Ventolin Injection is indicated in adults and adolescents.

RESPIRATORY

Ventolin Injection provides short-acting (4-6 hour) bronchodilation with a fast onset (within 5 minutes) in reversible airways obstruction. It is indicated for the relief of severe bronchospasm.

OBSTETRIC

VENTOLIN is a selective beta-₂ adrenoceptor agonist.  At therapeutic doses it acts on the beta-₂ adrenoceptors in the uterus, with little or no action on the beta-₁ adrenoceptors of the heart.  It is indicated to arrest uncomplicated labour between 22 and 37 weeks of gestation in patients with no medical or obstetric contraindication to tocolytic therapy, under the direction of a physician.

Ventolin Injection may be administered by the subcutaneous, intramuscular or intravenous route, under the direction of a physician.

Adults: 

Subcutaneous route: 500 micrograms (8 micrograms/kg body weight) and repeated every four hours as required.

Intramuscular route: 500 micrograms (8 micrograms/kg body weight) and repeated every four hours as required.

Slow intravenous injection:

250 micrograms (4 micrograms/kg bodyweight) injected slowly. If necessary the dose may be repeated.

The use of Ventolin Injection 500 micrograms in 1ml (500 micrograms/ml, for intravenenous administration may be facilitated by dilution to 10ml with Water for Injection BP (final concentration of 50 micrograms/ml) and 5mls of the diluted preparation (250 micrograms/5ml) administered by slow intravenous injection.

Paediatric Population

The safety and efficacy of Ventolin Injection in children under the age of 12 has not been established. From the available data no recommendation on posology can be made.

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

Instructions to open the ampoule

Ampoules are equipped with the OPC (One Point Cut) opening system and must be opened using the following instructions:

 hold with one hand the bottom part of the ampoule as indicated in Picture 1 put the other hand on the top of the ampoule positioning the thumb above the coloured point and press as indicated in Picture 2

Picture 1

Picture 2

In the management of premature labour

Treatment with VENTOLIN Injection/Solution for Infusion should only be initiated by obstetricians/physicians experienced in the use of tocolytic agents. Ideally, it should be carried out in facilities adequately equipped to perform continuous monitoring of maternal and foetal health status.

Duration of treatment should not exceed 48 hours as data show that the main effect of tocolytic therapy is a delay in delivery of up to 48 hours.  No statistically significant effect on perinatal mortality or morbidity has been observed in randomised, controlled trials.  This delay may be used to administer glucocorticoids or to implement other measures known to improve perinatal health.

VENTOLIN Injection/Solution for infusion should be administered as early as possible after the diagnosis of premature labour, and after evaluation of the patient to eliminate any contraindications to the use of VENTOLIN (see Contraindications). This should include an adequate assessment of the patient's cardiovascular status with continuous ECG monitoring throughout treatment (see Warnings and Precautions).

For this indication VENTOLIN Solution for Intravenous Infusion is recommended using a solution prepared as above. Infusion rates of 10 to 45 micrograms per minute are generally adequate to control uterine contractions but greater or lesser infusion rates may be required according to the strength and frequency of contractions. A starting rate of 10 micrograms per minute is recommended, increasing the rate at 10-minute intervals until there is evidence of patient response shown by diminution in strength, frequency or duration of contractions. Thereafter the infusion rate may be increased slowly until contractions cease. Careful attention should be given to cardio-respiratory function, including increases in pulse rate and changes in blood pressure, electrolytes, glucose and lactate levels and fluid balance monitoring. A maximum sustained maternal heart rate of 120 beats/min should not be exceeded.. Treatment should be discontinued should signs of pulmonary oedema or myocardial ischaemia develop (see Warnings and Precautions and Adverse Reactions).

Once uterine contractions have ceased the infusion rate should be maintained at the same level for 1 hour and then reduced by 50% decrements at 6-hourly intervals.

As an alternative procedure or to counteract inadvertent overdosage with oxytocic drugs, VENTOLIN Injection may be administered as a single injection by the intravenous route. The usual recommended dose is 100 to 250 micrograms of salbutamol. The dose may be repeated according to the response of the patient.

Bronchodilators should not be the only or main treatment in patients with severe or unstable asthma. Severe asthma requires regular medical assessment, including lung-function testing, as patients are at risk of severe attacks and even death.  Physicians should consider using the maximum recommended dose of inhaled corticosteroid and/or oral corticosteroid therapy in these patients.

The dosage or frequency of administration should only be increased on medical advice.

Patients being treated with Ventolin Injection may also be receiving short-acting inhaled bronchodilators to relieve symptoms. Increasing use of bronchodilators, in particular short-acting inhaled ₂-agonists to relieve symptoms, indicates deterioration of asthma control. 

The patient should be instructed to seek medical advice if short-acting relief bronchodilator treatment becomes less effective, or more inhalations than usual are required. In this situation the patient should be assessed and consideration given to the need for increased anti-inflammatory therapy (e.g. higher doses of inhaled corticosteroid or a course of oral corticosteroid).

Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol.  Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving salbutamol should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.

Salbutamol should be administered cautiously to patients suffering from thyrotoxicosis.

Potentially serious hypokalaemia may result from b₂-agonist therapy, mainly from parenteral and nebulised administration. Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations.

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

The use of Ventolin Injection in the treatment of severe bronchospasm does not obviate the requirement for corticosteroid therapy as appropriate. When practicable, administration of oxygen concurrently with Ventolin Injection is recommended. In common with other b-adrenoceptor agonists, salbutamol can induce reversible metabolic changes such as hypokalaemia and increased blood glucose levels. Diabetic patients may be unable to compensate for the increase in blood glucose and the development of ketoacidosis has been reported. Concurrent administration of corticosteroids can exaggerate this effect. Diabetic patients and those concurrently receiving corticosteroids should be monitored frequently.

Lactic acidosis has been reported in association with high therapeutic doses of intravenous and nebulised short-acting beta-agonist therapy, mainly in patients being treated for an acute asthma exacerbation (see Section 4.8). Increase in lactate levels may lead to dyspnoea and compensatory hyperventilation, which could be misinterpreted as a sign of asthma treatment failure and lead to inappropriate intensification of short-acting beta-agonist treatment. It is therefore recommended that patients are monitored for the development of elevated serum lactate and consequent metabolic acidosis in this setting.

As maternal pulmonary oedema has been reported during or following management of premature labour with b₂-agonists, careful attention should be given to fluid balance and cardio-respiratory function should be monitored. If signs of pulmonary oedema develop, discontinuation of treatment should be considered (see section 4.8).

Obstetric use only:

In the treatment of premature labour, before VENTOLIN parenteral preparations are given to any patient with known or suspected heart disease, an adequate assessment of the patient's cardiovascular status should be made by a physician experienced in cardiology.

Tocolysis with VENTOLIN parenteral preparations is not recommended when membranes have ruptured or the cervix has dilated beyond 4 cm.As maternal pulmonary oedema and myocardial ischaemia have been reported during or following treatment of premature labour with beta-2 agonists, careful attention should be given to fluid balance and cardio-respiratory function, including ECG should be monitored. If signs of pulmonary oedema or myocardial ischaemia develop, discontinuation of treatment should be considered. (see Dosage and Administration and Adverse Reactions)

In the treatment of premature labour by intravenous infusion of VENTOLIN increases in maternal heart rate of the order 20 to 50 beats per minute usually accompany the infusion. The maternal pulse rate should be monitored and not normally allowed to exceed a sustained rate of 120 beats per minute.  The effect of infusion on foetal rate is less marked but increases of up to 20 beats per minute may occur.

Maternal blood pressure may fall slightly during the infusion; the effect being greater on diastolic than on systolic pressure. Falls in diastolic pressure are usually within the range of 10 to 20mmHg.

Salbutamol and non-selective beta-blocking drugs such as propranolol, should not usually be prescribed together.

VENTOLIN is not contra-indicated in patients under treatment with monoamine oxidase inhibitors (MAOIs).

Owing to the additional antihypertensive effect, there is increased uterine inertia with risk of haemorrhage; in addition, serious ventricular rhythm disorders due to increased cardiac reactivity have been reported on interaction with halogenated anaesthetics. Treatment should be discontinued, whenever possible, at least 6 hours before any scheduled anaesthesia with halogenated anaesthetics.

Systemic corticosteroids are frequently given during premature labour to enhance foetal lung development. There have been reports of pulmonary oedema in women concomitantly administered with beta-agonists and corticosteroids. Corticosteroids are known to increase blood glucose and can deplete serum potassium, therefore concomitant administration should be undertaken with caution with continuous patient monitoring owing to the increased risk of hyperglycaemia and hypokalaemia.

The administration of beta-agonists is associated with a rise of blood glucose, which can be interpreted as an attenuation of anti-diabetic therapy; therefore individual anti-diabetic therapy may need to be adjusted.

Owing to the hypokalaemic effect of beta-agonists, concurrent administration of serum potassium depleting agents known to exacerbate the risk of hypokalaemia, such as diuretics, digoxin, methyl xanthines and corticosteroids, should be administered cautiously after careful evaluation of the benefits and risks with special regard to the increased risk of cardiac arrhythmias arising as a result of hypokalaemia.

Pregnancy

Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus. 

As with the majority of drugs, there is little published evidence of the safety of salbutamol in the early stages of human pregnancy, but in animal studies there was evidence of some harmful effects on the foetus at very high dose levels.

Breast-feeding

As salbutamol is probably secreted in breast milk its use in nursing mothers is not recommended unless the expected benefits outweigh any potential risk. In such situations the use of the inhaled route may be preferable although it is not known whether salbutamol has a harmful effect on the neonate.

Fertility

There is no information on the effects of salbutamol on human fertility. There were no adverse effects on fertility in animals (see section 5.3).

Not applicable.

Adverse events are listed below by system organ class and frequency.  Frequencies are defined as: very common (³1/10), common (³1/100 and <1/10), uncommon (³1/1000 and <1/100), rare (³1/10,000 and <1/1000) and very rare (<1/10,000).  Very common and common events were generally determined from clinical trial data.  Rare, very rare and unknown events were generally determined from spontaneous data.

Immune system disorders

Very rare:        Hypersensitivity reactions including angioedema, urticaria, bronchospasm, hypotension and collapse.

Metabolism and nutrition disorders

Rare:               Hypokalaemia.

Potentially serious hypokalaemia may result from beta-agonist therapy.

Unknown:       Lactic acidosis (see section 4.4)

Nervous system disorders

Very common:            Tremor.

Common:                    Headache.

Very rare:                    Hyperactivity.

Cardiac disorders

Very common:            Tachycardia.

Common:                    Palpitations.

Rare:                           Cardiac arrhythmias including atrial fibrillation, supraventricular tachycardia and extrasystoles.

Unknown:                   Myocardial ischaemia* ( see section 4.4)

Vascular disorders

Rare:                           Peripheral vasodilatation.

Respiratory, thoracic and mediastinal disorders

Uncommon:                Pulmonary oedema.

In the management of pre-term labour, Ventolin Injection has uncommonly been associated with pulmonary oedema. Patients with predisposing factors including multiple pregnancies, fluid overload, maternal infection and pre-eclampsia may have an increased risk of developing pulmonary oedema.

Gastrointestinal disorders

Unknown:                   Nausea, vomiting *.

Musculoskeletal and connective tissue disorders

Common:                    Muscle cramps.

Injury, poisoning and procedural complications

Unknown:                   Slight pain or stinging on intramuscular use of undiluted injection*.

* reported spontaneously in post-marketing data therefore frequency regarded as

unknown.

To report any Undesirable Effects:

Kingdom of Saudi Arabia

-National Pharmacovigilance centre (NPC)

·       Fax: +966-11-205-7662

·       Call NPC at +966-11-2038222, Ext: 2317-2356-2340

·       Reporting hotline: 19999

·       E-mail: npc.drug@sfda.gov.sa

·       Website: www.sfda.gov.sa/npc

-GlaxoSmithKline - Head Office, Jeddah

·       Tel:  +966-12-6536666

·       Mobile: +966-56-904-9882

·       Email: sa.aermi-saudi@gsk.com

·       website: https://healthksa.gsk.com/

·       P.O. Box 55850, Jeddah 21544, Saudi Arabia

The most common signs and symptoms of overdose with salbutamol are transient beta agonist pharmacologically mediated events, including tachycardia, tremor, hyperactivity and metabolic effects including hypokalaemia and lactic acidosis (see sections 4.4 and 4.8).

Hypokalaemia may occur following overdose with salbutamol. Serum potassium levels should be monitored.

Lactic acidosis has been reported in association with high therapeutic doses as well as overdoses of short-acting beta-agonist therapy, therefore monitoring for elevated serum lactate and consequent metabolic acidosis (particularly if there is persistence or worsening of tachypnea despite resolution of other signs of bronchospasm such as wheezing) may be indicated in the setting of overdose.

Nausea, vomiting and hyperglycaemia have been reported, predominantly in children and when salbutamol overdose has been taken via the oral route.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

Pharmacotherapeutic group: Selective beta-2-adrenoreceptor agonists

ATC Code: R03CC02

Salbutamol is a selective beta-₂ adrenoceptor agonist. At therapeutic doses it acts on beta-₂ adrenoceptors of bronchial muscle providing short-acting (4-6 hour) bronchodilation in reversible airways obstruction.

Salbutamol administered intravenously has a half-life of 4 to 6 hours and is cleared partly renally and partly by metabolism to the inactive 4’-O-sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. The majority of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. Salbutamol is bound to plasma proteins to the extent of 10%.

In common with other potent selective β2-agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of fetuses were found to have cleft palate at 2.5mg/kg dose, 4 times the maximum human oral dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50mg/kg/day orally throughout pregnancy resulted in no significant fetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care. Reproductive studies in the rabbit at doses of 50mg/kg/day orally (i.e. much higher than the normal human dose) have shown fetuses with treatment related changes; these included open eyelids (ablepharia), secondary palate clefts (palatoschisis), changes in ossification of the frontal bones of the cranium (cranioschisis) and limb flexure.

In an oral fertility and general reproductive performance study in rats at doses of 2 and 50 mg/kg/day, with the exception of a reduction in number of weanlings surviving to day 21 post partum at 50 mg/kg/day, there were no adverse effects on fertility, embryofetal development, litter size, birth weight or growth rate.

Sodium chloride

Sodium hydroxide pellets

Dilute sulfuric acid

Water for injections

Nitrogen (oxygen free)

None stated

Store below 30°C and keep the ampoule in the outer container in order to protect from light.

Clear, neutral glass ampoules, packed in plastic trays with a cardboard sleeve over the trays.

Pack size: 1ml ampoules in plastic trays of 5.

The only recommended diluents for Ventolin Injection are water for injections BP, sodium chloride injection BP, sodium chloride and dextrose injection BP or dextrose injection BP.

All unused admixtures of Ventolin Injection should be discarded 24 hours after preparation.

Ventolin Injection should not be administered in the same syringe as any other medication.