Umeclidinium + Vilanterol

Inhalation/Respiratory
Maintenance therapy in chronic obstructive pulmonary disease

Asthma. Acute episodes of bronchospasm or acutely deteriorating COPD. Concomitant use with other long-acting β₂-agonists.

Patient with CV disease (e.g. cardiac insufficiency, arrhythmias, hypertension), diabetes mellitus, narrow-angle glaucoma, hypokalaemia, prostatic hyperplasia/bladder neck obstruction, seizure disorders, thyrotoxicosis. Concomitant use with other long-acting muscarinic antagonists. Not indicated for the relief of acute bronchospasm or for asthma treatment. Pregnancy and lactation.

Significant: Hypersensitivity reactions (e.g. anaphylaxis, angioedema, rash, urticaria), blood pressure and tachycardia, atrial fibrillation, hyperglycaemia, diabetes mellitus and ketoacidosis exacerbation; hypokalaemia, urinary retention, narrow-angle glaucoma, bladder outlet obstruction, CNS stimulation/excitation; thyrotoxicosis exacerbation.
Gastrointestinal disorders: Constipation, dry mouth, diarrhoea, abdominal pain, nausea, toothache.
Musculoskeletal and connective tissue disorders: Muscle pain, pain in extremity, neck pain.
Nervous system disorders: Headache, vertigo, tremor, dysgeusia.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Sinusitis, nasopharyngitis, pharyngitis, upper respiratory tract infection, cough, pleuritic chest pain.
Potentially Fatal: Increased risk of asthma-related deaths. Rarely, paradoxical bronchospasm.

Inhalation/Respiratory: C

Monitor pulmonary function test (e.g. FEV₁, peak flow). Obtain blood pressure and heart rate. Assess ocular changes and signs of CNS stimulation.

Umeclidinium: Additive effect with other anticholinergic drugs.
Vilanterol: Increased exposure with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin). Increased risk of hypokalaemia with methylxanthine derivative, steroids or non-K-sparing diuretics. Diminished bronchodilatory effect with β-adrenergic blockers. Increased risk of CV adverse effects with MAOIs, and TCAs.
Potentially Fatal: Enhanced adverse effect with other long-acting β₂-adrenergic agonists (e.g. formoterol, salmeterol).

Description: Umeclidinium is a long-acting quaternary ammonium antimuscarinic agent. It competitively and reversibly inhibits acetylcholine at type 3 muscarinic (M₃) receptors in the bronchial smooth muscles thereby causing bronchodilation.
Vilanterol is a selective, long-acting β₂-adrenergic agonist. It stimulates the production of cyclic adenosine-3’,5’-monophosphate (cAMP) by activation of adenyl cyclase which results in the relaxation of bronchial smooth muscle.
Pharmacokinetics:
Absorption: Rapidly absorbed via lungs. Time to peak plasma concentration: 5-15 minutes.
Umeclidinium: Absolute bioavailability: Approx 13%.
Vilanterol: Absolute bioavailability: Approx 27%.
Distribution: Umeclidinium: Volume of distribution: 86 L. Plasma protein binding: Approx 89%.
Vilanterol: Volume of distribution: 165 L. Plasma protein binding: Approx 94%.
Metabolism: Umeclidinium: Metabolised in the liver by CYP2D6 by oxidation via hydroxylation and O-dealkylation, followed by glucuronidation into metabolites and is a substrate of P-glycoprotein transporter.
Vilanterol: Undergoes extensive 1st pass metabolism in the liver by CYP3A4 via O-dealkylation into metabolites.
Excretion: Umeclidinium: Mainly via faeces (92%); urine (<1%). Plasma elimination half-life: 11 hours.
Vilanterol: Mainly via urine (70% as metabolites); faeces (30% as metabolites). Plasma elimination half-life: Approx 11 hours.

Source: National Center for Biotechnology Information. PubChem Database. Umeclidinium, CID=11519070, https://pubchem.ncbi.nlm.nih.gov/compound/Umeclidinium (accessed on Jan. 23, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Vilanterol, CID=10184665, https://pubchem.ncbi.nlm.nih.gov/compound/Vilanterol (accessed on Jan. 23, 2020)

Store between 20-25°C. Protect from direct heat or sunlight.

Antiasthmatic & COPD Preparations

R03AL03 - vilanterol and umeclidinium 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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