Salbutamol

What Is Salbutamol?

Salbutamol is a bronchodilator medication in the class of beta-2 adrenergic agonists. It is commonly used to relieve bronchoconstriction in conditions such as asthma and chronic obstructive pulmonary disease (COPD). Salbutamol works by stimulating beta-2 adrenergic receptors in the smooth muscles of the airways, leading to bronchodilation and improved airflow. It is available in various forms, including inhalers and nebulizer solutions, making it convenient for both acute symptom relief and preventive use before exposure to triggers. As a short-acting bronchodilator, salbutamol rapidly relieves symptoms, but its effects are relatively short-lived. While generally considered safe, it should be used according to prescribed dosages to avoid potential side effects such as tremors, increased heart rate, and nervousness.

Pharmacokinetics

Salbutamol is readily absorbed from the gastrointestinal tract. When given by inhalation, 10 to 20% of the dose reaches the lower airways. The remainder is retained in the delivery system or is swallowed and absorbed from the gut.

Salbutamol is subject to first-pass metabolism in the liver and possibly in the gut wall, but it isn’t metabolized in the lungs. The main metabolite is the inactive sulfate conjugate.

Salbutamol is rapidly excreted, mainly in the urine, as metabolites and unchanged drag. A smaller proportion is excreted in the feces.

The plasma half-life of salbutamol has been estimated to range from 4 to 6 hours.

Stereoselectivity

The R(-)-enantiomer of salbutamol (levosalbutamol) is preferentially metabolised and is therefore cleared from the body more rapidly than the S(+)-enanti-omer, which lacks bronchodilator activity but may be implicated in some of the adverse effects of salbutamol.

Uses and Administration

Salbutamol is a direct-acting sympathomimetic with mainly beta-adrenergic activity and a selective action on beta receptors (a beta agonist). This results in its bronchodilating action being more prominent than its effect on the heart.

Salbutamol and salbutamol sulfate are used as bronchodilators in managing reversible airway obstruction, as in asthma and some patients with chronic obstructive pulmonary disease. Salbutamol also decreases uterine contractility and may be given as the sulfate to arrest premature labor.

Inhalation results in the rapid onset (within 5 minutes) of bronchodilatation, lasting about 3 to 6 hours. After oral doses, the onset of action is within 30 minutes, with a peak effect between 2 to 3 hours after the dose and a duration of action of up to 6 hours. Modified-release preparations that have a longer duration of action are available.

Salbutamol is used as the base or sulfate in aerosol inhalers and as the sulfate in other preparations. The dosage is expressed in salbutamol base salbutamol sulfate 1.2 mg, equivalent to about 1 mg of salbutamol.

To relieve acute bronchospasm, 1 or 2 inhalations of salbutamol 100 micrograms may be given from a conventional metered-dose aerosol as required, up to 4 times daily. Two inhalations may also be given just before exertion to prevent exercise-induced bronchospasm. (In the USA, these inhalations may be expressed as supplying 100 micrograms, the amount delivered into the mouthpiece, or 90 micrograms, the amount delivered/from the mouthpiece.) Current asthma guidelines recommend that inhaled short-acting beta2 agonists such as salbutamol be used on an as-required, not regular, basis.

In those patients requiring more than occasional use of salbutamol, anti-inflammatory therapy is also needed. An increased requirement for, or decreased duration of effect of, salbutamol indicates deterioration of asthma control and the need for increased anti-inflammatory therapy. Salbutamol sulfate is now available in chlorofluorocarbon (CFC)-free aerosols. Doses for these aerosols (expressed as salbutamol) are the same as for conventional aerosols.

Salbutamol may also be inhaled as the sulfate from dry powder inhalation capsules or discs, particularly by patients who experience difficulty using aerosol formulations. Owing to differences in the relative bio-availability to the lungs between these dry powder systems and the inhalation aerosol, a 200-microgram dose (expressed in terms of salbutamol) from an inhalation capsule or disc is about equivalent in activity to a 100-microgram dose from a conventional aerosol usual recommended doses are 200 or 400 micrograms up to four times daily.

When inhalation is ineffective, oral salbutamol may be given in a dose of 2 to 4 mg three or four times daily as the sulfate. Some patients may require doses of up to 8 mg three or four times daily. Still, such increased doses are unlikely to be tolerated or to provide much extra benefit. Elderly patients should be given the lower doses initially. Modified-release preparations are also available. A usual adult dose is 8 mg twice daily.

In more severe or unresponsive bronchospasm, salbutamol sulfate may be given intermittently via a nebulizer in adults and children. Licensed doses are 2.5 to 5 mg of salbutamol repeated up to 4 times daily. Continuous use is also possible, usually at a rate of 1 to 2 mg/hour. However, guidelines allow for more frequent or continuous use at a higher rate in acute severe asthma. Single-dose units of 0.1% or 0.2%, or a concentrated solution of salbutamol 0.5%, are available for nebulization. Continuous use is usually a 0.005 to 0.01% solution in sodium chloride 0.9%. Patients with acute severe asthma may require supplemental oxygen.

In acute severe asthma, where delivery via nebulizer is not available, 4 to 6 inhalations of salbutamol 100 micrograms from a metered-dose inhaler may be given at intervals of 10 to 20 minutes via a large volume spacer.

In the management of a severe attack of bronchospasm, slow intravenous injection of salbutamol 250 micrograms as a solution containing 50 micrograms/mL as the sulfate may be required; alternatively, salbutamol may be given by intravenous infusion of a solution containing 5 mg in 500 mL (10 micrograms/mL) at a usual rate of 3 to 20 micrograms/minute according to the patient’s need higher dosages have been used in patients with respiratory failure.

Salbutamol sulfate can also be given for bronchospasm by subcutaneous or intramuscular injection in doses of salbutamol 500 micrograms every 4 hours as required.

For the arrest of uncomplicated premature labor between 24 and 33 weeks of gestation, salbutamol sulfate is given by intravenous infusion, preferably with the aid of a syringe pump at a concentration of 200 micrograms/mL of salbutamol in glucose 5%. If no syringe pump is available, the infusion should be with a more dilute solution of 20 micrograms/mL in glucose 5%. The same dose is used as with the syringe pump.

The recommended initial infusion rate is 10 micrograms/minute, increased at intervals of 10 minutes until there is a response. The rate is then increased slowly until contractions cease. The usual effective dose is 10 to 45 micrograms/minute. The infusion should be maintained at the rate at which contractions cease for 1 hour, then reduced by decrements of 50% at intervals of 6 hours. Prolonged therapy should be avoided as the risks to the mother increase after 48 hours, and there is a lack of evidence of benefit from further treatment.

The maternal pulse should be monitored throughout the infusion, and the infusion rate should be adjusted to avoid a maternal heart rate of more than 140 beats/minute. A close watch should also be kept on the patient’s state of hydration since fluid overload is considered to be a key risk factor for pulmonary edema.

Salbutamol may subsequently be given orally at 4 mg three or four times daily. Still, such usage is not recommended by the BNF, given the problems with prolonged therapy already mentioned.

For doses of salbutamol used in children, see Administration in Children below.

Administration

Beta2 agonists are used extensively in the management of reversible airway obstruction. A standard, effective, and convenient method of dosage is by a pressurized aerosol inhaler. This route provides relief rapidly, and fewer systemic adverse effects are likely to occur than with oral use. Patients using conventional inhalers must employ the correct technique, which involves coordinating the actuation of the aerosol with inhalation. If patients have difficulty with this, alternatives are available. Spacer devices may be used with inhalers. These are added to the inhaler and reduce the velocity of the aerosol. Also, more propellant may evaporate before inhalation, allowing a greater proportion of the drug to reach the lungs, and coordination of actuation of the aerosol and inhalation is less important.

Breath-actuated aerosol inhalers and dry powder inhalers are also available and are actuated by the patient’s inspiration and thus avoid entirely the need for coordination of actuation and inhalation; however, inhalation of the dry powder has occasionally caused irritation of the throat or coughing. The oral route can be used, although generally, inhaled therapy is preferable. Formulations intended for oral use are commercially available, including modified-release formulations. Nebulization is an alternative method of delivery, and this may be used in the management of severe acute attacks, as may parenteral therapy.

Hydrofluoroalkane (HFA) propellants replace chlorofluorocarbon (CFC) propellants in pressurized aerosol inhalers. Conventional and breath-actuated HFA preparations are available. HFA aerosols may feel and taste different from CFC aerosols.

Administration in Children

For the treatment of reversible airway obstruction, including nocturnal asthma, and prevention of exercise-induced bronchospasm in children, the BNFC suggests the following doses:

• aerosol inhalation – 1 month to 18 years of age, 100 or 200 micrograms (1 or 2 inhalations) up to four times daily, for occasional use only;
• inhalation of dry powder from inhalation capsules or discs – 5 to 12 years of age, 200 micrograms up to four times daily, for occasional use only; over 12 years of age, doses as for adults. Inhaled therapy is generally considered first-line treatment, but oral therapy may be necessary if an inhaler device cannot be used. In the UK, salbutamol syrup is licensed for children from 2 years of age and modified-release oral preparations from 3 years of age.
• orally using an immediate-release preparation – 1 month to 2 years of age, 100 micrograms/kg (up to a maximum dose of 2 mg) three or four times daily; 2 to 6 years of age, 1 to 2 mg three or four times daily; 6 to 12 years of age, 2 mg three or four times daily; over 12 years of age, doses as for adults;
• orally using a modified-release preparation – 3 to 12 years of age, 4 mg twice daily; over 12 years of age, as for adults, see above.

In managing acute mild to moderate asthma exacerbations, salbutamol may be given using a metered-dose aerosol inhaler via a spacer device. For children of all ages, one inhalation (100 micrograms) may be given every 15 to 30 seconds up to a maximum of 10 inhalations. The dose may be repeated after 20 to 30 minutes if required. In more severe exacerbations, salbutamol can be given intermittently via a nebulizer.

A dose of 2.5 mg, which can be increased to 5 mg in children over five years of age, can be repeated every 20 to 30 minutes if necessary. Immediate transfer to the hospital and inhalation of oxygen is also required. Children under 18 months of age often respond poorly to bronchodilators; nebulized beta2 agonists have been associated with mild paradoxical bronchospasm and transient worsening of oxygen saturation.

Although parenteral salbutamol is not licensed in the UK for use in children, the BNFC recommends the following doses in the management of acute severe or life-threatening acute asthma:

• intravenous injection over 5 minutes – 1 month to 2 years of age, 5 micrograms/kg as a single dose; 2 to 18 years of age, 15 micrograms/kg (to a maximum of 250 micrograms) as a single dose;
• continuous intravenous infusion – 1 month to 18 years of age, 60 to 300 micrograms/kg per hour, adjusted according to response and heart rate. Doses above 120 micrograms/kg per hour require close monitoring.

Salbutamol can treat severe hyperkalemia in children (see Hyperkalemia section). The BNFC recommends:

• intravenous injection over 5 minutes – children of all ages, 4 micrograms/kg as a single dose repeated if necessary;
• inhalation of nebulized solution (although intravenous injection is preferred) – children of all ages, 2.5 or 5 mg as a single dose repeated if necessary.

Asthma

Short-acting beta2 agonists such as salbutamol are used for short-term relief in all patients with symptomatic asthma. High doses are used in acute asthma, but current recommendations for chronic asthma are for low doses to be inhaled as required rather than regularly. When patients with mild asthma find that symptomatic relief is needed more than 2 or 3 times a week, then that should be a sign for additional treatment with anti-inflammatory drugs. An increasing need for, or decreased effect of, short-acting beta2 agonists indicates deteriorating asthma and the requirement for stepping up therapy.

In one placebo-controlled study, patients with stable asthma receiving regular high doses of a short-acting inhaled beta2 agonist reduced the dose considerably with no change in asthma control, lending further support to the recommendation for ‘as-required’ rather than regular use of these drugs. The discussion under Fenoterol on the increased mortality that has been observed in asthma patients and the connection with asthma therapy includes a view that regular use might have contributed to the increased mortality. However, a systematic review of studies of short-acting beta2 agonists, most of which used salbutamol, found no clear clinical advantage or detriment from regular use compared with taking them as required.

Bronchiolitis

Acute bronchiolitis (inflammation of the bronchioles associated with viral respiratory tract infection, usually due to RSV) is a poorly defined respiratory condition seen in infants and young children. The diagnostic criteria and the usual management vary considerably from country to country. Beta2 agonists such as salbutamol are widely prescribed in the USA but not in the UK, and attempts to establish their benefits have produced conflicting results.

Modest benefit (but no difference in hospital admission rate) has been reported from a meta-analysis of bronchodilator therapy in general. Still, a meta-analysis of beta2-agonist therapy in bronchiolitis did not show effectiveness. Some comparative studies have suggested that nebulized adrenaline is more effective than salbutamol. However, one study in hospitalized children found no benefit from nebulized salbutamol in terms of improved oxygenation or length of hospital stay, and another found no difference in efficacy between nebulized adrenaline, salbutamol, and sodium chloride 0.9%.

Oral salbutamol in infants with acute viral bronchiolitis is no more effective than a placebo and is not recommended.

Chronic Obstructive Pulmonary Disease

Salbutamol and other beta2 agonist bronchodilators form part of the first-line treatment of chronic obstructive pulmonary disease.

Hyperkalemia

Salbutamol can lower plasma-potassium concentrations by promoting intracellular uptake, and this effect has been used in treating mild hyperkalemia associated with chronic disorders such as renal failure and hyperkalaemic periodic paralysis. However, such use is controversial: the effects of salbutamol may be inconsistent, and some clinicians prefer to avoid the use of beta2 agonists because of fears that large doses may induce cardiac arrhythmias. Salbutamol has been used to lower plasma-potassium concentrations in children and premature neonates with some success. For doses of salbutamol used to treat severe hyperkalemia in children, see Administration in Children above.

Lymphangioleiomyomatosis

Inhaled beta2 agonists are often helpful in treating the reversible component of airway obstruction in women with pulmonary lymphangioleiomyomatosis, and a trial of treatment is warranted. For mention of the use of medroxyprogesterone in this rare disease, see Respiratory Disorders.

Muscular Dystrophies

There is some evidence that beta2 agonists affect muscle strength and have an anabolic effect. Salbutamol has, therefore, been investigated in a small number of patients in the management of muscular dystrophies. Oral doses of modified-release salbutamol up to 12 mg daily have been used in boys aged between 5 and 11 years with Duchenne or Becker muscular dystrophies, and doses of 8 or 16 mg twice daily have been given to adults with facioscapulohumeral dystrophy. Although some improvements in muscle strength and muscle mass have been reported, only some muscle groups respond, and the long-term effects of treatment have yet to be discovered.

Premature Labour

Beta2 agonists such as salbutamol have been used as tocolytics in the management of premature labor. They can postpone labor for a few days. Still, the risk of adverse cardiovascular and metabolic events, including pulmonary edema, means that great care and appropriate monitoring of the patient’s heart rate and state of hydration is needed.

Proctalgia Fugax

Inhalation of salbutamol from a metered-dose inhaler at the beginning of an attack has been shown to reduce the duration of pain in patients with proctalgia fugax.

Adverse Effects

As for Sympathomimetics. Salbutamol has mainly beta-agonist effects and, like other beta agonists, may cause fine tremor of skeletal muscle (particularly the hands), palpitations, tachycardia, nervous tension, headaches, peripheral vasodilatation, and rarely muscle cramps. Inhalation causes fewer adverse effects than systemic dosage, and the more selective beta2 agonists cause fewer adverse effects than less selective beta-agonists.

Potentially serious hypokalaemia has been reported after large doses. Myocardial ischemia has also been reported. Hypersensitivity reactions have occurred, including paradoxical bronchospasm, angioedema, urticaria, hypotension, and collapse. The high doses of salbutamol used intravenously to delay premature labor have additionally been associated with nausea and vomiting and with severe adverse cardiac and metabolic effects and pulmonary edema.

Effects on the CNS

Visual hallucinations lasting for an hour have been reported after the use of nebulized salbutamol in an elderly patient. At the time of the report, the manufacturers were aware of 3 cases of hallucinations in children given oral salbutamol. Still, no such reaction had been previously reported in adults given recommended doses.

Hyperactivity and restlessness have been reported with the use of salbutamol; however, a small placebo-controlled study of 19 children failed to show a statistically significant difference in activity levels after a nebulized dose of salbutamol.

Effects on Electrolytes and Metabolism

Salbutamol with other beta2-agonists may cause hypokalaemia and hyperglycemia. These effects are related to the dose and route of salbutamol used hypokalaemia is more common after parenteral and nebulised use. Hypokalaemia may be potentiated by therapy with corticosteroids, diuretics, or xanthines, and by hypoxia; potassium concentrations should therefore be monitored in severe asthma.

Effects on the Eyes

It has been suggested that salbutamol and to a greater extent ritodrine may contribute to retinopathy in the premature infant when used for premature labour. A case of acute angle-closure glaucoma was attributed to pupil dilatation by stimulation of the sympathetic nervous system secondary to local absorption of nebulized salbutamol in the eye. The patient also had other risk factors for developing glaucoma. For reports of glaucoma precipitated by the combined use of ipratropium bromide and salbutamol via a nebulizer, see Ipratropium Bromide.

Effects on the Heart

The main adverse cardiac effect of salbutamol is tachycardia due to increased sympathetic effects on the cardiovascular system. Such tachycardia is dose-dependent and is more common after systemic than inhaled therapy. A meta-analysis of randomised, placebo-controlled studies in patients with asthma or chronic obstructive pulmonary disease (COPD) confirmed that single doses of beta2 agonists could cause an increase in heart rate and a reduction in potassium concentrations.

The longer-term effects of beta2 agonists on the cardiovascular system were also assessed, and an increased risk of adverse cardiovascular events due to sinus tachycardia was found. There was also a trend towards an increase in major adverse events including ventricular tachycardia, atrial fibrillation, syncope, heart failure, myocardial infarction, cardiac arrest, and sudden death. Myocardial ischemia has been reported in association with salbutamol when used to delay premature labor. Eleven of 17 reports were considered serious, including one fatality. Most of these reports involved the use of parenteral formulations, and none involved the use of inhaled salbutamol formulations for the relief of bronchospasm.

However, there is some evidence that high doses of inhaled salbutamol can decrease coronary flow reserve and might exacerbate ischemia in patients with coronary artery disease. Case-control studies have also suggested that the use of inhaled beta2 agonists is associated with an increased risk of myocardial infarction, and another case-control study found an increased risk of cardiac arrest in patients with asthma being treated with inhaled short-acting beta2 agonists but not in those with COPD. In contrast, however, a cohort study of patients with COPD found no increase in the risk of myocardial infarction associated with the use of beta2 agonists given by inhalation, nebulization, or mouth.

Case-control and cohort studies have also suggested that patients with pre-existing heart failure may be at increased risk of hospitalization from arrhythmias or exacerbation of heart failure with the use of beta2 agonists. A causal relationship cannot necessarily be established from these case-control and cohort studies, however, because of confounding factors such as co-morbidity, and because the extent of beta2 agonist use could only be estimated from prescription record systems. 

Effects on the Respiratory System

Paradoxical bronchoconstriction has occasionally been reported after bronchodilator therapy. With nebulizer solutions, it has been suggested that the preservatives present could be responsible or that the pH may contribute if non-neutral. In addition, regular use of beta2 agonists such as salbutamol (as opposed to use on an asneeded basis) has been shown to increase airway hyperresponsiveness to various stimuli and to lead to the possible development of tolerance to the bronchoprotective effect.

The Pulmonary Edema section mentions the increased risk of pulmonary edema associated with salbutamol.

Increased Mortality

The increased incidence of morbidity and mortality that occurred in asthmatic patients mainly involved fenoterol, but salbutamol has been implicated. The debate on the relevance of beta-agonist therapy to this increased morbidity and mortality is discussed under Fenoterol.

Overdosage

Reports of overdosage with salbutamol have generally only described the features that may be expected with beta2 agonists such as tachycardia, CNS stimulation, tremor, hypokalaemia, and hyperglycaemia. Symptomatic treatment of the adverse effects has proved successful, although it is unlikely to be required after repeated inhalation. Activated charcoal may be considered after oral overdose in patients who have taken a potentially toxic amount and present within 1 hour. The plasma-potassium concentration and pulse rate have been found to correlate with the plasma concentration of salbutamol.

Pregnancy

Most adverse effects associated with salbutamol in pregnancy relate to the cardiovascular and metabolic effects of the very high doses given by intravenous infusion in attempts to delay premature labor (see also under Pulmonary Oedema, below). Maternal effects include myocardial ischemia, unifocal ventricular ectopics associated with the hypokalaemic response to intravenous salbutamol, and heart failure in hypertensive women. Similarly, serious fetal and neonatal cardiovascular complications have also been associated with tocolytic salbutamol.

Metabolic acidosis after salbutamol infusions in diabetic women has also been reported.

For reports of retinopathy in the infant, see Effects on the Eyes above.

Pulmonary Edema

Pulmonary edema has occurred in women given beta2 agonists, including salbutamol, for premature labor. The risk factors, the most important of which is fluid overload, are discussed under Precautions, below.

Tolerance

Some studies suggest that regular inhalation of a short-acting beta2 agonist, although it continues to produce bronchodilatation, increases airway hyperresponsiveness and may reduce the protective effect against bronchoconstriction provoked by stimuli such as bradykinin, methacholine, or allergen. Such tolerance is considered another argument against the regular use of short-acting drugs. Reduced bronchoprotective effects have also been demonstrated with long-acting beta2 agonists.

It has been suggested that reduced benefit with salbutamol may be due to the S(+)-enantiomer, which unlike the R(-)-enantiomer (levosalbutamol) does not possess bronchodilating activity. Stereoselective metabolism (see under the Pharmacokinetics section) means that regular use of the racemate could lead to the accumulation of the S-enantiomer, which provides a possible mechanism for the effect. Genetic polymorphism of the beta2-adrenoceptor has also been proposed as another possible mechanism.

Precautions

Salbutamol and other beta-agonists should be given with caution in hyperthyroidism, myocardial insufficiency, arrhythmias, susceptibility to QT-interval prolongation, hypertension, and diabetes mellitus (especially on intravenous use — blood glucose should be monitored since ketoacidosis has been reported). In severe asthma, caution is also required to avoid inducing hypokalaemia, as this effect may be potentiated by hypoxia or other anti-asthma drugs on potassium (see Interactions); plasma-potassium concentrations should be monitored. Beta2 agonists such as salbutamol are not appropriate for use alone in the treatment of more than mild asthma.

Increasing need for, or decreased duration of effect of, inhaled salbutamol and other short-acting beta2 agonists indicates deterioration of asthma control and the likely requirement for increased anti-inflammatory therapy. In women being treated for premature labor, the risk of pulmonary edema means that the patient’s state of hydration and cardiac and respiratory function should be monitored very carefully. The volume of infusion fluid should be kept to the minimum (normally using glucose 5% as the diluent), beta2-agonist therapy should be stopped immediately, and diuretic therapy should be started if signs of pulmonary edema develop. Other risk factors for pulmonary edema include multiple pregnancy and heart disease.

Ischaemic heart disease or significant risk factors for ischaemic heart disease are specific contra-indications where heart disease is suspected and assessment by a physician experienced in cardiology is needed. Eclampsia and severe pre-eclampsia are also contra-indications, with special care needed in mild to moderate pre-eclampsia. Other contra-indications include intra-uterine infection, intra-uterine fetal death, antepartum hemorrhage (which requires immediate delivery), placenta praevia, and cord compression beta2 agonists should not be used for threatened miscarriage. See also the Uses and Administration section.

Abuse

Salbutamol inhalers have been subject to abuse, particularly by children and young adults. This has occurred in both asthmatic and non-asthmatic individuals and has been thought to be for the effect of sympathetic stimulation and for the effect of the fluorocarbon propellants. Introducing fluorocarbon-free inhalers should reduce the latter motivation, although not the former.

Interactions

Use of salbutamol and other beta2 agonists with corticosteroids, diuretics, or xanthines increases the risk of hypokalaemia, and monitoring of potassium concentrations is recommended in severe asthma, where such combination therapy is common (see also Effects on Electrolytes and Metabolism, above). For an outline of interactions associated with sympathomimetics in general.

Beta2 Agonists

Patients receiving salmeterol may require salbutamol to control an acute attack of bronchospasm. One study indicated that the effects might be additive, but another showed that patients receiving salmeterol had reduced sensitivity to salbutamol and might need higher doses of the latter for acute relief. However, a study in asthmatics admitted to a hospital emergency department with acute exacerbations of their illness found that previous salmeterol therapy did not reduce the effectiveness of standard doses of salbutamol. Others have also noted attenuation of the bronchoprotective effects of a beta2 agonist (in this case, fenoterol) by salmeterol.

Beta-Blockers

Non-cardioselective beta blockers oppose the bronchodilator effects of beta-agonist bronchodilators and are contra-indicated in asthmatic patients as they may cause serious bronchoconstriction, even if given as eye drops. No adverse interaction usually occurs between beta-agonist bronchodilators and cardioselective beta-blockers; however, bronchospasm can sometimes occur in asthmatic patients, particularly if high doses are used. In a case-control study in postoperative coronary artery bypass graft patients, the use of sotalol with salbutamol led to an increased risk for postoperative atrial fibrillation.

Cardiac Glycosides

Hypokalaemia produced by beta2 agonists may increase susceptibility to digitalis-induced arrhythmias, although salbutamol intravenously and by mouth can also decrease serum concentrations of digoxin (see Beta2 Agonists).

Corticosteroids

Corticosteroids and beta2 agonists may both produce falls in plasma potassium concentrations. There is evidence that such falls can be exacerbated by use together. The possibility of enhanced hyperglycaemic effects from such a combination should also be borne in mind.

It has been suggested that in acute severe asthma, corticosteroids may modify beta receptors, reversing the beta receptor desensitization and downregulation caused by beta2 agonists and enhancing the bronchodilator response. In chronic asthma, there is little evidence to support this theory. However, combination therapy with corticosteroids and beta2 agonists has been found to have beneficial effects on asthma control. The exact mechanism for this remains unclear.

Diuretics

Hypokalaemia is known to be a possible adverse effect during treatment with beta2 agonists such as salbutamol or terbutaline, and this may be enhanced if diuretics are also given. In addition, the arrhythmogenic potential of this interaction may be clinically important in patients with ischaemic heart disease.

Neuromuscular Blockers

Salbutamol, given intravenously, has been reported to enhance the neuromuscular blockade produced by pancuronium and vecuronium (see Sympathomimetics).

Xanthines

An enhanced hypokalaemic effect may occur when salbutamol is given with theophylline. 

Drug Approvals

(British Approved Name, rINN)

Synonyms: AH-3365; Salbutamol; Salbutamoli; Salbutamolis; Salbutamolum; Sch-13949W; Szalbutamol

BAN: Salbutamol

USAN: Albuterol

INN: Salbutamol [rINN (en)]

INN: Salbutamol [rINN (es)]

INN: Salbutamol [rINN (fr)]

INN: Salbutamolum [rINN (la)]

INN: Сальбутамол [rINN (ru)]

Chemical name: 2-tert-Butylamino-1-(4-hydroxy-3-hydroxymethylphenyl)ethanol

Molecular formula: C13H21NO3 =239.3

CAS: 18559-94-9

ATC code: R03AC02; R03CC02

Read code: y00UA [Obstetric]; y03Pw

Pharmacopoeias. In China, Europe, Int, US

European Pharmacopoeia, 6th ed. (Salbutamol). A white or almost white crystalline powder. Sparingly soluble in water, soluble in alcohol. Protect from light.

The United States Pharmacopeia 31, 2008 (Albuterol). A white crystalline powder. Sparingly soluble in water soluble in alcohol. Protect from light.

Salbutamol Sulfate

(rINNM)

Drug Nomenclature

Synonyms: Salbutamol Hemisulphate; Salbutamol Sulphate; Salbutamol, sulfato de; Salbutamol-sulfát; Salbutamoli Sulfas; Salbutamolio sulfatas; Salbutamolisulfaatti; Salbutamolsulfat; Szalbutamol-szulfát

BAN: Salbutamol Sulphate [BANM]

USAN: Albuterol Sulfate

INN: Salbutamol Sulfate [rINNM (en)]

INN: Sulfato de salbutamol [rINNM (es)]

INN: Salbutamol, Sulfate de [rINNM (fr)]

INN: Salbutamoli Sulfas [rINNM (la)]

INN: Сальбутамола Сульфат [rINNM (ru)]

Molecular formula: (C13H21NO3)2,H2SO4 =576.7

CAS: 51022-70-9

ATC code: R03AC02; R03CC02

Pharmacopoeias. In China, Europe, International, Japan, and US.

European Pharmacopoeia, 6th ed. (Salbutamol Sulphate). A white or almost white crystalline powder. Freely soluble in water, practically insoluble, or very slightly soluble in alcohol and in dichloromethane. Protect from light.

The United States Pharmacopeia 31, 2008 (Albuterol Sulfate). A white or practically white powder. Freely soluble in water, slightly soluble in alcohol, in chloroform, and in ether. Protect from light.

Stability. For mention of the stability of a 1:1 mixture of salbutamol and ipratropium nebulizer solutions, see under Ipratropium.

Preparations

British Pharmacopoeia 2008: Salbutamol Injection Salbutamol Nebuliser Solution Salbutamol Oral Solution Salbutamol Powder for Inhalation Salbutamol Pressurised Inhalation Salbutamol Tablets

The United States Pharmacopeia 31, 2008: Albuterol Tablet.

Proprietary Preparations

The symbol denotes a preparation no longer actively marketed.

Argentina: Airomir Airsalbu Amocasin Asmatol Butamol Duopack Medihaler Microterol Nebutrax Respiret Salbulin Salbutol Salbutral Salbutral + Aeromed Ventolin Yontal Zoom

Australia: Airomir Asmol Butamol Epaq Respax Ventolin

Austria: Buventol Sultanol

Belgium: Airomir Docsalbuta Ventolin

Brazil: Acobelin-P Aero-Ped-P Aerodini Aerogreenf Aerojet Aerolin Aerotamol Aerotrat Asmakil Asmaliv Bronconal Bronquil Butovent Dilamol Oxiterol Prodotamol Pulmoflux Salburin-P Salbutalin Salbutam Salbutamax Salbutibf Salrolin-P Teoden Tussiliv

Canada: Airomir Apo-Salvent Novo-Salmol Ventodisk Ventolin

Chile: Aero-Sal Aerolin Airomir Asmavent Broncoterol Bropil Butotal Fesema Respolin Salbutral Sinasmal

Czech Republic: Apo-Salvent Asthalin-P Broncovaleas-P Butovent Buventol Ecosal Etinoline Salamoll Steri-Neb Salamol-P Ventodisks-P Ventolin Volmax

Denmark: Airomir Buventol Salbudan Salbuvent Ventoline Volmax

Finland: Airomir Buventol Salbuvent Ventoline

France: Airomir Asmasal Buventol Salbumol Spreor Ventexxair Ventilastin Ventodisks Ventoline

Germany: Apsomol Asthmalitan Broncho Fertiginhalat Broncho Inhalat Bronchospray Epaq Loftan Padiamol Pentamol Salbu Salbubreathe Salbuhexal Salbulair Salbulind Salbupp Salmundin Salvent Sultanol Ventilastin Volmac

Greece: Aerolin Asthmotrat Buventol Normobron Salbunova

Hong Kong: Airomir Apo-Salvent- Azmacon Buto Asma Cybutol Respolin Resprevef Salamol Salmol Ventodisks Ventolin Ventomol Volmax Zenmolin

Hungary: Ac-Butamol Buventol Ecosal Huma-Salmol Salvuron Ventolin

India: Asthalin Derihaler Salbetol Salmaplon Salsol

Indonesia: Asmacare Azmacon Buventol Fartolin Glisend Hivent Lasal Librentin Pritasma Salbron Salbuven Suprasma Ventolin Volmax

Ireland: Aerolin Airomir Asmasal Gerivent Salamol Steri-Neb Salamol Ventamol Ventodisks Ventolin

Israel: Ventolin Volmax-

Italy: Aerotec Broncovaleas Salbufax Salbutard Ventmax Ventolin Volmax

Malaysia: Airomir Asmovent, Beatolin Butahale Buventol Colinf Respolin Salbuterol Salmax Salmol Ventamol Ventolin Volmax

Mexico: Anebron Apo-Salvent Assal Avedox-FC Azyrol Biorenyn Bolbasalt Bonair Butotal Capacit Cobamol Dicoterol Exafil Oladin Salamol Salbulin Salbutalan Salcomed Unibron Ventolin Volmax Zibil

The Netherlands: Airomir Butovent Ventolin

Norway: Airomir Buventol Ventoline

New Zealand: Airomir Apo-Salvent Asmigen Asmol Buventol Respigen Respolin Salamol Salapin Ventolin Volmax

Philippines: Activent Airomir Amoltex Asbunyl Asfrenon Asmacaire Asmalin Astagen Asvimol Axmaxolv Cletal Emplusal Hivent Librentin Provexel NS Prox-S Resdil Rhinol Salburned Salvex Sedalin Venalax Ventar Vento-Broncho Ventolin Ventosal

Poland: Steri-Neb Salamol Velaspir Ventodisk Ventolin

Portugal: Ventilan

Russia: Salamol Salben Salgim Saltos Ventolin

South Africa: Airomir Asthavent Breatheze Cybutol Salbulin Venteze Ventodisk Ventolin Volmax

Singapore: Airomir Azmasol Butahale Buto Asma Buventol Medolin Respolinl Sabutoll Salamol Salbuair Salmol Venderol Ventolin Volmax

Spain: Aldobronquial Asmasall Buto Air Buto Asma Emican Respiroma Ventadur Ventilastin Ventolin

Sweden: Airomir Buventol Ventoline

Switzerland: Airomir Buventol Ecovent Ventodisk Ventolin Volmax

Thailand: Airomir Asmasal Asthmolin Butamol Buto Asma Butovent Buventol Respolinl Salbusian Salbutac Salda Salmol Solia Venterol Ventolin Violin Volmax Zebu

Turkey: Asthavent Salbulin Salbutam Salbutol Ven-o-sal Ventodisks Ventolin Volmax

United Arab Emirates: Butalin

United Kingdom: Airomir Asmasal Kentamol Pulvinal Salbutamol Salamol Salapin Salbulin Ventmax Ventodisks Ventolin Volmax

USA: Accuneb ProAir Proventil Ventolin Volmax VoSpire

Venezuela: Asthalin Butahale Butoas Respolinl Salbulis Salbumed Salburol Salbutan Ventolin.

Multi-ingredient

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

Argentina: Beclasma; Butocort; Butosol; Combivent; Fatigan Bronquial; Iprasalb; Salbutol Beclo; Salbutral AC; Salbutrop; Ventide; Ventolin Compuesto¤;

Australia: Combivent;

Austria: Combivent; Di-Promal; Duospirel¤; Ventide;

Belgium: Combivent;

Brazil: Aeroflux; Aerotide; Beclotamol¤; Clenil Compositum; Combivent; Pneumolat Expectorante¤;

Canada: Combivent; ratio-Ipra Sal UDV;

Chile: Aero-Plus; Aerosoma; Asmavent-B; Beclasma¤; Belomet; Broncoterol-B¤; Butotal B; Combivent; Herolan Aerosol; Ventide;

Czech Republic: Combivent; Intal Plus;

Denmark: Combivent;

Finland: Atrodual; Redol Comp;

France: Combivent; Ventide¤;

Greece: Berovent;

Hong Kong: Combivent; Ventide; Ventolin Expectorant;

India: Aerocort; Albutamol; Ambrodil-S; Amcof; Asthacrom; Asthalin AX; Asthalin Expectorant; Axalin; Bronchilet; Budesal; Deletus A; Duolin; Kofarest; Mucolinc; Okaril; Pulmo-Rest Expectorant; Pulmo-Rest; Suprivent-A; Suprivent; Theo-Asthalin; Ventorlin;

Ireland: Combivent;

Italy: Breva; Clenil Compositum; Perventil¤; Plenaer; Ventolin Espettorante; Ventolin Flogo¤; Zarent;

Malaysia: Beatolin Expectorant¤; Combivent; Salbutamol Expectorant; Ventamol Expectorant; Ventolin Expectorant;

Mexico: Aerocrom¤; Aeroflux; Combivent; Fluxol; Mucoflux; Musaldox; Neumyn-AS; Ventide;

Netherlands: Combivent;

New Zealand: Combivent; Duolin; Portugal: Combivent; Propavente;

Russia: Ascoril Expectorant (Аскорил Експекторант); Biasten (Биастен);

South Africa: Combivent; Singapore: Clenil Compositum¤; Combivent; Ventide¤;

Spain: Aerosoma¤; Buto Asma Teofilina¤; Butosol; Combivent; Legis;

Sweden: Combivent; Switzerland: Dospir; Ventolin plus¤;

Thailand: Almasal; Asmasal Expectorant; Biovent; Clenil Compositum; Combivent; Royalin; Salceryl¤; Salmol Expectorant; Theosal¤; Ventide¤; Ventolin Expectorant;

United Kingdom: Aerocrom¤; Combivent; Ipramol; Ventide¤;

United States: Combivent; DuoNeb; Venezuela: Aeroflux; Beclomet Compositum; Broxodin; Butosol; Combivent; Salbomex; Salbutide; Venticort; Ventide