Rhinocort Aqua (Budesonide)

RHINOCORT® AQUA

Astra

Budesonide

Glucocorticosteroid

Action And Clinical Pharmacology: Budesonide is a potent nonhalogenated synthetic glucocorticosteroid with strong topical and weak systemic effects.

Budesonide has a high topical anti-inflammatory potency and it is rapidly biotransformed in the liver. This favorable separation between topical anti-inflammatory activity and systemic effect is due to strong glucocorticosteroid receptor affinity and an effective first pass metabolism with a short half-life. The mechanism of action of intranasally administered budesonide has not yet been completely defined.

Pharmacokinetics: The systemic availability of oral budesonide in man is low (about 10%). With reference to the metered dose, the systemic availability of budesonide from Rhinocort Aqua is 33%. After application of budesonide in solution directly on the nasal mucosa, all the dose is systemically available, indicating that budesonide does not undergo local metabolism in the nose.

The maximal plasma concentration after administration of 400 g budesonide from Rhinocort Aqua is 1 nmol/L and is reached within 0.7 hours.

Indications And Clinical Uses: The treatment of seasonal allergic and allergic/nonallergic perennial and vasomotor rhinitis unresponsive to conventional therapy. Also indicated for the treatment of nasal polyps and in the prevention of nasal polyps after polypectomy.

Contra-Indications: Hypersensitivity to any of the nasal spray’s components. Active or quiescent tuberculosis. Untreated fungal, bacterial, or viral infections. Children under 6 years of age.

Manufacturers’ Warnings In Clinical States: In patients previously on prolonged periods or high doses of systemic steroids, withdrawal of steroids may cause symptoms such as tiredness, aches and pains, and depression. In severe cases, adrenal insufficiency may occur necessitating a temporary resumption of systemic steroids.

Careful attention must be given to patients with asthma or other clinical conditions in whom a rapid decrease in systemic steroids may cause a severe exacerbation of their symptoms.

Pregnancy: See Precautions.

Precautions: Glucocorticosteroids may mask some signs of infection and new infections may appear during their use.

In transferring patients from a systemic steroid to budesonide, the reduction of the systemic steroid must be very gradual and carefully supervised by the physician since systemic withdrawal symptoms (e.g., joint and/or muscular pain, lassitude, depression) may occur in spite of maintenance or improvement of respiratory functions (see Dosage).

Patients should be informed that the full effect of budesonide therapy is not achieved until 2 to 3 days of treatment have been completed. In rare cases the full effect of budesonide therapy is not achieved until 2 weeks of treatment have been completed. Treatment of seasonal rhinitis should, if possible, start before the exposure to allergens.

Treatment with budesonide should not be stopped abruptly but tapered off gradually.

Special care is needed in patients with fungal and viral nasal infections. Children who are on immunosuppressant drugs are more susceptible to infections than healthy children. Chickenpox and measles, for example, can have a more serious or fatal course in children on immunosuppressant corticosteroids. In such children, or in adults who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled i.v. immunoglobulin (IVIG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

Concomitant treatment may sometimes be required to counteract eye symptoms caused by allergy.

The long-term effects of budesonide in human subjects are still unknown, in particular, its local effects, and on developmental or immunologic processes. The nasal mucosa of those patients receiving long-term, continuous therapy should be inspected at least twice a year. The possibility of atrophic rhinitis and/or pharyngeal candidiasis should be kept in mind.

Children: Until greater clinical experience has been gained, the continuous, long-term treatment of children is not recommended.

When budesonide is administered intranasally, the following should be kept in mind: a) glucocorticosteroid effects may be enhanced in patients with hypothyroidism and in those with cirrhosis. Reduced liver function may affect the elimination of corticosteroids. The i.v. pharmacokinetics of budesonide however, are similar in cirrhotic patients and in healthy subjects. The pharmacokinetics after oral ingestion of budesonide were affected by compromised liver function as evidenced by increased systemic availability. This is however, of limited clinical importance for intranasally administered budesonide, as the oral contribution to the systemic availability is relatively small. b) in hypoprothrombinemia, salicylates should be used cautiously in conjunction with glucocorticosteroids.

Because of the inhibitory effect of corticosteroids on wound healing in patients who have had recent nasal surgery or trauma, a nasal corticosteroid should be used with caution until healing has occurred.

Pregnancy: The safety of budesonide in pregnancy has not been established. Therefore, its use during pregnancy should be avoided unless there are compelling reasons, particularly in the first trimester of pregnancy. In experimental animal studies, budesonide was found to cross the blood-placenta barrier. Like other glucocorticosteroids, budesonide is teratogenic to rodent species. High doses of budesonide administered s.c. produced fetal malformations, primarily skeletal defects, in rabbits, rats, and in mice. The relevance of these findings to humans has not yet been established. In the absence of further studies in humans, budesonide should be used during pregnancy only if the potential benefits clearly outweigh the risk to the fetus. Infants born of mothers who have received substantial doses of glucocorticosteroids during pregnancy should be carefully observed for hypoadrenalism.

Lactation: Glucocorticosteroids are secreted in human milk. It is not known whether budesonide would be secreted in human milk, but it is suspected to be likely. The use of budesonide in nursing mothers requires that the possible benefits of the drug be weighed against the potential hazards to the mother or infant.

Children under 6 Years of Age: Budesonide is not presently recommended for children younger than 6 years of age due to limited clinical data in this age group.

Glucocorticosteroids may mask some signs of infections and new infections may appear. A decreased resistance to localized infection has been observed during glucocorticosteroid therapy. During long-term therapy, pituitary-adrenal function, hematological status and height (in children) should be periodically assessed.

Patients should be advised to inform subsequent physicians of the prior use of glucocorticosteroids.

To ensure the proper dosage and administration of the drug, the patient should be instructed by a physician or other health professional in the use of Rhinocort Aqua (see Blue Section – Information for the Patient).

Dose-related suppression of plasma and urinary cortisol has been observed in healthy volunteers after short-term administration of budesonide. Although no important changes in basal plasma cortisol levels were manifested in patients with rhinitis using budesonide at recommended doses, caution is advised.

Drug Interactions: To date budesonide has not been observed to interact with other drugs used for the treatment of rhinitis.

Cimetidine: The kinetics of budesonide were investigated in a study in healthy subjects without and with cimetidine, 1 000 mg daily. After a 4 mg oral dose the values for Cmax (nmol/L) and systemic availability (%) of budesonide without and with cimetidine (3.3 vs 5.1 nmol/L and 10 vs 12%, respectively) indicated a slight inhibitory effect on hepatic metabolism of budesonide, caused by cimetidine. This should be of little clinical importance.

Ketoconazole: Ketoconazole, a potent inhibitor of cytochrome P450 3A, the main metabolic enzyme for corticosteroids, increases plasma levels of orally ingested budesonide.

Omeprazole: At recommended doses, omeprazole has no effect on the pharmacokinetics of oral budesonide.

Adverse Reactions: The adverse reactions reported with budesonide are consistent with what one would expect when applying a topical treatment to an already inflamed membrane. All side effects were transient. The most commonly reported side effects include: nasal and throat irritation, nasal bleeding, crusting, dryness. Other adverse events reported are sneezing (at initiation of therapy), itching throat, sore throat, cough, fatigue, nausea/dizziness and headache. When patients are transferred to budesonide from a systemic steroid, allergic conditions such as asthma or eczema may be unmasked. In rare cases, skin reactions (urticaria, rash, dermatitis, angioedema, etc.) may occur in association with local corticosteroid therapy. Extremely rare cases of ulcerations of the mucous membranes and nasal septal perforation have been reported following the use of intranasal corticosteroids.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Like any other nasally administered corticosteroid, acute overdosing is unlikely in view of the total amount of active ingredient present. However, when used chronically in excessive doses or in conjunction with other corticosteroid formulations, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes recur, the dosage of budesonide should be discontinued slowly consistent with accepted procedures for discontinuation of chronic steroid therapy (see Dosage).

The restoration of the hypothalamic-pituitary-axis may be a slow process and during periods with pronounced physical stress such as severe infections, trauma, and surgical operations, a supplement with systemic steroids may be advisable.

Dosage And Administration: See Warnings.

Careful attention must be given to patients previously treated for prolonged periods with systemic corticosteroids when transferred to budesonide. Initially, budesonide and the systemic corticosteroid must be given concomitantly, while the dose of the latter is gradually decreased. The usual rate of withdrawal of the systemic steroid is the equivalent of 2.5 mg of prednisone every 4 days if the patient is under close supervision. If continuous supervision is not feasible, the withdrawal of the systemic steroid should be slower, approximately 2.5 mg of prednisone (or equivalent) every 10 days. If withdrawal symptoms appear, the previous dose of the systemic steroid should be resumed for a week before further decrease is attempted.

Rhinitis: Adults and Children Over 6 Years: Initially: The recommended starting dose is 256 g daily. The dose can be administered once daily in the morning or divided into 2 administrations morning and evening. For example: 128 g (2 sprays) into each nostril in the morning or, 64 g (1 spray) into each nostril morning and evening.

Maintenance: After the desired clinical effect is obtained, the maintenance dose should be reduced to the smallest amount necessary to control the symptoms.

Treatment or Prevention of Nasal Polyps: The recommended dose is 64 g (1 spray) into each nostril morning and evening (total daily dose is 256 g).

Children under 6 Years: Not recommended for children in this age group.

Patients should be informed that the full effect of budesonide therapy may not become evident until 2 to 3 days of treatment have been completed. Full therapeutic benefit requires regular usage. Explain the absence of an immediate effect to the patient in order to ensure cooperation and continuation of the treatment with a regular dosage regime. Treatment of seasonal rhinitis should, if possible, start before exposure to the allergens. Concomitant treatment may sometimes be necessary to counteract eye symptoms caused by the allergy. In continuous long-term treatment, the nasal mucosa should be inspected regularly, e.g., every 6 months.

If the nasal passages are severely blocked, the drug may fail to reach the site of action. In such cases, a course of oral steroids or decongestants may be required before initiating budesonide therapy.

Although systemic effects are negligible at recommended doses, budesonide treatment should not be continued beyond 3 weeks in the absence of significant symptomatic improvement. Budesonide should not be used in the presence of untreated localized infections involving the nasal mucosa.

Availability And Storage: Each metered dose contains: budesonide 64 g in a white to off-white, thixotropic suspension in water. Nonmedicinal ingredients: carboxymethylcellulose sodium, disodium edetate, glucose anhydrous, hydrochloric acid, microcrystalline cellulose, polysorbate 80, potassium sorbate and purified water. Amber glass bottles of 120 doses, provided with a pump spray mechanism, nasal adapter and patient instruction leaflet. Store at room temperature (15 to 30°C).

RHINOCORT® AQUA Astra Budesonide Glucocorticosteroid

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