VENTOLIN RESPIRATOR SOLUTION

Patient leaflet in accordance with the

Pharmacists’ Regulations (Preparations) – 1986

The medicine is dispensed according to a

physician’s prescription only

Ventolin

TM

Respirator Solution

Active substance:

Salbutamol (as Sulfate) 5 mg/ml

List of the additional ingredients detailed in section

Read the entire leaflet carefully before using the

medicine. This leaflet contains concise information

about the medicine. If you have any other questions,

refer to the physician or the pharmacist.

This medicine has been prescribed for you.

Do not pass it on to others. It may harm them even if it

seems to you that their medical condition is similar.

1.

What is the medicine intended for?

Ventolin Respirator Solution is used to treat

severe attacks of asthma and other forms of

bronchospasm.

Therapeutic group - Fast acting bronchodilators,

short acting selective agonist to beta-2 receptors.

2. Before using the medicine

Do not use the medicine:

If you are sensitive (allergic) to the active

ingredient or to any of the additional ingredients

contained in the medicine (as listed in section

In cases of unexpected early labour (premature

labour) or threatened abortion.

Special warnings regarding the use of the

medicine

Before the treatment with the medicine, tell the

physician if:

your asthma is active (for example you have

frequent symptoms or flare ups or limited physical

ability).

you have high blood pressure.

you are diabetic.

you have an overactive thyroid gland.

you have a history of heart problems such as an

irregular or fast heartbeat or angina pectoris.

you use another nebuliser solution e.g. ipratropium

bromide.

you are taking xanthine derivatives (such as

theophylline) or steroids to treat asthma.

you are taking diuretics, sometimes used to treat

high blood pressure or a heart condition.

you have taken other drugs used to relieve stuffy

nose (such as ephedrine or pseudoephedrine) or

other medicines used to treat asthma.

If you are taking or have recently taken other

medicines including non-prescription medicines

and food supplements, tell the physician or the

pharmacist. Especially if you are taking:

medicines for an irregular or fast heartbeat

(especially from the beta blockers group such as

propranolol)

other medicines for your asthma.

Using the medicine and food: You can take the

medicine at any time of day, with or without food.

Pregnancy, breast-feeding and fertility: If you

are pregnant or breast-feeding, think you may be

pregnant or are planning to become pregnant, ask

your physician or pharmacist for advice before taking

this medicine.

Driving and using machines: The medicine is not

likely to affect you being able to drive or use tools

or machines.

Important information about some of the

ingredients of the medicine: The medicine

contains benzalkonium chloride which may cause

bronchospasm.

3. How should you use the medicine?

Always use according to the physician’s instructions.

You should check with the physician or the

pharmacist if you are unsure.

The medicine must only be used by inhalation

from a nebuliser, and must not be injected or

swallowed. The nebuliser produces a fine mist which

you breathe in through a face mask or a mouthpiece.

Make sure that you know how to use it properly.

Do not let the medicine, or the mist produced by

the nebuliser, get into your eyes.

Use your nebuliser in a well ventilated room as some

of the mist will be released into the air and may be

breathed in by others.

The dosage and treatment will be determined only

by the physician. The usual dosage is:

Intermittent treatment - Can be given up to 4

times a day.

Adults and adolescents aged 12 years and

over - 0.5 ml to 1 ml (2.5 to 5 mg salbutamol).

Some patients may require up to 2 ml (10 mg

salbutamol).

Children aged 18 months to 12 years - 0.5 ml

to 1 ml (2.5 to 5 mg salbutamol).

Your physician may have told you to dilute the

medicine with a sterile saline solution before using it

in the nebuliser. Remember to follow the instructions

for dilution.

Continuous treatment

1 to 2 mg of salbutamol per hour. This dose can

be obtained by diluting 1 or 2 ml of the medicine

to 100 ml with sterile saline solution to produce

a solution containing 50 or 100 micrograms/ml of

salbutamol.

Do not exceed the recommended dose

How to use the medicine

1 Measure out the right quantity of the medicine

and put it in the nebuliser bowl.

2 Add the right amount of sterile saline solution.

3 Put the top on the nebuliser bowl and shake it

gently to mix the contents.

4 Assemble the nebuliser and use it as directed.

5 After use throw away any solution remaining in

the nebuliser bowl. Clean the nebuliser in the

recommended way.

If you accidently have taken a higher dosage,

talk to a physician as soon as possible.

The following effects may happen:

your heart beating faster than usual

you feel shaky

hyperactivity.

These effects usually wear off in a few hours.

If a child has accidentally swallowed the medicine,

refer immediately to a physician or to a hospital

emergency room and bring the package of the

medicine with you.

If you forgot to take the medicine, take it as soon

as you remember. However, if it is time for the next

dose, skip the forgotten dose. Do not take a double

dose to make up for a forgotten dose.

Persist with the treatment as recommended by the

physician.

Even if there is an improvement in your health, do

not stop the treatment with the medicine without

consulting the physician.

Do not take medicines in the dark! Check the label

and the dose each time you take a medicine. Wear

glasses if you need them.

If you have any other questions regarding the

use of the medicine, consult the physician or the

pharmacist.

4. Side effects

If your breathing or wheezing gets worse

straight after taking this medicine, stop using

it immediately, and tell your physician as soon

as possible.

As with any medicine, use of Ventolin Respirator

Solution may cause side effects in some of the users.

Do not be alarmed by reading the list of side effects.

You may not experience any of them. The following

side effects may happen with this medicine:

Allergic Reactions (may affect up to 1 in 10,000

people)

If you have an allergic reaction, stop taking Ventolin

Respirator Solution and see a physician straight

away. Signs of an allergic reaction include: swelling

of the face, lips, mouth, tongue or throat which may

cause difficulty in swallowing or breathing, itchy

rash, feeling faint and light headed, and collapse.

Talk to your physician as soon as possible if:

you feel your heart is beating faster or stronger

than usual (palpitations). This is usually harmless,

and usually stops after you have used the

medicine for a while

you may feel your heartbeat is uneven or it gives

an extra beat

These may affect up to 1 in 10 people (common).

If any of these happen to you, talk to your physician

as soon as possible. Do not stop using this

medicine unless told to do so.

Additional side effects

Tell your physician if you have any of the following

side effects which may also happen with this

medicine:

Common side effects (may affect up to 1 in 10

people)

feeling shaky

headache.

Uncommon side effects (may affect up to 1 in

100 people)

mouth and throat irritation

muscle cramps.

Rare side effects (may affect up to 1 in 1,000

people)

a low level of potassium in your blood

increased blood flow to your extremities

(peripheral dilatation).

Very rare side effects (may affect up to 1 in 10,000

people)

changes in sleep patterns and changes in

behaviour, such as restlessness and excitability.

The following side effects can also happen but

the frequency of these are not known:

chest pain, due to heart problems such as angina

pectoris. Tell your physician or pharmacist if this

occurs. Do not stop using this medicine unless

told to do so.

a condition known as lactic acidosis which may

cause stomach pain, hyperventilation, shortness

of breath, cold feet and hands, irregular heartbeat

or thirst.

If you think this medicine is not working well

enough for you

If your medicine does not seem to be working

as well as usual, talk to your physician as soon

as possible. Your chest problem may be getting

worse and you may need a different medicine. Do

not take extra Ventolin Respirator Solution unless

your physician tells you to.

If a side effect has appeared, if any of the side

effects get worse or when you suffer from a side

effect that has not been mentioned in the leaflet,

you should consult the physician. Adverse events

can be reported to the Ministry of Health by clicking

the link “Report Side Effects of Drug Treatment”

that is located on the Ministry of Health home page

(www.health.gov.il), which refers to on-line form for

adverse events reporting, or by entering the link:

https://forms.gov.il/globaldata/getsequence/getse

quence.aspx?formType=AdversEffectMedic@moh.

gov.il

5. How to store the medicine?

Avoid poisoning! This medicine and any other

medicine should be kept in a closed place out of the

sight and reach of children and/or infants in order to

avoid poisoning. Do not induce vomiting without an

explicit instruction from the physician.

Do not use the medicine after the expiry date

(exp. date) appearing on the package. The expiry

date refers to the last day of that month.

Store below 25°C. Keep the bottle in the outer carton

in order to protect from light. Do not use for more

than one month after the bottle is first opened.

6. Additional information

In addition to the active ingredient the medicine

also contains -

Benzalkonium chloride, sulfuric acid and water.

What does the medicine look like and what is the

content of the package -

Ventolin Respirator Solution comes in an amber

glass bottle containing 10 ml or 20 ml. The solution

is colourless to light yellow in colour.

Not all pack sizes may be marketed.

License Holder: GlaxoSmithKline (Israel) Ltd.,

25 Basel St., Petach Tikva.

Manufacturer: Glaxo Operation (UK) Limited,

Barnard Castle, UK.

This leaflet was checked and approved by the

Ministry of Health in: November 2016.

Registration number of the medicine in the National

Drug Registry of the Ministry of Health:

021-31-21046

The format of this leaflet was determined by the Ministry of Health and its content was checked and approved in July 2014

Ventolin

TM

Respirator Solution

1.

Name of the Medicinal Product

Ventolin

Respirator Solution.

2.

Qualitative and Quantitative Composition

Aqueous, colourless to light yellow solution, pH 3.5, providing 0.5% w/v

(5mg/ml) of salbutamol (as Salbutamol Sulfate BP).

Excipients with known effect:

Benzalkonium chloride solution

For the full list of excipients, see section 6.1.

3.

Pharmaceutical Form

Solution for nebulisation.

Clinical Particulars

4.1

Therapeutic indications

Salbutamol is a selective beta-2-adrenoceptor agonist. At therapeutic doses it

acts on the beta-2-adrenoceptors of bronchial muscle.

Bronchodilators should not be the only or main treatment in patients with

severe or unstable Asthma. Severe asthma requires regular medical assessment

as death may occur. Patients with severe asthma have constant symptoms and

frequent exacerbations, with limited physical capacity, and PEF values below

60% predicted at baseline with greater than 30% variability, usually not

returning entirely to normal after a bronchodilator. These patients will require

a high dose inhaled (e.g. >1mg/day) beclomethasone dipropionate) or oral

corticosteroid therapy. Sudden worsening of symptoms may require increased

costicosteroid dosage which should be administered under urgent medical

supervision.

Salbutamol Respirator Solution is indicated for the treatment of severe acute

asthma (status asthmaticus) and other forms of bronchospasm.

4.2

Posology and Method of Administration

Ventolin Respirator Solution is for inhalation use only, to be breathed in

through the mouth, under the direction of a physician, using a suitable

nebuliser. The solution should not be injected or swallowed. Ventolin

Respirator Solution may be administered intermittently or continuously.

Salbutamol has a duration of action of 4 to 6 hours in most patients.

Intermittent administration

Adults: Ventolin Respirator solution 0.5ml (2.5mg of salbutamol) should be

diluted to a final volume of 2ml with sterile normal saline. This may be

increased to 1ml (5mg of salbutamol) diluted to a final volume of 2.5ml. The

resulting solution is inhaled from a suitably driven nebuliser until aerosol

generation ceases. Using a correctly matched nebuliser and driving source this

should take about ten minutes.

Ventolin Respirator Solution may be used undiluted for intermittent

administration. For this, 2ml of Ventolin Respirator Solution (10mg of

salbutamol) is placed in the nebuliser and the patient allowed to inhale the

nebulised solution until bronchodilation is achieved. This usually takes 3 - 5

minutes. Some adult patients may require higher doses of salbutamol up to

10mg, in which case nebulisation of the undiluted solution may continue until

aerosol generation ceases. Intermittent treatment may be repeated up to four

times daily.

Paediatric Population

The same mode of administration for intermittent administration is also

applicable to children. The minimum starting dosage for children under the

age of 12 years is 0.5ml (2.5mg of salbutamol) diluted to 2 to 2.5ml with

sterile normal saline. Some children (over the age of 18 months) may,

however, require higher doses of salbutamol up to 5mg. Intermittent treatment

may be repeated up to four times daily.

Children aged 12 years and over: Dose as per adult population.

In infants under 18 months the clinical efficacy of nebulised salbutamol is

uncertain. As transient hypoxaemia may occur supplemental oxygen therapy

should be considered.

Continuous administration

Ventolin Respirator Solution is diluted with sterile normal saline to contain

50-100 micrograms of salbutamol per ml, (1-2ml solution made up to 100ml

with diluent). The diluted solution is administered as an aerosol by a suitably

driven nebuliser. The usual rate of administration is 1-2mg per hour.

4.3

Contraindications

Hypersensitivity to the active substance or any of the excipients listed in

section 6.1.

Non-i.v. formulations of salbutamol must not be used to arrest uncomplicated

premature labour or threatened abortion.

4.4

Special Warnings and Precautions for Use

Ventolin Respirator Solution must only be used by inhalation, to be breathed

in through the mouth, and must not be injected or swallowed.

Bronchodilators should not be the only or main treatment in patients with

severe or unstable asthma. Severe asthma requires regular medical

assessment, including lung-function testing, as patients are at risk of severe

attacks and even death. Physicians should consider using the maximum

recommended dose of inhaled corticosteroid and/or oral corticosteroid therapy

in these patients.

Patients receiving treatment at home should be warned to seek medical advice

if treatment with Ventolin Respirator Solution becomes less effective. As

there may be adverse effects associated with excessive dosing the dosage or

frequency of administration should only be increased on medical advice.

Patients being treated with Ventolin Respirator Solution may also be receiving

other dosage forms of short-acting inhaled bronchodilators to relieve

symptoms.

Increasing use of bronchodilators, in particular short-acting inhaled

agonists, to relieve symptoms, indicates deterioration of asthma control. The

patient should be instructed to seek medical advice if short-acting relief

bronchodilator treatment becomes less effective, or more inhalations than

usual are required. In this situation the patient should be assessed and

consideration given to the need for increased anti-inflammatory therapy (e.g.

higher doses of inhaled corticosteroid or a course of oral corticosteroid).

Severe exacerbations of asthma must be treated in the normal way.

Cardiovascular effects may be seen with sympathomimetic drugs, including

salbutamol. There is some evidence from post-marketing data and published

literature of rare occurrences of myocardial ischaemia associated with

salbutamol. Patients with underlying severe heart disease (e.g. ischaemic

heart disease, arrhythmia or severe heart failure) who are receiving salbutamol

should be warned to seek medical advice if they experience chest pain or other

symptoms of worsening heart disease. Attention should be paid to assessment

of symptoms such as dyspnoea and chest pain, as they may be of either

respirator or cardiac origin.

Ventolin Respirator Solution should be used with care in patients known to

have received large doses of other sympathomimetic drugs.

Potentially serious hypokalaemia may result from

-agonist therapy, mainly

from parenteral and nebulised administration. Particular caution is advised in

acute severe asthma as this effect may be potentiated by hypoxia and by

concomitant treatment with xanthine derivatives, steroids and diuretics.

Serum potassium levels should be monitored in such situations.

In common with other

-adrenoceptor agonists, salbutamol can induce

reversible metabolic changes such as increased blood glucose levels. Diabetic

patients may be unable to compensate for the increase in blood glucose and

the development of ketoacidosis has been reported. Concurrent administration

of corticosteroids can exaggerate this effect.

Lactic acidosis has been reported in association with high therapeutic doses of

intravenous and nebulised short-acting beta-agonist therapy, mainly in patients

being treated for an acute asthma exacerbation (see Section 4.8). Increase in

lactate levels may lead to dyspnoea and compensatory hyperventilation, which

could be misinterpreted as a sign of asthma treatment failure and lead to

inappropriate intensification of short-acting beta-agonist treatment. It is

therefore recommended that patients are monitored for the development of

elevated serum lactate and consequent metabolic acidosis in this setting.

A small number of cases of acute angle-closure glaucoma have been reported

in patients treated with a combination of nebulised salbutamol and ipratropium

bromide. A combination of nebulised salbutamol with nebulised

anticholinergics should therefore be used cautiously. Patients should receive

adequate instruction in correct administration and be warned not to let the

solution or mist enter the eye.

Salbutamol should be administered cautiously to patients suffering from

thyrotoxicosis.

Ventolin Respirator Solution contains Benzalkonium chloride which may

cause bronchospasm.

As with other inhalation therapy, paradoxical bronchospasm may occur with

an immediate increase in wheezing after dosing. This should be treated

immediately with an alternative presentation or a different fast-acting inhaled

bronchodilator. Ventolin Respirator Solution should be discontinued

immediately, the patient assessed, and if necessary a different fast-acting

bronchodilator instituted for on-going use.

4.5

Interaction with Other Medicaments and other forms of Interaction

Should not normally be prescribed with non-selective

-blocking drugs such

as propranolol.

4.6

Fertility, pregnancy and lactation

Pregnancy

Administration of drugs during pregnancy should only be considered if the

expected benefit to the mother is greater than any possible risk to the foetus.

As with the majority of drugs, there is little published evidence of the safety of

salbutamol in the early stages of human pregnancy, but in animal studies there

was evidence of some harmful effects on the foetus at very high dose levels.

Breast-feeding

As salbutamol is probably secreted in breast milk, its use in nursing mothers

requires careful consideration. It is not known whether salbutamol has a

harmful effect on the neonate, and so its use should be restricted to situations

where it is felt that the expected benefit to the mother is likely to outweigh any

potential risk to the neonate.

Fertility:

There is no information on the effects of salbutamol on human fertility. There

were no adverse effects on fertility in animals (see section 5.3).

4.7

Effect on Ability to Drive and Use Machines

None reported.

4.8

Undesirable Effects

Adverse events are listed below by system organ class and frequency.

Frequencies are defined as: very common (

1/10), common (

1/100 and

1/10), uncommon (

1/1000 and

1/100), rare (

1/10,000 and

1/1000) and

very rare (

1/10,000). Very common and common events were generally

determined from clinical trial data. Rare, very rare and unknown events were

generally determined from spontaneous data.

Immune system disorders

Very rare:

Hypersensitivity reactions including angioedema, urticaria,

bronchospasm, hypotension and collapse

Metabolism and nutrition disorders

Rare:

Hypokalaemia.

Potentially serious hypokalaemia may result from beta

agonist therapy.

Unknown: Lactic acidosis (see section 4.4)

Nervous system disorders

Common:

Tremor, headache.

Very rare:

Hyperactivity.

Cardiac disorders

Common:

Tachycardia.

Uncommon:

Palpitations

Very rare:

Cardiac arrhythmias including atrial fibrillation,

supraventricular tachycardia and extrasystoles

Unknown:

Myocardial ischaemia* (see section 4.4)

Vascular disorders

Rare:

Peripheral vasodilatation.

Respiratory, thoracic and mediastinal disorders

Very rare:

Paradoxical bronchospasm.

Gastrointestinal disorders

Uncommon:

Mouth and throat irritation.

Musculoskeletal and connective tissue disorders

Uncommon:

Muscle cramps.

* reported spontaneously in post-marketing data therefore frequency regarded

as unknown

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal

product is important. It allows continued monitoring of the benefit/risk

balance of the medicinal product. Healthcare professionals are asked to report

any suspected adverse reactions.

4.9

Overdose

The most common signs and symptoms of overdose with salbutamol are

transient beta agonist pharmacologically mediated events, including

tachycardia, tremor, hyperactivity and metabolic effects including

hypokalaemia and lactic acidosis (see sections 4.4 and 4.8).

Hypokalaemia may occur following overdose with salbutamol. Serum

potassium levels should be monitored. Lactic acidosis has been reported in

association with high therapeutic doses as well as overdoses of short-acting

beta-agonist therapy, therefore monitoring for elevated serum lactate and

consequent metabolic acidosis (particularly if there is persistence or worsening

of tachypnea despite resolution of other signs of bronchospasm such as

wheezing) may be indicated in the setting of overdose.

Pharmacological Properties

5.1

Pharmacodynamic Properties

Pharmacotherapeutic group: Andrenergics, inhalants. Selective beta-2-

andrenoreceptor agonists

ATC code: R03AC02

Salbutamol is a selective

2-agonist providing short-acting (4-6 hour)

bronchodilation with a fast onset (within 5 minutes) in reversible airways

obstruction. At therapeutic doses it acts on the

-adrenoceptors of bronchial

muscle. With its fast onset of action, it is particularly suitable for the

management and prevention of attack in asthma.

5.2

Pharmacokinetic Properties

Salbutamol administered intravenously has a half-life of 4 to 6 hours and is

cleared partly renally and partly by metabolism to the inactive 4'-0-sulfate

(phenolic sulfate) which is also excreted primarily in the urine. The faeces are

a minor route of excretion. Most of a dose of salbutamol given intravenously,

orally or by inhalation is excreted within 72 hours. Salbutamol is bound to

plasma proteins to the extent of 10%.

After administration by the inhaled route between 10 and 20% of the dose

reaches the lower airways. The remainder is retained in the delivery system or

is deposited in the oropharynx from where it is swallowed. The fraction

deposited in the airways is absorbed into the pulmonary tissues and

circulation, but is not metabolised by the lung. On reaching the systemic

circulation it becomes accessible to hepatic metabolism and is excreted,

primarily in the urine, as unchanged drug and as the phenolic sulfate.

The swallowed portion of an inhaled dose is absorbed from the gastrointestinal

tract and undergoes considerable first-pass metabolism to the phenolic sulfate.

Both unchanged drug and conjugate are excreted primarily in the urine.

5.3

Preclinical Safety Data

In an oral fertility and general reproductive performance study in rats at doses

of 2 and 50 mg/kg/day, with the exception of a reduction in number of

weanlings surviving to day 21 post partum at 50 mg/kg/day, there were no

adverse effects on fertility, embryofetal development, litter size, birth weight

or growth rate.

Pharmaceutical Particulars

6.1

List of Excipients

Preservative: Benzalkonium chloride solution.

Sulphuric acid dilute if required to adjust to pH 3.5.

Purified water.

6.2

Incompatibilities

None known.

6.3

Shelf life

The expiry date of the product is indicated on the label and packaging.

6.4

Special Precautions for Storage

Store below 25

C. Protect from light. Discard any contents remaining one

month after opening the bottle.

6.5

Nature and Contents of Container

Screw-capped 10ml amber glass bottle.

Screw-capped 20ml amber glass bottle.

6.6

Special precautions for disposal and other handling

Inhalation use only, using a suitable nebuliser.

The nebulised solution may be inhaled through a face mask, “T” piece or via

an endotracheal tube. Intermittent positive pressure ventilation (IPPV) may be

used, but is rarely necessary. When there is a risk of anoxia through

hypoventilation, oxygen should be added to the inspired air.

As many nebulisers operate on a continuous flow basis, it is likely that

nebulised drug will be released into the local environment. Ventolin

Respirator Solution should therefore be administered in a well ventilated

room, particularly in hospitals when several patients may be using nebulisers

at the same time.

Ventolin Respirator Solution may be diluted with sterile normal saline (see

section 4.2).

Administrative Data

7.

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