Saltropium

Salbutamol sulfate, ipratropium bromide.

A clear colourless solution.
Each unit-dose vial (2.5 mL) solution for inhalation contains: Salbutamol Sulphate equivalent to Salbutamol 2.5 mg, Ipratropium Bromide 500 mcg.

Pharmacology: Pharmacodynamics: Ipratropium bromide is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties.
In preclinical studies, it appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve. Anticholinergics prevent the increase in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) caused by the interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle.
The bronchodilation following inhalation of ipratropium bromide is primarily local and site-specific to the lung and not systemic in nature.
Salbutamol sulfate is a β2-adrenergic agent that acts on airway smooth muscle resulting in relaxation.
Salbutamol relaxes all smooth muscle from the trachea to the terminal bronchioles and protects against all bronchoconstrictor challenges.
Salbutamol + Ipratropium Bromide (Saltropium) provides the simultaneous release of ipratropium bromide and salbutamol sulfate allowing the additive effect on both muscarinic and β2-adrenergic receptors in the lung resulting in a bronchodilation which is superior to that provided by each single agent.
Controlled studies in patients with reversible bronchospasm have demonstrated that Salbutamol + Ipratropium Bromide (Saltropium) has a greater bronchodilator effect than either of its components and there was no potentiation of adverse events.
Pharmacokinetics: Ipratropium bromide is quickly absorbed after oral inhalation. The systemic bioavailability after inhalation is estimated to be <10% of the dose. Renal excretion of ipratropium bromide is given as 46% of the dose after IV administration. The half-life (t¹/₂) of the terminal elimination phase is about 1.6 hours as determined after IV administration.
The t¹/₂ for elimination of drug and metabolites is 3.6 hours, as determined after radiolabeling. Ipratropium bromide does not penetrate the blood-brain barrier.
Salbutamol sulfate is rapidly and completely absorbed following oral administration either by the inhaled or gastric route. Peak plasma salbutamol concentrations are seen within 3 hours of administration and are excreted unchanged in the urine after 24 hours. The elimination t¹/₂ is 4 hours.
Salbutamol will cross the blood-brain barrier reaching concentrations amounting to about 5% of the plasma concentrations.
It has been shown that co-nebulization of ipratropium bromide and salbutamol sulfate does not potentiate the systemic absorption of either component and that therefore, the additive activity of Salbutamol + Ipratropium Bromide (Saltropium) is due to the combined local effect on the lung following inhalation.

Management of reversible bronchospasm associated with obstructive airway diseases.

Salbutamol + Ipratropium Bromide (Saltropium) inhalation solution in a unit-dose vial may be administered from a suitable nebulizer or an intermittent positive pressure ventilator.
Each unit dose vial of Salbutamol + Ipratropium Bromide (Saltropium) contains 2500 mcg of Salbutamol base and 500 mcg of Ipratropium Bromide.
Adults and Children >12 years: 1 unit-dose vial every 6-8 hours.
Children 2-12 years: 3 drops/kg/dose (maximum dose of 2500 mcg salbutamol) every 6-8 hours.
Administration: The unit-dose vials are intended only for inhalation with suitable nebulizing devices and should not be taken orally.
Prepare the nebulizer for filling, according to the instructions provided as follows: Tear 1 unit-dose vial from the strip.
Open the unit-dose vial by firmly twisting the top.
Squeeze the contents of the unit-dose vial into the nebulizer reservoir.
Assemble the nebulizer and use it as directed.
After use, throw away any solution left in the reservoir and clean the nebulizer.
It is strongly recommended not to mix Salbutamol + Ipratropium Bromide (Saltropium) solution for inhalation with other drugs in the same nebulizer.
Or as prescribed by the physician.

Symptoms: The effects of overdosage are expected to be primarily related to salbutamol.
The expected symptoms with overdosage are those of excessive β-adrenergic stimulation, the most prominent being tachycardia, palpitation, tremor, hypertension, hypotension, widening of the pulse pressure, anginal pain, arrhythmias and flushing. Expected symptoms of overdosage with ipratropium bromide (e.g., dry mouth, visual accommodation disturbances) are mild and transient in nature in view of the wide therapeutic range and topical administration.
Treatment: Administration of sedatives, tranquilizers, in severe cases intensive therapy.
Beta-receptor blockers, preferably β1-selective, are suitable as specific antidotes; however, a possible increase in bronchial obstruction must be taken into account and the dose should be adjusted carefully in patients suffering from bronchial asthma.

Hypersensitivity to atropine, its derivatives, or any other component of Salbutamol + Ipratropium Bromide (Saltropium).
Patients with hypertrophic obstructive cardiomyopathy or tachyarrhythmia.

Immediate hypersensitivity reactions may occur after administration of Salbutamol + Ipratropium Bromide (Saltropium), as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.
Ocular Complications: There have been isolated reports of ocular complications (i.e., mydriasis, increased intraocular pressure, narrow-angle glaucoma, eye pain) when aerosolized ipratropium bromide, either alone or in combination with an adrenergic β2-agonist, has escaped into the eyes.
Eye pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival congestion and corneal edema may be signs of acute narrow-angle glaucoma. Should any combination of these symptoms develop, treatment with miotic drops should be initiated and specialist advice sought immediately.
Patients must be instructed in the correct administration of Salbutamol + Ipratropium Bromide (Saltropium). Care must be taken not to expose the eyes to the aerosol or solution of Salbutamol + Ipratropium Bromide (Saltropium).
It is recommended that the nebulized solution be administered via a mouthpiece. If this is not available and a nebulizer mask is used, it must fit properly.
Patients who may be predisposed to glaucoma should be warned specifically to protect their eyes.
In the following conditions, Salbutamol + Ipratropium Bromide (Saltropium) should only be used after careful risk/benefit assessment, especially when doses higher than recommended are used: Insufficiently controlled diabetes mellitus, recent myocardial infarction, severe organic heart or vascular disorders, hyperthyroidism, pheochromocytoma, risk of narrow-angle glaucoma, prostatic hypertrophy or bladder-neck obstruction.
Potentially serious hypokalemia may result from β2-agonist therapy. Additionally, hypoxia may aggravate the effects of hypokalemia on cardiac rhythm.
Patients with cystic fibrosis may be more prone to gastrointestinal motility disturbances.
In the case of acute, rapidly worsening dyspnea (difficulty in breathing), a doctor should be consulted immediately.
If higher than recommended doses of Salbutamol + Ipratropium Bromide (Saltropium) are required to control symptoms, the patient's therapy plan should be reviewed by a doctor.

The safety of Salbutamol + Ipratropium Bromide (Saltropium) during human pregnancy is not established. The usual precautions regarding the use of drugs in pregnancy, especially during the 1st trimester, should be observed.
The inhibitory effect of Salbutamol + Ipratropium Bromide (Saltropium) on uterine contraction should be taken into account.
Salbutamol sulfate and ipratropium bromide are probably excreted in breast milk and their effects on the neonate are not known. Although lipid-insoluble quaternary bases pass into breast milk, it is unlikely that ipratropium bromide would reach the infant to an important extent, especially when taken by inhalation. However, because many drugs are excreted in breast milk, caution should be exercised when Salbutamol + Ipratropium Bromide (Saltropium) is administered to a nursing woman.

In common with other β-agonist-containing products, more frequent undesirable effects of Salbutamol + Ipratropium Bromide (Saltropium) are headache, dizziness, nervousness, tachycardia, fine tremor of skeletal muscles and palpitations, especially in susceptible patients.
Potentially serious hypokalemia may result from β2-agonist therapy.
As with use of other inhalation therapy, cough, local irritation and less common, inhalation-induced bronchospasm can occur.
As with other β-mimetics, nausea, vomiting, sweating, weakness and myalgia/muscle cramps may occur. In rare cases, decrease in diastolic blood pressure, increase in systolic blood pressure, arrhythmias, particularly after higher doses, may occur.
In individual cases, psychological alterations have been reported under inhalational therapy with β-mimetics.
The most frequently non-respiratory anticholinergic-related adverse events were dryness of the mouth and dysphonia.
There have been isolated reports of ocular complications (ie, mydriasis, increased intraocular pressure, angle-closure glaucoma, eye pain) when aerosolized ipratropium bromide, either alone or in combination with an adrenergic β2-agonist, has escaped into the eyes.
Ocular side effects, gastrointestinal motility disturbances and urinary retention may occur in rare cases and are reversible (see Precautions).
Allergic-type reactions eg, skin rash, angioedema of the tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reactions have been reported, with positive rechallenge in some cases.

The concurrent administration of xanthine derivatives as well as other β-adrenergics and anticholinergics may increase the side effects.
Beta-agonist induced hypokalaemia may be increased by concomitant treatment with xanthine derivatives, glucocorticosteroids and diuretics. This should be taken into account particularly in patients with severe airway obstruction.
Hypokalaemia may result in an increased susceptibility to arrhythmias in patients receiving digoxin.
It is recommended that serum potassium levels are monitored in such situations.
A potentially serious reduction in bronchodilator effect may occur during concurrent administration of β-blockers.
Beta-adrenergic agonists should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of β-adrenergic agonists may be enhanced.
Inhalation of halogenated hydrocarbon anaesthetics eg, halothane, trichloroethylene and enflurane may increase the susceptibility to the cardiovascular effects of β-agonists.

Store at temperatures not exceeding 30°C. Protect from light.

Antiasthmatic & COPD Preparations

R03AL02 - salbutamol and ipratropium bromide ; Belongs to the class of combination of adrenergics with anticholinergics, that may also include a corticosteroid. Used in the treatment of obstructive airway diseases.

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