Consumer medicine information

Omnaris Nasal Spray

Ciclesonide

BRAND INFORMATION

Brand name

Omnaris

Active ingredient

Ciclesonide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Omnaris Nasal Spray.

What is in this leaflet

This leaflet answers some common questions about OMNARIS.

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

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available. You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on this medicine. Those updates may contain important information about the medicine and its use of which you should be aware.

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

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

Keep this leaflet with the medicine. You may need to read it again.

What OMNARIS is used for

The medicine is sprayed into the nose to help treat symptoms of seasonal allergic rhinitis in adults and children 6 years of age and older, and perennial allergic rhinitis in adults and adolescents 12 years of age and older.

Allergic rhinitis (hay fever) is an inflammation or swelling of the nose lining, which may cause blockage, runny nose, itching and/or sneezing.

You may have symptoms only during spring or summer (seasonal). This type of allergy is generally due to various pollens. Some people may experience symptoms all year round (perennial). This is usually caused by house dust mites, pets or moulds.

The medicine contains ciclesonide. 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 it has been prescribed for you. Your doctor may have prescribed it for another purpose.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Before you use OMNARIS

When you must not use it

Do not use OMNARIS if you have an allergy to:

  • any medicine containing ciclesonide or any other corticosteroid medicines
  • any of the ingredients listed at the end of this leaflet

Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing.

Do not give OMNARIS to a child under the age of 6 years.

Do not use it after the expiry date printed on the pack or if the packaging is damaged 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 this medicine, talk to your doctor or pharmacist.

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:

  • frequent nose bleeds
  • nasal or sinus infection
  • recent injury or surgery to your nose
  • ulcers or sores in your nose
  • any type of infection caused by bacteria, virus, fungus, or parasites
  • a history of tuberculosis (TB) infections
  • herpes simplex (virus) infection of the eye.

Tell your doctor if you are pregnant, intend to become pregnant, or are breastfeeding Your doctor or pharmacist can discuss the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start using OMNARIS.

Taking other medicines

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

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

  • other corticosteroid medicines such as tablets, asthma inhalers, nasal sprays, or eye/nose drops
  • medicines that suppress the immune system (e.g. cyclosporine)
  • some antifungal medicines (e.g. ketoconazole, itraconazole)
  • some antiviral medicines (e.g. ritonavir, nelfinavir).

These medicines may be affected by OMNARIS or may affect how well it works. You may need to use different amounts of your medicine or use different medicines.

Your doctor or pharmacist has more information on medicines to be careful with or to avoid while taking OMNARIS.

How to use OMNARIS

  1. Remove OMNARIS from its foil pouch. Count 4 months from this date and write the date (that is 4 months from removing the bottle from the foil pouch) on the space provided on the nasal spray bottle. It is important to throw away the nasal spray bottle after this date.
  2. Before you use OMNARIS for the first time, you will need to prime the bottle. Hold the bottle upright and shake the bottle gently. To prime OMNARIS Nasal Spray, fully press down on the finger rests of the applicator eight times (See Figure 1). If you do not use the nasal spray for 4 days, you will need to shake the bottle gently, and prime the pump again by spraying one time, or until you see a fine mist.

Using the spray

  1. Gently blow your nose to clear your nostrils if needed
  2. Shake the bottle gently and remove the cap
  3. Hold the bottle firmly with your index and middle finger on either side of the nozzle while supporting the base of the bottle with your thumb (Figure 1)
  4. Insert the nozzle tip into one nostril, and close the other nostril with your finger (Figure 2)

  1. Tilt your head forward slightly and keeping the bottle upright, press the pump quickly and firmly and inhale through your nose as you spray (Figure 3).
Do not spray in eyes or directly onto the nasal septum (the wall between the two nostrils).

  1. Repeat steps 3-5 for the second spray in the same nostril and for each spray in the other nostril.

How to clean it

After daily use of your nasal spray, wipe the nozzle tip with a clean tissue and replace the cap.

If the nozzle is clogged or requires more thorough cleaning, use the following cleaning instructions:

  1. Remove the cap, grasp the white plastic pump firmly with one hand and then carefully pull upwards on the shoulders of the nozzle with the other hand to free the nozzle
  2. Wash the cap and nozzle with warm water
  3. Dry and replace the nozzle. The nozzle will snap into place when properly positioned
  4. Prime the pump by spraying one time or until a fine mist appears
  5. Replace the cap.

Do not try to unblock the tiny spray hole on the nozzle tip with a pin or other sharp object.

Do not twist or attempt to remove the white plastic pump attached to the medication bottle.

How to know when your nasal spray bottle is empty

The amount of nasal spray left can be seen through a window on the bottle. You should discard the bottle after using 120 sprays (or 60 sprays if your bottle is a 60 spray pack) or 4 months after opening the foil pouch, whichever comes first.

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

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

How much to use

The recommended dosage is 2 sprays in each nostril once daily.

The maximum total daily dosage should not exceed 2 sprays in each nostril (200 micrograms per day).

Do not use more than the recommended dose.

Your doctor may change this dosage, depending on your response to this medicine.

Use the lowest dose that controls your symptoms.

How long to use it

Continue using your medicine for as long as your doctor tells you.

If you forget to take it

If you miss a dose, use OMNARIS when the next dose is due.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of getting an unwanted side effect.

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

If you have trouble remembering when to take your medicine, ask your pharmacist for hints.

If you take too much (overdose)

If you or someone else accidentally uses too much OMNARIS on one occasion, there is nothing to worry about.

However, if you use too much of it over a long time (months or years), you may start to get unwanted side effects inside your nose and body.

Discuss any worries you may have about this with your doctor or pharmacist.

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26) if you think you or anyone else may have used too much OMNARIS. Do this even if there are no signs of discomfort or poisoning.

While you are using OMNARIS

Things you must do

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

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 this medicine.

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are using this medicine. It may affect other medicines used during surgery.

If you become pregnant while you are taking this medicine, tell your doctor immediately.

Things you must not do

Do not use this medicine to treat any other complaints unless your doctor or pharmacist tells you to.

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

Things that may be helpful

If possible, avoid situations that you know will trigger your symptoms.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using OMNARIS.

It helps most people with seasonal and perennial allergic rhinitis, but it may have unwanted side effects in a few people. All medicines have some unwanted side effects. Sometimes they are serious, but 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 this list of possible 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
  • nose bleeds
  • burning or irritation inside the nose
  • irritated throat.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • frequent nose bleeds
  • signs or symptoms of a nasal or sinus infection such as fever, pain or swelling, or discoloured nasal discharge
  • allergic reactions such as swelling of the face, lips, tongue or other parts of the body, loss of consciousness, shortness of breath, or nasal congestion.

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

Tell your doctor if you notice any issues with your eyes such as blurred vision or other problems with your eyesight. Your doctor may need to send you to an ophthalmologist (eye doctor) to check that you don't have eye problems such as cataracts (clouding of the eye lens), glaucoma (increased pressure in your eyeballs) or other rare eye conditions reported with corticosteroid use.

In rare cases, corticosteroids taken through the nose for long periods can affect how children grow. If your child uses OMNARIS for a long period of time, your doctor may need to monitor your child's height.

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

After using OMNARIS

Storage

Keep OMNARIS in a cool, dry place where the temperature stays below 30°C. Do not freeze the bottle.

Do not store it or any other medicine in the bathroom, near a sink, or on a windowsill. Do not leave it 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 or pharmacist tells you to stop taking this medicine, or the medicine has passed its expiry date, ask your pharmacist what to do with any that are left over.

Discard the bottle after using 60 or 120 sprays, or 4 months after opening the foil pouch, whichever comes first.

Product description

What it looks like

OMNARIS nasal spray is a white to off-white suspension contained in a brown glass bottle, fitted with a manual spray pump. The bottle is enclosed in a foil pouch.

Also enclosed within the foil pouch is an oxygen-absorber sachet, this is included to help protect the product prior to use and should be discarded with the foil pouch after opening.

OMNARIS is registered* in pack sizes of 60 or 120 sprays.

*not all registered pack sizes might be available in Australia

Ingredients

OMNARIS contains ciclesonide as the active ingredient. Each spray delivers 50 micrograms of ciclesonide.

OMNARIS also contains the following inactive ingredients:

  • microcrystalline cellulose
  • carmellose sodium
  • hypromellose
  • potassium sorbate
  • disodium edetate
  • purified water
  • hydrochloric acid to adjust pH of the solution.
  • nitrogen

OMNARIS does not contain gluten, sucrose, lactose, tartrazine or any other azo dyes.

Supplier

Chiesi Australia Pty Ltd
Suite 3, 22 Gillman Street,
Hawthorn East, VIC 3123
Email: [email protected]
Website: www.chiesi.com.au

This leaflet was prepared on September 2021

Australian Registration Number

AUST R 167910

Published by MIMS November 2021

BRAND INFORMATION

Brand name

Omnaris

Active ingredient

Ciclesonide

Schedule

S4

 

1 Name of Medicine

Ciclesonide.

2 Qualitative and Quantitative Composition

Omnaris Nasal Spray is a metered-dose, manual-pump spray. Once primed (see Section 4.2 Dose and Method of Administration), each actuation of the pump delivers 50 microgram ciclesonide in a volume of 70 microL from the nasal actuator.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Nasal spray presented as a white to off-white suspension in brown glass bottle with a pump.

4 Clinical Particulars

4.1 Therapeutic Indications

Omnaris Nasal Spray is indicated for:
the treatment of seasonal allergic rhinitis in adults and children 6 years of age and older;
the treatment of perennial allergic rhinitis in adults and adolescents 12 years of age and older.

4.2 Dose and Method of Administration

Omnaris should only be administered by the intranasal route.

Dosage consideration.

The recommended dose of Omnaris is 200 microgram per day administered as 2 actuations (50 microgram/actuation) in each nostril once daily.
The maximum total daily dosage should not exceed 2 actuations in each nostril (200 microgram/day).

Administration.

Prior to initial use, Omnaris must be shaken gently and then the pump must be primed by actuating 8 times. If not used for 4 or more consecutive days, it should be shaken gently and reprimed with 1 actuation or until a fine mist appears.
During dosing, users are advised to tilt the head forward slightly and, while keeping the bottle upright, users are advised to press the pump quickly and firmly and inhale through the nose as they spray.

4.3 Contraindications

Patients with a hypersensitivity to ciclesonide or any of its ingredients.

4.4 Special Warnings and Precautions for Use

Immune system.

Rarely, immediate hypersensitivity reactions or contact dermatitis may occur after the administration of intranasal corticosteroids. Patients with a known hypersensitivity reaction to other corticosteroid preparations should use caution when using ciclesonide nasal spray since cross reactivity to other corticosteroids including ciclesonide may also occur. Patients who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In children or adults who have not had these diseases or have not been properly immunised, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

Local effects.

Rare instances of nasal septum perforation have been reported following the intranasal application of corticosteroids.
Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred.

Respiratory.

Rare instances of wheezing have been reported following the intranasal application of corticosteroids.

Infection.

In clinical studies with corticosteroids administered intranasally, the development of localised infections of the nose and pharynx with Candida albicans have been reported only rarely. When such an infection develops, it may require treatment with appropriate local therapy and discontinuation of treatment with the intranasal corticosteroid. Therefore, patients using intranasal corticosteroids over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.
Corticosteroid should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; or in patients with untreated local or systemic fungal or bacterial infections; systemic viral or parasitic infections; or ocular herpes simplex because of the potential for worsening of these infections.

Systemic effects.

Although systemic effects have been minimal with recommended doses of Omnaris, any such effect is likely to be dose dependent. Therefore, larger than recommended doses of Omnaris should be avoided. If recommended doses of intranasal corticosteroids are exceeded or if individuals are particularly sensitive or predisposed by virtue of recent systemic steroid therapy, symptoms of hypercorticism may occur, including very rare cases of menstrual irregularities, acneiform lesions, and cushingoid features. If such changes occur, topical corticosteroids should be discontinued slowly, consistent with accepted procedures for discontinuing oral steroid therapy.

Visual disturbance.

Visual disturbance may be reported with systemic and topical corticosteroid use. Rare instances of cataracts, glaucoma, and increased intraocular pressure have been reported following the intranasal application of corticosteroids. 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.
The risk of glaucoma was evaluated by assessments of intraocular pressure in 3 studies including 943 patients. Of these, 390 adolescents or adults were treated for up to 52 weeks and 186 children ages 2 to 11 received treatment with ciclesonide 200 microgram daily for up to 12 weeks. In these trials, no significant differences in intraocular pressure changes were observed between ciclesonide- and placebo-treated patients. Additionally, no significant differences between the two patient groups were noted during the 52-week study of adults and adolescent patients in whom thorough ophthalmologic assessments were performed including evaluation of cataract formation using slit lamp examinations.

Growth.

Intranasal corticosteroids may cause a reduction in growth velocity when administered to paediatric patients. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route (see Paediatric use).

Systemic steroid replacement by a topical steroid.

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. In addition, some patients may experience symptoms of corticosteroid withdrawal, e.g. joint and/or muscular pain, lassitude, and depression. Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In those patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause a severe exacerbation of their symptoms.

Use in the elderly.

A total of 31 patients above 65 years of age (age range 65 to 75 years) have been treated with Omnaris 200 microgram/day for up to one year. The adverse reactions reported in this population were similar in type and incidence to those reported by younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Paediatric use.

The efficacy of Omnaris in children 6 years of age and older for the treatment of the symptoms of allergic rhinitis is supported by evidence from four adequate and well-controlled studies in adults and adolescents 12 years of age and older with seasonal or perennial allergic rhinitis and one study in patients 6 to 11 years of age with seasonal allergic rhinitis (see Section 5.1 Pharmacodynamic Properties, Clinical trials). The efficacy of Omnaris in children under 5 years of age has not been established. The safety of Omnaris in children 2 to 11 years of age was evaluated in four controlled clinical studies of 2 to 12 weeks duration (see Section 5.1 Pharmacodynamic Properties, Clinical trials). The growth of paediatric patients receiving intranasal corticosteroids, including Omnaris, should be monitored routinely (e.g. via stadiometry). The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of safe and effective noncorticosteroid treatment alternatives. To minimise the systemic effects of intranasal corticosteroids, each patient should be titrated to the lowest dose that effectively controls his/her symptoms (see Section 4.4 Special Warnings and Precautions for Use, Systemic effects; Section 4.8 Adverse Effects (Undesirable Effects)).

Effects on laboratory tests.

Interactions with laboratory tests have not been established. Drug-laboratory interactions are unlikely for intranasal corticosteroids.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Based on in vitro studies in human liver microsomes and hepatocytes, des-ciclesonide is not an inhibitor of cytochrome (CYP) isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 or 3A4 at therapeutic concentrations, and ciclesonide is not an inducer of CYP1A2, 2C9, 2C19 or 3A4. The inhibitory potential of ciclesonide on CYP450 isoenzymes has not been studied. In vitro studies demonstrated that the plasma protein binding of des-ciclesonide was not affected by warfarin or salicylic acid, indicating that protein binding-based drug interactions are unlikely.
In vitro data indicate that CYP 3A4 is the major enzyme involved in the metabolism of the active metabolite, des-ciclesonide, in man. A drug interaction study with orally inhaled ciclesonide and oral erythromycin, a substrate and weak inhibitor of CYP 3A4, had no relevant effect on the pharmacokinetics of either des-ciclesonide or erythromycin. In another drug interaction study at steady state with orally inhaled ciclesonide and oral ketoconazole, a potent CYP 3A4 inhibitor, the exposure (AUC) of des-ciclesonide increased by approximately 3.5-fold, while levels of ciclesonide remained unchanged.
The serum levels of ciclesonide and des-ciclesonide are negligible following administration of ciclesonide nasal spray. Therefore, the potential for clinically relevant drug-drug interactions is very low. However, co-administration with potent inhibitors of the CYP 3A4 (e.g. protease inhibitors for the treatment of HIV infections) should be considered with caution because there might be an increase in systemic drug levels of des-ciclesonide.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No evidence of impairment of fertility was observed in a reproductive study conducted in male and female rats both dosed orally with ciclesonide at up to 900 microgram/kg/day (approximately 41 times the maximum human daily intranasal dose in adults based on microgram/m2 body surface area in a 50 kg adult).
(Category B3)
No adverse effects on embryofoetal development were observed in rats treated with ciclesonide at oral doses up to 900 microgram/kg/day (41 times the maximum human daily intranasal dose in adults on a body surface area basis) during the period of organogenesis. In a study in rats in which this dose was administered throughout gestation and lactation, pup birth weight and postnatal bodyweight gain were reduced; this occurred in the context of maternotoxicity. In rabbits, adverse effects on embryofoetal development occurred at subcutaneous doses ≥ 5 microgram/kg/day (0.6 times the maximum adult human dose based on body surface area), and comprised cleft palate, fore and/or hind leg flexure, enlarged fontanelle, incomplete ossification of skull bones, parchment-like skin and decreased foetal weight. Ciclesonide increased foetal loss in the rabbit with subcutaneous administration at doses ≥ 100 microgram/kg/day (11 times the maximum adult human dose based on body surface area).
There are no adequate and well controlled studies with Omnaris in pregnant women. As with other corticosteroids, ciclesonide should only be used during pregnancy when the potential benefit to the mother justifies the potential risk to the mother, foetus or infant. Infants born to mothers who received corticosteroids during pregnancy should be observed carefully for hypoadrenalism.
 It is unknown if ciclesonide is excreted in human milk. There was limited excretion of ciclesonide and/or its metabolites in to milk in lactating rats after intravenous or oral administration. Oral administration of ciclesonide to rats from early pregnancy until weaning was associated with reduced bodyweight in pups (see Use in pregnancy - Category B3). As with other corticosteroids, Omnaris should only be used in nursing women when the potential benefit to the mother justifies the potential risk to the mother and/or infant.

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.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials experience.

In controlled clinical studies with patients receiving ciclesonide aqueous nasal spray, the overall incidence of adverse events for patients treated with ciclesonide aqueous nasal spray was comparable to that in patients treated with placebo. Adverse reactions reported at an incidence of 1% or greater and more commonly reported in ciclesonide aqueous nasal spray versus placebo were as follows:

Nervous system disorders.

Headache.

Respiratory, thoracic and mediastinal disorders.

Nasopharyngitis, epistaxis, sinusitis.
Adult and adolescent patients aged 12 years and older. In controlled clinical studies, a total of 1524 patients ages 12 years and older received treatment with ciclesonide administered intranasally. In studies of 2 to 6 weeks duration in patients 12 years and older, 546 patients were treated with Omnaris 200 microgram daily, and in a study of up to one year in duration, 441 patients were treated with Omnaris 200 microgram daily. The overall incidence of adverse events for patients treated with Omnaris was comparable to that in patients treated with placebo. Adverse events did not differ appreciably based on age, gender, or race. Approximately 2% of patients treated with Omnaris in clinical trials discontinued because of adverse events; this rate was similar for patients treated with placebo. Table 1 displays adverse events, irrespective of drug relationship, that occurred with an incidence of 2% or greater and more frequently with Omnaris than with placebo in clinical trials of 2 to 6 weeks in duration.
In a 52-week long-term safety trial that included 663 adults and adolescent patients (441 treated with ciclesonide: 227 males and 436 females) with perennial allergic rhinitis, the adverse event profile over the treatment period was similar to the adverse event profile in trials of shorter duration. Adverse events considered likely or definitely related to Omnaris that were reported at an incidence of 1% or greater of patients and more commonly in Omnaris versus placebo were epistaxis, nasal discomfort, and headache. No patient experienced a nasal septal perforation or nasal ulcer during long-term use of Omnaris nor was there any evidence of HPA-axis suppression in this study.
Less common adverse reactions reported in controlled clinical trials 2 to 52 weeks in duration in patients 12 years of age and older with seasonal or perennial allergic rhinitis were:

Gastrointestinal disorders.

Dry mouth (0.2%), dyspepsia (0.2%).

Infections and infestations.

Candidiasis (0.2%), rhinitis (0.2%).

Investigations.

Laboratory test abnormal NOS (0.2%), white blood cell count increased (0.3%).

Nervous system disorders.

Dysgeusia (0.2%).

Respiratory, thoracic and mediastinal disorders.

Nasal dryness (0.4%), pharyngolaryngeal pain (0.4%), rhinorrhoea* (0.3%), nasal septum disorder (0.2%), throat irritation* (0.2%).
* Occurred at rates ≤ placebo.
Paediatric patients aged 6 to 11 years. Two controlled clinical studies 2 and 12 weeks in duration were conducted in a total of 1282 patients with allergic rhinitis ages 6 to 11 years, of which 913 were treated with Omnaris 200 microgram, 100 microgram or 25 microgram daily. The overall incidence of adverse events for patients treated with Omnaris was comparable to that in patients treated with placebo. Adverse events did not differ appreciably based on age, gender, or race. In clinical trials, 1.6% and 2.7% of patients treated with Omnaris 200 microgram or 100 microgram, respectively, discontinued because of adverse events; these rates were lower than the rate in patients treated with placebo (2.8%). Table 2 displays adverse events, irrespective of drug relationship, that occurred with an incidence of 3% or greater and more frequently with Omnaris 200 microgram than with placebo.
The effect of orally inhaled ciclesonide (Alvesco) on growth in 609 children aged 5 to 9 years was investigated in a placebo controlled multi-centre, double-blind, randomised parallel-group study of 12 months duration. In the modified intention-to-treat (mITT) analysis, the mean growth velocities observed during the double-blind treatment period were 5.76 cm/year in the placebo group, 5.75 cm/year in the 40 microgram ciclesonide group, and 5.60 cm/year in the 160 microgram ciclesonide group. It can be concluded that doses of ciclesonide administered at 40 microgram or 160 microgram once daily were non-inferior to placebo with respect to growth velocity. In addition, no significant difference was observed between ciclesonide and placebo as measured by 24 hour urinary free cortisol in 292 patients who were studied for HPA axis function.
These effects described above were observed with ciclesonide administered as a metered dose inhaler utilising a different formulation and at different dosages to Omnaris.

Post-marketing experience.

Hypersensitivity reactions, including angioedema, loss of consciousness, nasal oedema, dyspnoea, and nasal septum perforation have been reported in association with post-market use of Omnaris. Because these reactions are reported voluntarily from a population of uncertain size and are not always confirmed with a health care professional, it is not possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.
Eye disorders, such as blurred vision with frequency unknown, have been reported with systemic and topical corticosteroid use (see Section 4.4 Special Warnings and Precautions for Use, Systemic effects).

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

There are no data available on the effects of acute or chronic overdosage with Omnaris. Because of low systemic bioavailability, acute overdosage is unlikely to require any therapy other than observation. A single oral dose of up to 10 mg of ciclesonide in healthy volunteers was well tolerated and serum cortisol levels were virtually unchanged in comparison with placebo treatment. Chronic overdosage with any corticosteroid may result in signs or symptoms of hypercorticism.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ciclesonide is a pro-drug that is enzymatically hydrolysed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound.
The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g. mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g. histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation.
The anti-inflammatory properties of ciclesonide and des-ciclesonide were shown in several in vitro and in vivo investigations, including experiments using a guinea pig model of allergic rhinitis and several investigations in primary human nasal epithelial cells, bronchial epithelial and smooth muscle cells.

Pharmacodynamics.

In a study of 40 healthy adult volunteers and 8 asymptomatic seasonal allergic rhinitis patients, no significant differences between the active and placebo groups were observed in 24-hour plasma or urine cortisol after administration of 50-800 microgram daily of ciclesonide for 14 days. In a 1-year safety study including 174 patients treated with ciclesonide 200 microgram once daily and 92 patients treated with placebo who had cortisol assessments, no significant differences in morning plasma and 24 hour urine cortisol levels were observed with ciclesonide versus placebo treatment.
In two studies conducted in children with perennial allergic rhinitis, daily doses of 200 microgram, 100 microgram, and 25 microgram of ciclesonide were compared to placebo nasal spray. The ciclesonide-treated groups had a numerically greater decline in 24 hour urinary free cortisol compared to the placebo group. In the 12 week study in children 6-11 years of age, the difference (and 95% confidence intervals) from placebo in the mean change from baseline to 12 weeks was -0.81 (-4.0, 2.4) microgram/day for the 200 microgram dose group. The mean morning plasma cortisol value did not show any consistent treatment effect. In the 6 week study in children 2-5 years of age, the difference (and 95% confidence intervals) from placebo in the mean change from baseline to 6 weeks was -2.04 (-4.4, 0.3) microgram/day for the 200 microgram dose groups. The plasma cortisol decreased numerically after treatment with ciclesonide with the difference (and 95% confidence intervals) from placebo in the mean change in plasma cortisol from baseline to 6 weeks being -1.04 (-2.7, 0.7) microgram/dL for the 200 microgram dose group. In the studies, serum was assayed for ciclesonide and des-ciclesonide (see Section 5.2 Pharmacokinetic Properties, Absorption).

Clinical trials.

Seasonal allergic rhinitis and perennial allergic rhinitis.

Adult and adolescent patients aged 12 years and older.

The efficacy and safety of Omnaris were evaluated in 4 randomised, double-blind, parallel group, multi-centre, placebo controlled clinical trials of 2 weeks to 1 year in duration conducted in adults and adolescents with allergic rhinitis. Three of these trials were 2 to 6 weeks in duration and primarily designed to assess efficacy. One of these trials was 1 year in duration and primarily designed to assess safety. The three trials of 2 to 6 weeks duration included a total of 1524 patients (495 males and 1029 females) of whom 79 were adolescents, ages 12 to 17 years. Of the 1524 patients, 546 patients received Omnaris 200 microgram once daily. Patients enrolled in the studies were 12 to 86 years of age with a history of seasonal or perennial allergic rhinitis, a positive skin test to at least one relevant allergen, and active symptoms of allergic rhinitis at study entry. Assessment of efficacy in these trials was based on patient recording of four nasal symptoms (runny nose, nasal itching, sneezing, and nasal congestion) on a 0-3 categorical severity scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe) as reflective or instantaneous scores. Reflective scoring required the patients to record symptom severity over the previous 12 hours; the instantaneous scoring required patients to record symptom severity at the time of recording. The results of these trials showed that patients treated with Omnaris 200 microgram once daily exhibited statistically significantly greater decreases in total nasal symptom scores than placebo treated patients. Secondary measures of efficacy were generally supportive.
In the 2-week dose-ranging trial that evaluated efficacy of Omnaris in patients with seasonal allergic rhinitis, the primary efficacy endpoint was the difference from placebo in the change from baseline of the sum of morning and evening reflective total nasal symptom score averaged over the 2-week treatment period. In this trial Omnaris 200 microgram once daily was statistically significantly different from placebo.
In the 4-week single dose level trial conducted in patients with seasonal allergic rhinitis and the 6 week single dose level trial conducted in patients with perennial allergic rhinitis, the primary efficacy endpoints were the difference from placebo in the change from baseline of the average of morning and evening reflective total nasal symptom score averaged over the first 2 weeks of treatment and over the 6 weeks of treatment, respectively. In these trials, Omnaris 200 microgram once daily was statistically significantly different from placebo. Statistically significant differences in the morning pre-dose instantaneous total nasal symptom score indicate that the effect was maintained over the full 24 hour dosing interval.
Results of the primary efficacy endpoint in these trials are shown in Table 3.
The long-term effectiveness of Omnaris was demonstrated in a 52-week safety study. Over the full course of the study (days 2-365), the mean decrease in 24-hour reflective total nasal symptom score from baseline was greater in the treatment group versus placebo (p < 0.001) with no evidence of tachyphylaxis.
Onset of action was evaluated in two environmental exposure unit studies with a single dose of Omnaris 200 microgram. Results from these two studies did not demonstrate a replicate onset of action within the assessment period. Onset of action was also evaluated in the 4-week seasonal allergic rhinitis and in the 6-week perennial allergic rhinitis trial by frequent recording of instantaneous symptom score after the first dose. In these trials, onset of effect was seen within 24 to 48 hours with further symptomatic improvement observed over 1 to 2 weeks in seasonal allergic rhinitis and 5 weeks in perennial allergic rhinitis.

Paediatric patients aged 6 to 11 years.

The efficacy of Omnaris was evaluated in 618 children aged 6 to 11 years old with seasonal allergic rhinitis in a randomised, double-blind, parallel group, multi-centre, placebo-controlled clinical trial. The 2-week trial conducted in patients compared the efficacy of ciclesonide 200 microgram and 100 microgram once daily nasal spray. The primary efficacy endpoint was the difference from placebo in the change from baseline of the average of morning and evening reflective total nasal symptom score averaged over 2 weeks of treatment. In the study, the ciclesonide 200 microgram once daily dose was statistically significantly different from placebo, but the 100 microgram once daily dose was not statistically significantly different from placebo. The efficacy results for the seasonal allergic rhinitis trial are shown in Table 4.

5.2 Pharmacokinetic Properties

Absorption.

Ciclesonide and des-ciclesonide have negligible oral bioavailability (both less than 1%) due to low gastrointestinal absorption and high first pass metabolism. The intranasal administration of ciclesonide at recommended doses results in negligible serum concentrations of ciclesonide. However, the known active metabolite (des-ciclesonide) is detected in the serum of some patients after nasal inhalation of ciclesonide. The bioanalytical assay used has a lower limit of quantification of 25 picogram/mL and 10 picogram/mL, for ciclesonide and des-ciclesonide, respectively.
In healthy adults treated for two weeks with 50 to 800 microgram of ciclesonide nasal spray daily, the peak serum concentrations of des-ciclesonide in all subjects were found to be below 30 picogram/mL. Of those treated with 800 microgram and 400 microgram daily, 100% and 67% had detectable levels of des-ciclesonide, respectively. With daily doses of 200 microgram or less, detectable serum levels of des-ciclesonide were not observed. The low systemic exposure following ciclesonide nasal spray administration was confirmed in a crossover study in twenty-nine healthy adults. The median Cmax was less than 10 picogram/mL and 602 picogram/mL following a single dose of ciclesonide nasal spray (300 microgram) and orally inhaled ciclesonide (320 microgram, Alvesco), respectively.
In paediatric subjects treated with 25 to 200 microgram of ciclesonide nasal spray daily, serum concentrations of des-ciclesonide were below 45 picogram/mL, with the exception of one value of 64.5 picogram/mL. In a 12 week study in children 6 to 11 years of age with perennial allergic rhinitis, des-ciclesonide was detected in 50% of the subjects treated with 200 microgram and in 5% of those treated with 100 microgram ciclesonide nasal spray daily.

Distribution.

Following intravenous administration of 800 microgram of ciclesonide, the volumes of distribution of ciclesonide and des-ciclesonide were approximately 2.9 L/kg and 12.1 L/kg, respectively. The percentage of ciclesonide and des-ciclesonide bound to human plasma proteins averaged ≥ 99% each, with approximately 1% of unbound drug detected in the systemic circulation. Des-ciclesonide is not significantly bound to human transcortin.

Metabolism.

Intranasal ciclesonide is hydrolysed to a biologically active metabolite des-ciclesonide by esterases in the nasal mucosa. Des-ciclesonide undergoes further metabolism in the liver to additional metabolites mainly by the CYP 450 3A4 isozyme and to a lesser extent by CYP 2D6. The full range of potentially active metabolites of ciclesonide has not been characterised. After intravenous administration of 14C-ciclesonide, 19.3% of the resulting radioactivity in the plasma is accounted for by ciclesonide or des-ciclesonide; the remainder may be a result of other, as yet, unidentified multiple metabolites.

Excretion.

Following intravenous administration of 800 microgram of ciclesonide, the clearance values of ciclesonide and des-ciclesonide were high (approximately 152 L/h and 228 L/h, respectively). 14C-labelled ciclesonide was predominantly excreted via the faeces after intravenous administration (66%) indicating that excretion through bile is the major route of elimination. Approximately 20% or less of drug related radioactivity was excreted in the urine.

Special populations.

The pharmacokinetics of intranasally administered ciclesonide have not been assessed in patient subpopulations because the resulting blood levels of ciclesonide and des-ciclesonide are insufficient for pharmacokinetic calculations. However, population pharmacokinetic analysis showed that characteristics of des-ciclesonide after oral inhalation of ciclesonide were not appreciably influenced by a variety of subject characteristics such as bodyweight, age, race, and gender.
Studies in renal impaired patients were not conducted since renal excretion of des-ciclesonide is a minor route of elimination (≤ 20%).

5.3 Preclinical Safety Data

Genotoxicity.

Ciclesonide did not induce gene mutations in bacterial (Ames) or mammalian (HPRT) tests in vitro, nor induce chromosomal aberrations in human lymphocytes or micronuclei in Chinese hamster V79 cells in vitro. Racemic ciclesonide was also negative in the Ames test. In contrast, ciclesonide induced micronuclei in mouse bone marrow in vivo (at ≥ 75 mg/kg in females and > 1000 mg/kg in males). Positive in vivo clastogenicity results have also been observed with high doses of other corticosteroids and may reflect effects on erythrocyte differentiation. The clinical relevance of these clastogenicity findings is unknown but likely limited.

Carcinogenicity.

The carcinogenic potential of ciclesonide was investigated in a 2 year oral study in mice and in a 2 year inhalation study in rats. Gastric adenomas (benign tumour) were significantly increased in female mice at 900 microgram/kg/day (approximately 20 and 11 times the maximum human daily intranasal dose in adults and children, respectively, based on microgram/m2 body surface area).
This effect may arise from a local action in the stomach, with local exposure (based on microgram/kg doses being ≥ 90 times higher in the animals compared with humans receiving the maximum recommended dose of Omnaris. No tumourigenicity was observed in rats administered ciclesonide by inhalation at up to 89 microgram/kg/day (males) or 104 microgram/kg/day (females) (approximately 4 and 2 times the maximum human dose in adults and children, respectively, based on body surface area).

6 Pharmaceutical Particulars

6.1 List of Excipients

Omnaris Nasal Spray contains cellulose microcrystalline, carmellose sodium, hypromellose, potassium sorbate, disodium edetate, hydrochloric acid to adjust the pH to 4.5, purified water and nitrogen.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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.
Store in the foil pouch and only open pouch immediately before first use. Discard 4 months after first opening of pouch.

6.5 Nature and Contents of Container

Omnaris Nasal Spray is a metered-dose, manual-pump spray formulation containing a hypotonic aqueous suspension of ciclesonide. Each pack of Omnaris contains one spray pump bottle containing 60 actuations (10 mL bottle) or 120 actuations (15 mL bottle) actuations of 50 microgram/actuation of ciclesonide after initial priming (see Section 4.2 Dose and Method of Administration).
* 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

Ciclesonide is a white to yellow-white powder, practically insoluble in water and freely soluble in ethanol and acetone.
Chemical name (CAS): [11β,16α(R)] -16,17-[(Cyclohexylmethylene)bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxopropoxy) pregna-1,4-diene-3,20-dione.

Chemical structure.


CAS number.

126544-47-6 (as the R-epimer).
Molecular formula: C32H44O7.
Molecular weight: 540.7.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

Summary Table of Changes