Fluticasone + Formoterol

Inhalation/Respiratory
Asthma

Patient w/ active or quiescent pulmonary TB, untreated systemic infections, ocular herpes simplex, or w/ fungal, viral or airway infections, thyrotoxicosis, phaeochromocytoma, DM, hypokalaemia, CV disorders (e.g. arrhythmia, heart failure, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe HTN, aneurysm). Not intended for acute asthma attack. Hepatic impairment. Pregnancy and lactation.

Significant: Hypokalaemia, paradoxical bronchospasm, increased wheezing, shortness of breath, QTc interval prolongation.
Nervous: Insomnia, headache, tremor, dizziness, abnormal dreams, agitation, asthenia.
CV: Palpitations, ventricular extrasystoles, angina pectoris, tachycardia, HTN, peripheral oedema.
GI: Oral candidiasis/fungal infections, hoarseness, stomatitis, dry mouth, diarrhoea, dyspepsia, nausea.
Resp: Asthma exacerbation, dysphonia, throat irritation, sinusitis.
Endocrine: Hyperglycaemia, increased blood lactate levels, decrease BMD.
Ophthalmologic: Cataract/glaucoma.
Dermatologic: Rash, pruritus, contusion, skin atrophy.
Immunologic: Anaphylaxis reactions.
Potentially Fatal: Arrhythmia, cardiac arrest.

Rinse mouth thoroughly every after inhalation. Avoid abrupt withdrawal.

Perform FEV₁, peak flow, and/or other pulmonary function tests. Monitor serum K, BMD level, BP, hepatic function, hypothalamic-pituitary-adrenal (HPA) axis suppression/adrenal insufficiency, ocular changes, signs of asthma deterioration, growth degradation, and symptom relief.

Symptoms: Fluticasone: Adrenocortical suppression, headache, nausea, vomiting, hypotension, variable sugar level, seizures, HTN/hypotension. Management: Symptomatic and supportive treatment.

Fluticasone: Increased plasma concentration w/ CYP3A4 inhibitors (e.g. ketoconazole, HIV protease inhibitors, clarithromycin, ketoconazole). Formoterol: May induce hypokalaemia w/ xanthine derivatives, steroids and diuretics. Increased risk of ventricular arrhythmias w/ digitalis glycoside, halogenated hydrocarbon anaesthetics. May prolong QTc-interval w/ TCAs, MAOIs, antipsyschotics, quinidine, disopyramide, procainamide, and antihistamines. Reduced therapeutic effect w/ β-blockers. May impair cardiac tolerance w/ L-dopa, L-thyroxine, oxytocin.

May impair cardiac tolerance w/ alcohol.

Description:
Mechanism of Action: Fluticasone is a corticosteroid w/ glucocorticoid activity. It utilises a fluorocarbothioate ester linkage at the 17 carbon position. It has potent vasoconstrictive and anti-inflammatory activity hence, reduces the symptoms, improves lung function and prevents asthma exacerbation.
Formoterol is a long-acting selective β₂ adrenoceptor agonist. It relaxes bronchial smooth muscles by stimulation of adenyl cyclase, thereby increasing cyclic-3’-5’-adenosine monophosphate (cAMP) levels.
Onset: Formoterol: W/in 3 min.
Duration: Formoterol: 12 hr.
Pharmacokinetics:
Absorption: Fluticasone: Absorbed systemically primarily via lungs. Bioavailability: 13.9%. Time to peak plasma concentration: 0.5-1 hr.
Formoterol: Rapidly absorbed into plasma.
Distribution: Fluticasone: Extensively distributed in the body. Volume of distribution: 4.2 L/kg. Plasma protein binding: Approx 91%.
Formoterol: Plasma protein binding: 61-64% (34% primarily to albumin).
Metabolism: Fluticasone: Undergoes extensive hepatic first-pass metabolism, converted to 17β-carboxylic acid by CYP3A4 isoenzyme.
Formoterol: Metabolised via glucuronidation and O-demethylation to inactive O-demethylated glucuronate conjugate and deformylated metabolites.
Excretion: Fluticasone: Mainly via faeces (75% as parent compound and metabolites); urine (<5% as metabolites). Terminal elimination half-life: Approx 8 hr.
Formoterol: Mainly via urine (15-18% as glucuronide metabolite; 2-10% as unchanged drug). Terminal elimination half-life: Approx 10-14 hr.

Source: National Center for Biotechnology Information. PubChem Database. Fluticasone propionate, CID=444036, https://pubchem.ncbi.nlm.nih.gov/compound/Fluticasone-propionate (accessed on Jan. 21, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Arformoterol, CID=3083544, https://pubchem.ncbi.nlm.nih.gov/compound/Arformoterol (accessed on Jan. 21, 2020)

Store below 25°C.

Antiasthmatic & COPD Preparations

R03AK11 - formoterol and fluticasone ; Belongs to the class of adrenergics in combination with corticosteroids or other drugs, excluding anticholinergics. Used in the treatment of obstructive airway diseases.

Anon. Fluticasone (Oral Inhalation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/09/2017.

Anon. Formoterol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/09/2017.

Buckingham R (ed). Fluticasone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/09/2017.

Joint Formulary Committee. Fluticasone with Formoterol. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/09/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Fluticasone Propionate (EENT). AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 04/09/2017.