Ventolin Injection

Update the section 6.3 to extend the shelf-life from 36 months to 48 months.

Update the information for medical or healthcare professionals only to extend the shelf-life from 36 months to 48 months.

Section 4.1

Simplified indication and added:

It provides short acting bronchodilation in reversible airways obstruction due to asthma and chronic obstructive pulmonary disease (COPD) such as chronic bronchitis and emphysema.

Section 4.2:

Removed the intramuscular route of administration for the short term management of uncomplicated premature labour.

Regarding the delay in childbirth of up to 48 hours following tocolytic therapy, the administration of glucocoricoids is added to the description of measures known to improve perinatal health.

Replaced the text ‘The dose must be individually titrated, with reference to suppression of contractions, increase in pulse rate and changes in blood pressure, which are limiting factors’ with ‘The dose must be individually titrated. Careful attention should be given to cardio-respiratory function, including increases in pulse rate and changes in blood pressure’

Strengthened the advice that ‘Treatment should be discontinued should signs of pulmonary oedema or myocardial ischaemia develop’,

Section 4.4:

Updated the warning ‘Bronchodilators should not be the only or main treatment in patients with persistent asthma...’, to read:  Bronchodilators should not be the only or main treatment in patients with persistent asthma. In patients with persistent asthma unresponsive to salbutamol, treatment with inhaled corticosteroids is recommended to achieve and maintain control. Failing to respond to treatment with salbutamol may signal a need for urgent medical advice or treatment.

Added the warning ‘In the treatment of premature labour, before salbutamol 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’,

Regarding Pulmonary oedema, added advice to monitor by ECG.

Section 4.6:

Added the following statement regarding 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)’.

Section 4.9:

Added statement regarding Lactic acidosis: ‘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’.

Regarding the treatment of overdose, updated the statement ‘Further management should be as clinically indicated or as recommended by the national poisons centre, where available’

Section 5.1:

Updated the following statement to include duration of affect and indication and to remove the statement ‘with little or no action on the beta-1 adrenoceptors of the heart’, to read: ‘Salbutamol is a selective beta-2 adrenoceptor agonist. At therapeutic doses it acts on the beta-2 adrenoceptors of bronchial muscle providing short acting (4 to 6 hour) bronchodilation in reversible airways obstruction’.

Section 5.3:

Added ‘Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses of salbutamol up to 50 mg/kg’.

Section 6.6:

Removed ‘0.3% Potassium Chloride’ from the list of infusion fluids.

Editorial updates to amend the spelling of ‘sulphate’ to ‘sulfate’ and to re-position texts in following sections :  2, 4.4, 4.8, 5.2 and 9

Section 4.1 - Simplified indication statement. Added following statement - For the short term management of uncomplicated premature labour

Section 4.2 - Updated the instructions regarding use in short term management of uncomplicated premature labour.

Section 4.3 - Contraindications more clearly stated as Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Updated with specific contraindications in relation to use in obstetrics.

Section 4.4 - Paradoxical bronchodilator warning added. Updated and grouped warnings regarding use in obstetrics under the subheading ‘Tocolysis’.

Section 4.5 - Updated with subheadings and associated statements for ‘Halogenated anaesthetics’, ‘Corticosteroids’, ‘Anti-diabetics’ and ‘Potassium depleting agents’.

Section 4.6 - Added subheading, updated fertility statement
Section 4.7 - Added statement on no negligible influence on ability to drive or operate machinery
Section 4.8 - Side effects and their frequencies were updated to specify whether they were reported when used for respiratory or obstetric indication. AE reporting details updated.
Section 4.9 - Removed instructions on treatment of overdose. Added statement on lactic acidosis
Section 5.1 - Updated ATC Code
Section 5.3 - Added preclinical study data
Section 6.4 - Added protect from frost and sunlight
Section 6.6 - No special requirements for disposal

PROPOSED REVISED SUMMARY OF PRODUCT CHARACTERISTICS (MARKED)

1.     NAME OF THE MEDICINAL PRODUCT

Ventolin 500 micrograms/ml Solution for Injection

2.     QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 500 micrograms salbutamol as salbutamol sulphate.

For a full list of excipients, see section 6.1.

4.9       Overdose

The preferred antidote for overdosage with salbutamol is a cardioselective â-blocking agent. However,

Symptoms and Signs

The most common signs and symptoms of overdose with salbutamol are transient beta agonist pharmacologically mediated events (see Special Warnings and Precautions for Use and Undesirable Effects).

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

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

Treatment

Consideration should be given to discontinuation of treatment and appropriate symptomatic therapy such as cardio-selective beta-blocking agents in patients presenting with cardiac symptoms (e.g. tachycardia, palpitations). 

Beta-blocking drugs should be used with caution in patients with a history of bronchospasm.

6.6     Instructions for Use and Handling

No special requirements.

Salbutamol syrup may be diluted with Purified Water BP (50% v/v).  The resulting mixture should be protected from light and used within 28 days.

A 50% v/v dilution of salbutamol syrup has been shown to be adequately preserved against microbial contamination.

Admixture of salbutamol syrup with other liquid preparation is not recommended.

Summary of Product Characteristics additional wording – Obstetric and Respiratory Indications (Ventolin Conc. For IV, Injection & Tablets)

4.3 Contraindications

Salbutamol should not be used as a tocolytic agent in patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.

4.4 Special Warnings and Precautions for Use

Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of myocardial ischaemia associated with salbutamol.

Tocolysis

Salbutamol should be used with caution in tocolysis and supervision of cardiorespiratory function, including ECG monitoring, should be considered.  Treatment should be discontinued if signs of myocardial ischaemia (such as chest pain or ECG changes) develop.  Salbutamol should not be used as a tocolytic agent in patients with significant risk factors for or pre-existing heart disease (see section 4.3).

Respiratory indications

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.

4.8 Undesirable Effects

Respiratory indications

Unknown: Myocardial ischaemia* (see section 4.4)

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

Obstetric indications

Uncommon: Myocardial ischaemia*.

*In the management of pre-term labour with salbutamol injection/solution for infusion.