VENTOLINE 5 mg/2,5 ml S p inh/nébulis en récipient unidose 60Récip-unid/2,5ml

VIDAL
Medicines
Update of the 10/09/2024

VENTOLINE solution for inhalation by nebulizer
salbutamol

Forms and presentations

Solution for inhalation by nebulizer at 2,5 mg/2,5 ml and 5 mg/2,5 ml:  Single-dose containers of 2,5 ml, box of 60.

Composition

	per single dose
Salbutamol	2,5 mg
or	5 mg
(as sulfate: 3 mg or 6 mg per single dose)

Excipients (common): sodium chloride, dilute sulfuric acid, water for injectable preparations.

Indications

• Symptomatic treatment of severe acute asthma attacks in adults, adolescents, children and infants.
  
• Treatment of acute exacerbations of chronic obstructive bronchopneumopathies in adults.
  

Dosage and administration

Dosage

The bronchodilator duration of action of inhaled salbutamol is 4 to 6 hours.

Under medical supervision, the nebulization may be repeated every 20 to 30 minutes depending on the clinical result and treatment tolerance, without generally exceeding 4 nebulizations per day.

Method of administration:

For inhalation use only.

This salbutamol solution must be administered by inhalation using a nebulisation device (nebuliser) fitted with a mouthpiece.

Do not inject. Do not drink the contents of the single-dose vials.

For the use and maintenance of the nebulisation device, follow the instructions provided by the manufacturer of the device used.

Many nebulisers on the market operate with a continuous flow and the aerosol containing the medicine may be released into the environment. Salbutamol nebulisations should therefore be carried out in a properly ventilated room.

The solution is ready to use; however, if dilution is necessary, it must be carried out in sterile physiological saline.

Remove a single-dose container from the strip.

Open the container by vigorously twisting its upper end.

Squeeze the container to empty it into the reservoir of the nebuliser.

Assemble the nebuliser for administration according to the manufacturer's instructions.

Avoid contact with the eyes from the aerosol generated by the nebuliser.

With pneumatic nebulisers, the flow of air or oxygen intended to pulse the solution will be adjusted according to the patient's condition and the recommendations of the nebulisation device manufacturer.

Nebulisation should generally not exceed 10 to 20 minutes.

The technique of use by the patient must be checked regularly.

After nebulisation, the unused solution remaining in the device chamber must be discarded. Cleaning and maintenance of the equipment should be carried out according to the manufacturer's recommendations.

Single-dose containers contain no preservative; they must be used immediately after opening. A new container must be used for each nebulisation.

The contents of partially opened or damaged single-dose containers must not be administered.

Contraindications

• Allergy to one of the constituents.
  
• Intolerance to this medication (onset of cough or bronchospasm occurring immediately after inhalation of the product). In this case, this treatment should be discontinued and other therapies or other forms of administration should be prescribed.
  

Warnings and precautions

Warnings:

Administration of salbutamol using a nebuliser should be reserved for serious acute situations requiring inhalation of a high dose of the product by the inhaled route. These situations require medical monitoring with the possibility of resuscitation being set up (venous access and respiratory support); oxygen therapy and systemic corticosteroid therapy should generally be associated.

As with other inhaled treatments, paradoxical bronchospasm may occur, manifested by an increase in dyspnoea and bronchial wheezing immediately after inhalation of the product. Bronchospasm will be treated with another presentation or another fast-acting inhaled bronchodilator (if available). Treatment with Ventoline nebulisation must be discontinued and, if necessary, replaced by a fast-acting bronchodilator medicine.

Medicines with sympathomimetic activity, of which salbutamol is one, may cause cardiovascular effects. Cases of myocardial ischaemia associated with salbutamol have been reported through spontaneous notifications since marketing, as well as in the literature. Patients with severe underlying heart disease (for example, ischaemic heart disease, arrhythmias or severe heart failure) should be informed of the need to consult their doctor in case of chest pain or other symptoms suggestive of worsening of their heart disease. A cardiac origin of respiratory symptoms such as dyspnoea should also be considered.

Patients for whom regular anti-inflammatory treatment is prescribed (e.g., inhaled corticosteroids) should be advised to continue taking their anti-inflammatory treatment even when symptoms improve and they no longer need inhaled salbutamol-based medicine.

The increase in the use of short-acting bronchodilators (in particular the beta-2 agonists used to relieve symptoms) indicates a deterioration in asthma control, and patients must be advised that in this case they must consult a doctor as soon as possible. The patient's therapeutic management must then be reassessed.

Overuse of short-acting beta-agonist bronchodilators may mask the progression of the underlying disease and contribute to the deterioration of asthma control, resulting in an increased risk of severe asthma exacerbations and mortality.

Patients who take an inhaled salbutamol-based medicine "on demand" more than twice a week (in addition to administrations as preventive treatment of exercise-induced asthma) are at risk of salbutamol overuse and should therefore be reassessed (daytime symptoms, night-time awakenings, limitation of activities due to asthma) in order to readjust their treatment.

Precautions for use

In case of bronchial infection or abundant bronchorrhea, appropriate treatment is necessary in order to promote optimal distribution of the product in the airways.

Salbutamol should be used with caution in patients who have received high doses of other sympathomimetic medicines.

Salbutamol by nebulisation should be administered with caution in cases of hyperthyroidism, cardiovascular disorders, in particular obstructive cardiomyopathy, coronary disorders, arrhythmias, arterial hypertension, and in cases of diabetes.

High doses of beta-2 mimetics (in particular by parenteral route or by nebulisation) may cause potentially serious hypokalaemia, which may promote the occurrence of cardiac rhythm disorders. Monitoring of serum potassium is recommended where possible, in particular during concomitant administration of hypokalaemic therapies, in cases of hypoxia or in subjects in whom the risk of occurrence of torsades de pointes is increased (long QT or treatments likely to increase the QTc).

Like other beta-adrenergic receptor agonists, salbutamol may induce an increase in blood glucose. Cases of ketoacidosis have been reported in diabetic patients. Concomitant administration of corticosteroids may increase these effects.

Cases of lactic acidosis have very rarely been reported in association with high doses of short-acting beta-2 agonists given intravenously or by inhaled nebulisation, mainly in patients treated for an acute exacerbation of their asthma (see Undesirable effects). An increase in lactic acid levels may lead to dyspnoea and compensatory hyperventilation, which may be wrongly interpreted as a sign of treatment failure in asthma, leading to inappropriate increase of short-acting beta-agonist treatment. Therefore, the risk of lactic acidosis should be carefully monitored, particularly in severe situations.

Interactions

Combinations not recommended:

• Non-selective beta-blockers: salbutamol and non-selective beta-blockers, such as propranolol, should generally not be prescribed concomitantly.
  
• Halogenated anaesthetics (halothane): in case of obstetric intervention, increased uterine inertia with risk of haemorrhage; moreover, risk of serious ventricular rhythm disorders due to increased cardiac reactivity.
  

Associations subject to precautions for use:

• Antidiabetics: administration of beta-2 mimetics is associated with an increase in blood glucose, which may be interpreted as a decrease in the effect of antidiabetic treatment; consequently, it may be necessary to readjust antidiabetic treatment (see Warnings and Precautions for Use). Reinforce blood and urine monitoring.
  

Fertility, pregnancy and breastfeeding

Pregnancy:

In clinical practice, there is a significant body of experience, with a sufficient number of documented pregnancies, to conclude on the safety of salbutamol during pregnancy.

Consequently, inhaled salbutamol may be administered during pregnancy.

When administered during pregnancy, an acceleration of foetal heart rate may be observed in parallel with maternal tachycardia. It is exceptional for it to persist at birth.

Similarly, post-natal blood glucose values are only exceptionally disturbed.

In case of administration before delivery, take into account the peripheral vasodilator effect of beta-2-mimetics.

Breastfeeding:

Beta-2-mimetics pass into breast milk.

Fertility:

There is no information on the effects of salbutamol on human fertility. No undesirable effect on fertility has been demonstrated in animals (see Preclinical safety).

Adverse effects

Side effects are listed below, by organ class and by frequency.

Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1 000 and < 1/100), rare (≥ 1/10 000 and < 1/1 000), and very rare (< 1/10 000), including isolated reports.

Very common and common effects have generally been described in clinical trials. Rare and very rare undesirable effects are generally derived from spontaneous reports after marketing.

Organ class
Frequency	Adverse effects
Immune system disorders
Very rare	Hypersensitivity reactions including: angioneurotic oedema, urticaria, pruritus, bronchospasm, hypotension, collapse
Metabolism and nutrition disorders
Very rare	Hypokalaemia*, lactic acidosis**
Nervous system disorders
Common	Headache, tremor
Psychiatric disorders
Very rare	Behavioural disorders: nervousness, agitation
Cardiac disorders
Common	Tachycardia
Uncommon	Palpitations
Very rare	Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles)
Not known	Myocardial ischaemia*** (see Warnings and Precautions for Use)
Vascular disorders
Very rare	Peripheral vasodilation
Respiratory, thoracic and mediastinal disorders
Very rare	Paradoxical bronchospasm****
Gastrointestinal disorders
Uncommon	Irritation of the mouth and throat
Musculoskeletal and systemic disorders
Uncommon	Muscle cramps

^* Beta-2 mimetics at high doses may cause hyperglycaemia and hypokalaemia, reversible upon discontinuation of treatment.
^**  Cases of lactic acidosis have been very rarely reported in patients receiving salbutamol intravenously or by nebulised inhalation for the treatment of acute asthma exacerbations.
^***  The frequency of occurrence of myocardial ischaemia cannot be determined because the reported cases come from spontaneous notifications since marketing.
^****  As with other inhaled products, cough and rarely paradoxical bronchospasm may occur following inhalation. Do not repeat administration of this medicine and use another fast-acting bronchodilator to relieve the bronchospasm. Treatment should then be re-evaluated to consider, where appropriate, prescribing a therapeutic alternative.

Gastrointestinal disorders (nausea, vomiting) may also be observed.

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres. Website: https://signalement.social-sante.gouv.fr.

Overdose

The signs and symptoms of salbutamol overdose correspond to the exacerbation of the pharmacodynamic effects of beta2-agonists (see Warnings and Precautions for UseAdverse effects).

Hypokalaemia may occur following salbutamol overdose. Serum potassium should therefore be monitored in cases of overdose.

Nausea, vomiting and hyperglycaemia have been reported, particularly in children and when the overdose is due to oral salbutamol intake.

Cases of lactic acidosis have been reported with high doses of short-acting beta-2 agonists. In case of overdose, it is therefore advisable to monitor serum lactate levels and the risk of lactic acidosis, particularly if tachypnoea persists or worsens despite the disappearance of bronchospasm symptoms such as wheezing, which may be related to metabolic acidosis.

Action to be taken:

Monitoring and symptomatic treatment.

Pharmacodynamics

Pharmacotherapeutic class: Short-acting, rapid-onset inhaled beta-2-mimetic bronchodilator, ATC code: R03AC02.

Salbutamol is a selective agonist of beta-2 adrenergic receptors.

After inhalation, salbutamol exerts a stimulating action on the beta-2 receptors of bronchial smooth muscle, thus ensuring rapid bronchodilation, significant within minutes, lasting for 4 to 6 hours.

Pharmacokinetics

After repeated nebulisations, the plasma concentrations observed at therapeutic doses are not negligible, but remain lower than those observed orally or by injection.

There is no correlation between blood level and efficacy.

After pulmonary absorption, elimination, mainly urinary, occurs essentially via the renal route as sulfoconjugated derivatives (less than 2% in unchanged form).

Preclinical safety

In a study on reproduction and fertility conducted in rats with oral doses of 2 and 50 mg/kg/day, no undesirable effect was demonstrated on fertility, embryonic development, size, birth weight or growth of the offspring, with the exception of a reduction in the number of pups surviving until day 21 after birth at the dose of 50 mg/kg/day.

Storage conditions

To be stored at a temperature not exceeding + 30 °C.

Store the single-dose container in the outer packaging, protected from light.

Discard the single-dose container after use.

HANDLING/DISPOSAL INSTRUCTIONS

No special requirements.

Prescription, supply and reimbursement

LIST I

Medicinal product subject to prescription restricted to specialists in pneumology or paediatrics. Medicinal product that may be administered by any physician intervening in an emergency situation or within a mobile medical assistance or health repatriation structure (article R.5143-5-8 of the French Public Health Code).

Marketing authorisation (AMM)	3400935320742 (2000, SmPC rev 09.07.2024) 60 single-dose units at 2,5 mg/2,5 ml.
	3400935321114 (2000, SmPC rev 09.07.2024) 60 single-dose units at 5 mg/2,5 ml.

Price:	10,81 euros (60 single-dose units at 2,5 mg/2,5 ml).
	16,08 euros (60 unit-dose vials at 5 mg/2,5 mL).
Social Security reimbursement at 65 % based on the TFR: 10,81 euros (2,5 mg/2,5 mL); 16,08 euros (5 mg/2,5 mL). Collect.

GlaxoSmithKline Laboratories
23, rue François-Jacob. 92500 Rueil-Malmaison
Tel: 01 39 17 80 00
Medical information:
Tel: 01 39 17 84 44. Fax: 01 39 17 84 45
www.fr.gsk.com