Friday, 16 September 2016

Rhinocort Aqua 64 micrograms, nasal spray





1. Name Of The Medicinal Product



Rhinocort® Aqua, 64 micrograms, nasal spray


2. Qualitative And Quantitative Composition



Each actuation contains: Budesonide 64 micrograms (1.28 mg/ml).



For excipients, see 6.1.



3. Pharmaceutical Form



Nasal spray, suspension.



4. Clinical Particulars



4.1 Therapeutic Indications



Seasonal and perennial allergic rhinitis and vasomotor rhinitis. Treatment of nasal polyps.



4.2 Posology And Method Of Administration



For nasal inhalation. Dosage should be individualised.



Rhinitis (Adults including elderly)










Recommended



start dose




Once daily dosing




Twice daily dosing




 



256 micrograms per day




 



Two applications of 64 micrograms into each nostril each morning



 



or



 



If good effect is achieved, one application of 64 micrograms




 



One application of 64 micrograms into each nostril morning and evening



 



 



 



Nasal Polyps (Adults including elderly)










Recommended



start dose




Once daily dosing




Twice daily dosing




 



256 micrograms per day




 



Not applicable




 



One application of 64 micrograms into each nostril morning and evening.



Treatment can be continued for up to 3 months.



Patients should be reminded of the importance of taking this medicine regularly.



The dose should be titrated to the lowest dose at which effective control of symptoms is achieved.



Children: There are insufficient data to recommend the use of Rhinocort Aqua in children. However, it is unlikely that the risk/benefit ratio in children is different from that in adults.



4.3 Contraindications



Hypersensitivity to any of the ingredients.



4.4 Special Warnings And Precautions For Use



Special care is demanded in treatment of patients transferred from oral steroids to Rhinocort where disturbances of the hypothalamic-pituitary-adrenal (HPA) axis could be expected.



Special care is needed in patients with fungal and viral infections of the airways and in patients with lung tuberculosis.



The patient should be informed that the full effect of Rhinocort is not achieved until after a few days treatment. 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.



Systemic effects of nasal corticosteroids may occur, particularly at high doses prescribed for prolonged periods. Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses.



It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid, if possible, to the lowest dose at which effective control of symptoms is maintained. In addition, consideration should also be given to referring the patient to a paediatric specialist.



Treatment with higher than recommended doses may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.



In vivo studies have shown that oral administration of itraconazole and ketoconazole (known inhibitors of CYP3A4 activity in the liver and in the intestinal mucosa, see also section 4.5 Interactions) may cause an increase in the systemic exposure to budesonide. This is of limited clinical importance for short-term (1



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



The metabolism of budesonide is primarily mediated by CYP3A4, a subfamily of cytochrome P450. Inhibitors of this enzyme, e.g. itraconazole and ketoconazole, can therefore increase systemic exposure to budesonide. However, the use of itraconazole or ketoconazole concomitant with Rhinocort Aqua for shorter periods is of limited importance, see section 4.4 Special warnings and precautions for use.



4.6 Pregnancy And Lactation



Administration during pregnancy should be avoided unless there are compelling reasons. Results from prospective epidemiological studies and from worldwide post marketing experience indicate no increased risk for overall congenital malformations from the use of inhaled or intranasal budesonide during early pregnancy. Budesonide is excreted in breast milk. However, at therapeutic doses of Rhinocort no effects on the breast fed child are anticipated. Rhinocort can be used during breastfeeding.



4.7 Effects On Ability To Drive And Use Machines



Rhinocort Aqua does not affect the ability to drive or operate machinery.



4.8 Undesirable Effects



Adverse reactions, which have been associated with budesonide, are given below, listed by system organ class and frequency. Frequency is defined as: very common (



















Immune system disorders




Uncommon




Immediate and delayed hypersensitivity reactions including urticaria, rash, dermatitis angioedema and pruritus




Not Known




Anaphylactic reaction


 


Eye disorders




Rare




Raised intraocular pressure or glaucoma




Respiratory, thoracic and mediastinal disorders




Common




Haemorrhagic secretion and epistaxis



Nasal Irritation (sneezing, stinging and dryness)




Very rare




Nasal septum perforation



Ulceration of mucus membrane


 


Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods (see section 4.4).



4.9 Overdose



Acute overdose with Rhinocort should not present clinical problems.



Inhalation of high doses of corticosteroids may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis function.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Budesonide is a non-halogenated glucocorticosteroid with a high local anti-inflammatory action within the respiratory tract.



ATC code: R01A D05



5.2 Pharmacokinetic Properties



Bioavailablity of oral budesonide in man is low (11



The systemic availability of budesonide from Rhinocort Aqua, with reference to the metered dose is 33%. In adults, the maximal plasma concentration after administration of 256 micrograms budesonide from Rhinocort Aqua is 0.64 nM and is reached within 0.7 hours. The AUC after administration of 256 micrograms budesonide from Rhinocort Aqua is 2.7 nmolxh/L in adults.



5.3 Preclinical Safety Data



The acute toxicity of budesonide is low and of the same order of magnitude and type as that of the reference glucocorticoids studied (beclomethasone dipropionate, flucinolone acetonide). Results from subacute and chronic toxicity studies show that the systemic effects of budesonide are less severe than or similar to those observed after administration of the other glucocorticosteroids e.g. decreased body weight gain and atrophy of lymphoid tissues and adrenal cortex. An increased incidence of brain gliomas in male rats in a carcinogenicity study could not be verified in a repeat study, in which the incidence of gliomas did not differ between any of the groups on active treatment (budesonide, prednisolone, triamcinolone acetonide) and the control groups. Liver changes (primary hepatocellular neoplasms) found in male rats in the original carcinogenicity study were noted again in the repeat study with budesonide, as well as with the reference glucocorticosteroids. These effects are most probably related to a receptor effect and thus represent a class effect.



Available clinical experience shows no indication that budesonide or other glucocorticosteroids induce brain gliomas or primary heptocellular neoplasms in man. Budesonide has been used successfully in the treatment of seasonal allergic rhinitis for several years.



In animal reproduction studies, corticosteroids such as budesonide have been shown to induce malformations (cleft plate, skeletal malformations). However these animal experimental results do not appear to be relevant in humans at the recommended doses.



Animal studies have also identified an involvement of excess prenatal glucocorticosteroids in increased risk for intrauterine growth retardation, adult cardiovascular disease and permanent changes in glucocorticoid receptor density, neurotransmitter turnover and behaviour at exposures below the teratogenic dose range.



6. Pharmaceutical Particulars



6.1 List Of Excipients



Disodium edetate



Potassium sorbate (E202)



Glucose anhydrous



Microcrystalline cellulose (E460)



Carboxymethylcellulose sodium (E466)



Polysorbate 80 (E433)



Hydrochloric acid



Purified water



6.2 Incompatibilities



None known.



6.3 Shelf Life



2 years.



6.4 Special Precautions For Storage



Use within 2 months of starting treatment.



Do not store above 30°C. Do not refrigerate or freeze.



6.5 Nature And Contents Of Container



Rhinocort Aqua is an aqueous solution of budesonide in either a 10 ml or 20 ml amber/brown glass (type II) bottle. Each bottle is fitted with a spray pump and contains either 120 or 240 actuations. Not all pack sizes may be available in the UK.



6.6 Special Precautions For Disposal And Other Handling



Before using Rhinocort Aqua for the first time the nozzle must be primed (filled with the medicine). To do this the bottle is shaken and the protective cap removed. The bottle is then held upright and the nozzle pumped up and down several times (5-10 times) spraying into the air, until an even mist is seen. The priming effect remains for approximately 24 hours. If a longer period of time passes before the next dose is taken, the nozzle must be loaded with medicine again. This time it is sufficient to spray just once into the air.



a. The patient is then instructed to blow their nose. Next, the bottle needs to be shaken and the protective cap removed.



b. The bottle is then held upright, with one finger held on either side of the nozzle.



c. The tip of the nozzle is inserted into the nostril and the nozzle pressed down once (or more as instructed by the doctor). The spray is then administered into the other nostril in the same way. Note: it is not necessary to inhale at the same time as spraying.



d. The nozzle needs to be wiped with a clean tissue after use and the protective cap replaced. The bottle should be stored in an upright position.



e. Keeping the Rhinocort Aqua nozzle clean



The plastic nozzle of Rhinocort Aqua should be cleaned regularly and at any time the spray of medicine is not coming out as it should. If this happens, first the nozzle should be checked to ensure that it is primed with medicine (see earlier). If, after the nozzle is primed again, the pump is still not working, the nozzle should be cleaned by using the following instructions:



The plastic nozzle is removed with a clean tissue and washed in warm, not hot, water. The nozzle is then rinsed thoroughly, dried and then replaced onto the top of the bottle. The nozzle should not be unblocked with a pin or other sharp object. After cleaning, the nozzle must be primed (filled with medicine) again before use.



7. Marketing Authorisation Holder



AstraZeneca UK Ltd.,



600 Capability Green,



Luton, LU1 3LU, UK.



8. Marketing Authorisation Number(S)



PL 17901/0074



9. Date Of First Authorisation/Renewal Of The Authorisation



12 December 2003



10. Date Of Revision Of The Text



8th April 2009




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