Ipratropium bromide + Salbutamol

COPD.

Adult : Inhalation As inhalation spray releasing ipratropium bromide 20 mcg and salbutamol 100 mcg/actuation: 1 inhalation 4 times daily. Max: 6 inhalations/24 hours. As solution for nebulisation containing ipratropium bromide 500 mcg and salbutamol 2.5 mg/2.5 mL: 2.5 mL 3 or 4 times daily.

Inhalation/Respiratory
Chronic obstructive pulmonary disease

Hypersensitivity to salbutamol, ipratropium or fenoterol, atropine or its derivatives. Hypertrophic obstructive cardiomyopathy, tachyarrhythmia.

Patient with CV disorders (e.g. ischaemic heart disease, arrhythmia, severe heart failure), severe airway obstruction, cystic fibrosis, prostatic hyperplasia or bladder-neck obstruction, convulsive disorders, hyperthyroidism, diabetes mellitus. Pregnancy and lactation.

Significant: Hypersensitivity reactions (e.g. urticaria, angioedema, rash, anaphylaxis, bronchospasm, oropharyngeal oedema), paradoxical bronchospasm, ocular complications (e.g. mydriasis, blurred vision, narrow-angle glaucoma, eye pain), serious hypokalaemia, gastrointestinal motility disturbances, rapidly worsening dyspnoea, ECG changes, lactic acidosis, urinary retention. Rarely, myocardial ischaemia.
Cardiac disorders: Palpitations, tachycardia.
Eye disorders: Accommodation disorders.
Gastrointestinal disorders: Dry mouth, nausea.
Nervous system disorders: Headache.
Respiratory, thoracic and mediastinal disorders: Coughing, dysphonia.

Inhalation/Respiratory: C

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

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

Symptoms: Salbutamol: Anginal pain, hyper/hypotension, hypokalaemia, tachycardia, arrhythmia, chest pain, tremor, flushing, restlessness and dizziness. Management: Supportive therapy. Administer cardioselective beta-blocking agent (e.g. metoprolol) if necessary.

Increased adverse adverse effects with corticosteroids, xanthine derivatives, diuretics.
Salbutamol: Enhanced effect with MAOIs or TCAs. Increased CV effects with anaesthetics containing halogenated hydrocarbons (e.g. halothane, enflurane).

Description: Ipratropium is a nonselective competitive antimuscarinic agent. It causes bronchodilation by blocking the action of acetylcholine-induced stimulation of guanyl cyclase, hence reducing formation of cyclic guanosine monophosphate (cGMP) at parasympathetic site.
Salbutamol activates adenyl cyclase, the enzyme that stimulates the production of cyclic adenosine-3’, 5’-monophosphate (cAMP). Increased cAMP leads to activation of protein kinase A, which inhibits phosphorylation of myosin and lowers intracellular ionic Ca concentrations, resulting in smooth muscle relaxation.
Synonym: Salbutamol: Albuterol.
Onset: Ipratropium: Bronchodilation: Within 15 minutes.
Salbutamol: Within 5 minutes.
Duration: Ipratropium: 4-8 hours.
Salbutamol: Approx 3-6 hours.
Pharmacokinetics:
Absorption: Ipratropium: Rapidly absorbed after inhalation. Bioavailability: <10%.
Salbutamol: Rapidly and completely absorbed after inhalation. Time to peak plasma concentration: Within 3 hours.
Distribution: Ipratropium: Plasma protein binding: <20%.
Metabolism: Ipratropium: Partially metabolised to inactive ester hydrolysis products.
Salbutamol: Undergoes first-pass metabolism in the liver and possibly in the gut wall. Metabolised to inactive sulfate conjugate.
Excretion: Ipratropium: Via urine and faeces. Terminal elimination half-life: 1.6 hours.
Salbutamol: Via urine (as metabolites and unchanged drug); faeces (small amounts). Elimination half-life: 3-7 hours.

Source: National Center for Biotechnology Information. PubChem Database. Ipratropium bromide, CID=657308, https://pubchem.ncbi.nlm.nih.gov/compound/Ipratropium-bromide (accessed on Jan. 21, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Salbutamol, CID=2083, https://pubchem.ncbi.nlm.nih.gov/compound/Salbutamol (accessed on Jan. 21, 2020)

Store below 25°C. Do not freeze. 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.

Anon. Ipratropium and Albuterol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/07/2018.

Buckingham R (ed). Ipratropium Bromide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/07/2018.

Buckingham R (ed). Salbutamol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/07/2018.

Combivent Respimat Spray, Metered (Boehringer Ingelheim Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/07/2018.