ARNUITY ELLIPTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARNUITY ELLIPTA (ARNUITY ELLIPTA).
Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. It binds to the glucocorticoid receptor, leading to inhibition of inflammatory mediators such as cytokines, prostaglandins, and leukotrienes. This reduces airway inflammation and hyperresponsiveness.
| Metabolism | Fluticasone furoate is extensively metabolized in the liver via CYP3A4 to a less active metabolite. Systemic exposure is low due to high first-pass metabolism and oral bioavailability of less than 2%. |
| Excretion | Fluticasone furoate is eliminated primarily via hepatic metabolism and subsequent biliary excretion. Following oral administration, approximately 90% of the dose is excreted in feces as metabolites, with less than 1% excreted unchanged in urine. Renal excretion of unchanged drug is negligible. |
| Half-life | The terminal elimination half-life of fluticasone furoate is approximately 24 hours. This long half-life supports once-daily dosing and contributes to sustained anti-inflammatory effects in the lungs. |
| Protein binding | Fluticasone furoate is highly protein bound (>99%) primarily to albumin. Minimal binding to alpha-1-acid glycoprotein occurs. |
| Volume of Distribution | The volume of distribution of fluticasone furoate is approximately 4.2 L/kg, indicating extensive tissue distribution. This large Vd reflects high lipophilicity and tissue binding. |
| Bioavailability | The absolute bioavailability of inhaled fluticasone furoate is approximately 15.2%. Oral bioavailability is extremely low (<2%) due to extensive first-pass metabolism. The swallowed portion contributes minimally to systemic exposure. |
| Onset of Action | Inhaled fluticasone furoate demonstrates onset of action within 2-4 hours after administration, with peak bronchodilator effects observed by 12 hours for the LABA component (vilanterol) when present. For fluticasone furoate alone, onset of anti-inflammatory effect is typically seen within 24 hours. |
| Duration of Action | The duration of action for fluticasone furoate is approximately 24 hours, allowing once-daily dosing. Clinical efficacy in asthma and COPD is maintained over 24 hours with consistent dosing. |
| Molecular Weight | 323.35 |
| Action Class | Inhaled Corticosteroid (ICS) |
1 inhalation (100 mcg fluticasone furoate) once daily via oral inhalation, with or without a spacer.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | For Child-Pugh class C: use with caution; maximum dose 100 mcg once daily. For Child-Pugh A or B: no adjustment needed. |
| Pediatric use | Not approved for children under 12 years of age. For adolescents 12 years and older: same as adult dose (100 mcg once daily). |
| Geriatric use | No specific dose adjustment required; use with caution due to potential decreased renal function and increased risk of adverse effects. |
| 1st trimester | Limited human data; based on animal studies, no evidence of teratogenicity at clinically relevant doses. Avoid use unless benefit outweighs risk. |
| 2nd trimester | May be used if indicated; no known associated with fetal harm. Monitor for maternal hypoglycemia and fetal effects. |
| 3rd trimester | May cause maternal hypoglycemia and fetal hyperinsulinemia if maternal glucose levels exceed pancreatic beta-cell capacity. Use with caution. |
Clinical note
Comprehensive clinical and safety monograph for ARNUITY ELLIPTA (ARNUITY ELLIPTA).
| Placental transfer | Minimal data; case reports of short half-life and rapid clearance suggest low placental transfer. However, sulfonylurea class known to cross placenta. Renal clearance negligible. |
| Breastfeeding | Not recommended during breastfeeding due to lack of safety data. Drug may appear in breast milk and cause hypoglycemia in infant. Alternative agents preferred. |
■ FDA Black Box Warning
Long-term use of inhaled corticosteroids may result in a reduction of growth velocity in children. The lowest effective dose should be used to minimize systemic effects.
| Common Effects | Nasopharyngitis, Headache, Upper respiratory tract infection, Throat irritation, Hoarseness/dysphonia, Cough, Oral candidiasis |
| Serious Effects | Adrenal insufficiency (especially with high doses or prolonged use, or when switching from systemic corticosteroids), Increased risk of pneumonia in patients with COPD, Oropharyngeal candidiasis (thrush), Paradoxical bronchospasm (wheezing immediately after inhalation), Reduced bone mineral density with long-term use, Glaucoma and cataracts, Growth suppression in children, Cushing's syndrome with excessive doses |
Type 1 diabetes mellitusDiabetic ketoacidosis with or without comaHypersensitivity to glimepiride or any sulfonylurea
| Precautions | Candida albicans infection of the mouth and pharynx, Increased risk of pneumonia in patients with COPD, Systemic corticosteroid effects with prolonged use (e.g., HPA axis suppression, growth reduction in children), Paradoxical bronchospasm, Hypersensitivity reactions including anaphylaxis, rash, urticaria, and angioedema, Monitor for ocular effects (e.g., glaucoma, cataracts) |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) or 'Avoid' |
| Teratogenic Risk | No human data; animal studies show no teratogenicity at clinically relevant doses. Avoid use in first trimester unless benefit outweighs risk. In second/third trimester, use with caution due to potential for fetal growth restriction from systemic corticosteroid exposure. |
| Fetal Monitoring | Monitor maternal lung function, fetal growth (ultrasound) and amniotic fluid index if used long-term; assess for maternal adrenal suppression. |
| Fertility Effects | No reported effects on fertility in animal studies; human data lacking. |
| Food/Dietary | No significant food interactions known. Avoid grapefruit juice? No specific interactions reported; routine dietary restrictions are not required. |
| Clinical Pearls | ARNUITY ELLIPTA (fluticasone furoate) is an inhaled corticosteroid (ICS) indicated for once-daily maintenance treatment of asthma in patients aged ≥5 years. It is not indicated for acute bronchospasm or status asthmaticus. Rinse mouth with water after each use to reduce risk of oropharyngeal candidiasis. Monitor for signs of adrenal insufficiency during stress or conversion from systemic corticosteroids. Not for use in COPD. |
| Patient Advice | Use exactly as prescribed; do not use for sudden breathing problems. · Rinse mouth with water after each inhalation; do not swallow. · Do not stop therapy abruptly; consult healthcare provider before discontinuing. · Store at room temperature away from moisture and heat; keep the device closed. · Clean the mouthpiece weekly with a dry cloth; do not wash with water. · Seek medical attention if symptoms worsen or if rescue inhaler use increases. |