AHFS Class:

• Corticosteroids 52:08.08

Generic Name(s):

• Budesonide

Budesonide is a synthetic, non-halogenated corticosteroid that has potent glucocorticoid and weak mineralocorticoid activity. 1,16

Allergic Rhinitis

Budesonide nasal spray is used for the symptomatic management of seasonal or perennial allergic rhinitis.1,7,8,9 12,13,14,15,16,17,18,19

In patients with seasonal or perennial allergic rhinitis, intranasal administration of budesonide generally provides symptomatic relief of rhinorrhea, nasal congestion, sneezing, and itching.1,7,14 15,16,17,18 In patients with seasonal or perennial rhinitis, symptomatic relief is evident within 1-2 days of continuous intranasal budesonide therapy; however, usually about 2 weeks of continuous therapy may be required for optimum effectiveness.1 Onset of response occasionally occurs within 8-12 hours following initiation of intranasal budesonide in patients with seasonal or perennial allergic rhinitis.1,7

Results of several placebo-controlled trials of 3-6 weeks' duration in adults and children 6 years of age and older indicate that budesonide nasal spray (32, 64, 128, and 256 mcg daily) is more effective than placebo in relieving symptoms of seasonal or perennial allergic rhinitis.1,7 14,15,17 Intranasal administration of budesonide (128, 140, and 256 mcg) given once daily appears to be at least as effective as intranasal fluticasone propionate (200 mcg given once daily)8,13 or mometasone furoate (200 mcg given once daily),1,9 in the treatment of seasonal or perennial allergic rhinitis.

General

For intranasal use, budesonide is commercially available as a metered-dose pump spray containing a microcrystalline (micronized) suspension of the drug in an aqueous vehicle.1 The inhaler should be shaken gently immediately prior to use.1,17 After initial priming (8 actuations), each actuation of the spray pump delivers from the nasal adapter 32 mcg of budesonide per spray and 120 metered doses per 8.6-g container.1,10 If the spray pump is not used for 2 consecutive days or more than 14 days, it may need to be partially primed (1 actuation when not used for 2 consecutive days or 2 actuations or until a fine spray is observed when not used for more than 14 days); the applicator should be rinsed when not used for more than 14 days.1,17

For the symptomatic management of seasonal or perennial allergic rhinitis, the usual initial dosage of intranasal budesonide in adults and children 6 years of age or older is 32 mcg (1 spray) in each nostril once daily (total daily dosage of 64 mcg).1,17 In adults and children 12 years of age or older, dosage of budesonide may be increased to 256 mcg daily, administered in each nostril as 128 mcg (4 sprays) once daily.1 In children younger than 12 years of age, dosage of budesonide may be increased to 128 mcg daily, administered in each nostril as 64 mcg (2 sprays) once daily.1

Special Populations

No special population recommendations at this time.1

Contraindications

Known hypersensitivity to budesonide or any ingredient of the formulation.1

Warnings/Precautions

Warnings

Withdrawal of Systemic Corticosteroid Therapy

Patients being switched from systemic corticosteroids to topical corticosteroids should be carefully monitored, since corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression), acute adrenal insufficiency, or severe symptomatic exacerbation of asthma or other clinical conditions may occur.1 For additional information, see Discontinuance of Therapy under Dosage and Administration: Dosage, in the Corticosteroids General Statement 68:04.

Immunosuppressed Patients

Patients who are taking immunosuppressant drugs have increased susceptibility to infections compared with healthy individuals, and certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients, particularly in children.1 In patients who have not had these diseases, particular care should be taken to avoid exposure.1 It is not known how the dosage, route, and duration of administration of a corticosteroid or the contribution of the underlying disease and/or prior corticosteroid therapy affect the risk of developing a disseminated infection.1 If exposure to varicella (chickenpox) or measles occurs in such individuals, administration of varicella zoster immune globulin (VZIG) or pooled IM immune globulin (IG) respectively, may be initiated.1,10 If varicella (chickenpox) develops, treatment with an antiviral agent may be considered.1 For additional information, see Cautions: Increased Susceptibility to Infection and also see Precautions and Contraindications, in the Corticosteroids General Statement 68:04.

Sensitivity Reactions

Rarely, immediate or delayed hypersensitivity reactions may occur following intranasal administration of budesonide.1,16 Wheezing has been reported very rarely.1

General Precautions

Systemic Corticosteroid Effects

Intranasal corticosteroids such as budesonide may cause growth suppression in children and adolescents.1,20 See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.

To minimize the systemic effects of intranasal corticosteroids, including budesonide, dosage should be titrated to the lowest possible effective level.1 When nasal corticosteroids are used in excessive dosages, systemic corticosteroid effects such as hypercorticism or adrenal suppression can occur.1 If such changes are apparent, intranasal budesonide should be discontinued gradually according to accepted procedures for discontinuing oral corticosteroid therapy.1

Nasopharyngeal and Ocular Effects

Localized candidal infections of the nose and/or pharynx have occurred rarely during intranasal budesonide therapy.1 When infection occurs, appropriate local or systemic treatment of the infection may be necessary, and/or discontinuance of intranasal budesonide therapy may be required.1 Patients receiving the drug for several months or longer should be examined periodically for candidal infections or changes in the nasal mucosa.1 Nasal septum perforation and increased intraocular pressure (IOP) have been reported rarely in patients receiving budesonide nasal spray.1 Because corticosteroid therapy may inhibit wound healing, patients with recent nasal septum ulcers, nasal surgery, or nasal trauma should not use nasal corticosteroids until healing has occurred.1

Concomitant Infections

Intranasal budesonide therapy should be used with caution, if at all, in patients with clinical or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract; untreated fungal or bacterial infections; or ocular herpes simplex or untreated, systemic viral infections.1

Specific Populations

Pregnancy

Category C.1 (See Users Guide.) Hypoadrenalism may occur in infants of mothers receiving corticosteroid therapy during pregnancy.1 These infants should be carefully monitored.1

Lactation

Not known whether budesonide is distributed in milk.1 Caution is advised if the drug is administered in nursing women.1

Pediatric Use

Safety and efficacy of intranasal budesonide have not been established in children younger than 6 years of age.1 Intranasal corticosteroids may cause growth suppression in children or adolescents, and clinicians should routinely monitor (e.g., via stadiometry) the growth of pediatric patients receiving these drugs.1,20 See Cautions: Pediatric Precautions, in the Corticosteroids General Statement 68:04.

Geriatric Use

Although no overall differences in safety and efficacy were observed between geriatric and younger patients, frequency of epistaxis appears to increase with age.1 In addition, the possibility that some older individuals may exhibit increased sensitivity to the drug cannot be ruled out.1

Hepatic Impairment

May affect elimination of corticosteroids; increased systemic availability of budesonide may occur.1 The relevance of these findings to intranasally applied budesonide is unknown.1

Common Adverse Effects

Adverse effects of budesonide occurring in 2% or more of patients receiving budesonide nasal spray and with an incidence more frequent than that of placebo include epistaxis, pharyngitis, bronchospasm, cough, and nasal irritation.1

Drugs Affecting Hepatic Microsomal Enzymes

Since budesonide is metabolized in the liver by the cytochrome P-450 (CYP) 3A4 isoenzyme, concomitant use with drugs that are potent inhibitors of this isoenzyme may result in increased plasma budesonide concentrations.1 Concomitant use of oral budesonide with oral ketoconazole (a potent inhibitor of the CYP3A4 isoenzyme) resulted in a more than sevenfold increase in plasma budesonide concentrations.1 When administered concomitantly, known inhibitors of the CYP3A4 isoenzyme (e.g., clarithromycin, erythromycin, itraconazole) may inhibit metabolism of budesonide resulting in increased systemic exposure of budesonide.1

Omeprazole, a known inhibitor of the CYP2C19 isoenzyme, does not appear to affect the pharmacokinetics of oral budesonide.1 However, a slight decrease in budesonide clearance and an increase of budesonide oral bioavailability was observed when cimetidine, an inhibitor of the CYP1A2 isoenzyme, was administered concomitantly with the corticosteroid.1

Description

Budesonide is a synthetic, nonhalogenated corticosteroid.1 Budesonide has high glucocorticoid and weak mineralocorticoid activity.1 For further information on the pharmacology of corticosteroids, see Pharmacology in the Corticosteroids General Statement 68:04.

The exact mechanism(s) of action of corticosteroids in allergic rhinitis remains unknown,1 but may involve reductions in the following: number of mediator cells (basophils,5,15 eosinophils,1,5,15 T-helper cells,6 mast cells,1,4 and neutrophils)1,5 in the nasal mucosa, nasal reactivity to allergens, and release of inflammatory mediators1,4 and proteolytic enzymes.4 (See Pharmacology, in Fluticasone Propionate 52:08.08.)

When budesonide is administered intranasally, approximately 34% of a dose reaches systemic circulation.1 Mean peak plasma budesonide concentrations are achieved in about 0.7 hours.1

Following administration of budesonide nasal spray at a dosage of 256 mcg daily for 7 days in healthy individuals, a small, but statistically significant reduction in the area under the plasma cortisol concentration-time curve (AUC_{0-24 hours}) has been observed.1 A dose-related suppression of the HPA response was observed in patients receiving budesonide nasal spray at dosages ranging from 100-800 mcg daily for up to 4 days.1 However, in a 4-week clinical trial in adult patients receiving budesonide nasal spray at a dosage of 256 mcg daily, no significant differences in plasma cortisol concentrations, compared with placebo, were observed when measured before and 60 minutes after IM administration of a 0.25-mg dose of cosyntropin.1

Budesonide is metabolized in the liver by the cytochrome P-450 (CYP) isoenzyme 3A4; the 2 main metabolites have less than 1% of affinity for glucocorticoid receptors than the parent compound.1 Budesonide is excreted in urine and feces as metabolites.1

Advice to Patients

Patients should be carefully instructed in the use of the nasal inhaler or spray pump.1,17 To obtain optimum results, patients also should be given a copy of the patient instructions provided by the manufacturer.1,17

Provide information regarding the importance of adherence to the prescribed directions for use at regular intervals, not exceeding prescribed dosage, and the understanding of proper storage, preparation, and administration techniques.1

Advise that the drug usually will provide symptomatic relief within 2 days, but 2 weeks of continuous therapy usually are required for optimum effects.1

Importance of shaking containers of budesonide nasal spray gently prior to each use1 and discarding the container after 120 actuations.1,10

Caution against spraying drug into eyes.1,17

Importance of contacting a clinician if symptoms worsen or fail to improve within 2 weeks.1

Necessity of reporting recurrent epistaxis or nasal septum discomfort to clinicians.1

Importance of avoiding exposure to chickenpox or measles in patients receiving immunosuppressant doses of corticosteroids and, if exposure occurs, consulting a clinician.1

Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. AstraZeneca. Rhinocort Aqua^® (budesonide nasal spray) prescribing information. Wilmington, DE; 2001 Oct.

2. AstraZeneca. Rhinocort^® (budesonide nasal inhaler) prescribing information (dated 2001 Apr). In: Physicians' desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:640-2.

3. Anon. Dear Pharmacist letter concerning discontinuance of the manufacture of Rhinocort^® (budesonide nasal inhaler). Wilmington, DE: AstraZeneca; 2002 Nov 15.

4. Meltzer EO, Jalowayski AA, Field EA et al. Intranasal fluticasone propionate reduces histamine and tryptase in the mucosa of allergic rhinitis patients. J Allergy Clin Immunol . 1993; 91:298.

5. Bryson HM, Faulds D. Intranasal fluticasone propionate: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in allergic rhinitis. Drugs . 1992; 43:760-75. [PubMed 1379151]

6. Masuyama K, Jacobson MR, Rak S et al. Topical glucocorticosteroid (fluticasone propionate) inhibits cells expressing cytokine mRNA for interleukin-4 in the nasal mucosa in allergen-induced rhinitis. Immunology . 1994; 82:192- 9. [PubMedCentral][PubMed 7927488]

7. Fokkens WJ, Cserhati E, dos Santos JM et al. Budesonide aqueous nasal spray is an effective treatment in children with perennial allergic rhinitis, with an onset of action within 12 hours. Ann Allergy Asthma Immunol . 2002; 89:279-84. [PubMed 12269648]

8. Ciprandi G, Canonica WG, Grosclaude M et al. Effects of budesonide and fluticasone propionate in a placebo-controlled study on symptoms and quality of life in seasonal allergic rhinitis. Allergy . 2002; 57:586-91. [PubMed 12100298]

9. Bende M, Carrillo T, Vona I et al. A randomized comparison of the effects of budesonide and mometasone furoate aqueous nasal sprays on nasal peak flow rate and symptoms in perennial allergic rhinitis. Ann Allergy Asthma Immunol . 2002; 88:617-23. [PubMed 12086370]

10. AstraZeneca, Wilmington, DE: Personal communication.

11. Mygind N, Clark TJH. Topical steroid treatment for asthma and rhinitis. London: Bailliere Tindall; 1980:89,91,152,159,172.

12. Andersson M, Svensson C, Persson C et al. Dose-dependent effects of budesonide agueous nasal spray on symptoms in a daily nasal allergen challenge model. Ann Allergy Asthma Immunol . 2000; 85:279-83. [PubMed 11061470]

13. Day J, Carrillo T. Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis. J Allergy Clin Immunol . 1998; 102(6 Part 1):902-8. [PubMed 9847429]

14. Creticos P, Fireman P, Settipane G et al, for the Rhinocort Aqua Study Group. Intranasal budesonide aqueous pump spray (Rhinocort Aqua) for the treatment of seasonal allergic rhinitis. Allergy Asthma Proc . 1998;19:285-94. [PubMed 9801742]

15. Meltzer EO. Clinical and antiinflammatory effects of intranasal budesonide aqueous pump spray in the treatment of perennial allergic rhinitis. Ann Allergy Asthma Immunol . 1998; 81:128-34. [PubMed 9723557]

16. Brogden RN, McTavish D. Budesonide: an updated review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis. Drugs . 1992;44:375-407.

17. AstraZeneca. How to use Rhinocort^® Aqua. Wilmington, DE; April 2002. From AstraZeneca website ([Web]). Accessed 2003 March 4.

18. Yanez A, Rodrigo GJ. Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol . 2002; 89:479-84. [PubMed 12452206]

19. Galant SP, Wilkinson R. Clinical prescribing of allergic rhinitis medication in the preschool and young school-age child: what are the options? BioDrugs . 2001; 15:453-63.

20. Pedersen S. Assessing the effect of intranasal steroids on growth. J Allergy Clin Immunol . 2001; 108(1 Suppl):S40-4. [PubMed 11449205]