Canada - English - Health Canada
(Salbutamol Sulphate Solution)
1 mg salbutamol/mL
2 mg salbutamol/mL
Teva Canada Limited
30 Novopharm Court
Submission Control No: 187916
Date of Revision:
December 21, 2017
Table of Contents
PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3
USE ...................................................................................... 3
CONTRAINDICATIONS ........................................................................................................... 3
PRECAUTIONS .......................................................................................... 4
REACTIONS ........................................................................................................... 7
INTERACTIONS ............................................................................................................ 9
ADMINISTRATION ...................................................................................... 10
OVERDOSAGE ........................................................................................................................ 12
PHARMACOLOGY ..................................................................... 13
STABILITY .................................................................................................. 14
PACKAGING ...................................................... 14
PART II: SCIENTIFIC INFORMATION ............................................................................... 15
INFORMATION ................................................................................. 15
TRIALS .................................................................................................................. 17
PHARMACOLOGY ............................................................................................. 19
TOXICOLOGY ......................................................................................................................... 20
REFERENCES .......................................................................................................................... 23
PART III: CONSUMER INFORMATION .............................................................................. 31
PART I: HEALTH PROFESSIONAL INFORMATION
SUMMARY PRODUCT INFORMATION
Dosage Form / Strength
Clinically Relevant Nonmedicinal
Sterinebs/unit dose/2.5 or
5.0 mg salbutamol base/2.5
sodium chloride, sulphuric acid and
INDICATIONS AND CLINICAL USE
P.F. (salbutamol sulphate Solution) is indicated for:
the treatment of severe bronchospasm associated with exacerbations of chronic bronchitis
and bronchial asthma. It can be used by “wet” nebulization. When administered through a
nebulizer, it should be used with compressed air or oxygen.
Pediatrics (< 5 years of age):
Experience is insufficient for recommending the treatment of children under 5 years of age.
Patients who are hypersensitive to this drug or to any of the ingredients in the formulation
or component of the container and in patients with tachyarrythmias. (see DOSAGE
FORMS, COMPOSITION, AND PACKAGING).
As a tocolytic in patients at risk of premature labour or threatened abortion.
WARNINGS AND PRECAUTIONS
Patients should always carry their salbutamol aerosol or dry powder to use immediately if an
episode of asthma is experienced. If therapy does not produce a significant improvement or if the
patient’s condition worsens, medical advice must be sought to determine a new plan of
treatment. In the case of acute or rapidly worsening dyspnea, a doctor should be consulted
The application of these inhalation systems in children depends on the ability of the individual
child to learn the proper use of the devices. During inhalation, children should be assisted or
supervised by an adult who knows the proper use of the devices.
P.F must only be used by inhalation, to be breathed in
through the mouth, and must not be injected or swallowed.
A small number of cases of acute angle closure glaucoma have been reported in patients treated
with a combination of nebulized salbutamol and ipratropium bromide. A combination of
nebulized salbutamol with nebulized 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.
Use of Anti-Inflammatory Agents
In accordance with the present practice for asthma treatment, concomitant anti-inflammatory
therapy (e.g. corticosteroid) should be part of the regimen if inhaled salbutamol needs to be used
on a regular daily basis (see DOSAGE AND ADMINISTRATION). It is essential that the
physician instruct the patient in the need for further evaluation if the patient's asthma becomes
In individual patients, any beta
-adrenergic agonist, including salbutamol, may have a clinically
significant cardiac effect. Care should be taken with patients suffering from cardiovascular
disorders, especially coronary insufficiency, cardiac arrhythmias and hypertension. Special care
and supervision are required in patients with idiopathic hypertrophic subvalvular aortic stenosis,
in whom an increase in the pressure gradient between the left ventricle and the aorta may occur,
causing increased strain on the left ventricle.
Fatalities have been reported in association with excessive use of inhaled sympathomimetic
drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest following
an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is
Endocrine and Metabolism
In common with other beta-adrenergic agents, salbutamol can induce reversible metabolic
changes such as potentially serious hypokalemia, particularly following nebulized or especially
infused administration. Particular caution is advised in acute severe asthma since hypokalemia
may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics
and by hypoxia. Hypokalemia will increase the susceptibility of digitalis-treated patients to
cardiac arrhythmias. It is recommended that serum potassium levels be monitored in such
Care should be taken with patients with diabetes mellitus. Salbutamol can induce reversible
hyperglycemia during nebulized administration or especially during infusions of the drug. The
diabetic patient may be unable to compensate for this and the development of ketoacidosis has
been reported. Concurrent administration of corticosteroids can exaggerate this effect.
Lactic acidosis has been reported very rarely in association with high therapeutic doses of
intravenous and nebulized short-acting beta-agonist therapy, mainly in patients being treated for
an acute asthma exacerbation (see ADVERSE REACTION section). Increase in lactate levels
may lead to dyspnea 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.
Care should be taken with patients with hyperthyroidism.
Immediate hypersensitivity reactions may occur after administration of salbutamol sulphate, as
demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, hypotension,
anaphylaxis, and oropharyngeal edema.
Care should be taken with patients who are unusually responsive to sympathomimetic amines.
Care should be taken with patients with convulsive disorders.
As with other inhaled medications, paradoxical bronchospasm may occur characterized by an
immediate increase in wheezing after dosing. This should be treated immediately with an
alternative presentation or a different fast-acting inhaled bronchodilator to relieve acute
asthmatic symptoms. Salbutamol should be discontinued immediately, the patient assessed and if
necessary, alternative therapy instituted (see ADVERSE REACTIONS).The cause of either the
refractory state or death is unknown. However, it is suspected in the fatal episodes that cardiac
arrest occurred following the unexpected development of a severe acute asthmatic crisis and
subsequent hypoxia. Several cases have been reported in which intermittent positive pressure
ventilation in acute asthma attacks was related to lethal episodes of hypoxia and pneumothorax.
This method of drug administration may be ineffective in patients with severe obstruction and
greatly increased airway resistance, and it may induce severe hypercapnia and hypoxia. During
intermittent ventilation therapy, the monitoring of arterial blood gases is highly desirable. It is
advisable that in the event of either hypoxia and pneumothorax or paradoxical bronchospasm the
use of the preparation should be discontinued immediately and alternate therapy instituted, since
in the reported cases the patients did not respond to other forms of therapy until the drug was
Salbutamol has been in widespread use for many years in humans without
apparent ill consequence. However, there are no adequate and well-controlled studies in pregnant
women and there is little published evidence of its safety in the early stages of human pregnancy.
Administration of any drug to pregnant women should only be considered if the anticipated
benefits to the expectant woman are greater than any possible risks to the foetus (see
TOXICOLOGY, Teratogenicity Studies).
During worldwide marketing experience, rare cases of various congenital anomalies, including
cleft palate and limb defects have been reported in the offspring of patients being treated with
salbutamol. Some of the mothers were taking multiple medications during their pregnancies.
Because no consistent pattern of defects can be discerned, and baseline rate for congenital
anomalies is 2-3%, a relationship with salbutamol use cannot be established.
Labour and Delivery:
Although there have been no reports concerning the use of inhaled
salbutamol during labour and delivery, intravenously administered salbutamol given at high
doses may inhibit uterine contractions. While this effect is extremely unlikely as a consequence
of using inhaled formulations, it should be kept in mind. Oral salbutamol has been shown to
delay preterm labour in some reports but there are no well-controlled studies which demonstrate
that it will stop preterm labour or prevent labour at term. When given to pregnant patients for
relief of bronchospasm, cautious use of Salbutamol Sulphate Respirator Solution is required to
avoid interference with uterine contractility.
Since salbutamol is probably excreted in breast milk and because of its
observed tumorigenicity in animal studies, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the benefit of the drug to the mother. It is
not known whether salbutamol in breast milk has a harmful effect on the neonate.
P.F should be used under the supervision of an adult
who understands the proper use of the nebulizer (and TEVA-SALBUTAMOL STERINEBS
applicable) and only as presented by the doctor.
Rarely, in children, hyperactivity occurs and occasionally, sleep disturbances, hallucination or
atypical psychosis have been reported.
Pediatrics (< 5 years of age):
Experience is insufficient for recommending the treatment of
children under 5 years of age.
Monitoring and Laboratory Tests
The management of asthma should normally follow a stepwise program and patient response
should be monitored clinically and by lung function tests.
Monitoring Control of Asthma
Failure to respond for at least three hours to a previously effective dose of salbutamol indicates a
deterioration of the condition and the physician should be contacted promptly. Patients should be
warned not to exceed the recommended dose
as there may be adverse effects associated with
The increasing use of fast acting, short duration inhaled beta
-adrenergic agonists to control
symptoms indicates deterioration of asthma control and the patient’s therapy plan should be
reassessed. In worsening asthma it is inadequate to increase beta
-agonist use only, especially
over an extended period of time. In the case of acute or rapidly worsening dyspnea, a doctor
should be consulted immediately. Sudden or progressive deterioration in asthma control is
potentially life threatening; the treatment plan must be re-evaluated, and consideration be given
to corticosteroid therapy (see DOSAGE AND ADMINISTRATION).
As with other beta
-agonists, special caution should be observed when using
salbutamol in elderly patients who have concomitant cardiovascular disease that could be
adversely affected by this class of drug.
Because clinical trials are conducted under very specific conditions the adverse reaction
rates observed in the clinical trials may not reflect the rates observed in practice and
should not be compared to the rates in the clinical trials of another drug. Adverse drug
reaction information from clinical trials is useful for identifying drug-related adverse
events and for approximating rates
Adverse Drug Reaction Overview
Adverse events are listed below; 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) including isolated reports. Very common and common events were generally determined
from clinical trial data. Rare, very rare and unknown events were generally determined from
As with other bronchodilator inhalation therapy, the potential for paradoxical bronchospasm
should be kept in mind. If it occurs, the preparation should be discontinued immediately and
alternative therapy instituted.
Potentially serious hypokalemia may result from beta
-agonist therapy, primarily from parenteral
and nebulized routes of administration (see WARNINGS and PRECAUTIONS, Endocrine and
Peripheral vasodilation and a compensatory small increase in heart rate may occur in some
patients. Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and
extrasystoles) have been reported, usually in susceptible patients.
The most frequent adverse reactions associated with salbutamol inhalation aerosol, dry powder
or respirator solution formulations are nervousness and tremor. In some patients inhaled
salbutamol may cause a fine tremor of skeletal muscle, particularly in the hands. This effect is
common to all beta
-adrenergic-agonists. Adaptation occurs during the first few days of dosing
and the tremor usually disappears as treatment continues.
Headache, palpitations, transient muscle cramps, insomnia, nausea, weakness and dizziness have
been reported as untoward effects following salbutamol administration.
Rarely reported adverse effects include drowsiness, flushing, restlessness, irritability, chest
discomfort, difficulty in micturition, hypertension, angina, vomiting, vertigo, central nervous
system stimulation, hyperactivity in children, unusual taste and drying or irritation of the
Immediate hypersensitivity reactions including angioedema, urticaria, bronchospasm,
hypotension, rash, oropharyngeal oedema, anaphylaxis and collapse have been reported very
Rarely, in children, hyperactivity occurs and occasionally, sleep disturbances, hallucination or
atypical psychosis have been reported.
Lactic acidosis has been reported very rarely in patients receiving intravenous and nebulized
salbutamol therapy for the treatment of acute asthma exacerbation.
Table 1 Established or Potential Drug-Drug Interactions
inhibitors or tricyclic
Salbutamol should be administered with
extreme caution to patients being treated with
monoamine oxidase inhibitors or tricyclic
May lead to
Other inhaled sympathomimetic
bronchodilators or epinephrine should not be
used concomitantly with salbutamol. If
additional adrenergic drugs are to be
administered by any route to the patient
using inhaled salbutamol, the adrenergic
drugs should be used with caution. Such
concomitant use must be individualized and
not given on a routine basis. If regular
coadministration is required then
alternative therapy must be considered.
Beta-adrenergic blocking drugs, especially the
non-cardioselective ones, such as
propranolol, should not usually be prescribed
May lead to
these effects is not
The ECG changes and/or hypokalemia that
may result from the administration of non-
potassium sparing diuretics (such as loop or
thiazide diuretics) can be acutely worsened
by beta-agonists, especially when the
recommended dose of the beta-agonist is
exceeded. Caution is advised in the
coadministration of beta-agonists with non-
potassium sparing diuretics.
May lead to
decrease in serum
these findings for
digoxin on a
chronic basis is
Mean decreases of 16-22% in serum
digoxin levels were demonstrated after
single dose intravenous and oral
administration of salbutamol, respectively, to
normal volunteers who had received digoxin
for 10 days. It would be prudent to carefully
evaluate serum digoxin levels in patients who
are currently receiving digoxin and
glaucoma has been
A small number of cases of acute angle
closure glaucoma have been reported in
patients treated with a combination of
nebulized salbutamol and ipratropium
bromide. Therefore, a combination of
nebulized salbutamol with nebulized
anticholinergics should be used cautiously.
Patients should receive adequate
instruction in correct administration and be
warned not to let the solution or mist enter
Legend: CS=Class Statement
DOSAGE AND ADMINISTRATION
The dosage should be individualized, and the patient’s response should be monitored by the
prescribing physician on an ongoing basis.
In patients with asthma, if salbutamol is required for relief of symptoms more than twice a
day on a regular daily basis or for an extended period of time, anti-inflammatory therapy
(e.g. Corticosteroid) should be part of the regimen.
Increasing demand for Teva-Salbutamol
(salbutamol sulphate) Solution in bronchial asthma is
usually a sign of worsening asthma and indicates that the treatment plan should be reviewed.
If a previously effective dose fails to provide the usual relief, or the effects of a dose last for
less than three hours, patients should seek prompt medical advice since this is usually a
sign of worsening asthma.
As there may be adverse effects associated with excessive dosing the dosage or frequency of
administration should only be increased on medical advice. However, if a more severe attack has
not been relieved by the usual dose, additional doses may be required. In these cases, patients
should immediately consult their doctors or the nearest hospital.
P.F. may be preferred in the treatment of severe
bronchospasm associated with exacerbations of chronic bronchitis and bronchial asthma.
Recommended Dose and Dosage Adjustment
and Adolescents ≥ 13 years of age
Patients requiring single doses of 2.5 mg or 5.0 mg
may be administered the contents of a single unit dose (TEVA-SALBUTAMOL STERINEBS
2.5 mg or 5.0 mg of salbutamol). Treatment may be repeated 4 times a day if necessary.
Children (5 - 12 years):
Children requiring single doses of 2.5 mg may be administered the
contents of a single unit dose (TEVA-SALBUTAMOL STERINEBS
2.5 mg of Salbutamol).
For more refractory cases children may use a 5 mg unit dose (see dosage above). Treatment may
be repeated 4 times a day if necessary.
If a more severe attack has not been relieved by a treatment, further treatments may be required.
In these cases, patients should immediately consult their doctor or the nearest hospital.
If a single dose is missed, instruct the patient to take the next dose at the time when it is due or if
they become wheezy.
To ensure administration of the proper dose of the drug, the patient should be instructed by the
physician or other health professional in the proper use of the nebulizer system or respirator
Salbutamol is to be used only under the direction of a physician employing either a respirator or
nebulizer. Salbutamol can be taken by either the nebulization or intermittent positive pressure
ventilation method. The solution must not be injected or swallowed. When used in a nebulizer
delivery may be by a mouthpiece, a face mask, T piece or via an endotracheal tube. The
nebulizer should be connected to a compressed air or oxygen pump. Gas flow should be in the
range of 6 to 10 L/minute. With an average volume of 3 mL, a single treatment lasts
approximately 10 minutes. It is advisable to prepare one dose at a time of salbutamol or to utilize
the Unit Dose presentation.
When salbutamol is administered through intermittent positive pressure ventilation, the
inspiratory pressure is usually 10-20 cm H
O and the duration of administration varies from 5 to
20 minutes, depending upon the patient and the control of the apparatus. This length of
administration provides a more gradual and more complete lysis of bronchospasm. In several
cases it has been reported that the use of intermittent positive pressure ventilation in acute
asthma attacks was related to lethal episodes of hypoxia and pneumothorax. This method of drug
administration may be ineffective in patients with severe obstruction and may greatly increase
airway resistance and possibly induce severe hypercapnia and hypoxia. It is highly desirable to
monitor arterial blood gases during intermittent positive pressure ventilation therapy. When there
is a risk of anoxia through hypoventilation, oxygen should be added to the inspired air.
As many nebulizers operate on a continuous flow basis, it is likely that nebulized drug will be
released in the local environment. Salbutamol should therefore be administered in a well
ventilated room, particularly in hospitals when several patients may be using nebulizers at the
Salbutamol is to be used with a nebulizer, under the direction of a physician. Salbutamol is
intended to be used undiluted. However, if prolonged delivery time is desirable (more than 10
minutes) dilution using sterile normal saline as a diluent may be required.
Cleansing and maintenance of the nebulizer must be carefully exercised by strict adherence to
the manufacturer's instructions.
For management of a suspected drug overdose, contact your regional Poison Control Centre.
Symptoms and signs
The most common signs and symptoms of overdose with salbutamol are transient beta agonist
pharmacologically mediated events (see Warning and Precautions and Adverse Reactions).
Overdosage may cause tachycardia, cardiac arrhythmia, hypokalemia, hypertension and, in
extreme cases, sudden death. 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.
Consideration should be given to discontinuation of treatment and appropriate symptomatic
therapy. To antagonise the effect of salbutamol, the judicious use of a cardioselective beta-
adrenergic blocking agent (e.g. metoprolol, atenolol) may be considered, bearing in mind the
danger of inducing an asthmatic attack.
During continuous administration of salbutamol solution, any sign of overdosage can usually be
counteracted by withdrawal of the drug
ACTION AND CLINICAL PHARMACOLOGY
Mechanism of Action
Salbutamol produces bronchodilation through stimulation of beta
-adrenergic receptors in
bronchial smooth muscle, thereby causing relaxation of bronchial muscle fibres. This action is
manifested by an improvement in pulmonary function as demonstrated by spirometric
measurements. Although beta
-receptors are the predominant adrenergic receptors in bronchial
smooth muscle and beta
-receptors are the predominant receptors in the heart, there are also
-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors.
The precise function of these receptors has not been established, but they raise the possibility that
even highly selective beta
-agonists may have cardiac effects.
At therapeutic doses, salbutamol
has little action on the beta
- adrenergic receptors in cardiac muscle.
A measurable decrease in airway resistance is typically observed within 5 to 15 minutes after
inhalation of salbutamol. The maximum improvement in pulmonary function usually occurs 60
to 90 minutes after salbutamol treatment, and significant bronchodilator activity has been
observed to persist for 3 to 6 hours.
After inhalation of recommended doses of salbutamol, plasma drug levels are very low. When
100 mcg of tritiated salbutamol aerosol was administered to two normal volunteers, plasma
levels of drug-radioactivity were insignificant at 10, 20 and 30 minutes following inhalation. The
plasma concentration of salbutamol may be even less as the amount of plasma drug-radioactivity
does not differentiate salbutamol from its principal metabolite, a sulphate ester. In a separate
study, plasma salbutamol levels ranged from less than 0.5 ng/mL to 1.6 ng/mL in ten asthmatic
children one hour after inhalation of 200 micrograms of salbutamol.
Five asthmatic patients were given tritium-labelled salbutamol from the nebulizer of an
intermittent positive pressure ventilator. In all patients, there was a rapid initial rise in plasma
concentration of total radioactivity. In four of the five patients, there was a further rise in plasma
concentration to a peak at 2 to 4 hours. All patients showed an improvement in FEV
improvement at 30 minutes to 2 hours. An average of 12.5% of the initial dose was recovered in
the urine. Of the radioactivity recovered, 88% was recovered in the first 24 hours. The metabolite
in the urine was the same as that in the plasma. During the first 2 hours, the ratio of free
salbutamol to metabolite average 2:1, whereas by 8 hours, the ratio was 9:11, and thereafter this
reversed ratio was maintained.
Approximately 10% of an inhaled salbutamol dose is deposited in the lungs. Eighty-five per cent
of the remaining salbutamol administered from a metered-dose inhaler is swallowed, however,
since the dose is low (100 to 200 mcg), the absolute amount swallowed is too small to be of
clinical significance. Salbutamol is only weakly bound to plasma proteins. Results of animal
studies indicate that following systemic administration, salbutamol does not cross the blood-
brain barrier but does cross the placenta using an
perfused isolated human placenta
model. It has been found that between 2% and 3% of salbutamol was transferred from the
maternal side to the fetal side of the placenta.
Salbutamol is metabolized in the liver. The principal metabolite in humans is salbutamol-o-
sulphate, which has negligible pharmacologic activity. Salbutamol may also be metabolized by
oxidative deamination and/or conjugation with glucuronide.
Salbutamol is longer acting than isoprenaline in most patients by any route of administration
because it is not a substrate for the cellular uptake processes for catecholamines nor for catechol-
O-methyl transferase. Salbutamol and its metabolites are excreted in the urine (>80%) and the
feces (5% to 10%). Plasma levels are insignificant after administration of aerosolized
salbutamol; the plasma half-life ranges from 3.8 to 7.1 hours.
STORAGE AND STABILITY
Keep out of the sight and reach of children.
P.F. Store between 2 to 25°C. Leave product in the
carton when not used.
In the home, the unit dose preparation (TEVA-SALBUTAMOL STERINEBS
) which is pre-
diluted and ready to use, is the most convenient preparation. Any unused solution in the
nebulizer should be discarded.
DOSAGE FORMS, COMPOSITION AND PACKAGING
P.F. (Salbutamol Sulphate Solution) contains
salbutamol sulphate in an aqueous solution, equivalent to 1.0 mg or 2.0
mg of salbutamol base
per mL. It contains salbutamol sulphate as salbutamol base 1 mg/mL or 2 mg/ml with normal
saline solution of sodium chloride (0.9%) in sterile water for inhalation. Sulphuric acid may be
included to adjust pH.
P.F. is supplied in nebules containing 2.5 mL unit
doses. Each individual carton contains 20 plastic sterinebs with enclosed leaflet.
PART II: SCIENTIFIC INFORMATION
Molecular formula and molecular mass:
S ; 576.7
White to almost white powder. It is odourless or almost odourless.
Soluble in 4 parts of water; slightly soluble in ethanol
(96%), in chloroform and in ether.
9.3 and 10.3
The distribution coefficient of salbutamol between two phases of
octanol and water, as determined by HPLC, is log D=-0.5 at pH
7.42 at room temperature.
C, with decomposition.
In controlled clinical trials, the onset of improvement in pulmonary function was within 15
minutes, as determined by both maximum mid-expiratory flow rate (MMEF) and FEV
measurements also showed that near maximum improvement in pulmonary function generally
occurs within 60 to 90 minutes following two inhalations of salbutamol and that clinically
significant improvement generally continues for three to four hours in most patients. In clinical
trials some patients with asthma showed a therapeutic response (defined as maintaining FEV
values 15% or more above baseline) that was still apparent at six hours. Continued effectiveness
of salbutamol was demonstrated over a 13-week period in these same trials.
In clinical studies, two inhalations of salbutamol taken approximately 15 minutes before exercise
prevented exercise-induced bronchospasm, as demonstrated by the maintenance of FEV
80% of baseline values in the majority of patients. One of these studies also evaluated the
duration of the prophylactic effect to repeated exercise challenges which was evident at four
hours in the majority of patients and at six hours in approximately one third of the patients.
The ability of salbutamol to produce bronchodilation in humans has been demonstrated in many
spirometric and plethysmographic studies. Following a challenge with acetylcholine aerosol, in a
study examining the effects of salbutamol in airway resistance following challenge testing in 12
patients, the mean airway resistance increased 250%. After salbutamol aerosol (200
micrograms), the mean airway resistance decreased to 78% of the initial value. Challenges with
grass pollen or house dust aerosols in five and eight patients, respectively, increased activity
resistance 265% and 255%, respectively. Administration of salbutamol decreased airway
resistance to initial levels.
Controlled clinical studies and other clinical experience have shown that inhaled salbutamol, like
other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some
patients, as measured by pulse rate, blood pressure, symptoms, and/or ECG changes.
When salbutamol was administered as a metered-dose inhaler preparation to six normal
volunteers, at doses of three or seven inhalations of 100 micrograms, it was observed that three
inhalations of salbutamol did not alter serum potassium while seven inhalations resulted in a
decrease in serum potassium from 4.4 to 3.8 mEq/L. Thus, recommended doses of salbutamol
aerosol (two inhalations) would not be expected to alter serum potassium levels.
A double-blind placebo controlled comparison of the bronchodilator effects of salbutamol,
inhaled either as a dry powder or as a conventional aerosol, was carried out in 20 adult patients
with chronic bronchial asthma. All treatments were significantly better than placebo. There was
no significant difference between responses to any of the three dry powder doses (100 mcg, 200
mcg, 300 mcg) but the average response to 200 mcg aerosol was significantly greater than that to
200 mcg dry powder.
Salbutamol dry powder (400 mcg) and conventional aerosol (200 mcg) were administered to 10
adult asthmatics. There was no statistically significant difference between the improvement in
obtained 10 minutes after administration of either the dry powder or the aerosol
Salbutamol was administered as a dry powder (50 mcg, 100 mcg, 200 mcg, 400 mcg) and as an
aerosol (200 mcg) to 10 adult asthmatics. The greatest responses were obtained with salbutamol
400 mcg administered as a dry powder. No effect on blood pressure or pulse rate was observed.
Daily improvement in PEFR in response to single doses of inhaled salbutamol (200 mcg dry
powder and 100 mcg conventional aerosol) was measured in nine asthmatic children (aged 5-13
years) for six weeks. The order of administration of powder and aerosol was reversed at the end
of three weeks. There was no statistically significant difference between the increase in PEFR 5
minutes after either 200 mcg dry powder or after 100 mcg aerosol. The total mean increases in
PEFR 10 minutes after inhalation of powder and aerosol (weeks 1-3) and inhalation of aerosol
and powder (weeks 4-6) were not significantly different.
In a double-blind placebo-controlled study, salbutamol (200 mcg) completely prevented
exercise-induced bronchospasm in three of five children, and greatly reduced the effects in the
other two patients.
Administration of 10 mg salbutamol as a 0.5% solution through IPPV from a Bennett ventilator,
given in a 3 minute period, resulted in a 40% increase of FEV
with maximum effect in about 90
minutes. The average duration of effect was 3 hours. The heart rate had an average increase of 9
beats/minute, peaking after 25 minutes, and lasting for about 36 minutes. No ECG changes were
Salbutamol solution 0.5% was self-administered at home via a portable nebulizer, without IPPV,
by 28 adult patients with severe chronic asthma. The dose was 0.5 mL (2.5 mg salbutamol) in 4.5
mL normal saline, 2 to 4 times daily, and the duration of treatment period ranged from 0.9 to 2.7
years (mean 1.7 years). For each patient the treatment period was compared retrospectively with
a control period of the same duration preceding nebulizer therapy. No statistically significant
differences between treatment and control periods were found for pulmonary function tests
performed before and after 5 puffs of a salbutamol pressurized aerosol, or for number of out-
patient emergency department visits, hospitalizations, sick leaves, and days hospitalized.
However, there were significant reductions during the treatment period in the duration of sick
leaves and medical ward treatments, while half of the patients reported that it was easier to sleep
and two-thirds said it was easier to exercise.
In 10 pediatric studies, a total of 189 patients up to 14 years of age were treated with salbutamol
solution 0.5% administered via a portable nebulizer. In most cases, the dose was between 0.5 mL
and 1.0 mL per treatment, diluted with normal saline, bringing the total volume to 2.0 mL.
Children with asthma had very good results from the treatment, while children with bronchitis or
bronchiolitis did not respond well. Salbutamol was very well tolerated in these studies. One
author reported 2 cases of skeletal muscle tremor, but drew attention to the fact that both patients
received concurrent oral bronchodilator. Otherwise, the only reported side effect was occasional
Prolonged use of salbutamol in most patients caused no significant changes in ECG pattern,
blood sugar, liver and kidney functions and hematological values.
The hemodynamic effects of intravenous salbutamol were studied in patients with mitral valve
disease. At the dose of l mcg/kg, salbutamol reduced mean aortic pressure by 7 mmHg, increased
the cardiac output by 0.6 L/minute and reduced systemic vascular resistance by 7 units. It caused
no change in left ventricular ejection time. At the dose of 2 mcg/kg, salbutamol increased the
mean oxygen uptake by 21 mL/minute, narrowing the mean arteriovenous oxygen difference by
10 mL/minute. Salbutamol has no effect on the pulmonary ventilation/perfusion ratio, therefore,
unlike isoprenaline, it does not increase hypoxia during acute asthmatic attacks.
pharmacologic studies have demonstrated that salbutamol has a
preferential effect on beta
-adrenergic receptors compared with isoprenaline. While it is
recognized that beta2-adrenergic receptors are the predominant receptors in bronchial smooth
muscle, recent data indicate that there is a population of beta
-receptors in the human heart
existing in a concentration between 10% and 50%. The precise function of these, however, is not
The pharmacologic effects of beta-adrenergic agonist drugs, including salbutamol, are at least in
part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase,
the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-
adenosine monophosphate (cAMP). Increased cAMP levels are associated with relaxation of
bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity
from cells, especially from mast cells.
The muscle-relaxing effect of salbutamol was found to be more prolonged than when the effect
was induced by isoprenaline. As suggested from the results of experiments in isolated animal
tissues, salbutamol has been shown to produce a substantial bronchodilator effect in the intact
animal. In the anaesthetised guinea pig, salbutamol completely prevents acetylcholine-induced
bronchospasm at the dose of 100 micrograms/kg intravenously.
Administration of salbutamol aerosol at a dose of 250 microgram/mL for one minute to guinea
pigs prevented acetylcholine-induced bronchospasm without any chronotropic effect. A
prolonged bronchodilator effect of salbutamol compared to isoprenaline (in terms of mean times
to dyspnea following acetylcholine challenge) was observed following oral administration of
salbutamol to conscious guinea pigs. The protective action of salbutamol in this case persisted
for up to six hours.
In anaesthetised cats and dogs, salbutamol prevented the bronchospasm elicited by vagal
stimulation without any significant effect on heart rate and blood pressure. Comparative tests of
salbutamol and isoprenaline in isolated dog papillary muscle, guinea pig atrial muscle and human
heart muscle have shown that the effect of salbutamol on beta
- adrenergic receptors in the heart
In a number of studies using guinea pig atria, it was found that on a weight-to-weight basis,
salbutamol was from 2,000 to 2,500 times less active in terms of inotropic effect and 500 times
less active in terms of chronotropic effect than isoprenaline. Compared to orciprenaline,
salbutamol was about 40 times less active in terms of inotropic effect and four times less potent
in terms of chronotropic effect. Salbutamol has been shown to be one-fifth as potent a
vasodilator in skeletal muscle as isoprenaline, as measured by effects on hind limb blood flow in
the anaesthetised dog. In the perfused rabbit ear, salbutamol was shown to possess only one-tenth
the activity of isoprenaline in terms of vasodilating effect. In dogs, salbutamol was shown to
increase coronary blood flow, which was subsequently shown to be the result of a direct
coronary vasodilating effect of salbutamol.
In six dogs with right-sided cardiac by-pass, salbutamol, given at the dose of
25 micrograms/kg, improved left ventricular efficiency and increased coronary blood flow.
Recent studies in minipigs, rodents, and dogs recorded the occurrence of cardiac arrhythmias and
sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and
methylxanthines were administered concurrently. The significance of these findings when
applied to humans is currently unknown.
Animal studies show that salbutamol does not pass the blood brain barrier.
2 week old (90)
The rate of respiration in test animals initially increased, but subsequently became abnormally
slow and deep. Death, preceded by convulsions and cyanosis, usually occurred within four hours
after drug administration.
Rabbits, cats and dogs survived a single dose of 50 mg/kg salbutamol.
Intermediate (Four Months) Toxicity
Rats received salbutamol twice daily, in oral doses from 0.5 to 25 mg/kg, on an increasing scale.
The only significant hematological changes were a small increase in hemoglobin and packed cell
volume. BUN and SGOT values were elevated while blood glucose and plasma protein levels
remained unchanged. Pituitaries had increased amount of PAS-positive material in the cleft at the
higher dose levels.
Salbutamol was given to dogs twice daily, in oral doses from 0.05 to 12.5 mg/kg, on an
increasing scale. The rate of increase of hemoglobin and packed cell volume was depressed,
particularly at higher doses. Leukocyte count decreased after sixteen weeks of treatment at each
dose level. Platelet count was increased after eight weeks at the highest dose. No significant
biochemical effects were observed. The only significant histological change was the appearance
of corpora amylacea in the stomach which was attributed to altered mucus secretion. Inhalation
of 1000 mcg of salbutamol aerosol twice daily for three months did not produce any
morphological changes in the lungs, trachea, lymph nodes, liver or heart.
Fifty female, Charles River CD Albino rats received salbutamol orally at 2, 10 and
50 mg/kg/day for one hundred and four weeks; fifty female Charles River CD Sprague-Dawley-
derived rats received 20 mg/kg/day salbutamol orally for fifty weeks, and fifty female Charles
River Long-Evans rats received 20 mg/kg/day salbutamol orally for ninety-six weeks. These rat
studies demonstrated a dose-related incidence of mesovarian leiomyomas. No similar tumors
were seen in mice.
tests involving four micro-organisms revealed no mutagenic activity.
In a two-year study in the rat, salbutamol sulphate caused a significant dose-related increase in
the incidence of benign leiomyomas of the mesovarium at doses corresponding to 111, 555, and
2,800 times the maximum human inhalation dose. In another study, the effect was blocked by the
co-administration of propranolol. The relevance of these findings to humans is not known. An
18-month study in mice and a lifetime study in hamsters revealed no evidence of tumorigenicity.
Salbutamol has been shown to be teratogenic in mice when given in doses corresponding to 14
times the human aerosol dose; when given subcutaneously in doses corresponding to 0.2 times
the maximum human (child weighing 21 kg) oral dose; and when given subcutaneously in doses
corresponding to 0.4 times the maximum human oral dose.
A reproduction study in CD-1 mice given salbutamol at doses of 0.025, 0.25, and
2.5 mg/kg subcutaneously, corresponding to 1.4, 14, and 140 times the maximum human aerosol
dose respectively, showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in
10 of 108 (9.3%) fetuses at 2.5 mg/kg. No cleft palates were observed at a dose of 0.025 mg/kg
salbutamol. Cleft palate occurred in 22 of 72 (30.5%) fetuses treated with 2.5 mg/kg isoprenaline
In rats, salbutamol treatment given orally at 0.5, 2.32, 10.75 and 50 mg/kg/day throughout
pregnancy resulted in no significant fetal abnormalities. However, at the highest dose level there
was an increase in neonatal mortality. Reproduction studies in rats revealed no evidence of
Salbutamol had no adverse effect when given orally to Stride Dutch rabbits, at doses of 0.5, 2.32
and 10.75 mg/kg/day throughout pregnancy. At a dose of 50 mg/kg/day, which represents 2800
times the maximum human inhalation dose and 78 times the maximum human oral dose
cranioschisis was observed in 7 of 19 (37%) fetuses.
Ahrens RC, Smith GD. Albuterol: an adrenergic agent for use in the treatment of asthma
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Product Monograph for
VENTOLIN, revised October 2. 2014. GlaxoSmithKline Inc.
IMPORTANT: PLEASE READ
PART III: CONSUMER INFORMATION
(salbutamol sulphate solution)
This leaflet is part III of a three-part "Product
Monograph" for TEVA-SALBUTAMOL
P.F. and is designed specifically for
Consumers. This leaflet is a summary and will not
tell you everything about TEVA-SALBUTAMOL
P.F. Please read this insert carefully
before you start your medicine. Contact your doctor
or pharmacist if you have any questions about the
drug. This medicine is for you only. Only your doctor
can prescribe it for you. Never give it to someone
else. It may harm them even if his/her symptoms are
the same as yours.
ABOUT THIS MEDICATION
What the medication is used for:
P.F. is used
in Adults and Children 5 years or older. It treats
severe, worsening breathing problems
(bronchospasm) associated with:
Bronchospasm is a sudden worsening of shortness of
breath and wheezing.
The safety and effectiveness of TEVA-
P.F. in children
below the age of 5 years are not known.
What it does:
It can relieve chest tightness and wheezing if you
have asthma or another chest illness.
Salbutamol is one of a group of medicines called
bronchodilators. Salbutamol relaxes the muscles in
the walls of the small air passages in the lungs. This
helps to open up the airways and so helps to relieve
chest tightness, wheezing and cough so that you can
breathe more easily.
When it should not be used:
Do not use TEVA-SALBUTAMOL STERINEBS
you are allergic to it or any of the components of
its formulation (see What the important
nonmedicinal ingredients are).
your heart beats faster than normal.
for the treatment of preterm labour or
What the medicinal ingredient is:
contains the active ingredient, salbutamol sulphate.
What the important nonmedicinal ingredients are:
Sodium chloride, dilute sulphuric acid and water.
What dosage forms it comes in:
contains salbutamol sulphate equivalent to 1 mg/mL,
or 2.0 mg/mL salbutamol base.
unit doses (each ampoule contains 1 dose
that is ready for use)
WARNINGS AND PRECAUTIONS
BEFORE you use TEVA-SALBUTAMOL
P.F. talk to your doctor or pharmacist
You have ever had to stop taking another
medicine for this illness because you were
allergic to it or because it caused problems.
You are having treatment for a thyroid condition.
You are having treatment for high blood pressure
or a heart problem.
You have diabetes.
You have a past history of seizures.
You have low levels of potassium in your blood
(hypokalemia), especially if you are taking:
Drugs known as xanthine derivatives (such as
Steroids to treat asthma
Water pills (diuretics)
You are pregnant or intend to become pregnant.
P.F. during pregnancy may cause harm to your
baby. Your doctor will consider the benefit to
you and the risk to your baby of taking TEVA-
You are breastfeeding. It is not known if TEVA-
into breast milk.
Rare cases of lactic acidosis (too much lactic acid in
the blood) have been reported in patients receiving
high doses of TEVA-SALBUTAMOL
P.F. If you suffer symptoms (see
Serious Side Effects Table), contact your doctor
IMPORTANT: PLEASE READ
If the relief of wheezing or chest tightness is not as
good as usual, or the effect lasts for less than three
hours, tell your doctor as soon as possible. If you
notice a sudden worsening of your shortness of
breath and wheeze shortly after taking your medicine,
tell your doctor as soon as possible. It may be that
your chest condition is worsening and you may need
to add another type of medicine to your treatment.
You should always carry other asthma medication
with you to use immediately in case you experience
an asthma attack.
Effects on Children
Children may experience:
Changes in sleep patterns
Changes in behaviour such as restlessness,
excitability ( hyperactivity)
Seeing or hearing things that are not there
INTERACTIONS WITH THIS MEDICATION
As with most medicines, interactions with other
drugs are possible. Tell your doctor, nurse, or
pharmacist about all the medicines you take,
including drugs prescribed by other doctors,
vitamins, minerals, natural supplements, or
The following may interact with TEVA-
Blood pressure-lowering drugs, including
Diuretics (“water pills”)
Bronchodilators used to open the airway
(such as other asthma medication)
Digoxin, a heart medication
PROPER USE OF THIS MEDICATION
only be inhaled
from a nebulizer. It must not be
injected or swallowed.
Do not let the TEVA-SALBUTAMOL
P.F. or the mist produced by the
nebulizer, get in your eyes.
Use your nebulizer in a well ventilated room. Some
of the mist will be released into the air and may be
breathed in by others.
Use TEVA-SALBUTAMOL STERINEBS
only as directed by your doctor. During
administration your doctor may want to monitor your
The action of TEVA-SALBUTAMOL
P.F. may last for up to 6 hours and
should last at least 4 hours.
Call your doctor
immediately if the effect of your usual dose lasts
for less than 3 hours or if you suddenly get worse
shortness of breath and you wheeze after using
your TEVA-SALBUTAMOL STERINEBS
this is usually a sign of worsening asthma.
increase the dose or how often you take your
medicine without informing your doctor,
as this may
make you feel worse
. If symptoms get worse, tell
your doctor as soon as possible.
When using TEVA-SALBUTAMOL STERINEBS
P.F., other medicines (including asthma medicines)
should only be used when prescribed by your doctor.
If you regularly use TEVA-SALBUTAMOL
P.F. two or more times a day, and
take no other asthma medication, you should talk
to your doctor who may want to reassess your
treatment plan. If you do not get relief from 3 or 4
treatments during a day, contact your physician.
exceed the prescribed dose or frequency of
administration without contacting your physician.
Adults and Adolescents 13 years and older:
ampoule (either 2.5 mg or 5 mg), repeated 4 times a
day if necessary.
Children (5-12 years)
: 1 ampoule (2.5 mg), repeated
4 times a day if necessary.
Patients who have not improved on this dose, may
need 1 ampoule (5mg), repeated 4 times a day if
How to Use TEVA-SALBUTAMOL
1. The contents of TEVA-SALBUTAMOL
P.F. are to be inhaled from a
nebulizer. Do not open the foil pack until the
2. Prepare the nebulizer for filling according to the
3. Open the foil pouch and remove the ampoules.
IMPORTANT: PLEASE READ
4. To detach a TEVASALBUTAMOL
P.F. push one ampoule
downwards and away while holding
the remaining ampoules securely (diagram 2). Return
the remaining ampoules to the foil pouch and place
the foil pouch back into the carton.
5. Holding the top of the ampoule securely, twist the
body to open (diagram 3).
6. Place the open end of the ampoule well into the
nebulizer cup and squeeze slowly (diagram 4).
Ensure the contents are emptied into the nebulizer
7. Gently shake the nebulizer and connect it with the
mouthpiece or face mask. Connect the apparatus to
the air pump or oxygen and start the treatment.
8. Breathe calmly and evenly as much as possible
until no more mist is formed in the nebulizer
chamber. At this point, treatment is finished.
9. After use discard any solution remaining in the
– TEVA-SALBUTAMOL STERINEBS
P.F should be used under the supervision of an adult
who understands the proper use of the nebulizer and
only as prescribed by the doctor.
Care of the TEVA-SALBUTAMOL
P.F. and Nebulizer
Open only one foil pack at a time and use all 5
ampoules before opening the next foil pack. Record
the date when the foil pack is first opened. Always
place foil tray (covered with lid) back in the carton
To clean the Nebulizer:
Cleaning: After each use, clean the nebulizer as
Disassemble the supply tube and the nebulizer.
Wash in warm detergent solution. Rinse the tube
To wash the suction tubes:
Place 3 mL of detergent solution in the vial,
assemble the unit and operate for 2 minutes.
Disassemble and rinse the vial with warm
water, place 3 mL of warm water in the vial,
assemble the unit and operate for 2 minutes.
Disassemble and rinse with warm water.
To dry the external passage:
Connect the nebulizer tube to the pump with
the supply tube.
Turn on the pump and blow air through for 1
minute. If there is evidence of clogging,
clean the openings and tube connectors with
the detergent, then rinse with water.
Do not swallow or inject TEVA-SALBUTAMOL
inhaled into your lungs using a nebulizer.
In case of drug overdose, contact a health care
practitioner, hospital emergency department or
regional Poison Control Centre immediately, even if
there are no symptoms. Take this leaflet or your
medication with you so that the hospital or poison
control centre will know what you have taken.
If you accidentally take a
larger dose than
, you are more likely to get side effects
like a faster heart beat, headaches and feeling shaky
or restless. These effects usually wear off within a
IMPORTANT: PLEASE READ
few hours, but you should tell your doctor as soon as
If you forget to inhale a dose do not worry: inhale the
next dose at the time you would normally take it or
inhale a dose sooner than when it is due if you
SIDE EFFECTS AND WHAT TO DO ABOUT
Side effects may include:
Effects on heart
Faster heart beat than usual
Effects on nervous system
Feeling a little shaky
Feeling anxious or irritable
Feeling tired or weak
Trouble sleeping (insomnia)
Hyperactivity in children
Effects on muscles and joints
Nausea and vomiting
Chest pain or discomfort
Unusual taste in your mouth
Dry or irritated throat
SERIOUS SIDE EFFECTS, HOW OFTEN THEY
HAPPEN AND WHAT TO DO ABOUT THEM
Symptom / effect
your doctor or
tightness in the
chest or difficulty
in breathing (sign
Swelling of the
eyelids, face, lips,
tongue or throat,
Skin rash, skin
eruption or other
effect on the skin
or eyes, itching or
when the blood
pressure is too
low (sign of
Deep and rapid
(sign of lactic
much lactic acid
in the blood).
Low level of
potassium in your
or hear things that
are not there
This is not a complete list of side effects. If you have
any unexpected effects after receiving
doctor or pharmacist.
IMPORTANT: PLEASE READ
HOW TO STORE IT
Keep your TEVA-SALBUTAMOL
P.F. in a safe place, out of reach
and sight of children. Your medicines may harm
Store TEVA-SALBUTAMOL STERINEBS
between 2-25°C. Leave product in the carton when
Reporting Side Effects
You can report any suspected side effects associated
with the use of health products to Health Canada by:
Visiting the Web page on Adverse Reaction
reporting.html) for information on how to
report online, by mail or by fax; or
Calling toll-free at 1-866-234-2345.
NOTE: Contact your health professional if you need
information about how to manage your side effects. The
Canada Vigilance Program does not provide medical
You may need to read this leaflet again.
DO NOT THROW IT AWAY
until you have
finished your medicine.
This document plus the full product monograph,
prepared for health professionals can be found by
contacting Teva Canada Limited by:
Phone: 1-800-268-4127 ext. 3;
Email: email@example.com; or
This leaflet was prepared by:
Teva Canada Limited
30 Novopharm Court
Last revised: December 21, 2017