Adult: Available preparations:
Ipratropium 20 mcg and fenoterol 50 mcg/actuation soln for inhalation
Acute asthma attack: 1 puff for prompt relief. If there is no improvement after 5 min, 1 further dose may be given; further doses may be required if there is no relief after 2 admin. Intermittent and long-term treatment: 1 puff up to 4 times daily. Max: 6 puffs daily.
Ipratropium 0.5 mg and fenoterol 1.25 mg/4 mL soln for nebulisation
4 mL (in NaCl soln) via nebuliser as soon as asthma attack starts. A 2nd dose may be required in severe cases. Child: As soln for inhalation: >6 yr 1 puff, up to Max 3 puffs daily. As soln for nebulisation: ≥12 yr Same as adult dose.
Contraindications
Hypersensitivity to ipratropium or fenoterol, atropine, or its derivatives. Hypertrophic obstructive cardiomyopathy, tachyarrhythmia.
Rinse mouth every after inhalation. This drug may cause dizziness, tremor and visual disturbances, if affected, do no drive or operate machinery. Avoid contact w/ eyes.
Monitoring Parameters
Monitor spirometry [e.g. FEV (forced expiratory volume), FVC (forced vital capacity)] and serum K level.
Overdosage
Symptoms: Tachycardia, palpitation, tremor, hypotension, HTN, angina pain, widening of the pulse pressure, arrhythmia, flushing, dry mouth, visual disturbances. Management: Administer sedatives or tranquilisers. For severe cases, employ intensive therapy. β1-selective blockers may be given as specific antidote.
Drug Interactions
Enhanced bronchodilatory effect w/ β-adrenergic drugs and xanthine derivatives (e.g. theophylline). Increased risk of adverse effects w/ MAOIs or TCAs. Increased risk of CV effects w/ halogenated hydrocarbons (e.g. halothane). Reduced bronchodilatory effect w/ β-blockers. Increased risk of hypokalaemia w/ xanthine derivatives, corticosteroids, diuretics.
Action
Description: Ipratropium bromide 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.
Fenoterol is a direct-acting β2 sympathomimetic agent. It relaxes bronchial smooth muscles via protein phosphorylation (protein kinase A) by stimulating adenylate cyclase, thereby increasing cyclic-3’- 5’-adenosine monophosphate (cAMP) levels. Onset: Ipratropium: Bronchodilation: W/in 15 min.
Fenoterol: Bronchodilation: 5 min. Duration: Ipratropium: 4-8 hr.
Fenoterol: 6-8 hr. Pharmacokinetics: Absorption: Ipratropium: 10-30% of a dose is deposited in the lungs while only a small amount reaches systemic circulation. Bioavailability: 7-28%.
Fenoterol: Incompletely absorbed from the GI tract. Bioavailability: 7%. Distribution: Deposited in lungs (10-39%).
Ipratropium: Plasma protein binding: <20%.
Fenoterol: Enters breast milk. Plasma protein binding: Approx 40-55%. Metabolism: Ipratropium: Metabolised in the liver to α-phenylacrylic acid, phenylacetic acid-N-isopropylnortropine ester methobromide, N- isopropylnortropine methobromide.
Fenoterol: Undergoes extensive first-pass metabolism via sulfate conjugation. Excretion: Ipratropium: Via urine and faeces. Elimination half-life: 1.6 hr.
Fenoterol: Via urine and bile (mainly as inactive sulfate conjugate). Elimination half-life: Approx 3 hr.
Chemical Structure
Ipratropium bromide 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)
Fenoterol Source: National Center for Biotechnology Information. PubChem Database. Fenoterol, CID=3343, https://pubchem.ncbi.nlm.nih.gov/compound/Fenoterol (accessed on Jan. 20, 2020)
Storage
Store between 15-25°C. Protect from light and heat.
R03AL01 - fenoterol 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.
References
Anon. Ipratropium and Fenoterol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/08/2017.Buckingham R (ed). Fenoterol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/08/2017.Buckingham R (ed). Ipratropium Bromide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/08/2017.McEvoy GK, Snow EK, Miller J et al (eds). Ipratropium Bromide. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 01/08/2017.