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Medication Safety Issues
Sound-alike/look-alike issues:
Flunisolide may be confused with Flumadine®, fluocinonide
Nasarel® may be confused with Nizoral®
Pronunciation
(floo NISS oh lide)
U.S. Brand Names
Generic Available
Yes: Nasal spray
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Steroid-dependent asthma; nasal solution is used for seasonal or perennial rhinitis
Pregnancy Risk Factor
C
Pregnancy Considerations
No data on crossing the placenta or effects on the fetus.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to flunisolide or any component of the formulation; acute status asthmaticus (oral formulation); infections of the nasal mucosa (intranasal formulation)
Warnings/Precautions
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections. Do not use this product to transfer patients from oral corticosteroid therapy.
• Bronchospasm: May occur with wheezing after inhalation; if this occurs stop steroid and treat with a fast-acting bronchodilator.
•Delayed wound healing: Avoid nasal corticosteroid use in patients with recent nasal septal ulcers, nasal surgery or nasal trauma until healing has occurred.
• Immunosuppression: Prolonged use of corticosteroids may also increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Exposure to chickenpox should be avoided; corticosteroids should not be used to treat ocular herpes simplex. Corticosteroids should not be used for cerebral malaria. Close observation is required in patients with latent tuberculosis and/or TB reactivity; restrict use in active TB (only in conjunction with antituberculosis treatment).
• Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered.
• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Pre-existing psychiatric conditions may be exacerbated by corticosteroid use.
Disease-related concerns:
• Asthma: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Not to be used in status asthmaticus or for the relief of acute bronchospasm.
• Cardiovascular disease: Use with caution in patients with HF; long-term use has been associated with fluid retention and hypertension.
• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.
• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, peptic ulcer, ulcerative colitis) due to perforation risk.
• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.
• Myocardial infarct (MI): Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.
• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Consider routine eye exams in chronic users.
• Osteoporosis: Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.
• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.
• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.
Special populations:
• Pediatrics: Orally-inhaled and intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients (~1 centimeter per year [range 0.3-1.8 cm per year] and related to dose and duration of exposure). To minimize the systemic effects of orally-inhaled and intranasal corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.
Other warnings/precautions:
• Discontinuation of therapy: Withdraw systemic therapy with gradual tapering of dose. There have been reports of systemic corticosteroid withdrawal symptoms (eg, joint/muscle pain, lassitude, depression) when withdrawing oral inhalation therapy.
Adverse Reactions
>10%:
Central nervous system: Headache (25%)
Gastrointestinal: Nausea (25%), vomiting (25%), sore throat (20%), aftertaste (8% to 17%)
Respiratory: Upper respiratory infection (25%), cold symptoms (15%), nasal congestion (15%), nasal burning/stinging (intranasal 13%)
1% to 10%:
Cardiovascular: Chest pain, chest tightness, edema, hypertension, palpitation, peripheral edema, tachycardia
Central nervous system: Anxiety, chills, dizziness, depression, fatigue, faintness, fever, hyper-/hypoactivity, insomnia, malaise, moodiness, nervousness, shakiness, vertigo
Dermatologic: Acne, eczema, hives, pruritus, rash, urticaria
Endocrine & metabolic: Menstrual disturbances
Gastrointestinal: Appetite decreased/increased, constipation, diarrhea, dyspepsia, dry throat, flatulence, glossitis, heartburn, loss of taste, mouth discomfort, oral candidiasis, stomach upset, throat irritation, weight gain
Neuromuscular & skeletal: Numbness, weakness
Ocular: Blurred vision, discomfort
Respiratory: Bronchitis, chest congestion, cough increased, dyspnea, epistaxis, hoarseness, laryngitis, nasal dryness, nasal irritation, pharyngitis, pleurisy, pneumonia, rhinitis, sinusitis, sneezing, wheezing
Miscellaneous: Diaphoresis, flu-like syndrome, infection, loss of smell, lymphadenopathy
<1%: Abdominal fullness, shortness of breath, nasal ulcer (intranasal formulation)
Metabolism/Transport Effects
Substrate of CYP3A4 (major)
Drug Interactions
Amphotericin B: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Antidiabetic Agents: Corticosteroids (Orally Inhaled) may diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Loop Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Thiazide Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Storage
AeroBid®, AeroBid®-M: Store below 49°C (below 120°F). Do not store near heat or flame.
Nasarel®: Store at 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability; does not depress hypothalamus
Pharmacodynamics/Kinetics
Absorption: Nasal inhalation: ~50%
Metabolism: Rapidly hepatic to active metabolites
Bioavailability: 40% to 50%
Half-life elimination: 1.8 hours
Excretion: Urine and feces (equal amounts)
Dosage
Oral inhalation: Asthma (AeroBid®, AeroBid®-M):
Children 6-15 years: 2 inhalations twice daily (morning and evening); up to 4 inhalations/day
Children ?16 years and Adults: 2 inhalations twice daily (morning and evening); up to 8 inhalations/day maximum
NIH Asthma Guidelines (NIH, 2007) (administer in divided doses twice daily):
Children 5-11 years:
“Low” dose: 500-750 mcg/day
“Medium” dose: 1000-1250 mcg/day
“High” dose: >1250 mcg/day
Children ?12 years and Adults:
“Low” dose: 500-1000 mcg/day
“Medium” dose: >1000-2000 mcg/day
“High” dose: >2000 mcg/day
Intranasal: Rhinitis:
Children 6-14 years: 1 spray each nostril 3 times daily or 2 sprays in each nostril twice daily; not to exceed 4 sprays/day in each nostril
Children ?15 years and Adults: 2 sprays each nostril twice daily (morning and evening); may increase to 2 sprays 3 times daily; maximum dose: 8 sprays/day in each nostril
Administration: Inhalation
Aerosol inhalation: Shake well before using. Rinse mouth following use of oral inhalers. Prime inhaler before first use.
Nasal spray: Before first use, prime by pressing pump 5-6 times or until a fine spray appears. Repeat priming if ?5 days between use, or if dissembled for cleaning. Administer at regular intervals. Blow nose to clear nostrils. Insert applicator into nostril, keeping bottle upright, and close off the other nostril. Breathe in through nose. While inhaling, press pump to release spray.
Patient Education
This medication is not intended to treat an acute asthma attack. Full benefit of regular use may not be seen for 2-4 weeks. Use as directed; do not use nasal preparations for oral inhalation. Do not increase dosage or discontinue abruptly without consulting prescriber. Review use of inhaler or spray with prescriber or follow package insert for directions. Keep oral inhaler clean and unobstructed. Always rinse mouth and throat after use of inhaler to prevent opportunistic infection. If you are also using an inhaled bronchodilator, wait 10 minutes before using this steroid aerosol. You may be susceptible to infections. Avoid measles and chickenpox. You may experience dizziness, anxiety, or blurred vision (rise slowly from sitting or lying position and use caution when driving or engaging in tasks requiring alertness until response to drug is known); or taste disturbance or aftertaste (frequent mouth care and mouth rinses may help). Report pounding heartbeat or chest pain; acute nervousness or inability to sleep; severe sneezing or nosebleed; respiratory difficulty, sore throat, hoarseness, or bronchitis; respiratory difficulty or bronchospasms; disturbed menstrual pattern; vision changes; loss of taste or smell perception; or worsening of condition or lack of improvement. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Inhaler: Sit when using. Take deep breaths for 3-5 minutes, and clear nasal passages before administration (use decongestant as needed). Hold breath for 5-10 seconds after use, and wait 1-3 minutes between inhalations. Follow package insert instructions for use. Do not exceed maximum dosage. If also using inhaled bronchodilator, use before flunisolide. Rinse mouth and throat after use to reduce aftertaste and prevent candidiasis.
Geriatric Considerations
Many elderly patients have difficulty using metered dose inhalers, which can limit their effectiveness. Assess technique in all older patients. A spacer device may be beneficial for the oral inhaler.
Additional Information
Effects of inhaled/intranasal steroids on growth have been observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally-inhaled and intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch up” growth following discontinuation of treatment with inhaled corticosteroids has not been adequately studied.
Anesthesia and Critical Care Concerns/Other Considerations
Surgery: For patients who have received oral systemic corticosteroids during the past 6 months and for selected patients on long-term, high-dose, inhaled corticosteroid (ICS), give stress doses of hydrocortisone intravenously during the surgical period and reduce the dose rapidly within 24 hours after surgery (Expert Panel Report 3, 2007). Clinically important adrenal suppression has been reported in patients receiving high doses of an ICS, particularly children.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Candida infections of the nose or pharynx, atrophic rhinitis, sore throat, bitter taste, palpitations, dizziness, headache, nervousness, GI irritation, sneezing, coughing, upper respiratory tract infection, bronchitis, nasal congestion, nasal dryness and burning, increased susceptibility to infections, xerostomia (normal salivary flow resumes upon discontinuation), dry throat, loss of taste, epistaxis, and diaphoresis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness and nervousness are common; may cause insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Not to be used to treat status asthmaticus or fungal infections of nasal passages. Monitor therapeutic effectiveness and adverse reactions. When changing from systemic steroids to inhalational steroid, taper reduction of systemic medication slowly. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Aerosol for oral inhalation:
AeroBid®: 250 mcg/actuation (7 g) [100 metered inhalations; contains chlorofluorocarbon]
AeroBid®-M: 250 mcg/actuation (7 g) [100 metered inhalations; contains chlorofluorocarbon; menthol flavor]
Solution, intranasal [spray]: 25 mcg/actuation (25 mL); 29 mcg/actuation (25 mL) [200 sprays]
Nasarel®: 29 mcg/actuation (25 mL) [200 sprays; contains benzalkonium chloride] [DSC]
Pricing: U.S. (www.drugstore.com)
Aerosol solution (Aerobid)
250 mcg/ACT (7): $88.38
Aerosol solution (Aerobid-M)
250 mcg/ACT (7): $84.99
Solution (Flunisolide)
0.025% (25): $39.99
29 mcg/ACT (25): $45.99
References
Expert Panel Report 3, “Guidelines for the Diagnosis and Management of Asthma,” Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 08-4051, prepublication 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
Goedert JJ, Vitale F, Lauria C, et al, “Risk Factors for Classical Kaposi's Sarcoma,” J Natl Cancer Inst, 2002, 94(22):1712-8.
Todd GR, Acerini CL, Buck JJ, et al, "Acute Adrenal Crisis in Asthmatics Treated With High-Dose Fluticasone Propionate," Eur Respir J, 2002, 19(6):1207-9.
Todd GR, Acerini CL, Ross-Russell R, et al, "Survey of Adrenal Crisis Associated With Inhaled Corticosteroids in the United Kingdom," Arch Dis Child, 2002, 87(6):457-61.
International Brand Names
Lexi-Comp.com
Last full review/revision July 2009
Content last modified July 2009
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