Ipratropium bromide + Salbutamol

Inhalation/Respiratory
Chronic obstructive pulmonary disease

History of hypersensitivity to ipratropium bromide, salbutamol, atropine or its derivatives. Hypertrophic obstructive cardiomyopathy, tachyarrhythmia.

Patient with narrow-angle glaucoma or susceptibility to glaucoma; CV disorders (e.g. ischaemic heart disease, arrhythmia, severe heart failure, hypertension), severe airway obstruction, cystic fibrosis, prostatic hyperplasia or bladder-neck obstruction, seizure disorder, hyperthyroidism, diabetes mellitus, phaeochromocytoma, sensitivity to sympathomimetic amines, hypokalaemia. Renal and hepatic impairment. Children. Pregnancy and lactation.

Significant: Serious hypokalaemia; ECG changes (e.g. flattening of T-wave, QTc interval prolongation, ST-segment depression); lactic acidosis (high doses), urinary retention. Rarely, hypersensitivity reactions (e.g. urticaria, angioedema, rash, anaphylaxis, oropharyngeal oedema), myocardial ischaemia, ocular complications such as mydriasis, blurred vision, increased IOP, eye pain and worsening or precipitation of narrow-angle glaucoma (when the solution comes into contact with the eyes).
Cardiac disorders: Palpitations, tachycardia, chest pain.
Gastrointestinal disorders: Dry mouth, throat irritation, nausea, dysgeusia, constipation, diarrhoea, vomiting, dyspepsia.
General disorders and administration site conditions: Pain.
Investigations: Increased systolic blood pressure.
Musculoskeletal and connective tissue disorders: Leg cramps.
Nervous system disorders: Headache, dizziness, tremor.
Psychiatric disorders: Nervousness.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Cough, dysphonia, dyspnoea, bronchitis, pharyngitis, pneumonia, nasopharyngitis.
Potentially Fatal: Paradoxical bronchospasm.

Inhalation/Respiratory: C

This drug may cause dizziness and blurred vision, if affected, do not drive or operate machinery. Avoid spraying into or contact with the eyes.

Monitor FEV₁, peak flow, and/or other pulmonary function tests; blood pressure, heart rate, serum glucose, and serum K. Observe for signs and symptoms of glaucoma, hypersensitivity reactions, urinary retention, shortness of breath, and CNS stimulation.

Symptoms: Ipratropium bromide: Dry mouth and visual accommodation disturbances. Salbutamol: Dizziness, headache, dry mouth, palpitation, fatigue, malaise, sleep disturbances, hypertension, hypotension, hypokalaemia, hyperglycaemia, tachycardia, arrhythmia, chest pain, tremor, flushing, restlessness, and metabolic acidosis (including lactic acidosis). Management: Symptomatic and supportive treatment. Consider cautious administration of cardioselective β-blockers as an antidote. Volume substitution (e.g. plasma substitutes) is recommended in case of more pronounced hypotension. Administer IV infusion of nitrate (e.g. glyceryl trinitrate) for persistent hypertension; Ca channel blockers may also be used as an alternative. Monitor for elevated serum lactate and consequent metabolic acidosis (particularly if with worsening or persistent tachypnoea despite resolution of bronchospasm symptoms), acid-base balance and electrolyte.

Increased risk of adverse CV effects with other sympathomimetic agents.
Ipratropium bromide: May potentiate the effects of other anticholinergic agents.
Salbutamol: May significantly reduce efficacy with β-blockers (e.g. propranolol). May enhance the effect with MAOIs or TCAs. Increased risk of CV adverse effects with anaesthetics containing halogenated hydrocarbons (e.g. halothane, enflurane, trichloroethylene). β-agonist-induced hypokalaemia may be potentiated by concomitant use with xanthine derivatives (e.g. theophylline), diuretics, and corticosteroids. Hypokalaemic effect of salbutamol may increase the risk of digitalis-induced arrhythmias.

Salbutamol: May lead to positive result in tests for non-clinical substance abuse (e.g. doping).

Description:
Mechanism of Action: Ipratropium bromide is a quaternary ammonium compound with anticholinergic properties. It causes bronchodilation by blocking the action of acetylcholine at the parasympathetic sites in bronchial smooth muscle.
Salbutamol is a β₂-adrenoceptor agonist that activates adenyl cyclase which leads to an increase in intracellular concentration of cyclic adenosine monophosphate (cAMP). This action results in protein kinase activation, which inhibits phosphorylation of myosin and reduces intracellular ionic Ca concentrations, resulting in smooth muscle relaxation.
Synonym(s): Salbutamol: Albuterol.
Onset: Ipratropium bromide: Bronchodilation: Within 15 minutes.
Salbutamol: Bronchodilation: Within 5 minutes.
Duration: Ipratropium bromide: Metered-dose inhaler: 2-4 hours; nebuliser solution: 4-5 hours (up to 7-8 hours in some patients).
Salbutamol: Approx 3-6 hours.
Pharmacokinetics:
Absorption: Ipratropium bromide: Not readily absorbed into the systemic circulation from the lung surface or gastrointestinal tract. Bioavailability: <10%.
Salbutamol: Rapidly and completely absorbed after oral inhalation. Bioavailability: Approx 50%. Time to peak plasma concentration: Within 3 hours.
Distribution: Ipratropium bromide: Plasma protein binding: <20%.
Salbutamol: Crosses the blood-brain barrier (5%) and placenta. Plasma protein binding: 10%.
Metabolism: Ipratropium bromide: Partially metabolised to inactive ester hydrolysis products.
Salbutamol: Metabolised via conjugation to salbutamol 4'-O-sulfate (inactive).
Excretion: Ipratropium bromide: Via urine and faeces. Elimination half-life: 2 hours.
Salbutamol: Mainly via urine (80-100%); faeces (<20%). Elimination half-life: 3-7 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 657308, Ipratropium bromide. https://pubchem.ncbi.nlm.nih.gov/compound/Ipratropium-bromide. Accessed Oct. 24, 2023.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2083, Salbutamol. https://pubchem.ncbi.nlm.nih.gov/compound/Salbutamol. Accessed Oct. 24, 2023.

Nebuliser solution: Store below 25°C. Do not freeze. Protect from light. Metered-dose inhaler: Store between 20-25°C. Storage recommendations may vary among countries and individual products. Refer to specific product guidelines.

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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