhoea
Nausea
Abdominal pain
Tremor
Vertigo
Dizziness
Palpitations
Gastritis
Vomiting
Gastro0esophageal
reflux disease
Dyspepsia
Hepatobiliary
disorders
Skin
and
subcutaneous tissue
disorders
Muscoloskeletal and
connective
tissue
disorders
General disorders and
administration
site
conditions
Rash
Muscle spasms and
weakness
Myalgia
Back pain
Malaise
Asthenia
Fatigue
Nervousness
Dysgeusia
Respiratory
tract
infections (excluding
pneumonia)
Haematochezia
Constipation
Gamma-GT increased
Aspartate
aminotransferase
(AST) increased
Urticaria
Blood
creatine
phosphokinase (CPK)
increased
In clinical studies, rare Instances of suicidal thinking and behaviour (Including completed
suicide) were reported. Patients should be Instructed to notify the prescriber of any
suicidal ideation (see also section 2.4).
2.9 Overdose
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.
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 dialyzable by
peritoneal dyalysis.
3. PHARMÄCOLOQIOÄI PROPERTIES
3.1 Pharmacodynamic properties
Pharmacotherapetic group: drug for obstructive airway disease, Other systemic drug for
obstructive airway disease.
ATC code: RS3DX07
Mechanism of action
Roflumilast is a PDE4 inhibitor, a non-steroid, anti-inflammatory agent 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 variant is 5 to
10-fold lower. This mechanism of action and the selectivity also apply to roflumilast Noxide, which is the major active metabolite of roflumilast.
Pharmacodynamic effects
inhibition of PDE4 leads to elevated Intracellular cAMP levels and mitigates COPDrelated malfunctions of leukocytes. airway and pulmonary vascular smooth muscle cells,
endothelial and airway epithelial cells and fibroblast in experimental models. Upon in
vitro stimulation of human neutrophils, monocytes, macrophages or lymphocytes,
roflumilast and roflumilast N-oxide suppress the release of 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
In two confirmative replicate one-year studies (M2-124 and M2-125) and two
supplementary six- rnonth study (M2-127 and M2-128), a total number of 4.768 patients
were randomized and treated of whom 2,374 were treated with Daxas. The design of the
studies was parallel-group, double-blind and placebo-controlled.
The one-year study 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 betaagonists (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 exacerbation were excluded.
In a pooled analysis of the one-year studies M2-124 and M2-125, Daxas 500 micrograms
once daily significantly improved lung function comparad to placebo, on average by 48
ml (pre-Bronchodilator FEV1, primary endpoint, p<0.0001), and by 55 ml (postbronchodilator 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 hospitallation and/or
leading to death) after 1 years was 1.142 with roflumilast and 1.374 with placebo
corresponding to 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 execerbations 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
Daxas end LABA compared to placebo and LABA was on average 21% (P=0.0011) The
respective reduction in exacerbations seen in patients without concominant 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 (12 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 snd 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.
Daxas 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 (postbronchodilator FEV1, p<0.0001). The rate of exacerbations (as defined in the protocol)
were not significantly reduced by roflumilast in the individual syudy (relative risk
reduction: 13.5% in study M2-111 and 6.6% in study M2-112; p = not significant).
Adverse event rate were independent of concomitent treatment with inhaled
corticosteroids.
Two six-month supportive studies (M2-127 and M2-128) included patients with a history
of COPD tor at least 12 months pior 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 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 concomitant treatment with tiotropium in study M2-128.
No study has been conducted to compare Daxas to the combination of LABA plus inhaled
corticosteroids or on top of the combination of LABA plus Inhaled corticosteroids.
3.2 Pharmacokinetic properties
Roflumilast is extensively metabolized 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 500 micrograms oral dose is
approximately 80%. Maximum plasma concentration 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 alter 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 to 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 tissues of mice, hamster and rat. An early distribution phase with marked
penetration into tissue 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 matabolised via Phase 1 (cytochrome P450) and Phase II
(conjugation) reactions. The N-oxide metabolite ls the major metabolite observed in the
plasma of humans. The plasma AUC of the N-oxide metabolite on average ls about 10fold greater than tha 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 end 3A4. Based on further in vitro
result in human hepatic microsomes, therapeutic plasma concentration of roflumilast and
roflumilast N-oxide do not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9,2C19, 2D6, 2E1, 3A4/5,
of 4A9/11. Therefore, there is a low probability of relevant interactions with substance
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.
Elimination
Tha plasma clearance after short-term intravenous infusion of roflumiast is about 9,6 l/h.
Following an oral dose, the median plasma effective half-life of roflumilast and Its Noxide metabolites are approximately 17 end 30 hours, respectively. Steady state plasma
concentrations of roflumilast and its N-oxide metabolite are reached after approximately
4 days for roflumilast and 8 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 Population
In elderly famales and In on-caucasian, total PDE4 inhibitory activity was increased.
Total PDE4 inhibitory activity was likely decreased in smokers none of these changes
were considered to be clinically meaningful, No dose adjustment is recommended in
these patients. A combination of factor, such as in black, non-smoking females might
lead to an increase of exposure and persistent intolerability, in this case, Daxas treatment
should reassessed (see section 2.4).
Renal Impairment
Total PDE4 Inhibitory activity decreased by 9% in patients with severe impairment
(creatinine cleareance 10-30 ml/min). No dose adjustment is necessary.
Hepatic impairment
The pharmacokinetics of Daxas 250 micrograms once-daliy was tested in 8 patients with
mild to moderate hepaticimpairment classified as Child-Pugh A and B. In these patients,
the total PDE4 inhibitory activity was increased by about 20% in patient with Child-Pugh
A and about 90% in patients with Child-PughB. Simulations suggest dose proportionality
between Daxas 250 and 500 micrograms in patients with mild and moderate hepatic
impairment. Caution is necessary in Child-Pugh A patients (see section 2.2). Patients
with moderate or severe hepatic impairment calssified as Child-Pugh B or C should not
take Daxas (see section 2.3).
3.3 Preclinical safety data
There is no evidence for an immunotoxic, skin sensitising or phototoxic potential.
A slight reduction in male fertility was seen in conjuction with epididymal toxicity I rats.
No epididymal toxicity or changes in semen parameters wer 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. Prolong action of
gestation was seen in mice.
The relevance of these findings to humans is unknown.
Most relevant finding in safety pharmacology and toxicology studies occurred at higher
doses and exposure than that intended for clinical use. These findings consisted mainly at
gastrointestinal finding (I.e. vommiting, increased gastric secretion, gastric erosions,
intestine inflamation) and cardiac finding (l.e. focalhaemorrages, haemosiderin
deposits and limpho-histiolytics 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-Ammino-3,5-dichloro
-pyridine) N-oxide. Intermediate specifically formed in rodent olfactory mucosa, with
special binding affinity in these species( l.e. mouse. rat and hamster).
4. PHARMACEUTICAL PARTICULARS
4.1 List of exicipents
Core
Lactose monohydrate
Maize starch
Povidone (K90)
Magnesium stearate
Coating
Hypermellose 2910
Macrogol 4000
Titanium dioxide (E171)
Iron oxide yellow (E172)
4.2 Incompabilites
Not applicable
4.3 Shelf life
3 years
4.4 Special precautions for storage
Store below 30oC
4.5 Nature and contains of container
PVC/PVDC alumunium blisters in pack of 30 film-coated tablets
4.6 Special precautions for disposal
No special requirements
Manufactured by:
Nycomed GmbH
Production site Oranienburg
Lehnitzatrasse 70-98
D-16515, Oranienburg
Germany
Registration Holder :
PT. Apex Pharma Indonesia, tangerang, Indonesia
Prescription medicine only
Harus dengan resep dokter
Based on EU SmPC – 05 Jul 2010
Daxas 500 microgram tablet salut
Roflumilast
Baca brosur ini dengan seksama sebelum Anda mulai menggunakan obat ini.
- Simpan brosur ini. Mungkin diperlukan untuk dibaca kembali.
- Jika Anda memiliki pertanyaan lebih lanjut, hubungi Dokter atau Apoteker anda.
- Bila obat ini telah diresepkan untuk Anda, jangan diberikan kepada orang lain karena
akan membahayakannya, walaupun gejala mereka sama dengan gejala anda.
- Jika terjadi efek samping yang serius, atau jika anda menderita efek samping yang
tidak tercantum dalam brosur ini, silahkan hubungi Dokter atau Apoteker anda.
Informasi yang tercantum dalam brosur ini :
1. Apakah tablet Daxas itu dan apa kegunaannya
2. Sebelum Anda menggunakan tablet Daxas
3. Bagaimana cara mengkonsumsi Daxas
4. Efek samping yang mungkin terjadi
5. Bagaimana cara penyimpanan tablet Daxas
6. Informasi lebih lanjut
1. APAKAH TABLET DAXAS ITU DAN APA KEGUNAANNYA
Daxas mengandung bahan aktif roflumilast, yang merupakan obat anti- inflamasi yang
disebut inhibitor phosphodiesterase 4. Roflumilast mengurangi aktivitas
phosphodiesterase 4, protein yang terjadi secará alami dalam sel tubuh. Ketika
aktifitas protein ini berkurang, peradangan yang ada di paru- paru juga berkurang. Hal
ini membantu untuk menghentikan penyempitan saluran udara yang terjadi pada
penyakit paru obstruktif kronik (PPOK). Jadi Daxas meringankan masalah pernapasan.
Daxas digunakan untuk mengobati PPOK berat pada orang dewasa. PPOK adalah
penyakit kronis paru-paru yang mengakibatkan penyempitan saluran napas (obstruksi)
dan pembengkakan dan iritasi pada dinding saluran udara kecil (peradangan)
menyebabkan gejala seperti batuk, nafas yang berbunyi (mengi), dada sesak atau
kesulitan bernafas. Selain itu, Daxas juga digunakan bersama-sama dengan
bronkodilator (pelega saluran nafas).
2. SEBELUM MENGGUNAKAN TABLET DAXAS
Jangan mengkonsumsi tablet Daxas
- Jika Anda alergi (hipersensitif) terhadap roflumilast atau terhadap salah satu bahan
tambahan dari tablet Daxas (tercantum dalam bagian 6 'Apa saja kandungan tablet
Daxas’)
- Jika Anda menderita penyakit hati sedang atau berat.
Hal-hal yang harus diperhatikan sebelum mengkonsumsi Daxas
Daxas tidak ditujukan untuk pengobatan serangan mendadak sesak napas (bronkospasme
akut). Untuk membantu meringankan serangan mendadak sesak napas, dokter Anda
perlu memberikan obat lain yang dapat mengatasi serangan itu. Anda harus memeriksa
berat badan Anda secara teratur. Informasikan kepada dokter jika saat minum obat ini,
Anda mengalami penurunan berat badan yang tidak diinginkan (tidak berhubungan
dengan program diet atau olahraga).
Daxas tidak direkomendasikan untuk pasien yang memiliki penyakit imunologi parah
(seperti infeksi HIV, muitipel sklerosis, lupus eritematosus, leukoencefalopati multifokal
progresif, dan lainnya), penyakit menular akut yang parah (seperti TBC, atau hepatitis
akut), kanker (kecuali karsinoma basal sel, sejenis kanker kulit yang tumbuh lambat),
atau gangguan berat pada fungsi jantung, karena kurangnya pengalaman penggunaan
Daxas pada kondisi ini. Informasikan kepada dokter, jika Anda didiagriosis dengan
penyakit ini.
Pengalaman penggunaan Daxas juga masih terbatas pada pasien yang sebelumnya
didiagnosis tuberkulosis, hepatitis virus, infeksi herpes virus atau herpes zoster.
Anda mungkin mengalami diare, mual, sakit perut atau sakit kepala selama mingguminggu pertama pengobatan dengan Daxas. Hubungi dokter jika efek samping ini tidak
berhenti dalam minggu pertama pengobatan.
Anda mungkin mengalami sulit tidur, gelisah, gugup, atau mood depresi. Sebelum
memulai pengobatan dengan Daxas, beritahu dokter jika Anda menderita gejala tersebut
dan beritahu obat lain yang digunakan karena mungkin dapat meningkatkan efek
samping ini. Segera beritahu dokter bila Anda merasa mengalami perubahan mood dan
perilaku yang mengarah pada usaha atau percobaan bunuh diri.
Anak-anak
Daxas tidak boleh digunakan untuk anak-anak dan remaja di bawah 18 tahun.
Mengkonsumsi obat-obatan lain
Informasikan kepada Dokter atau Apoteker jika Anda sedang minum obat lain, termasuk
obat bebas yang dibeli tanpa resep Dokter.
Daxas dapat diminum bersamaan dengan obat-obatan lain yang digunakan dalam
pengobatan PPOK seperti kortikosteroid inhalasi atau oral atau bronkodilator. Jangan
berhenti minum obat-obatan tersebut atau mengurangi dosisnya kecuali disarankan oleh
Dokter Anda.
Informasikan dokter sebelum Anda mulai menggunakan Daxas, Jika anda sudah
menggunakan:
Obat yang mengandung teofilin (obat untuk mengobati penyakit pernapasan),
atau pengobatan penyakit imunologi, seperti methotrexate, azathioprine,
infliximab, etanercept, atau kortikosteroid oral yang harus dikonsumsi dalam
jangka panjang; atau obat yang mengandung fluvoksamine, enoksacin atau
simetidin.
Efek Daxas dapat berkurang jika ditelan bersama dengan rifampisin (obat antibiotik)
atau dengan obat yang biasanya diresepkan untuk pengobatan epilepsi (fenobarbital,
fenitoin atau karbamazepin). Hubungi dokter Anda untuk meminta saran.
Penggunaan Daxas dengan makanan dan minuman
Anda bisa minum obat ini dengan atau tanpa makanan.
Kehamilan dan menyusui
Jangan minum Daxas jika Anda merencanakan untuk hamil, sedang hamil atau
menyusui.
Tanyakan kepada dokter atau apoteker untuk saran sebelum mengkonsumsi obat
apapun.
Mengemudi dan menggunakan mesin
Daxas tidak berpengaruh pada kemampuan mengemudi dan menggunakan mesin.
Informasi penting tentang beberapa bahan Daxas
Daxas tablet mengandung laktosa. Jika Dokter telah menginformasikan bahwa Anda
sensitif terhadap beberapa jenis gula, hubungi dokter Anda sebelum mengkonsumsi
obat ini.
3. BAGAIMANA CARA MENGKONSUMSI TABLET DAXAS
Gunakan Daxas sesuai petunjuk dokter. Hubungi Dokter atau Apoteker jika Anda
membutuhkan informasi lebih lanjut.
Dosis umum adalah satu tablet Daxas 500 mikrogram sekali sehari. Jangan minum
tablet melebihi yang telah diresepkan dokter.
Telan tablet dengan air. Obat ini dapat diminum dengan atau tanpa makanan. Minum
tablet pada waktu yang sama setiap hari.
Anda mungkin perlu minum Daxas selama beberapa minggu untuk mencapai efek
yang diinginkan.
Jika Anda mengkonsumsi Daxas iebih dari yang seharusnya
Segera hubungi Dokter atau Apoteker. Jika mungkin bawalah obat dan juga brosur
ini.
Jika Anda lupa minum tablet Daxas
Jika Anda lupa minum tablet pada waktu yang ditentukan, minum tablet segera setelah
Anda ingat. Jika pada satu hari Anda lupa untuk minum tablet Daxas, lanjutkan minum
Daxas pada hari berikutnya dengan dosis seperti biasa. Jangan meningkatkan dosisnya
untuk menggantikan tablet yang lupa diminum.
Jika Anda berhenti minum Daxas
Penting untuk mengkonsumsi Daxas selama diresepkan oleh dokter Anda, bahkan
ketika Anda tidak memiliki gejala, untuk mempertahankan kontrol fungsi paru-paru
Anda.
Jika Anda membutuhkan informasi lebih lanjut yang berhubungan dengan penggunaan
obat ini, tanyakan kepada Dokter atau Apoteker.
4.
EFEK SAMPING YANG MUNGKIN TERJADI
Seperti semua obat-obatan, Daxas dapat menyebabkan efek samping, meskipun tidak
semua orang mengalaminya.
Efek samping dapat terjadi dengan frekuensi tertentu, yang didefinisikan sebagai
berikut:
 Sangat umum: mempengaruhi lebih dari 1 dari 10 pasien,
 Umum: mempengaruhi 1 sampai 10 dari 100 pasien.
 biasa: mempengaruhi 1 sampai 10 dari 1.000 pasien.
 Jarang: mempengaruhi 1 sampai 10 dari 10.000 pasien.
 Sangat jarang: mempengaruhi kurang dari 1 dari 10.000 pasien.
 Tidak diketahui: frekuensi tidak dapat diperkirakan dari data yang tersedia.
Efek samping umum
Berat badan menurun, nafsu makan menurun, sulit tidur, sakit kepala, diare, mual, sakit
perut.
Efek samping tidak umum
Hipersensitivitas (reaksi alergi yang umum yang dapat mempengaruhi kulit, mulut dan
lidah, mungkin menyebabkan kesulitan bernafas dan / atau penurunan tekanan darah dan
detak jantung dipercepat); merasa cemas; gemetar, sensasi kepala berputar (vertigo),
pusing; sensasi denyut jantung yang cepat atau tidak teratur (palpitasi); gastritis, muntah,
refluks asam lambung ke kerongkongan (regurgitasi asam), gangguan pencernaan, ruam,
nyeri otot atau kram, sakit punggung, lemah atau kelelahan; badan.
Efek samping yang Jarang
Pembesaran payudara laki-laki; merasa gugup atau tertekan; penurunan indera
pengecap; infeksi saluran pernafasan (tidak termasuk pneumonia); tinja berdarah,
sembelit, peningkatan enzim hati atau otot (terlihat dalam tes darah); bercak (urtikaria).
Bila terjadi reaksi alergi yang parah (jarang terjadi), berhenti minum Daxas dan
hubungi Dokter Anda atau segera pergi ke Unit Gawat Darurat di rumah sakit terdekat.
Bawalah obat Anda dan brosur ini untuk memberikan informasi lengkap dan perawatan
yang tepat. Gejala khas reaksi alergi yang parah adalah: pembengkakan wajah, bibir,
mulut, lidah dan / atau
tenggorokan, yang dapat menyebabkan kesulitan menelan
atau bernapas, kaligata (bengkak gatal-gatal karena alergi), pusing berat dengan detak
jantung yang sangat cepat dan banyak berkeringat.
Dalam studi klinis sempat dilaporkan adanya keinginan, rencana percobaan dan tindakan
bunuh diri. Harap segera memberitahu Dokter bila Anda merasa mengalami perubahan
mood dan perilaku yang mengarah pada usaha atau percobaan bunuh diri.
Jika terjadi efek samping yang serius, atau jika anda menderita efek samping yang tidak
tercantum dalam brosur ini, silahkan menghubungi Dokter atau Apoteker.
5.
BAGAIMANA CARA PENYIMPANAN TABLET DAXAS
Jauhkan dari jangkauan dan penglihatan anak-anak.
Jangan gunakan Daxas melewati tanggai kadaluwarsa yang tertera pada karton dan
blister.
Obat ini disimpan pada suhu di bawah 30°C.
Obat tidak boleh dibuang melalui air limbah atau limbah rumah tangga. Tanyakan
Apoteker Anda bagaimana cara membuang obat-obatan bila tidak lagi diperlukan.
Langkah-langkah ini akan membantu untuk melindungi lingkungan.
6.
INFORMASI LEBIH LANJUT
Apa saja kandungan tablet Daxas
- Bahan baku aktifnya adalah roflumilast. Tiap tablet salut film mengandung 500
mikrogram roflumilast.
- Bahan tambahan lainnya adalah:
Tablet inti: monohidrat laktosa, pati jagung, povidone (K90), magnesium stearat,
Penyalut: hipromelose 2910, Makrogol 4000, titanium dioksida (E171), dan oksida
besi kuning (E172).
Bagaimana bentuk dan kemasan tablet Daxas
Tablet Daxas 500 mikrogram bersalut selaput warna kuning, berbentuk D, ditandai
dengan tulisan “D" pada salah satu sisinya.
Tablet inti berwana putih sampai hampir putih dan mengandung roflumilast 500
mikrogram pada setiap tabletnya.
Tablet Daxas dikemas dalam box berisi 3 aluminium blister yang masing- masing berisi
10 tablet.
Pemegang ijin edar
PT Apex Pharma Indonesia
Diproduksi oleh:
Nycomed GmbH
Production site Oranienburg
Lehnitzstraße 70-98
16515 Oranienburg
Jerman