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Flovent Hfa
Flovent Hfa Generic Name & Formulations General DescriptionFluticasone propionate 44mcg/inh, 110mcg/inh, 220mcg/inh; metered dose inhaler; CFC-free.
Pharmacological ClassSteroid.
How SuppliedInhaler w. Actuator (44mcg)—10.6g (120 inh); 110mcg, 220mcg—12g (120 inh)
How SuppliedFlovent HFA is supplied in the following boxes of 1 as a pressurized aluminum canister fitted with a counter and supplied with a dark orange actuator with a peach cap:
Flovent HFA 44 mcg: 10.6-g canister containing 120 actuations
Flovent HFA 110 mcg: 12-g canister containing 120 actuations
Flovent HFA 220 mcg: 12-g canister containing 120 actuations
Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) [See USP Controlled Room Temperature]. Store the inhaler with the mouthpiece down. For best results, the inhaler should be at room temperature before use.
Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw canister into fire or incinerator.
Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Corticosteroids have been shown to have a wide range of actions on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma.
Flovent Hfa Indications IndicationsMaintenance treatment of asthma as prophylactic therapy.
Limitations of UseNot for the relief of acute bronchospasm.
Flovent Hfa Dosage and Administration AdultPreviously on bronchodilators alone: initially 88mcg twice daily (approx. 12hrs apart); max 880mcg twice daily. Rinse mouth after use. Titrate to lowest effective dose after stability achieved. Re-evaluate if inadequate control.
Children<4yrs: not established. 4–11yrs: 88mcg twice daily (approx. 12hrs apart). Rinse mouth after use. Titrate to lowest effective dose after stability achieved. Re-evaluate if inadequate control.
Flovent Hfa Contraindications ContraindicationsPrimary treatment of status asthmaticus or other acute attacks requiring intensive measures.
Flovent Hfa Boxed WarningsNot Applicable
Flovent Hfa Warnings/Precautions Warnings/PrecautionsMaintain regular regimen. Immunosuppression. Tuberculosis. Systemic infections (eg, fungal, bacterial, viral, parasitic). Ocular herpes simplex. If exposed to chickenpox or measles, consider immune globulin or antiviral prophylactic therapies. Monitor for adrenal insufficiency when transferring from systemic steroids. Reevaluate periodically. Monitor for hypercorticism and HPA axis suppression (if occurs, discontinue gradually), growth in children, IOP, glaucoma, or cataracts. Consider eye exams if ocular symptoms develop or in long-term use. Discontinue and treat if paradoxical bronchospasm occurs; use alternative therapy. Assess bone mineral density if risk factors exist (eg, prolonged immobilization, osteoporosis, postmenopausal, tobacco use, advanced age, poor nutrition, others). Eosinophilic conditions. Hepatic impairment; monitor. Transferring from oral corticosteroids: see full labeling. Pregnancy. Nursing mothers.
Warnings/PrecautionsOropharyngeal Candidiasis
Localized Infections of the mouth and pharynx with Candida albicans has occurred in clinical trials.
Infections should be treated with appropriate local or systemic antifungal therapy while remaining on Flovent HFA, though Flovent HFA may need to be interrupted in some cases.
To reduce the risk of orpharyngeal candidiasis, patients should rinse their mouth after inhalation of Flovent HFA.
Acute Asthma Episodes
Flovent HFA is not to be regarded as a bronchodilator and is not indicated for rapid relief of bronchospasm.
During treatment with Flovent HFA, advise patients to contact their physician immediately if episodes of asthma that are unresponsive to bronchodilators occur. During these episodes, patients may require therapy with oral corticosteroids.
Immunosuppression and Risk of Infections
Patients who are using drugs that suppress the immune system are more susceptible to infections.
For patients who have not previously had chickenpox or measles or been vaccinated against these diseases, consider immunoglobulin prophylactic therapy if exposure occurs. Treatment with antivirals should be considered if chickenpox develops.
Inhaled corticosteroids should be used with caution in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
Transferring Patients from Systemic Corticosteroid Therapy
Hypercorticism and Adrenal Suppression
Monitor for hypercorticism and HPA axis suppression (if occur, reduce dose gradually).
Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.
Reduction in Bone Mineral Density
Decreases in bone mineral density have been observed with long-term administration of ICS; patients with risk factors should be monitored and treated appropriately.
Major risk factors for decreased bone mineral content are: prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (eg, anticonvulsants, oral corticosteroids).
Effect on Growth
Monitor growth in pediatric patients.
To minimize the systemic effects, titrate each patient's dosage to the lowest effective dose to control symptoms.
Glaucoma and Cataracts
Glaucoma, increased intraocular pressure and cataracts have been reported following administration of inhaled corticosteroids, including fluticasone propionate.
Consider referral to an ophthalmologist in patients who develop ocular symptoms or use Flovent HFA long term.
Paradoxical Bronchospasm
Eosinophilic Conditions and Churg-Strauss Syndrome
In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions. Some of these patients have clinical features of vasculitis consistent with ChurgStrauss syndrome, a condition that is often treated with systemic corticosteroid therapy.
These events usually have been associated with the reduction and/or withdrawal of oral corticosteroid therapy after the use of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other ICS in this clinical setting.
Be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.
Risk Summary
There are no available data on the presence of fluticasone propionate in human milk, the effects on the breastfed child, or the effects on milk production; other corticosteroids are excreted in human milk.
Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for Flovent HFA and any potential adverse effects on the breastfed child from Flovent HFA or from the underlying maternal condition.
The safety and effectiveness of Flovent HFA in children under 4 years of age have not been established.
Monitor for growth suppression in children. To minimize the systemic effects of orally inhaled corticosteroids, including Flovent HFA, each patient should be titrated to the lowest effective dose.
Studies using Flovent HFA have not been conducted in patients with renal impairment.
Hepatic Impairment ConsiderationsPatients with hepatic disease should be closely monitored.
Flovent Hfa Pharmacokinetics AbsorptionFluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed.
Following IV dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of ~7.8 hours.
The total clearance of fluticasone propionate is high (average, 1,093 mL/min), with renal clearance accounting for <0.02% of the total.
Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.
Concomitant strong CYP3A4 inhibitors (eg, ritonavir, atazanavir, clarithromycin, ketoconazole, nefazodone, others): not recommended.
InteractionsUpper respiratory tract infection/inflammation, throat irritation, sinusitis, dysphonia, candidiasis, cough, bronchitis, headache; immunosuppression, adrenal suppression, bronchospasm, hypersensitivity reactions.
Flovent Hfa Clinical Trials Clinical TrialsAdult and Adolescent Patients Aged 12 Years and Older
The efficacy and safety of Flovent HFA was assessed in 3 randomized, double-blind, parallel-group, placebo-controlled, US clinical trials in 980 adult and adolescent patients 12 years of age and older with asthma.
Fixed doses of 88, 220, and 440 mcg twice daily and 880 mcg twice daily were compared with placebo.
Patients included those inadequately controlled with bronchodilators alone (Trial 1), those already receiving daily ICS (Trial 2), and those requiring oral corticosteroid therapy (Trial 3). In all 3 trials, patients were allowed to use Ventolin Inhalation Aerosol as needed for relief of acute asthma symptoms. In Trials 1 and 2, other maintenance asthma therapies were discontinued.
In Trial 1: Results showed that all 3 dosages (88, 220, and 440 mcg twice daily) of Flovent HFA achieved a statistically significant improvement in lung function, as measured by improvement in AM pre-dose FEV1, compared with placebo. This improvement was seen after the first week then maintained over the 12-week period.
In Trial 2: Results showed that all 3 dosages (88, 220, and 440 mcg twice daily) of Flovent HFA achieved a statistically significant improvement in lung function, as measured by improvement in FEV1, compared with placebo. This improvement was seen after the first week then maintained over the 12-week period.
In Trial 3: Results showed that patients treated with either 440 or 880 mcg twice daily of Flovent HFA required a statistically significantly lower mean daily oral prednisone dose (6 mg) compared with placebo-treated patients (15 mg). Additionally, patients in the Flovent HFA arm achieved statistically significantly improved lung function, fewer asthma symptoms, and less use of Ventolin Inhalation Aerosol compared with those in the placebo arm.
Two long-term safety trials (Trial 4 and Trial 5):
Trial 4 evaluated the safety of 2 doses of Flovent HFA, while Trial 5 compared fluticasone propionate HFA with fluticasone propionate CFC. Each trial was at least 6 months' duration and included adult and adolescent subjects with asthma.
Trial 4 enrolled 182 subjects who were treated daily with low to high doses of ICS, beta-agonists (short-acting [as needed or regularly scheduled] or long-acting), theophylline, inhaled cromolyn or nedocromil sodium, leukotriene receptor antagonists, or 5-lipoxygenase inhibitors at baseline. Flovent HFA at dosages of 220 and 440 mcg twice daily was evaluated over a 26-week treatment period in 89 and 93 subjects, respectively.
Trial 5 enrolled 325 subjects who were treated daily with moderate to high doses of ICS, with or without concurrent use of salmeterol or albuterol, at baseline. Fluticasone propionate HFA at a dosage of 440 mcg twice daily and fluticasone propionate CFC at a dosage of 440 mcg twice daily were evaluated over a 52-week treatment period in 163 and 162 subjects, respectively.
Both formulations of fluticasone propionate maintained asthma control throughout the 52-week treatment period compared with baseline. In both trials, none of the subjects were withdrawn due to lack of efficacy.
Pediatric Subjects Aged 4 to 11 Years
Flovent Hfa NoteNot Applicable
Flovent Hfa Patient Counseling Patient CounselingAdvise patients to rinse mouth after inhalation to prevent oropharyngeal candidiasis.
Acute asthma symptoms should be treated with an inhaled, short-acting beta2 agonist (eg, albuterol).
Patients who are on immunosuppressant doses of corticosteroids: Avoid exposure to chickenpox or measles, and if exposed, immediately contact their physicians. Advise patients that they may potentially worsen any existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
Advise patients that Flovent HFA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Deaths have occurred in patients due to adrenal insufficiency during and after transfer from systemic corticosteroids. Gradually taper patients from systemic corticosteroids if transferring to Flovent HFA.
Patients who have been withdrawn from systemic corticosteroids: Instruct them to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.
Discontinue immediately if hypersensitivity reactions, including anaphylaxis, occur (eg, urticaria, angioedema, rash bronchospasm, hypotension).
Advise patients that the use of corticosteroids may potentially increase the risk for decreased bone mineral density.
The use of corticosteroids may cause a reduction in growth velocity. Monitor the growth of children and adolescents closely.
Increased risk for eye problems (eg, cataracts or glaucoma) with the long-term use of ICS; consider regular eye examinations.
Arnuity Ellipta
Arnuity Ellipta Generic Name & Formulations General DescriptionFluticasone furoate 50mcg, 100mcg, 200mcg; per inhalation; dry pwd for oral inhalation.
Pharmacological ClassCorticosteroid.
How SuppliedDry pwd inhaler—30 doses
Mechanism of ActionFluticasone furoate is a synthetic trifluorinated corticosteroid with anti‑inflammatory activity. The precise mechanism through which fluticasone furoate affects asthma symptoms is not known. Corticosteroids have been shown to have a wide range of actions on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. Specific effects of fluticasone furoate demonstrated in in vitro and in vivo models included activation of the glucocorticoid response element, inhibition of pro-inflammatory transcription factors such as NFkB, and inhibition of antigen-induced lung eosinophilia in sensitized rats. These anti-inflammatory actions of corticosteroids may contribute to their efficacy.
Arnuity Ellipta Indications IndicationsMaintenance treatment of asthma in patients ≥5yrs.
Limitations of UseNot for relief of acute bronchospasm.
Arnuity Ellipta Dosage and Administration AdultBase initial dose on previous asthma therapy and disease severity. Not on inhaled corticosteroid: usually initiate at 100mcg once daily; may increase to 200mcg once daily if inadequate response after 2 weeks. Max 200mcg/day. Rinse mouth after use.
Children<5yrs: not established. 5–11yrs: 50mcg once daily. Rinse mouth after use.
Arnuity Ellipta Contraindications ContraindicationsPrimary treatment of status asthmaticus or acute asthma episodes. Severe hypersensitivity to milk proteins.
Arnuity Ellipta Boxed WarningsNot Applicable
Arnuity Ellipta Warnings/Precautions Warnings/PrecautionsDo not exceed recommended dose. Prescribe a short-acting, inhaled β2-agonist for acute symptoms; monitor for increased need. Immunosuppressed. Tuberculosis. Systemic infections (eg, fungal, bacterial, viral, parasitic). Ocular herpes simplex. If exposed to chickenpox or measles, consider immune globulin or antiviral prophylactic therapies. Monitor for adrenal insufficiency when transferring from systemic steroids. Reevaluate periodically. Monitor for hypercorticism and HPA axis suppression (if occurs, discontinue gradually), growth in children, IOP, glaucoma, or cataracts. Consider eye exams if ocular symptoms develop or in long-term use. Discontinue and treat if paradoxical bronchospasm occurs; use alternative therapy. Assess bone mineral density if risk factors exist (eg, prolonged immobilization, osteoporosis, postmenopausal, tobacco use, advanced age, poor nutrition, others). Moderate or severe hepatic impairment; monitor. Elderly. Labor & delivery. Pregnancy; monitor. Nursing mothers.
Arnuity Ellipta Pharmacokinetics AbsorptionPeak plasma concentrations: within 0.51 hour.
Absolute bioavailability by inhalation: 13.9%.
DistributionMean volume of distribution at steady state: 661 L.
Plasma protein bound: 99.6%.
EliminationFecal.
Half-life: ~24 hours.
Arnuity Ellipta Interactions InteractionsCaution with concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole).
Arnuity Ellipta Adverse Reactions Adverse ReactionsNasopharyngitis, upper respiratory tract infection, headache, bronchitis, oral candidiasis; hypersensitivity reactions (discontinue if occurs); children: also pharyngitis, viral infection.
Arnuity Ellipta Clinical TrialsSee Literature
Arnuity Ellipta NoteNot Applicable
Arnuity Ellipta Patient CounselingSee Literature
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