SERETIDE DISKUS 50500 MCG

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
FLUTICASONE PROPIONATE; SALMETEROL AS XINAFOATE
Available from:
GLAXO SMITH KLINE (ISRAEL) LTD
ATC code:
R03AK06
Pharmaceutical form:
POWDER FOR INHALATION
Composition:
FLUTICASONE PROPIONATE 500 MCG; SALMETEROL AS XINAFOATE 50 MCG
Administration route:
INHALATION
Prescription type:
Required
Manufactured by:
GLAXO OPERATIONS UK LIMITED
Therapeutic group:
SALMETEROL AND OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
Therapeutic area:
SALMETEROL AND OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
Therapeutic indications:
Seretide is indicated in the regular treatment of asthma in children and adults, where use of a combination (bronchodilator and inhaled corticosteroid) has been found to be appropriate. Seretide (50/500 mcg) is indicated for the symptomatic treatment of patients with COPD, with a FEV1 <60% predicted normal (pre-bronchodilator) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy.
Authorization number:
114 14 29552 00
Authorization date:
2014-05-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

24-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

08-05-2018

: ךיראת יאמ

2018

:ןודנה

Seretide Diskus 50/100 mcg, Seretide Diskus 50/250 mcg, Seretide Diskus 50/500 mcg

ג"קמ 50/500 סוקסיד דייטרס ,ג"קמ 50/250 סוקסיד דייטרס ,ג"קמ 50/100 סוקסיד דייטרס

50 micrograms of salmeterol (as salmeterol xinafoate) and

100, 250 or 500 micrograms of fluticasone propionate

Powder for inhalation

ה/דבכנ ה/אפור

,ה/דבכנ ת/חקור

תרבח

ג

ןיילקתימסוסקל

) מ"עב לארשי

GSK

לש ןכרצלו אפורל םינולעה ןוכדע לע עידוהל תשקבמ ( :םירישכתה

"Seretide Diskus 50/100 mcg, Seretide Diskus 50/250 mcg, Seretide Diskus 50/500 mcg"

.

רישכתל המושרה היוותהה םי

:לארשיב

Seretide is indicated in the regular treatment of asthma in children and adults, where use of a combination

(bronchodilator and inhaled corticosteroid) has been found to be appropriate.

Seretide (50/250 & 50/500mcg) is indicated for the symptomatic treatment of patients with COPD, with a

<60% predicted normal (pre-bronchodilator) and a history of repeated exacerbations, who have

significant symptoms despite regular bronchodilator therapy.

ושענ םייתוהמ םינוכדע םיפיעסב

אבה םי

אפורל ןולעב

:

4.4

Special warnings and precautions for use

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient

presents with symptoms such as blurred vision or other visual disturbances, the patient should

be considered for referral to an ophthalmologist for evaluation of possible causes, which may

include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR)

which have been reported after use of systemic and topical corticosteroids.

4.8

Undesirable effects

System Organ Class

Adverse Event

Frequency

Eye Disorders

Cataract

Glaucoma

Vision, blurred

Uncommon

Rare

Not known

4

ושענ םייתוהמ םינוכדע םיפיעסב

אבה םי

: ןכרצל ןולעב

2

.

הפורתב שומיש ינפל

...

תודחוימ תורהזא

הפורתב שומישל תועגונה

:ךל שי םא אפורל רפס ,סוקסיד דייטרסב לופיטה ינפל

ריהמ וא רידס אל בל בצק ללוכ ,בל תלחמ

סירתה תטולב לש רתי תוליעפ

םד ץחל רתי

(ךלש םדב רכוסה תא תולעהל הלולע סוקסיד דייטרס) תרכוס

ךלש םדב ךומנ ןגלשא

) תפחש

םירחא האיר ימוהיז וא ,רבעב וא םויכ (

אפורה םע רשק רוצ

.תורחא הייאר תוערפה וא הייארב שוטשיט הווח התא םא ךלש

...

4

.

יאוול תועפות

...

הנשחרתת םגו ןכתי ךא ,העודי הניאש תורידתב יאוול תועפות

.םידליב ושחרתיש רתוי ההובג תוריבס הלא תועפותל .תונפקות וא ןואכיד

.הייאר שוטשיט

...

: םינמוסמה םינוכדעל ארקמ

תפסות

הרמחה

בתכ

לוחכ

רקרמ בוהצב ןמוסמ

ןולעה

אפורל

ןולעהו

ןכרצל

וחלשנ

םוסרפל

רגאמב

תופורתה

רתאבש

דרשמ

תואירבה

https://www.old.health.gov.il/units/pharmacy/trufot/index.asp?safa=h

ןתינו םיספדומ םלבקל

לע

הינפ ידי לזב 'חר ןיילקתימסוסקלג תרבחל

:ןופלטב הוקת חתפ

03-9297100

,הכרבב

לט תניע

הנוממ תחקור

Page

1

19

Seretide Diskus 50/100 MCG

Seretide Diskus 50/250 MCG

Seretide Diskus 50/500 MCG

NAME OF THE MEDICINAL PRODUCT

Seretide Diskus 50/100 mcg.

Seretide Diskus 50/250 mcg.

Seretide Diskus 50 /500 mcg.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each single inhalation provides a delivered dose (the dose leaving the mouthpiece) of 47

micrograms of salmeterol (as salmeterol xinafoate) and 92, 231 or 460 micrograms of

fluticasone propionate. This corresponds to a pre-dispensed dose of 50 micrograms of

salmeterol (as salmeterol xinafoate) and 100, 250 or 500 micrograms fluticasone propionate.

Excipients with known effect:

Each delivered dose contains up to 12.5 mg of lactose (as monohydrate).

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Inhalation powder, pre-dispensed.

Moulded plastic device containing a foil strip with 60 regularly placed blisters.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Asthma

Seretide is indicated in the regular treatment of asthma in children and adults, where use of a

combination (bronchodilator

and inhaled corticosteroid) has been found to be

appropriate.

Chronic Obstructive Pulmonary Disease (COPD)

Seretide (50/250 & 50/500mcg) is indicated for the symptomatic treatment of patients with

COPD, with a FEV

<60% predicted normal (pre-bronchodilator) and a history of repeated

exacerbations, who have significant symptoms despite regular bronchodilator therapy.

4.2

Posology and method of administration

Posology

Route of administration: Inhalation use.

Page

2

19

Patients should be made aware that Seretide Diskus must be used daily for optimum benefit,

even when asymptomatic.

Patients should be regularly reassessed by a doctor, so that the strength of Seretide they are

receiving remains optimal

and is only changed on medical advice.

Patients should be given the strength of Seretide containing the appropriate fluticasone

propionate dosage for the severity of their disease. If an individual patient should require

dosages outside the recommended regimen, appropriate doses of

agonist and/or

corticosteroid should be prescribed.

Recommended Doses:

Asthma

Adults and adolescents 12 years and older:

One inhalation of 50 micrograms salmeterol and 100 micrograms fluticasone

propionate twice daily.

One inhalation of 50 micrograms salmeterol and 250 micrograms fluticasone

propionate twice daily.

One inhalation of 50 micrograms salmeterol and 500 micrograms fluticasone

propionate twice daily.

The dose should be titrated to the lowest dose at which effective control of symptoms is

maintained. Where the control of symptoms is maintained with the lowest strength of

the combination given twice daily then the next step could include a test of inhaled

corticosteroid alone.

As an alternative, patients requiring a long-acting

agonist could be titrated to Seretide

given once daily if, in the opinion of the prescriber, it would be adequate to maintain disease

control. In the event of once daily dosing when the patient has a history of nocturnal

symptoms the dose should be given at night and when the patient has a history of mainly

daytime symptoms the dose should be given in the morning.

A short-term trial of Seretide may be considered as initial maintenance therapy in adults or

adolescents with moderate persistent asthma (defined as patients with daily symptoms, daily

rescue use and moderate to severe airflow limitation) for whom rapid control of asthma is

essential. In these cases, the recommended initial dose is one inhalation of 50 micrograms

salmeterol and 100 micrograms fluticasone propionate twice daily. Once control of asthma is

attained treatment should be reviewed and consideration given as to whether patients should

be stepped down to an inhaled corticosteroid alone. Regular review of patients as treatment is

stepped down is important.

A clear benefit has not been shown as compared to inhaled fluticasone propionate alone used

as initial maintenance therapy when one or two of the criteria of severity are missing. In

general inhaled corticosteroids remain the first line treatment for most patients. Seretide is not

intended for the initial management of mild asthma. Seretide 50 microgram/100 micrograms

strength is not appropriate in adults and children with severe asthma; it is recommended to

establish the appropriate dosage of inhaled corticosteroid before any fixed-combination can

be used in patients with severe asthma.

Page

3

19

Paediatric population

Children 4 years and older:

One inhalation of 50 micrograms salmeterol and 100 micrograms fluticasone

propionate twice daily.

The maximum licensed dose of fluticasone propionate delivered by Seretide Diskus in

children is 100 microgram twice daily.

There are no data available for use of Seretide in children aged under 4 years.

COPD

Adults:

One inhalation of 50 micrograms salmeterol and 250 micrograms fluticasone

propionate twice daily.

One inhalation of 50 micrograms salmeterol and 500 micrograms fluticasone

propionate twice daily.

Special patient groups:

There is no need to adjust the dose in elderly patients or in those with renal impairment. There

are no data available for use of Seretide in patients with hepatic impairment.

Using the Diskus:

The device is opened and primed by sliding the lever. The mouthpiece is then placed in the

mouth and the lips closed round it. The dose can then be inhaled and the device closed.

4.3

Contraindications

Hypersensitivity

to the active substances or to any of the excipients listed in section 6.1.

4.4

Special warnings and precautions for use

Deterioration of disease

Seretide Diskus should not be used to treat

acute asthma

symptoms for which

a fast and short-

acting bronchodilator is required. Patients should be advised to have their inhaler to be used

for relief in an acute asthma attack available at all times.

Patients should not be initiated on Seretide during an exacerbation, or if they have

significantly worsening or acutely deteriorating asthma.

Serious asthma-related adverse events and exacerbations may occur during treatment with

Seretide. Patients should be asked to continue treatment but to seek medical advice if asthma

symptoms remain uncontrolled or worsen after initiation on Seretide.

Increased requirements for use of reliever medication (short-acting bronchodilators), or

decreased response to reliever medication indicate deterioration of control and patients should

be reviewed by a physician.

Page

4

19

Sudden and progressive deterioration in control of asthma is potentially life-threatening and

the patient should undergo urgent medical assessment.

Consideration should be given to

increasing corticosteroid therapy.

Once asthma symptoms are controlled, consideration may be given to gradually reducing the

dose of Seretide. Regular review of patients as treatment is stepped down is important. The

lowest effective dose of Seretide should be used (see section 4.2).

For patients with COPD experiencing exacerbations, treatment with systemic corticosteroids

is typically indicated, therefore patients should be instructed to seek medical attention if

symptoms deteriorate with Seretide

Treatment with Seretide should not be stopped abruptly in patients with asthma due to risk of

exacerbation. Therapy should be down-titrated under physician supervision. For patients with

COPD cessation of therapy may also be associated with symptomatic decompensation and

should be supervised by a physician.

As with all inhaled medication containing

corticosteroids, Seretide should be administered

with caution in patients with active or quiescent pulmonary tuberculosis and fungal, viral or

other infections of the airway. Appropriate treatment should be promptly instituted, if

indicated.

Cardiovascular effects

Rarely, Seretide may cause cardiac arrhythmias e.g. supraventricular tachycardia,

extrasystoles and atrial fibrillation, and a mild transient reduction in serum potassium at high

therapeutic doses. Seretide should be used with caution in patients with severe cardiovascular

disorders or heart rhythm abnormalities and in patients with diabetes mellitus,

thyrotoxicosis,

uncorrected hypokalaemia or patients predisposed to low levels of serum potassium.

Hyperglycaemia

There have been very rare reports of increases in blood glucose levels (see section 4.8) and

this should be considered when prescribing to patients with a history of diabetes mellitus.

Paradoxical bronchospasm

As with other inhalation therapy paradoxical bronchospasm may occur with an immediate

increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm

responds to a rapid-acting bronchodilator and should be treated straightaway. Seretide Diskus

should be discontinued immediately, the patient assessed and alternative therapy instituted if

necessary.

The pharmacological side effects of

agonist treatment, such as tremor, palpitations and

headache, have been reported, but tend to be transient and reduce with regular therapy.

Excipients

Seretide contains lactose monohydrate up to 12.5 milligram /dose. This amount does not

normally cause problems in lactose intolerant people. The excipient lactose contains small

amounts of milk proteins, which may cause allergic reactions.

Systemic corticosteroid effects

Page

5

19

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses

prescribed for long periods. These effects are much less likely to occur than with oral

corticosteroids. Possible systemic effects include

Cushing’s syndrome, Cushingoid features,

adrenal suppression, decrease in bone mineral density, cataract and glaucoma and more

rarely, a range of psychological or behavioural effects including psychomotor hyperactivity,

sleep disorders, anxiety, depression or aggression (particularly in children) (see Paediatric

population sub-heading below for information on the systemic effects of inhaled

corticosteroids in children and adolescents).

It is important, therefore, that the patient is

reviewed regularly and the dose of inhaled corticosteroid is reduced to the lowest dose at

which effective control of asthma is maintained.

Prolonged treatment of patients with high doses of inhaled corticosteroids may result in

adrenal suppression and acute adrenal crisis. Very rare cases of adrenal suppression and acute

adrenal crisis have also been described with doses of fluticasone propionate between 500 and

less than 1000 micrograms. Situations, which could potentially trigger acute adrenal crisis

include trauma, surgery, infection or any rapid reduction in dosage. Presenting symptoms are

typically vague and may include anorexia, abdominal pain, weight loss, tiredness, headache,

nausea, vomiting, hypotension, decreased level of consciousness, hypoglycaemia, and

seizures. Additional systemic corticosteroid cover should be considered during periods of

stress or elective surgery.

The benefits of inhaled fluticasone propionate therapy should minimise the need for oral

steroids, but patients transferring from oral steroids may remain at risk of impaired adrenal

reserve for a considerable time. Therefore these patients should be treated with special care

and adrenocortical function regularly monitored. Patients who have required high dose

emergency corticosteroid therapy in the past may also be at risk. This possibility of residual

impairment should always be borne in mind in emergency and elective situations likely to

produce stress, and appropriate corticosteroid treatment must be considered.

The extent of the

adrenal impairment may require specialist advice before elective procedures.

Ritonavir can greatly increase the concentration of fluticasone propionate in plasma.

Therefore, concomitant use should be avoided, unless the potential benefit to the patient

outweighs the risk of systemic corticosteroid side effects. There is also an increased risk of

systemic side effects when combining fluticasone propionate with other potent CYP3A

inhibitors (see section 4.5).

Pneumonia in patients with COPD

An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation,

has been observed in patients with COPD receiving inhaled corticosteroids. There is some

evidence of an increased risk of pneumonia with increasing steroid dose but this has not been

demonstrated conclusively across all studies.

There is no conclusive clinical evidence for intra-class differences in the magnitude of the

pneumonia risk among inhaled corticosteroid products.

Physicians should remain vigilant for the possible development of pneumonia in patients with

COPD as the clinical features of such infections overlap with the symptoms of COPD

exacerbations.

Risk factors for pneumonia in patients with COPD include current smoking, older age, low

body mass index (BMI) and severe COPD.

Page

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19

Interactions with potent CYP3A4 inhibitors

Concomitant use of systemic ketoconazole significantly increases systemic exposure to

salmeterol. This may lead to an increase in the incidence of systemic effects (e.g.

prolongation in the QTc interval and palpitations). Concomitant treatment with ketoconazole

or other potent CYP3A4 inhibitors should therefore be avoided unless the benefits outweigh

the potentially increased risk of systemic side effects of salmeterol treatment (see section 4.5).

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient

presents with symptoms such as blurred vision or other visual disturbances, the patient should

be considered for referral to an ophthalmologist for evaluation of possible causes, which may

include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR)

which have been reported after use of systemic and topical corticosteroids.

Paediatric Population

Children and adolescents <16 years taking high doses of fluticasone propionate (typically

1000 micrograms/day) may be at particular risk. Systemic effects may occur, particularly at

high doses prescribed for long periods. Possible systemic effects include Cushing’s syndrome,

Cushingoid features

,

adrenal suppression, acute adrenal crisis and growth retardation in

children and adolescents and more rarely, a range of psychological or behavioural effects

including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression.

Consideration should be given to referring the child or adolescent to a paediatric respiratory

specialist.

It is recommended that the height of children receiving prolonged treatment with inhaled

corticosteroid is regularly monitored.

The dose of inhaled corticosteroid should be reduced

to the lowest dose at which effective control of asthma is maintained.

4.5

Interaction with other medicinal products and other forms of interaction

adrenergic blockers may weaken or antagonise the effect of salmeterol. Both non-selective

and selective

blockers should be avoided unless there are compelling reasons for their use.

Potentially serious hypokalaemia may result from

agonist therapy. Particular caution is

advised in acute severe asthma as this effect may be potentiated by concomitant treatment

with xanthine derivatives, steroids and diuretics.

Concomitant use of other

adrenergic containing drugs can have a potentially additive effect.

Fluticasone Propionate

Under normal circumstances, low plasma concentrations of fluticasone propionate are

achieved after inhaled dosing, due to extensive first pass metabolism and high systemic

clearance mediated by cytochrome CYP3A4 in the gut and liver. Hence, clinically significant

drug interactions mediated by fluticasone propionate are unlikely.

In an interaction study in healthy subjects with intranasal fluticasone propionate, ritonavir (a

highly potent cytochrome CYP3A4 inhibitor) 100 mg b.i.d. increased the fluticasone

propionate plasma concentrations several hundred fold, resulting in markedly reduced serum

cortisol concentrations. Information about this interaction is lacking for inhaled fluticasone

propionate, but a marked increase in fluticasone propionate plasma levels is expected. Cases

Page

7

19

of Cushing’s syndrome and adrenal suppression have been reported. The combination should

be avoided unless the benefit outweighs the increased risk of systemic glucocorticoid side

effects.

In a small study in healthy volunteers, the slightly less potent CYP3A inhibitor ketoconazole

increased the exposure of fluticasone propionate after a single inhalation by 150%. This

resulted in a greater reduction of plasma cortisol as compared with fluticasone propionate

alone. Co-treatment with other potent CYP3A inhibitors, such as itraconazole and cobicistat-

containing products, and moderate CYP3A inhibitors, such as erythromycin, is also expected

to increase the systemic fluticasone propionate exposure and the risk of systemic side effects.

Combinations should be avoided unless the benefit outweighs the potential increased risk of

systemic corticosteroid side-effects, in which case patients should be monitored for systemic

corticosteroid side-effects.

Salmeterol

Potent CYP3A4 inhibitors

Co-administration of ketoconazole (400 mg orally once daily) and salmeterol (50 micrograms

inhaled twice daily) in 15 healthy subjects for 7 days resulted in a significant increase in

plasma salmeterol exposure (1.4-fold Cmax and 15-fold AUC). This may lead to an increase

in the incidence of other systemic effects of salmeterol treatment (e.g. prolongation of QTc

interval and palpitations) compared with salmeterol or ketoconazole treatment alone (see

section 4.4).

Clinically significant effects were not seen on blood pressure, heart rate, blood glucose and

blood potassium levels. Co-administration with ketoconazole did not increase the elimination

half-life of salmeterol or increase salmeterol accumulation with repeat dosing.

The concomitant administration of ketoconazole should be avoided, unless the benefits

outweigh the potentially increased risk of systemic side effects of salmeterol treatment. There

is likely to be a similar risk of interaction with other potent CYP3A4 inhibitors (e.g.

itraconazole, telithromycin, ritonavir).

Moderate CYP 3A4 inhibitors

Co-administration of erythromycin (500 mg orally three times a day) and salmeterol (50

micrograms inhaled twice daily) in 15 healthy subjects for 6 days resulted in a small but non-

statistically significant increase in salmeterol exposure (1.4-fold C

and 1.2-fold AUC). Co-

administration with erythromycin was not associated with any serious adverse effects.

4.6

Fertility, pregnancy and lactation

Fertility

There are no data in humans. However, animal studies showed no effects of salmeterol or

fluticasone propionate on fertility.

Pregnancy

A large amount of data on pregnant women (more than 1000 pregnancy outcomes) indicates

no malformative or feto/neonatal toxicity related to Seretide . Animal studies have shown

reproductive toxicity after administration of

adrenoreceptor agonists and

glucocorticosteroids (see section 5.3).

Administration of Seretide to pregnant women should only be considered if the expected benefit

to the mother is greater than any possible risk to the fetus.

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19

The lowest effective dose of fluticasone propionate needed to maintain adequate asthma control

should be used in the treatment of pregnant women.

Breastfeeding

It is unknown whether salmeterol and fluticasone propionate/metabolites are excreted in

human milk.

Studies have shown that salmeterol and fluticasone propionate, and their metabolites, are

excreted into the milk of lactating rats.

A risk to breastfed newborns/infants cannot be excluded. A decision must be made whether to

discontinue breastfeeding or to discontinue Seretide therapy taking into account the benefit of

breastfeeding for the child and the benefit of therapy for the woman.

4.7

Effects on ability to drive and use machines

Seretide Diskus has no or negligible influence on the ability to drive and use machines.

4.8

Undesirable effects

As Seretide contains salmeterol and fluticasone propionate, the type and severity of adverse

reactions associated with each of the compounds may be expected. There is no incidence of

additional adverse events following concurrent administration of the two compounds.

Adverse events which have been associated with

salmeterol/fluticasone propionate

are given

below, listed by system organ class and frequency. Frequencies are defined as: very common

(≥1/10), common (

1/100 to

<

1/10), uncommon (

1/1000 to

<

1/100), rare (

1/10,000 to

<1/1000) and not known (cannot be estimated from the available data). Frequencies were

derived from clinical trial data. The incidence in placebo was not taken into account.

System Organ Class

Adverse Event

Frequency

Infections &

Infestations

Candidiasis of the mouth and throat

Pneumonia (in COPD patients)

Bronchitis

Oesophageal candidiasis

Common

Common

1,3,5

Common

Rare

Immune System

Disorders

Hypersensitivity reactions with the following

manifestations:

Cutaneous hypersensitivity reactions

Angioedema (mainly facial and oropharyngeal

oedema)

Respiratory symptoms (dyspnoea)

Respiratory symptoms (bronchospasm)

Anaphylactic reactions including anaphylactic shock

Uncommon

Rare

Uncommon

Rare

Rare

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19

System Organ Class

Adverse Event

Frequency

Endocrine Disorders

Cushing’s syndrome, Cushingoid features,

Adrenal

suppression, Growth retardation in children and

adolescents, Decreased bone mineral density

Rare

Metabolism &

Nutrition Disorders

Hypokalaemia

Hyperglycaemia

Common

Uncommon

Psychiatric Disorders

Anxiety

Sleep disorders

Behavioural changes, including psychomotor

hyperactivity and irritability (predominantly in

children)

Depression, aggression (predominantly in children)

Uncommon

Uncommon

Rare

Not known

Nervous System

Disorders

Headache

Tremor

Very Common

Uncommon

Eye Disorders

Cataract

Glaucoma

Vision, blurred

Uncommon

Rare

Not known

Cardiac Disorders

Palpitations

Tachycardia

Cardiac arrhythmias (including supraventricular

tachycardia and extrasystoles).

Atrial fibrillation

Angina pectoris

Uncommon

Uncommon

Rare

Uncommon

Uncommon

Respiratory, Thoracic

& Mediastinal

Disorders

Nasopharyngitis

Throat irritation

Hoarseness/dysphonia

Sinusitis

Paradoxical bronchospasm

Very Common

Common

Common

Common

Rare

Skin and

subcutaneous tissue

disorders

Contusions

Common

Page

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19

System Organ Class

Adverse Event

Frequency

Musculoskeletal &

Connective Tissue

Disorders

Muscle cramps

Traumatic fractures

Arthralgia

Myalgia

Common

Common

Common

Common

Reported commonly in placebo

Reported very commonly in placebo

Reported over 3 years in a COPD study

See section 4.4

See section 5.1.

Description of selected adverse reactions

The pharmacological side effects of

agonist treatment, such as tremor, palpitations and

headache, have been reported, but tend to be transient and reduce with regular therapy.

As with other inhalation therapy paradoxical bronchospasm may occur with an immediate

increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm

responds to a rapid-acting bronchodilator and should be treated straightaway. Seretide Diskus

should be discontinued immediately, the patient assessed and alternative therapy instituted if

necessary.

Due to the fluticasone propionate component, hoarseness and candidiasis (thrush) of the mouth

and throat and, rarely, of the oesophagus can occur in some patients.

Both hoarseness and

incidence of mouth and throat candidiasis may be relieved by rinsing the mouth with water

and/or brushing the teeth after using the product. Symptomatic mouth and throat candidiasis

can be treated with topical anti-fungal therapy whilst still continuing with the Seretide Diskus.

Paediatric population

Possible systemic effects include Cushing’s syndrome, Cushingoid features

,

adrenal

suppression and growth retardation in children and adolescents (see section 4.4). Children

may also experience anxiety, sleep disorders and behavioural changes, including

hyperactivity and irritability.

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.

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form https://sideeffects.health.gov.il/

Additionally, you should also report to GSK Israel (il.safety@gsk.com)

4.9

Overdose

There are no data available from clinical trials on overdose with Seretide, however data on

overdose with both drugs are given below:

The signs and symptoms of salmeterol overdose are dizziness, increases in systolic blood

pressure, tremor, headache and tachycardia. If Seretide therapy has to be withdrawn due to

Page

11

19

overdose of the

agonist component of the drug, provision of appropriate replacement steroid

therapy should be considered. Additionally, hypokalaemia can occur and therefore serum

potassium levels should be monitored. Potassium replacement should be considered.

Acute:

Acute inhalation of fluticasone propionate doses in excess of those recommended may

lead to temporary suppression of adrenal function. This does not need emergency action as

adrenal function is recovered in a few days, as verified by plasma cortisol measurements.

Chronic overdose of inhaled fluticasone propionate:

Adrenal reserve should be monitored

and treatment with a systemic corticosteroid may be necessary. When stabilised, treatment

should be continued with an inhaled corticosteroid at the recommended dose. Refer to section

4.4: risk of adrenal suppression.

In cases of both acute and chronic fluticasone propionate overdose Seretide therapy should be

continued at a suitable dosage for symptom control.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic Group:

Adrenergics in combination with corticosteroids or other

drugs, excl.

anticholinergics.

ATC Code:

R03AK06

Mechanism of action and pharmacodynamic effects:

Seretide contains salmeterol and fluticasone propionate which have differing modes of action.

The respective mechanisms of action of both drugs are discussed below.

Salmeterol:

Salmeterol is a selective long-acting (12 hour)

adrenoceptor agonist with a long side chain

which binds to the exo-site of the receptor.

Salmeterol produces a longer duration of bronchodilation, lasting for at least 12 hours, than

recommended doses of conventional short-acting

agonists.

Fluticasone propionate:

Fluticasone propionate given by inhalation at recommended doses has a glucocorticoid anti-

inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of

asthma, with less adverse effects than when corticosteroids are administered systemically.

Clinical efficacy and safety

Seretide Asthma clinical trials

A twelve month study (Gaining Optimal Asthma ControL, GOAL), in 3416 adult and

adolescent patients with persistent

asthma, compared the safety and efficacy of Seretide

versus inhaled corticosteroid (Fluticasone Propionate) alone to determine whether the goals of

asthma management were achievable. Treatment was stepped up every 12 weeks until **

total

control

was achieved or the highest dose of study drug was reached. GOAL showed more

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12

19

patients treated with Seretide achieved asthma control than patients treated with ICS alone

and this control was attained at a lower corticosteroid dose.

*Well controlled

asthma was achieved more rapidly with Seretide than with ICS alone. The

time on treatment for 50% of subjects to achieve a first individual

well controlled

week was

16 days for Seretide compared to 37 days for the ICS group. In the subset of steroid naive

asthmatics the time to an individual

well controlled

week was 16 days in the Seretide

treatment compared to 23 days following treatment with ICS.

The overall study results showed:

Percentage of Patients Attaining *Well Controlled (WC) and **Totally Controlled

(TC) Asthma over 12 months

Pre-Study Treatment

Salmeterol/FP

FP

WC

TC

WC

TC

No ICS

(SABA alone)

Low dose ICS

≤500 micrograms BDP

or equivalent/day)

Medium dose ICS

(>500 to 1000

micrograms BDP or equivalent/day)

Pooled results across the 3 treatment

levels

*Well controlled asthma; less than or equal to 2 days with symptom score greater than 1

(symptom score 1 defined as ‘symptoms for one short period during the day’), SABA use on

less than or equal to 2 days and less than or equal to 4 occasions/week, greater than or equal

to 80% predicted morning peak expiratory flow, no night-time awakenings, no exacerbations

and no side effects enforcing a change in therapy

**Total control of asthma; no symptoms, no SABA use, greater than or equal to 80%

predicted morning peak expiratory flow, no night-time awakenings, no exacerbations and no

side effects enforcing a change in therapy

The results of this study suggest

that Seretide 50/100 micrograms bd may be considered as

initial maintenance therapy in patients with moderate persistent asthma for whom rapid

control of asthma is deemed essential (see section 4.2).

A double blind, randomised, parallel group study in 318 patients with persistent asthma aged

≥18 years evaluated the safety and tolerability of administering two inhalations twice daily

(double dose) of Seretide for two weeks. The study showed that doubling the inhalations of

each strength of Seretide for up to 14 days resulted in a small increase in

agonist-related

adverse events (tremor; 1 patient [1%] vs 0, palpitations; 6 [3%] vs 1 [<1%], muscle cramps;

6[3%] vs 1 [<1%]) and a similar incidence of inhaled corticosteroid related adverse events

(e.g. oral candidiasis; 6 [6%] vs 16 [8%], hoarseness; 2 [2%] vs 4 [2%]) compared to one

inhalation twice daily. The small increase in

agonist-related adverse events should be taken

into account if doubling the dose of Seretide is considered by the physician in adult patients

requiring additional short-term (up to 14 days) inhaled corticosteroid therapy.

Seretide COPD clinical trials

TORCH was a 3-year study to assess the effect of treatment with Seretide Diskus 50/500

micrograms bd, salmeterol Diskus 50 micrograms bd, fluticasone propionate (FP) Diskus 500

micrograms bd or placebo on all-cause mortality in patients with COPD. COPD patients with

a baseline (pre-bronchodilator) FEV

<60% of predicted normal were randomised to double-

blind medication. During the study, patients were permitted usual COPD therapy with the

exception of other inhaled corticosteroids, long-acting bronchodilators and long-term

systemic corticosteroids. Survival status at 3 years was determined for all patients regardless

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13

19

of withdrawal from study medication. The primary endpoint was reduction in all cause

mortality at 3 years for Seretide vs Placebo.

Placebo

N = 1524

Salmeterol 50

N = 1521

FP 500

N = 1534

Seretide

50/500

N = 1533

All cause mortality at 3 years

Number of deaths

(15.2%)

(13.5%)

(16.0%)

(12.6%)

Hazard Ratio vs

Placebo (CIs)

p value

0.879

(0.73, 1.06)

0.180

1.060

(0.89, 1.27)

0.525

0.825

(0.68, 1.00 )

0.052

Hazard Ratio

Seretide 50/500 vs

components (CIs)

p value

0.932

(0.77, 1.13)

0.481

0.774

(0.64, 0.93)

0.007

1. Non significant P value after adjustment for 2 interim analyses on the primary efficacy

comparison from a log-rank analysis stratified by smoking status

There was a trend towards improved survival in subjects treated with Seretide compared with

placebo over 3 years however this did not achieve the statistical significance level p≤0.05.

The percentage of patients who died within 3 years due to COPD-related causes was 6.0% for

placebo, 6.1% for salmeterol, 6.9% for FP and 4.7% for Seretide.

The mean number of moderate to severe exacerbations per year was significantly reduced

with Seretide as compared with treatment with salmeterol, FP and placebo (mean rate in the

Seretide group 0.85 compared with 0.97 in the salmeterol group, 0.93 in the FP group and

1.13 in the placebo). This translates to a reduction in the rate of moderate to severe

exacerbations of 25% (95% CI: 19% to 31%; p<0.001) compared with placebo, 12%

compared with salmeterol (95% CI: 5% to 19%, p=0.002) and 9% compared with FP (95%

CI: 1% to 16%, p=0.024). Salmeterol and FP significantly reduced exacerbation rates

compared with placebo by 15% (95% CI: 7% to 22%; p<0.001) and 18% (95% CI: 11% to

24%; p<0.001) respectively.

Health Related Quality of Life, as measured by the St George’s Respiratory Questionnaire

(SGRQ) was improved by all active treatments in comparison with placebo. The average

improvement over three years for Seretide compared with placebo was -3.1 units (95% CI: -

4.1 to -2.1; p<0.001), compared with salmeterol was -2.2 units (p<0.001) and compared with

FP was -1.2 units (p=0.017). A 4-unit decrease is considered clinically relevant.

The estimated 3-year probability of having pneumonia reported as an adverse event was

12.3% for placebo, 13.3% for salmeterol, 18.3% for FP and 19.6% for Seretide (Hazard ratio

for Seretide vs placebo: 1.64, 95% CI: 1.33 to 2.01, p<0.001). There was no increase in

pneumonia related deaths; deaths while on treatment that were adjudicated as primarily due to

pneumonia were 7 for placebo, 9 for salmeterol, 13 for FP and 8 for Seretide. There was no

significant difference in probability of bone fracture (5.1% placebo, 5.1% salmeterol, 5.4%

FP and 6.3% Seretide; Hazard ratio for Seretide vs placebo: 1.22, 95% CI: 0.87 to 1.72,

p=0.248.

Placebo-controlled clinical trials, over 6 and 12 months, have shown that regular use of

Seretide 50/500 micrograms improves lung function and reduces breathlessness and the use of

relief medication.

Page

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19

Studies SCO40043 and SCO100250 were randomised, double-blind, parallel-group, replicate

studies comparing the effect of Seretide 50/250 micrograms bd (a dose not licensed for COPD

treatment in the European Union) with salmeterol 50 micrograms bd on the annual rate of

moderate/severe exacerbations in subjects with COPD with FEV

less than 50% predicted and

a history of exacerbations. Moderate/ severe exacerbations were defined as worsening

symptoms that required treatment with oral corticosteroids and/or antibiotics or in-patient

hospitalisation.

The trials had a 4 week run-in period during which all subjects received open-label

salmeterol/ FP 50/250 to standardize COPD pharmacotherapy and stabilise disease prior to

randomisation to blinded study medication for 52 weeks. Subjects were randomised 1:1 to

salmeterol/ FP 50/250 (total ITT n=776) or salmeterol (total ITT n=778). Prior to run-in,

subjects discontinued use of previous COPD medications except short-acting bronchodilators.

The use of concurrent inhaled long-acting bronchodilators (

agonist and anticholinergic),

ipratropium/salbutamol combination products, oral

agonists, and theophylline preparations

were not allowed during the treatment period. Oral corticosteroids and antibiotics were

allowed for the acute treatment of COPD exacerbations with specific guidelines for use.

Subjects used salbutamol on an as-needed basis throughout the studies.

The results of both studies showed that treatment with Seretide 50/250 resulted in a

significantly lower annual rate of moderate/severe COPD exacerbations compared with

salmeterol (SCO40043: 1.06 and 1.53 per subject per year, respectively, rate ratio of 0.70,

95% CI: 0.58 to 0.83, p<0.001; SCO100250: 1.10 and 1.59 per subject per year, respectively,

rate ratio of 0.70, 95% CI: 0.58 to 0.83, p<0.001). Findings for the secondary efficacy

measures (time to first moderate/severe exacerbation, the annual rate of exacerbations

requiring oral corticosteroids, and pre-dose morning (AM) FEV

) significantly favoured

Seretide 50/250 micrograms bd over salmeterol. Adverse event profiles were similar with the

exception of a higher incidence of pneumonias and known local side effects (candidiasis and

dysphonia) in the Seretide 50/250 micrograms bd group compared with salmeterol.

Pneumonia-related events were reported for 55 (7%) subjects in the Seretide 50/250

micrograms bd group and 25 (3%) in the salmeterol group. The increased incidence of

reported pneumonia with Seretide 50/250 micrograms bd appears to be of similar magnitude

to the incidence reported following treatment with Seretide 50/500 micrograms bd in

TORCH.

Asthma

The Salmeterol Multi-center Asthma Research Trial (SMART)

The Salmeterol Multi-center Asthma Research Trial (SMART) was a 28-week US study that

evaluated the safety of salmeterol compared to placebo added to usual therapy in adult and

adolescent subjects. Although there were no significant differences in the primary endpoint of

the combined number of respiratory-related deaths and respiratory-related life-threatening

experiences, the study showed a significant increase in asthma-related deaths in patients

receiving salmeterol (13 deaths out of 13,176 patients treated with salmeterol versus 3 deaths

out of 13,179 patients on placebo). The study was not designed to assess the impact of

concurrent inhaled corticosteroid use, and only 47% of subjects reported ICS use at baseline.

Safety and efficacy of salmeterol-FP versus FP alone in asthma

Two multi-centre 26-week studies were conducted to compare the safety and efficacy of

salmeterol-FP versus FP alone, one in adult and adolescent subjects (AUSTRI trial), and the

other in paediatric subjects 4-11 years of age (VESTRI trial). For both studies, enrolled

subjects had moderate to severe persistent asthma with history of asthma-related

hospitalisation or asthma exacerbation in the previous year. The primary objective of each

Page

15

19

study was to determine whether the addition of LABA to ICS therapy (salmeterol-FP) was

non-inferior to ICS (FP) alone in terms of the risk of serious asthma related events (asthma-

related hospitalisation, endotracheal intubation, and death). A secondary efficacy objective of

these studies was to evaluate whether ICS/LABA (salmeterol-FP) was superior to ICS therapy

alone (FP) in terms of severe asthma exacerbation (defined as deterioration of asthma

requiring the use of systemic corticosteroids for at least 3 days or an in-patient hospitalisation

or emergency department visit due to asthma that required systemic corticosteroids).

A total of 11,679 and 6,208 subjects were randomized and received treatment in the AUSTRI

and VESTRI trials, respectively. For the primary safety endpoint, non-inferiority was

achieved for both trials (see Table below).

Serious Asthma-Related Events in the 26-Week AUSTRI and VESTRI Trials

AUSTRI

VESTRI

Salmeterol-FP

(n = 5,834)

FP Alone

(n = 5,845)

Salmeterol-FP

(n = 3,107)

FP Alone

(n = 3,101)

Composite endpoint

(Asthma-related

hospitalisation, endotracheal

intubation, or death)

34 (0.6%)

33 (0.6%)

27 (0.9%)

21 (0.7%)

Salmeterol-FP/FP Hazard

ratio (95% CI)

1.029

(0.638-1.662)

1.285

(0.726-2.272)

Death

Asthma-related

hospitalisation

Endotracheal intubation

If the resulting upper 95% CI estimate for the relative risk was less than 2.0, then non-

inferiority was concluded.

If the resulting upper 95% CI estimate for the relative risk was less than 2.675, then non-

inferiority was concluded.

For the secondary efficacy endpoint, reduction in time to first asthma exacerbation for

salmeterol-FP relative to FP was seen in both studies, however only AUSTRI met statistical

significance:

AUSTRI

VESTRI

Salmeterol-FP

(n = 5,834)

FP Alone

(n = 5,845)

Salmeterol-FP

(n = 3,107)

FP Alone

(n = 3,101)

Number of subjects with an

asthma exacerbation

480 (8%)

597 (10%)

265 (9%)

309 (10%)

Salmeterol-FP/FP Hazard

ratio (95% CI)

0.787

(0.698, 0.888)

0.859

(0.729, 1.012)

Paediatric population:

In trial SAM101667, in 158 children aged 6 to 16 years with symptomatic asthma, the

combination of salmeterol/fluticasone propionate is equally efficacious to doubling the dose

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19

of fluticasone propionate regarding symptom control and lung function. This study was not

designed to investigate the effect on exacerbations.

In a 12 week trial of children aged 4 to 11 years [n=257] treated with either

salmeterol/fluticasone propionate 50/100 or salmeterol 50 micrograms + fluticasone

propionate 100 micrograms both twice daily, both treatment arms experienced a 14% increase

in peak expiratory flow rate as well as improvements in symptom score and rescue salbutamol

use. There were no differences between the 2 treatment arms. There were no differences in

safety parameters between the 2 treatment arms.

In a 12 week trial of children 4 to 11 years of age [n=203] randomized in a parallel-group

study with persistent asthma and who were symptomatic on inhaled corticosteroid, safety was

the primary objective. Children received either salmeterol/fluticasone propionate (50/100

micrograms) or fluticasone propionate (100 micrograms) alone twice daily. Two children on

salmeterol/fluticasone propionate and 5 children on fluticasone propionate withdrew because

of worsening asthma. After 12 weeks no children in either treatment arm had abnormally low

24 hour urinary cortisol excretion. There were no other differences in safety profile between

the treatment arms.

Fluticasone propionate containing medications in asthma during pregnancy

An observational retrospective epidemiological cohort study utilising electronic health

records from the United Kingdom was conducted to evaluate the risk of MCMs following

first trimester exposure to inhaled FP alone and salmeterol-FP relative to non-FP containing

ICS. No placebo comparator was included in this study.

Within the asthma cohort of 5362 first trimester ICS-exposed pregnancies, 131 diagnosed

MCMs were identified; 1612 (30%) were exposed to FP or salmeterol-FP of which 42

diagnosed MCMs were identified. The adjusted odds ratio for MCMs diagnosed by 1 year

was 1.1 (95%CI: 0.5 – 2.3) for FP exposed vs non-FP ICS exposed women with moderate

asthma and 1.2 (95%CI: 0.7 – 2.0) for women with considerable to severe asthma. No

difference in the risk of MCMs was identified following first trimester exposure to FP alone

versus salmeterol-FP. Absolute risks of MCM across the asthma severity strata ranged from

2.0 to 2.9 per 100 FP-exposed pregnancies which is comparable to results from a study of

15,840 pregnancies unexposed to asthma therapies in the General Practice Research Database

(2.8 MCM events per 100 pregnancies).

5.2

Pharmacokinetic properties

For pharmacokinetic purposes each component can be considered separately.

Salmeterol:

Salmeterol acts locally in the lung therefore plasma levels are not an indication of therapeutic

effects. In addition there are only limited data available on the pharmacokinetics of salmeterol

because of the technical difficulty of assaying the drug in plasma due to the low plasma

concentrations at therapeutic doses (approximately 200 picogram/mL or less) achieved after

inhaled dosing.

Page

17

19

Fluticasone propionate:

The absolute bioavailability of a single dose of inhaled fluticasone propionate in healthy

subjects varies between approximately 5 to 11% of the nominal dose depending on the

inhalation device used. In patients with asthma or COPD a lesser degree of systemic exposure

to inhaled fluticasone propionate has been observed.

Systemic absorption occurs mainly through the lungs and is initially rapid then prolonged.

The remainder of the inhaled dose may be swallowed but contributes minimally to systemic

exposure due to the low aqueous solubility and presystemic metabolism, resulting in oral

availability of less than 1%. There is a linear increase in systemic exposure with increasing

inhaled dose.

The disposition of fluticasone propionate is characterised by high plasma clearance (1150

mL/min), a large volume of distribution at steady-state (approximately 300 L) and a terminal

half-life of approximately 8 hours.

Plasma protein binding is 91%

.

Fluticasone propionate is cleared very rapidly from the systemic circulation. The main

pathway is metabolism to an inactive carboxylic acid metabolite, by the cytochrome P450

enzyme CYP3A4. Other unidentified metabolites are also found in the faeces.

The renal clearance of fluticasone propionate is negligible. Less than 5% of the dose is

excreted in urine, mainly as metabolites. The main part of the dose is excreted in faeces as

metabolites and unchanged drug.

Paediatric population

In a population pharmacokinetic analysis utilizing data from 9 controlled clinical trials with

different devices (Diskus, metered dose inhaler) that included 350 patients with asthma aged

4 to 77 years (174 patients 4 to 11 years of age) higher fluticasone propionate systemic

exposure following treatment with Seretide Diskus 50/100 compared to fluticasone

propionate Diskus 100 were seen.

Geometric Mean Ratio [90% CI] for the Salmeterol/fluticasone propionate vs. fluticasone

propionate Diskus Comparison in Children and Adolescent/Adult Populations

Treatment (test vs. ref)

Population

AUC

C

max

Salmeterol/

fluticasone

propionate Diskus 50/100

fluticasone propionate Diskus

100

Children

(4–11yr)

1.20 [1.06 – 1.37]

1.25 [1.11 – 1.41]

Salmeterol/fluticasone

propionate Diskus 50/100

fluticasone propionate Diskus

100

Adolescent/Adult

( ≥12yr)

1.52 [1.08 – 2.13]

1.52 [1.08 – 2.16]

The effect of 21 days of treatment with Seretide Inhaler 25/50 micrograms (2 inhalations

twice daily with or without a spacer) or Seretide Diskus 50/100 micrograms (1 inhalation

twice daily) was evaluated in 31 children aged 4 to 11 years with mild asthma. Systemic

exposure to salmeterol was similar for Seretide Inhaler, Seretide Inhaler with spacer, and

Seretide Diskus (126 pg hr/mL [95% CI: 70, 225], 103 pg hr/mL [95% CI: 54, 200], and 110

pg hr/mL [95% CI: 55, 219], respectively). Systemic exposure to fluticasone propionate was

Page

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19

similar for Seretide Inhaler with spacer (107 pg hr/mL [95% CI: 45.7, 252.2]) and Seretide

Diskus (138 pg hr/mL [95% CI: 69.3, 273.2]), but lower for Seretide Inhaler (24 pg hr/mL

[95% CI: 9.6, 60.2]).”

5.3

Preclinical safety data

The only safety concerns for human use derived from animal studies of salmeterol and

fluticasone propionate given separately were effects associated with exaggerated

pharmacological actions.

In animal reproduction studies, glucocorticosteroids have been shown to induce

malformations (cleft palate, skeletal malformations). However, these animal experimental

results do not seem to be relevant for man given recommended doses. Animal studies with

salmeterol have shown embryofetal toxicity only at high exposure levels. Following co-

administration, increased incidences of transposed umbilical artery and incomplete

ossification of occipital bone were found in rats at doses associated with known

glucocorticoid-induced abnormalities. Neither salmeterol xinafoate or fluticasone propionate

have shown any potential for genetic toxicity.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Excipient: Lactose monohydrate (which contains milk proteins).

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

The expiry date of the product is indicated on the packaging materials.

6.4

Special precautions for storage

Do not store above 30

6.5

Nature and contents of container

The inhalation powder is contained in blisters held on a formed PVC coated base, with a

peelable foil laminate lid. The strip is contained in a moulded purple plastic device.

The plastic devices are available in cardboard containers, which hold 1 x 60 dose Diskus

6.6

Special precautions for disposal and other handling

The Diskus releases a powder which is inhaled into the lungs. A dose indicator on the Diskus

indicates the number of doses left. For detailed instructions for use see the Patient Information

Leaflet.

7.

Manufacturer

Glaxo Wellcome Production, Evreux, France.

Page

19

19

8.

License Holder and Importer

GlaxoSmithKline (Israel) Ltd., 25 Basel St., Petach Tikva

9.

License Number

50/100 MCG 114-13-29551

50/250 MCG 114-15-29553

50/500 MCG 114-14-29552

Revised on October 2020.

Trade marks are owned by or licensed to the GSK group of companies.

©2020 GSK group of companies or its licensor.

Seretide DR v7

אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכדועמ( ןכדועמ(

05.2013

05.2013

ךיראת

03.2015

םושירה רפסמו תילגנאב רישכת םש

Seretide Diskus 50/100 MCG )114-13-29551(, Seretide Diskus 50/250 MCG )114-15-29553(,

Seretide Diskus 50/500 MCG )114-14-29552(

:םושירה לעב םש

GlaxoSmithKline )ISRAEL( Ltd

! דבלב תורמחהה טורפל דעוימ הז ספוט אפורל ןולעב אפורל ןולעב תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט

Special

warnings

and

precautions

for use

As with all inhaled medication containing

corticosteroids, Seretide should be administered

with caution in patients with pulmonary

tuberculosis.

As with all inhaled medication containing corticosteroids, Seretide

should be administered with caution in patients with active or quiescent

pulmonary tuberculosis and fungal, viral or other infections of the

airway. Appropriate treatment should be promptly instituted, if

indicated.

The benefits of inhaled fluticasone propionate

therapy should minimise the need for oral steroids,

but patients transferring from oral steroids may

remain at risk of impaired adrenal reserve for a

considerable time. Patients who have required high

dose emergency corticosteroid therapy in the past

may also be at risk. This possibility of residual

impairment should always be borne in mind in

emergency and elective situations likely to produce

stress, and appropriate corticosteroid treatment

must be considered. The extent of the adrenal

impairment may require specialist advice before

elective procedures.

The benefits of inhaled fluticasone propionate therapy should minimise

the need for oral steroids, but patients transferring from oral steroids may

remain at risk of impaired adrenal reserve for a considerable time.

Therefore these patients should be treated with special care and

adrenocortical function regularly monitored. Patients who have required

high dose emergency corticosteroid therapy in the past may also be at

risk. This possibility of residual impairment should always be borne in

mind in emergency and elective situations likely to produce stress, and

appropriate corticosteroid treatment must be considered. The extent of

the adrenal impairment may require specialist advice before elective

procedures.

Interaction

with other

medicinal

products

and other

forms of

interaction

Both non-selective and selective beta-blockers

should be avoided unless there are compelling

reasons for their use.

adrenergic blockers may weaken or antagonise the effect of salmeterol.

Both non-selective and selective

blockers should be avoided unless

there are compelling reasons for their use. Potentially serious

hypokalaemia may result from

agonist therapy. Particular caution is

advised in acute severe asthma as this effect may be potentiated by

concomitant treatment with xanthine derivatives, steroids and diuretics.

Fluticasone Propionate

In a small study in healthy volunteers, the slightly

less potent CYP3A inhibitor ketoconazole

increased the exposure of fluticasone propionate

after a single inhalation by 150%. This resulted in a

greater reduction of plasma cortisol as compared

with fluticasone propionate alone. Co-treatment

with other potent CYP3A inhibitors, such as

itraconazole, is also expected to increase the

systemic fluticasone propionate exposure and the

risk of systemic side-effects. Caution is

recommended and long-term treatment with such

drugs should if possible be avoided.

Fluticasone Propionate

In a small study in healthy volunteers, the slightly less potent CYP3A

inhibitor ketoconazole increased the exposure of fluticasone propionate

after a single inhalation by 150%. This resulted in a greater reduction of

plasma cortisol as compared with fluticasone propionate alone. Co-

treatment with other potent CYP3A inhibitors, such as itraconazole, and

moderate CYP3A inhibitors, such as erythromycin, is also expected to

increase the systemic fluticasone propionate exposure and the risk of

systemic side effects. Caution is recommended and long-term treatment

with such drugs should if possible be avoided.

Undesirable

effects

Infections & Infestations

Candidiasis of the mouth and throat – Common

Pneumonia - Common

Bronchitis – Common

Infections & Infestations

Candidiasis of the mouth and throat – Common

Pneumonia - Common

Bronchitis – Common

Oesophageal candidiasis- Rare

Overdose

The signs and symptoms of salmeterol overdose are

tremor, headache and tachycardia. The preferred

antidotes are cardioselective beta-blocking agents,

which should be used with caution in patients with

a history of bronchospasm. If Seretide therapy has

to be withdrawn due to overdose of the beta agonist

component of the drug, provision of appropriate

replacement steroid therapy should be considered.

Additionally, hypokalaemia can occur and

potassium replacement should be considered.

The signs and symptoms of salmeterol overdose are dizziness, increases

in systolic blood pressure, tremor, headache and tachycardia. If Seretide

therapy has to be withdrawn due to overdose of the

agonist component

of the drug, provision of appropriate replacement steroid therapy should

be considered. Additionally, hypokalaemia can occur and therefore

serum potassium levels should be monitored. Potassium replacement

should be considered.

תושקובמה תורמחהה תונמוסמ ובש ,ןולעה ב"צמ .בוהצ עקר לע עבצב )ןולעב( ונמוס תורמחה רדגב םניאש םייוניש קורי

ןכרצל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכרצל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכדועמ( ןכדועמ(

05.2013

05.2013

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03.2015

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Seretide Diskus 50/100 MCG )114-13-29551(, Seretide Diskus 50/250 MCG )114-15-29553(,

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! דבלב תורמחהה טורפל דעוימ הז ספוט ןכרצל ןולעב ןכרצל ןולעב תושקובמה תורמחהה קרפ ןולעב יחכונ טסקט שדח טסקט ינפל שומיש הפורתב תודחוימ תורהזא

הפורתב שומישל תועגונה רתוי קודה ןפואב ךלש לופיטה לע חקפי ךלש אפורה :ןוגכ תויאופר תויעבמ לבוס התא םא

( תפחש

רבעב וא םויכ ) תודחוימ תורהזא

הפורתב שומישל תועגונה התא םא רתוי קודה ןפואב ךלש לופיטה לע חקפי ךלש אפורה :ןוגכ תויאופר תויעבמ לבוס

( תפחש

רבעב וא םויכ ) םירחא האיר ימוהיז וא ,

םיסוכרפ

)סיזורופואיטסוא( םצעה תופיפצב הדירי

ןוסיחה תכרעמב היעב

טקרטק וא המוקואלג ומכ םייניע תויעב תורחא תופורת תליטנ

...

:חקול התא םא חקורה וא אפורה תא עדייל שי דחוימב

,ריבנוטיר ןוגכ( תויתיירטפיטנאו תוילאריוויטנא תופורת וללה תופורתהמ קלח .)לוזאנוקארטיאו לוזאנוקוטק וא טאנויפורפ ןוזאקיטולפה תומכ תא תולעהל תולולע ךלש ןוכיסה תא ריבגהל לוכי הז .ךפוגב לורטמלאסה ,רידס אל בל בצק ללוכ ,דייטרס םע יאוול תועפות תווחל .יאוולה תועפות תא רימחהל לולע וא

תורחא תופורת תליטנ

...

:חקול התא םא חקורה וא אפורה תא עדייל שי דחוימב

םימוהיזב לופיטל תופורת ,לוזאנוקוטק ,ריבנוטיר ןוגכ( תולולע וללה תופורתהמ קלח .)ןיצימורתיראו לוזאנוקארטיא לורטמלאסה וא טאנויפורפ ןוזאקיטולפה תומכ תא תולעהל ךלש ןוכיסה תא ריבגהל לוכי הז .ךפוגב אל בל בצק ללוכ ,דייטרס םע יאוול תועפות תווחל .יאוולה תועפות תא רימחהל לולע וא ,רידס

.הובג םד ץחלב לופיטל םישמשמ ,םינתשמ

)לומאטובלאס ומכ( םירחא תונופמיס יביחרמ

.םיניתנאסק גוסמ תופורת םיתיעל תושמשמ הלא .המתסאב לופיטל תובורק

דציכ שמתשת ?הפורתב רתוי הובג ןונימ תועטב תלטנ םא

תחקל םא .תוארוהה יפל ףאשמב שמתשהל בושח וא אפורה םע חחוש ץלוממהמ הלודג הנמ תועטב רתוי רהמ םעופ ךבילש ךכב ןיחבתש ןכתיי .ךלש חקורה ,שאר באכ ךל היהיש םג ןכתיי .ביצי ךניאשו ליגרהמ .םיקרפמב םיבאכו םירירש תשלוח

רתוי הובג ןונימ תועטב תלטנ םא

הנמ תועטב תחקל םא .תוארוהה יפל ףאשמב שמתשהל בושח ןכתיי .ךלש חקורה וא אפורה םע חחוש ץלוממהמ הלודג ןכתיי .ביצי ךניאשו ליגרהמ רתוי רהמ םעופ ךבילש ךכב ןיחבתש ךל ויהיש םג ,תורוחרחס םיבאכו םירירש תשלוח ,שאר באכ .םיקרפמב

הפורתה תליטנ תא קיספמ התא םא .תיחנוהש יפכ םוי לכ ךלש דייטרסה תא חקיתש דואמ בושח לא .קיספהל ךל רמאי ךלש אפורהש דע התוא תחקל ךשמה וא קיספת םורגל לולע הז .ךלש דייטרסה תנמ תא ימואתפ ןפואב תיחפת תולולע דואמ תורידנ םיתעלו רימחהל ךלש המישנה תייעבל :תוללוכ הלא .יאוול תועפות עיפוהל

ןובאית ןדבואו תופייע

ךמדב ןגלשא לש תוכומנ תומר

הפורתה תליטנ תא קיספמ התא םא ךשמה .תיחנוהש יפכ םוי לכ ךלש דייטרסה תא חקיתש דואמ בושח וא קיספת לא .קיספהל ךל רמאי ךלש אפורהש דע התוא תחקל םורגל לולע הז .ךלש דייטרסה תנמ תא ימואתפ ןפואב תיחפת .ךלש המישנב הרמחהל ,תוימואתפב דייטרס תא תחקל קיספמ התא םא ,ףסונב תורידנ םיתיעל( תולולע דייטרס לש הנמה תא תיחפמ התא םא וא הילכה תרתוי תטולבב תויעב ךל םרגהל )דואמ םיתיעלש )הילכה תרתוי תטולב תקיפס יא( ךלש )לנרדא( .יאוול תועפות לולכל הלוכי :תואבהמ תחא לכ לולכל תולוכי הלא יאוול תועפות

ןובאית ןדבואו תופייע ילוח תשגרה ,

לש תוכומנ תומר רכוס ךמדב

תועפות יאוול ךלש המישנהש ןיחבתש ןכתי :תויגרלא תובוגת .דייטרסב שומישה רחאל תוימואתפב הרימחמ לולע התא .לעתשהלו דואמ ףצפצל לולע התא ,םינפה לש ללכ ךרדב( תוחיפנבו דרגב םג ןיחבהל .)ןורגה וא ןושלה ,םייתפשה לבוס התא םא ןפואב תושחרתמ ןה םא וא ולא תועפותמ תונפל שי ,דייטרסב שומישה רחאל ימואתפ .אפורל דימ תוצופנ ןניא דייטרסל תויגרלא תובוגת םדאמ תוחפ לע תועיפשמ ןה(

ךותמ

הרימחמ ךלש המישנהש ןיחבתש ןכתי :תויגרלא תובוגת .דייטרסב שומישה רחאל דימ תוימואתפב לולע התא לעתשהלו דואמ ףצפצל המישנ רצק תויהל וא לולע התא . ,דרגב םג ןיחבהל )תודרגמ תוישושבג( החירפב ךרדב( תוחיפנבו )ןורגה וא ןושלה ,םייתפשה ,םינפה לש ללכ לולע התאש וא התאש וא דואמ רהמ םעופ ךלש בלהש ימואתפ ןפואב שיגרהל וא תוטטומתהל איבהל לוכיש המ( ררחוסמ וא שלח שיגרמ )הרכהה ןדבואל

ולא תועפותמ תחא לכמ לבוס התא םא שומישה רחאל ימואתפ ןפואב תושחרתמ ןה םא וא .אפורל דימ תונפל שי ,דייטרסב דייטרסל תויגרלא תובוגת םדאמ תוחפ לע תועיפשמ ןה( תוצופנ ןניא

ךותמ

תורידנ יאוול תועפות ירחא דימ םירימחמה םיפוצפצ וא המישנ יישק ...דייטרס תחיקל

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תורידנ יאוול תועפות םדאמ תוחפב תועיפומ(

1

ךותמ

1000

)

תחיקל ירחא דימ םירימחמה םיפוצפצ וא המישנ יישק ...דייטרס

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.העילבב םיישקל םורגל לולעש ,טשוב יתיירטפ םוהיז תושקובמה תורמחהה תונמוסמ ובש ,ןולעה ב"צמ .בוהצ עקר לע עבצב )ןולעב( ונמוס תורמחה רדגב םניאש םייוניש קורי

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