Consumer medicine information

Rhinocort

Budesonide

BRAND INFORMATION

Brand name

Rhinocort Aqueous Nasal Spray

Active ingredient

Budesonide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Rhinocort.

What is in this leaflet

This leaflet answers some common questions about Rhinocort.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Rhinocort against the benefits they expect it will have for you.

If you have any concerns about using Rhinocort, ask your doctor or pharmacist.

Keep this leaflet with your Rhinocort. You may need to read it again.

What RHINOCORT is used for

Allergic rhinitis

Rhinocort is sprayed into the nose to help prevent and treat allergic rhinitis). Allergic rhinitis is an inflammation or swelling of the nose lining (which may cause blockage, runny nose, itching and/or sneezing). This is often, but not always, due to an allergy to something in the air (eg pollen, dust mites).

You may have symptoms only during spring or summer. This type of allergy is generally due to various pollens and is commonly referred to as hayfever. Some people may experience symptoms all year round. This is usually caused by house dust mites, pets or moulds and is commonly referred to as perennial allergic rhinitis

Nasal Polyps

Rhinocort is also used to treat nasal polyps, which are small masses of tissue that grow from the nose lining.

Rhinocort contains budesonide.

This belongs to a family of medicines called corticosteroids, which are used to help reduce inflammation.

Ask your doctor if you have any questions about why Rhinocort has been prescribed for you. Your doctor may have prescribed it for another reason.

Rhinocort is not addictive.

Rhinocort is available only with a doctor's prescription.

Before you use RHINOCORT

When you must not use it

Do not use Rhinocort if:

  1. you have an allergy to:
  • any medicines containing budesonide
  • any of the ingredients listed at the end of this leaflet.
  • Other corticosteroid medicines
Some of the symptoms of an allergic reaction may include:
− rash, itching or hives on the skin
− shortness of breath, wheezing or difficulty breathing
− swelling of the face, lips, tongue or other parts of the body.
  1. You have frequent nose bleeds.
Your condition may cause nose bleeds and still require treatment. Discuss with your doctor if you have any concerns.
  1. You have severe nasal infections especially candidiasis (thrush).

Do not give Rhinocort to a child under the age of 6 years. Rhinocort is not recommended for use in children under 6 years of age.

Do not use Rhinocort after the expiry date (EXP) printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start using Rhinocort, talk to your pharmacist or doctor.

Before you start to use it

Tell your doctor, if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • nasal, sinus or chest infection
  • recent injury that has not healed or surgery to your nose
  • open sores in your nose
  • severe nasal congestion or obstruction
  • tuberculosis (TB) or have been exposed to someone who has tuberculosis, chicken pox or measles
  • glaucoma
  • cataracts or have an eye infection
  • diabetes

It may not be safe for you to use Rhinocort if you have any of these conditions.

Tell your doctor if you are pregnant or plan to become pregnant, or breast-feeding. Your doctor will discuss the possible risks and benefits of using Rhinocort during pregnancy and while breastfeeding.

If you have not told your doctor about any of the above, tell them before you start using Rhinocort.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Rhinocort may interfere with each other. These include:

  • other corticosteroid medicines for conditions such as asthma, allergies or skin rash. These may include tablets, asthma inhalers, nasal sprays, or eye/nose drops.
  • medicines used to treat fungal infections (eg ketoconazole, itraconazole)
  • cimetidine, a medicine used to treat reflux and stomach ulcers
  • some antibiotic medicines (including erythromycin, clarithromycin).

These medicines may be affected by Rhinocort, or may affect how well it works. You may need different amounts of Rhinocort, or you may need to use a different medicine. Your doctor or pharmacist will advise you.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using Rhinocort.

How to use RHINOCORT

To prevent symptoms, start using Rhinocort:

  • before the hayfever season; or
  • before coming into contact with something you know will cause your allergic rhinitis.

If you start using Rhinocort early, it will help reduce the severity of your symptoms.

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

How to use it

Each pack of Rhinocort contains an instruction leaflet that tells you the correct way to use it. Please read the leaflet carefully.

If you do not understand the instruction leaflet, ask your doctor or pharmacist for help.

Gently blow your nose before using Rhinocort.

Use only in your nose.

How much to use

Your doctor may tell you to use doses that are different to those outlined below. If so, follow your doctor's instructions.

ALLERGIC RHINITIS/HAYFEVER:

When you first start using Rhinocort:

The usual starting dose is:

  • TWO sprays into EACH nostril in the morning; or
  • ONE spray into EACH nostril twice a day (in the morning and evening).

Do not exceed the recommended dose. It may take a few days (in rare cases after 2 weeks) of using Rhinocort before you notice any improvement in your symptoms.

Once your symptoms improve:

After your allergies have improved, your doctor may tell you to reduce the dose of Rhinocort. This may be ONE spray into EACH nostril in the morning.

NASAL POLYPS

(Adults 18 years and older):

The usual dose is:

  • ONE spray into EACH nostril twice a day (in the morning and evening).

How long to use it

Adults and children 12 years and older

Continue using your Rhinocort for as long as your doctor tells you to.

Children 6-12 years of age

Talk to your child's doctor if your child needs to use the spray for longer than two months a year.

If you forget to use it

If you miss a dose of Rhinocort, use it as soon as you remember.

Do not use a double dose to make up for the dose that you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

Immediately telephone your doctor, pharmacist or the Poisons Information Centre (telephone 131 126) if you think you or anyone else may have used too much Rhinocort.

Do this even if there are no signs of discomfort or poisoning.

While you are using RHINOCORT

Things you must do

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

Keep all of your doctor's appointments so that your progress can be checked.

If symptoms persist or worsen, or if new symptoms occur, stop use and see your doctor Ask your doctor to examine your nose from time to time to make sure the medicine is working and to prevent unwanted side effects.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using Rhinocort.

Tell any other doctors, dentists, and pharmacists who treat you that you are using Rhinocort.

If you become pregnant while using Rhinocort, tell your doctor.

Things you must not do

Do not use Rhinocort to treat any other complaints unless your doctor tells you to.

Do not give Rhinocort to anyone else, even if they have the same condition as you.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Rhinocort. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • headache
  • dizziness
  • tiredness
  • sneezing after spraying or irritated nose
  • nose bleeds
  • nasal crust
  • dry nose or mouth
  • itching or sore throat
  • cough
  • increased amount of sputum

The above list includes the more common side effects of your medicine. They are usually mild and only last for a short time.

Tell your doctor or pharmacist immediately if you notice any of the following:

  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • severe rash
  • an ulcer (open wound) in your nose
  • sign or symptoms of a nasal or sinus infection such as a persistent fever, pain or swelling, or discoloured nasal discharges.
  • If you have any change in vision or have blurred vision.

These may be serious side effects. You may need urgent medical attention. Serious side effects are rare.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

Corticosteroids taken through the nose for long periods may affect how children grow. In rare cases, some children may be sensitive to the growth effects of corticosteroids, so the doctor may monitor a child's height.

Ask your doctor to answer any questions you may have.

After using RHINOCORT

Storage

Keep your Rhinocort in a cool dry place where the temperature stays below 30 °C. Do not freeze.

Do not store Rhinocort or any other medicine in the bathroom or near a sink. Do not leave it on window sills or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using Rhinocort or it has passed its expiry date, ask your pharmacist what to do with any you have left.

Product description

Rhinocort comes in a brown glass bottle containing approximately 50 (sample pack) or 120 doses, with metered pump spray equipment and nasal adaptor. The 120 dose bottle is available as a 1 (120 doses) or 2 bottle (240 dose) pack (2 bottles).

Rhinocort contains 64 micrograms of budesonide per dose as the active ingredient, and the following inactive ingredients:

  • disodium edetate
  • potassium sorbate (E202)
  • glucose
  • dispersible cellulose
  • polysorbate 80 (E433)
  • purified water.

Hydrochloric acid (E507) may have been added to adjust pH of the solution.

Sponsor

Johnson & Johnson Pacific
AUSTRALIA · NEW ZEALAND
45 Jones Street, Ultimo NSW 2007
® Registered Trademark

Consumer Care Centre
Australia: 1800 029 979
New Zealand: 0800 446 147
Overseas Customers: +61 2 8260 8366

This leaflet was prepared in March 2019.

Australian Registration Number:

Rhinocort 64 micrograms Nasal Spray - AUST R 75658

Published by MIMS May 2019

BRAND INFORMATION

Brand name

Rhinocort Aqueous Nasal Spray

Active ingredient

Budesonide

Schedule

S4

 

1 Name of Medicine

Budesonide.

2 Qualitative and Quantitative Composition

Rhinocort contains 32 microgram (not available as a Prescription only medicine) or 64 microgram budesonide per actuation.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Spray suspension.
White to off-white, viscous thixotropic suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Rhinitis.

Prophylaxis and treatment of seasonal and perennial allergic rhinitis.

Nasal polyps.

Treatment of nasal polyps.

4.2 Dose and Method of Administration

There is no evidence that efficacy improves when the recommended dose is exceeded.

For the treatment of seasonal allergic rhinitis (adults and children 6 years and over) and perennial allergic rhinitis (adults).

Initially.

Total daily dose, 256 microgram given as either a single daily application of 128 microgram into each nostril in the morning, or divided into two applications of 64 microgram into each nostril, morning and evening.

Maintenance - individualisation of dosage.

When a satisfactory therapeutic response has been achieved, the maintenance dose should be titrated to the minimum effective dose. This may be a total daily dose of 128 microgram given as 64 microgram into each nostril in the morning, however clinical trials suggest that a maintenance dose of 32 microgram in each nostril in the morning may be sufficient in some patients.
Continuous long-term use in children is not recommended due to the possibility of growth suppression. Whilst no long-term studies are available for intranasal budesonide, long-term studies in a clinical practice environment suggest that children treated with orally inhaled budesonide on average achieve their adult target height. However, in a long-term double blind study, in which the budesonide dose was generally not titrated to the lowest effective dose, children treated with inhaled budesonide became on average 1.2 cm shorter as adults than those randomised to placebo. See Section 4.4 Special Warnings and Precautions for Use, Paediatric use.
Patients should be informed that full response may not occur until after 2-3 days of treatment (in rare cases not until after 2 weeks). Ideally, in seasonal allergic rhinitis treatment should start before exposure to the allergen.

Treatment of nasal polyps - adults (18 years and older).

Total daily dose, 256 microgram given as a divided daily application of 64 microgram into each nostril, morning and evening.

Patient instructions.

Patients should be instructed in the correct use of Rhinocort. An instruction leaflet is included in each pack of Rhinocort. Patients should also be advised to clear secretions from nasal passages prior to use and not to exceed the recommended dose.

4.3 Contraindications

Hypersensitivity to any component of the product.
Hypersensitivity to other corticosteroids.
Severe nasal infections, especially candidiasis.
Persons with haemorrhagic diatheses or with a history of recurrent nasal bleeding.

4.4 Special Warnings and Precautions for Use

If symptoms persist, worsen or if new symptoms occur, patients should stop use and consult a physician.

Clinical response.

The full effect of Rhinocort in allergic rhinitis is not achieved until after 2 to 3 days of treatment (in rare cases not until after 2 weeks).

Concomitant treatment.

Concomitant treatment may sometimes be necessary to counteract potential eye symptoms caused by the allergy.

Concomitant corticosteroid therapy.

If Rhinocort is prescribed for patients already using corticosteroids, care should be taken to ensure that the daily dosage of Rhinocort is included when determining total daily corticosteroid dose.
Consult a physician before use if you are using a steroid medicine for conditions such as asthma, allergies or skin rash.

Continuous, long-term use.

In continuous long-term treatment, care should be exercised to avoid the development of nasal mucosal atrophy. The nasal mucosa should be inspected at least twice per year.

Severe nasal obstruction/ congestion.

In some patients with severe nasal obstruction and congestion, concomitant treatment with local decongestants should be considered for 2-3 days only. The decongestant should be administered a few minutes before budesonide. Nasal polypectomy may be indicated initially for patients with nasal obstruction due to nasal polyposis.

Tuberculosis.

Whenever corticosteroid administration is required in patients with quiescent or active tuberculosis, the therapeutic advantages should be weighed against possible undesirable effects.
Consult a physician before use if patient has been exposed to someone who has tuberculosis, chicken pox or measles.

Infection.

If infection of the respiratory tract, nasal passages or paranasal sinuses is present or occurs during administration of Rhinocort, adequate antibacterial therapy should be promptly instituted (see Section 4.3 Contraindications).
Consult a physician if you develop signs or symptoms of an infection such as a persistent fever.

Wound healing.

Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal ulcers, nasal surgery or a nose injury that has not healed should not use a nasal corticosteroid until healing has occurred.

Adrenocortical function.

Topical corticosteroids may be absorbed in amounts that can have systemic effects. Use of higher than recommended doses may suppress HPA function. However, at recommended doses, Rhinocort does not cause any clinically important changes in basal cortisol levels. Similar effects have been noted with inhaled budesonide, whilst still retaining the physiological circadian rhythms of plasma cortisol. This indicates that the HPA axis suppression represents a physiological adaption in response to budesonide, not necessarily adrenal insufficiency. This is further supported by inhaled and intranasal budesonide studies, which found that, at recommended doses, there was no clinically relevant effect on the response to stimulation with ACTH (predictor for clinically manifest adrenal insufficiency).
Clinically important disturbances of the HPA axis and/or adrenal insufficiency induced by stress may be related to budesonide in specific patient populations, particularly patients administering concomitant medication metabolised by CYP3A4 (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Monitoring for signs of adrenal dysfunction is advisable in this patient group.

Visual disturbance.

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Stop use and consult a physician if you have any change in vision. Consult a physician before use if you have ever been diagnosed with glaucoma, cataracts or have an eye infection or if you have diabetes.

Use in hepatic impairment.

There are no intranasal budesonide pharmacokinetic data available in hepatic impaired patients. With oral administration, compromised liver function may decrease the rate of glucocorticoid elimination. Hepatic impairment increased the systemic availability of budesonide 2-fold after oral ingestion in adults with cirrhosis. However, after intravenous administration, the pharmacokinetics of budesonide were similar in patients with cirrhosis and healthy adults.

Use in the elderly.

No data available.

Paediatric use.

Controlled clinical trials have shown that intranasal corticosteroids may cause a reduction in growth velocity in children. Whilst no long-term studies are available for intranasal budesonide, long-term studies in a clinical practice environment suggest that children treated with orally inhaled budesonide on average achieve their adult target height. However, in a long-term double blind study, in which the budesonide dose was generally not titrated to the lowest effective dose, children treated with inhaled budesonide became on average 1.2 cm shorter as adults than those randomised to placebo.
Rare individuals may be exceptionally sensitive to intranasal corticosteroids. Height measurements (e.g. via stadiometry) should be performed to identify patients with increased sensitivity. The potential growth effects of prolonged treatment should be weighed against the clinical benefits and the availability of safe and effective noncorticosteroid alternatives. To minimise the systemic effects of intranasal corticosteroids, each patient should be titrated to his/her lowest effective dose (see Section 4.2 Dose and Method of Administration).
The continuous long-term use of budesonide nasal spray in children is not recommended due to the possibility of reduced growth velocity. Studies of children with seasonal allergic rhinitis did not extend beyond four weeks of treatment.
Safety and effectiveness of Rhinocort in children below 6 years of age has not been established.
This product may slow the growth rate in some children when used in combination with other steroids.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The metabolism of budesonide is primarily mediated by CYP3A, a subfamily of cytochrome P450. After oral administration of ketoconazole, a potent inhibitor of cytochrome P450 3A, the mean plasma concentration of budesonide increased by more than sevenfold. Concomitant administration of other known inhibitors of this enzyme (e.g. itraconazole, clarithromycin, erythromycin, ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir, telithromycin, itraconazole) may inhibit the metabolism of, and increase the concentration of budesonide in the plasma leading to increased risk of systemic side-effects such as Cushing's syndrome and adrenal suppression. If used, close monitoring of patients is advised for any systemic effects. Otherwise, the combination should be avoided unless the benefit outweighs the risk.
Cimetidine, primarily an inhibitor of cytochrome P450 1A2, caused a slight decrease in budesonide clearance and corresponding increase in its oral bioavailability.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are insufficient data available to determine whether intranasal administration of budesonide has the potential to impair fertility. This product should not be used during pregnancy or lactation unless the potential benefit of treatment to the mother outweighs the possible risks to the developing fetus or breastfeeding infant. Ask a physician before use if you are pregnant or breastfeeding.
(Category A)
It is not known if budesonide can cross the placenta but due to its relatively low molecular weight, placental transfer may be possible. When given at therapeutic doses, systemic exposure after intranasal administration is low. As with other drugs, the administration of budesonide during pregnancy requires that the benefits for the mother be weighed against the risks for the foetus.
Inhaled glucocorticosteroids such as budesonide, should be considered because of the lower systemic effects, compared to oral glucocorticosteroids.
Ask a physician before use if you are pregnant.
 Budesonide is excreted in breast milk. However, due to the relatively low doses used via the intranasal route the amount of drug present in the breast milk, if any, is likely to be low. There is a linear relationship between budesonide concentration in plasma and breast milk, where the concentration of budesonide in breast milk is less than plasma concentration. Breastfeeding can be considered if the potential benefit outweighs any potential risks.
Ask a physician before use if you are breastfeeding.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration. However, adverse effects of Rhinocort include blurred vision which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Adverse local reactions following Rhinocort use are mild and usually transient. Systemic corticosteroid side effects have not been reported during clinical studies of Rhinocort in adults (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use for details relating to children). Growth suppression has been reported in association with administration of intranasal corticosteroids. Whilst no long-term studies are available for intranasal budesonide, long-term studies in a clinical practice environment suggest that children treated with orally inhaled budesonide on average achieve their adult target height. However, in a long-term double blind study, in which the budesonide dose was generally not titrated to the lowest effective dose, children treated with inhaled budesonide became on average 1.2 cm shorter as adults than those randomised to placebo. See Section 4.4 Special Warnings and Precautions for Use, Paediatric use. See Table 1.

Laboratory variables.

All changes in haematology, biochemistry and urinalysis were within the normal range and were not considered clinically significant.

Post marketing data.

Adverse drug reactions (ADRs) identified during Post-marketing experience with budesonide are included in Tables 2 and 3. The frequencies are provided according to the following convention: very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1,000 and < 1/100; rare ≥ 1/10,000 and < 1/1,000; very rare < 1/10,000; not known (cannot be estimated from the available data).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at: www.tga.gov.au/reporting-problems.

4.9 Overdose

Acute overdosage with Rhinocort, even in excessive doses, is not expected to be a clinical problem.
In the unlikely event of prolonged excessive use of Rhinocort which could possibly lead to adrenal suppression, treatment should be discontinued. Overdosage may give rise to signs of Cushing's syndrome, such as increased bodyweight, lethargy, hypertension, hirsutism, cutaneous striae, personality change, ecchymosis, oedema, polyuria and polydipsia. In severe cases, the dosage of the corticosteroid should be gradually withdrawn to prevent the possibility of adrenal failure.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Keep out of reach of children. In the event of overdose, seek medical attention immediately.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The mechanism of action of intranasally administered budesonide has not yet been completely defined, however budesonide has been shown to counteract the mainly IgE mediated lung anaphylaxis in guinea pigs.

Clinical trials.

Studies in animals and humans have shown an advantageous ratio between topical anti-inflammatory activity and systemic glucocorticoid effect over a wide dose range.
Budesonide is approximately twice as potent as beclomethasone dipropionate as shown in the skin blanching test for anti-inflammatory activity of topical steroids in humans. Budesonide has, however, less systemic effect than beclomethasone dipropionate, as measured by depression of morning plasma cortisol and effect on differential WBC count. The improved ratio of topical anti-inflammatory activity to systemic effect of budesonide is due to high glucocorticoid receptor affinity combined with a high first-pass metabolism and a short half-life.
Pretreatment for one week with intranasal budesonide 400 microgram daily in asymptomatic patients with seasonal rhinitis significantly inhibited the immediate reaction to allergen challenge.

Seasonal and perennial allergic rhinitis.

The therapeutic efficacy of Rhinocort nasal spray has been evaluated in placebo controlled clinical trials of seasonal and perennial allergic rhinitis of 3-6 weeks duration. The number of patients (aged 6 years and above) treated with Rhinocort nasal spray in these 8 studies was 1,653.
Overall, the results of these clinical trials showed that Rhinocort nasal spray administered once daily provides statistically significant reduction in the severity of nasal symptoms of seasonal and perennial allergic rhinitis including runny nose, sneezing, and nasal congestion. In some studies, improvement versus placebo has been shown to occur within 24 hours of initiating treatment with Rhinocort nasal spray. Maximum benefit can take up to 2 weeks after initiation of treatment.

Nasal polyps.

A randomised, double blind placebo controlled study evaluated the efficacy of Rhinocort nasal spray 128 microgram bd over a 6 week treatment period in patients (n = 46) with moderate to severe nasal polyps. After 6 weeks, polyp size was significantly reduced and nasal symptoms improved compared to placebo (n = 47).

5.2 Pharmacokinetic Properties

The systemic availability of budesonide from Rhinocort, with reference to the metered dose, is 33%. Negligible biotransformation occurs in human nasal mucosa.

Absorption.

After nasal application of 256 microgram budesonide peak plasma concentrations of approximately 0.63 nanomol/L in adults and 1.53 nanomol/L in children were observed within 45 minutes. The area under the curve (AUC) after administration of 256 microgram budesonide from Rhinocort is 2.7 nanomol.hour/L in adults and 5.5 nanomol.hour/L in children.

Distribution.

Budesonide has a volume of distribution of approximately 3 L/kg. Plasma protein binding averages 85-90%.

Metabolism.

Budesonide is metabolised in the liver by cytochrome P450 3A to more polar metabolites with low glucocorticoid activity (i.e. 100-fold lower than the parent compound). The metabolites are inactive and excreted mainly via the kidneys. No intact budesonide has been detected in the urine. Budesonide has a high systemic clearance (approximately 1.2 L/min) and the plasma half-life after i.v. dosing averages 2-3 hours.

5.3 Preclinical Safety Data

Genotoxicity.

The mutagenic potential of budesonide was evaluated in 6 different test systems. No mutagenic or clastogenic effects of budesonide were found.

Carcinogenicity.

The carcinogenic potential of budesonide has been evaluated in mouse and rat at oral doses up to 200 and 50 microgram/kg/day, respectively. No oncogenic effect was noted in the mouse. One study indicated an increased incidence of brain gliomas in male Sprague-Dawley rats given budesonide, however the results were considered equivocal.
Further studies performed in male Sprague-Dawley and Fischer rats showed that the incidence of gliomas in the budesonide treated rats was low and did not differ from that in the reference glucocorticoid groups or the controls. It was concluded that treatment with budesonide does not increase the incidence of brain tumours in the rat.
In male rats dosed with 10, 25 and 50 microgram/kg/day, those receiving 25 and 50 microgram/kg/day showed an increased incidence of primary hepatocellular tumours. This was observed in all three steroid groups (budesonide, prednisolone, triamcinolone acetonide) in a repeat study in male Sprague-Dawley rats thus indicating a class effect of corticosteroids.

6 Pharmaceutical Particulars

6.1 List of Excipients

Disodium edetate, potassium sorbate, glucose anhydrous, dispersible cellulose, polysorbate 80, hydrochloric acid (for pH adjustment) and purified water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Do not freeze.

6.5 Nature and Contents of Container

Rhinocort nasal spray is available in an amber glass (type II) bottle with pump spray equipment and nasal adaptor.
Pack sizes:
32 microgram strength: 1 x 120 doses in 10 mL.
64 microgram strength: 1 x 50 doses in 10 mL (sample pack), 120 doses (1 x 120 dose in 10 mL bottle) and 240 doses (2 x 120 dose in 10 mL bottles).
Not all pack sizes may be available in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

The active ingredient, budesonide, is a non-halogenated glucocorticoid structurally related to 16α hydroxyprednisolone. Budesonide is a white to off-white powder, freely soluble in chloroform, sparingly soluble in ethanol and practically insoluble in water and heptane.
Budesonide melts between 224°C and 231.5°C with decomposition.

Chemical structure.


Chemical name.

16α, 17α-22 R, S-propylmethylenedioxypregna-1, 4- diene-11β, 21-diol-3, 20-dione; MW 430.5.

CAS number.

51333-22-3.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

Summary Table of Changes