Rhinocort aqua spc 11v030 (phvwp101200) rev

SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT

Rhinocort Aqua 32 micrograms/dose and 64 micrograms/dose, nasal spray, suspension
QUALITATIVE AND QUANTITATIVE COMPOSITION
One dose (0.05 ml) contains 32 micrograms or 64 micrograms of budesonide. For a full list of excipients see section 6.1. PHARMACEUTICAL FORM
CLINICAL PARTICULARS

4.1 Therapeutic indications
Seasonal and perennial allergic rhinitis and vasomotor rhinitis. Prophylactically in patients with nasal polyps following polypectomy. Symptomatic treatment in nasal Posology and method of administration
The posology must be adjusted individually. Adults and children from 6 years of age: The recommended initial dose is 256 micrograms per day. The dose can be administered once daily in the morning or divided into two administrations, morning and evening. This means 128 micrograms (2 x 64 micrograms) into each nostril in the morning or 64 micrograms into each No further effect has been shown for daily doses higher than 256 micrograms. For elderly patients the dosage is the same as for adults. When the desired clinical effect has been achieved, the dose is reduced to the lowest amount that is needed to control of the symptoms. Clinical trials show that a dose of 32 micrograms into each nostril in the morning may be sufficient for some patients. Rhinocort Aqua SPC 11v030 (PhVWP101200) rev In some patients relief of symptoms is already obtained within 5-7 hours after the start of treatment. The full effect is only obtained after several days of treatment (in rare cases only after 2 weeks). Treatment of seasonal allergic rhinitis should therefore start In cases of severe nasal congestion an initial addition of a vasoconstrictor may be Supplementary treatment may sometimes be necessary in order to counteract possible For the indication allergic rhinitis, the 32 micrograms/dose strength is available without prescription, for use for a maximum of 3 months. Symptomatic treatment and prevention of nasal polyps The recommended dose is 256 micrograms daily. The dose can be administered once daily in the morning or divided into two administrations morning and evening. When the desired clinical effect has been achieved, the dose should be reduced to the lowest amount that is needed to control the symptoms. Contraindications

Previous hypersensitivity to budesonide or to any of the excipients.
Special warnings and special precautions for use
Systemic effects of nasal corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, and glaucoma. A range of psychological or behavioural effects including restlessness, sleep disturbances, nervousness, depression and agitation may also occur (mainly in children). The long-term effects of nasal glucocorticosteroids in children are not fully known. Physicians should closely follow the growth of children taking glucocorticosteroids. For longer term by any route, and weigh the benefits of the glucocorticosteroid therapy against the possibility of growth suppression. Caution should be exercised in the treatment of patients with nasal fungal or herpes Care must be exercised in the treatment of patients who are being transferred from systemically acting glucocorticosteroids to Rhinocort Aqua and if there is suspected disturbed pituitary-adrenocortical function. In these patients there should be a careful reduction of the systemic steroid dose and testing of hypothalamic-pituitary- adrenocortical function should be considered. They may also need the addition of systemic steroids in connection with periods of stress, e.g. surgery, trauma, etc. Rhinocort Aqua SPC 11v030 (PhVWP101200) rev Severely impaired hepatic function affects the pharmacokinetics of orally administered budesonide, resulting in a reduced rate of elimination and increased systemic availability. Consideration may need to be given to possible systemic effects. Special care may be needed in patients with lung tuberculosis. Rhinocort Aqua should not come into contact with the eyes. If Rhinocort Aqua comes into contact with the eyes, rinse immediately with water. Concomitant treatment with ketoconazole or other potent CYP3A4-inhibiting drugs should be avoided. If this is not possible, the time interval between administrations of the agents should be as long as possible (see section 4.5). Interactions with other medicinal products and other forms of interaction
Oral ketoconazole 200 mg once daily increased the plasma concentrations of oral budesonide (3 mg in a single dose) on average six-fold when administered simultaneously. When oral ketoconazole was administered 12 hours after budesonide, the concentration increased on average three-fold. There is no information about this interaction for nasal budesonide, but also in such cases greatly increased plasma levels are expected. Since there are no data to enable dosage recommendations to be given in cases of nasal administration the combination should be avoided. If this is not possible, the time interval between administration of ketoconazole and that of budesonide should be as long as possible. A reduction of the budesonide dose should also be considered. Other potent inhibitors of CYP3A4 also probably cause a marked increase in the plasma levels of budesonide. Pregnancy and lactation
Data from just over 2000 pregnancies have not shown any generally increased risk of congenital defects in infants born to mothers treated with Rhinocort Aqua. A slightly increased occurrence of slight heart malformation compared to what might be expected has been confirmed in infants whose mothers were exposed to Rhinocort Aqua in early pregnancy, but a causal connection with the exposure is considered During pregnancy the aim should be the lowest effective dose and the shortest possible It is not known whether budesonide passes into human breast-milk. However, a risk of effects on the breast-fed infant is considered unlikely with therapeutic doses of Rhinocort aqua may be used during the lactation period. Effects on ability to drive and use machines
Rhinocort Aqua does not affect ability to drive or operate machinery. Rhinocort Aqua SPC 11v030 (PhVWP101200) rev Undesirable effects
Approx. 5 % of treated patients can be expected to experience side effects in the form Common (>1/100): Respiratory tract: Local irritation, slight haemorrhagic nasal Immediate or delayed hypersensitivity reactions including urticaria, rash, dermatitis angioedema and pruritus have been reported. In very rare cases, ulceration of mucous membrane and nasal septum perforation have occurred with use of nasally applied steroids. The cause of these side effects (the steroid, the underlying condition or other factors) is unclear. Systemic adverse drug reactions may occur, particularly at high doses when used for Growth retardation has been reported in children receiving intranasal steroids. Overdose
Acute overdose with Rhinocort Aqua, even high doses, is not expected to cause any clinical problems. When Rhinocort Aqua is used in high doses for a long period, the systemic effects characteristic of glucocorticosteroids such as hypercortisolism and PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
Pharmacotherapeutic group: Glucocorticoids. Budesonide is a glucocorticosteroid with a powerful local anti-inflammatory effect. The precise mechanism of action of glucocorticosteroids in the treatment of rhinitis is not fully understood. Anti-inflammatory effects such as inhibited release of inflammatory mediators and inhibition of cytokine-mediated immune response are probably important. The activity of budesonide, measured as the affinity for glucocorticosteroid receptors, is approx. 15 times higher than that of prednisolone. Budesonide given prophylactically prior to nasal provocation has proved to protect against immigration of eosinophils and hyperreactivity. Rhinocort Aqua SPC 11v030 (PhVWP101200) rev At recommended doses, Rhinocort Aqua does not cause any clinically significant changes either in basal plasma cortisol levels or in response to stimulation with ACTH. However, dose-related suppression of plasma and urinary cortisol has been observed in healthy volunteers following short-term administration of Rhinocort Aqua. A dose-response relationship has not been demonstrated in clinical trials in children with seasonal or perennial allergic rhinitis or in adults with perennial allergic rhinitis. Vasomotor rhinitis (non-allergic perennial rhinitis) has not been documented with Rhinocort Aqua in the strengths 32 and 64 micrograms/dose. Pharmacokinetic properties
The systemic availability of budesonide from Rhinocort Aqua is 33 % of the measured The kinetics are proportional to the dose in the therapeutic dose range. The peak plasma concentration in adults from 256micrograms of budesonide from Rhinocort Aqua is 0.64 nmol/l, and is reached within 0.7 hours. The AUC (area under the curve) after administration of 256 micrograms budesonide from Rhinocort Aqua is 2.7 nmol x hours/litre in adults and 5.5 nmol x hours/litre in children, which indicates a higher systemic exposure to glucocorticosteroids in children. Budesonide has a volume of distribution of approx. 3 l/kg. Binding to plasma proteins is 85-90 %. Budesonide undergoes extensive (~90%) first-passage metabolism in the liver to metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the principal metabolites, 6-beta-hydroxybudesonide and 16- alphahydroxyprednisolone, is less than 1 % of that of budesonide. Budesonide does not undergo local metabolism in the nose. Budesonide is eliminated by metabolism which is principally catalysed by the enzyme CYP3A4. The metabolites are excreted in the urine in unchanged or conjugated form. Only negligible amounts are found unchanged in the urine. Budesonide has high systemic clearance (~1.2 l/min) and the half-life in plasma after intravenous administration is on average approx. 4 hours. Preclinical safety data
Conventional studies with regard to general toxicity, genotoxicity and carcinogenicity did not show any particular risks for humans. In reproduction studies in animals corticosteroids, such as budesonide, were shown to be able to cause malformations of various kinds (cleft palate, skeletal malformation). However, the experimental animal results do not appear to have any relevance for humans with recommended doses of Rhinocort Aqua SPC 11v030 (PhVWP101200) rev PHARMACEUTICAL PARTICULARS
List of excipients
The amount of preservative, potassium sorbate (E 202), is 1.2 mg/ml in both strengths. 6.2 Incompatibilities
Shelf-life
Special precautions for storage
Do not store above 30 ºC. Do not freeze. Nature and contents of container
Instructions for use and handling, and disposal
Before Rhinocort Aqua is used for the first time, the nasal applicator must be primed with the drug. Therefore, shake the bottle, and spray into the air until there is an even. The effect of this lasts approx. 24 hours. If a longer period elapses before the next dose is taken, the nasal applicator must be primed with the drug again. This time it is sufficient to spray just once into the air. How the patient must take Rhinocort Aqua is described in detail in the package leaflet. MARKETING AUTHORISATION HOLDER
AstraZeneca AB, S-151 85 Södertälje, Sweden. MARKETING AUTHORISATION NUMBER(S)
Rhinocort Aqua SPC 11v030 (PhVWP101200) rev DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
DATE OF REVISION OF THE TEXT
Rhinocort Aqua SPC 11v030 (PhVWP101200) rev

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