Zetonna

Ciclesonide is a man-made steroid that prevents the release of substances in the body that cause inflammation.

Ciclesonide nasal (for the nose) is used to treat nasal symptoms (congestion, sneezing, runny nose) caused by seasonal allergies in adults and children as young as 6 years old. Ciclesonide nasal is also used to treat nasal symptoms caused by year-round allergies in adults and children who are at least 12 years old.

Ciclesonide may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use this medicine if you are allergic to ciclesonide.

To make sure ciclesonide nasal is safe for you, tell your doctor if you have:

• asthma, tuberculosis, or other lung problems;
• any type of infection caused by bacteria, virus, fungus, or parasites;
• glaucoma, cataracts, or herpes infection of the eyes;
• a sore inside your nose that has not yet healed;
• a recent nose injury or surgery; or
• if you have recently used any other steroid medicine (methylprednisolone, prednisone, beclomethasone, fluticasone, dexamethasone, and others).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether ciclesonide nasal passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Steroid medicine can affect growth in children. Tell your doctor if your child is not growing at a normal rate while using this medicine.

Before receiving ciclesonide, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to ciclesonide, or any other medication
• have or have ever had:
  • tuberculosis
  • cataracts
  • glaucoma
  • untreated infection
  • herpes infection
• are pregnant or plan to become pregnant
• are breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Use your nasal spray exactly as prescribed by your healthcare provider.

Seasonal allergy symptoms may improve over 1 to 2 weeks; year-round allergy symptoms may improve over 5 weeks. If your symptoms do not improve or get worse, call your healthcare provider.

Patient's Instructions for Use

Ciclesonide nasal spray is supplied in an amber glass bottle in a protective plastic sleeve and should be handled with care.

Preparing For Use

1. Remove ciclesonide nasal spray from its foil pouch. Count 4 months from today and write this new date on the sticker on the carton (the date that is 4 months after removing the bottle from the foil pouch). Peel off the sticker and place it in the space on your nasal spray bottle. It is important that you throw away the nasal spray bottle after this date.
2. Priming ciclesonide nasal spray. Before you use ciclesonide nasal spray for the first time, you will need to prime the bottle. Hold the bottle upright and shake the bottle gently. To prime ciclesonide nasal spray, fully press down on the finger rests of the applicator eight times. 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. Blow your nose to clear your nostrils, if needed.
2. Shake the bottle gently and remove the dust cap.
3. Hold the bottle firmly with your index and middle finger on either side of the applicator (on finger rests) while supporting the base of the bottle with your thumb.
4. Insert applicator tip into one nostril, and close the other nostril with your finger.
5. Tilt your head forward slightly. Keep the bottle upright, and press the finger rests quickly and firmly to activate the pump. Breathe in (inhale) through your nose as you spray. Try not to get any spray in your eyes or directly on your nasal septum (the wall between the two nostrils).
6. Repeat steps 3-5 for the second spray in the same nostril and for each spray in the other nostril.

Each bottle of ciclesonide nasal spray contains enough medicine for you to spray medicine from the bottle 120 times. Do not use a bottle of ciclesonide nasal spray after 120 sprays (not counting the priming sprays) have been used or after the “discard by date” you wrote on the sticker when you opened the foil pouch. You may still see some medicine in the bottle. Talk with your healthcare provider before your supply of ciclesonide nasal spray runs out to see if you should get a refill of your medicine.

Applicator Cleaning Instructions

Wipe the applicator tip with a clean tissue and replace the dust cap, after you use your nasal spray each day.

If the applicator is clogged or needs more thorough cleaning, use the following cleaning instructions (Do not try to unblock the tiny spray hole on the applicator with a pin or other sharp object. Do not twist or try to remove the white plastic pump attached to the medicine bottle.):

1. Remove the dust cap, hold the white plastic pump firmly with one hand and then carefully pull upwards to free the applicator.
2. Wash the dust cap and applicator with warm water.
3. Dry the applicator, and put it back on the bottle. The applicator will snap into place when properly positioned.
4. Prime the unit with one spray or until you see a fine mist.
5. Put the dust cap back on the applicator.

Use your ciclesonide inhalation exactly as prescribed by your healthcare provider.

Priming your ciclesonide inhalation for use

• Remove your ciclesonide inhalation from its package.
• Before you useciclesonide inhalation for the first time or if you have not used your medicine for 10 days in a row, you will need to prime your unit.
• Remove the plastic cap.
• Hold the actuator upright. Spray 3 times into the air away from the face, by pressing down fully onto the center of the dose indicator button.
• Make sure the canister is firmly placed in the mouthpiece each time you use your ciclesonide inhalation.
• You do not need to shake your ciclesonide inhalation unit before you use it.

Using your ciclesonide inhalation

1. Remove the cap from the mouthpiece.
2. Hold the actuator upright, between your thumb, forefinger, and middle finger with the mouthpiece pointing towards you.
3. Breathe out as fully as you comfortably can. Close your lips around the mouthpiece, keeping your tongue below it.
4. While breathing in deeply and slowly, press down on the center of the dose indicator with your finger. Press down fully on the canister until it stops moving in the actuator while delivering your dose.
   • When you have finished breathing in, hold your breath for about 10 seconds, or for as long as is comfortable.
   • Note: It is normal to hear a soft click from the indicator as it counts down during use.
5. Take your finger completely off the center of the dose indicator and remove the inhaler from your mouth. Breathe out gently.
6. Replace the cap to keep the mouthpiece clean.
7. Rinse your mouth with water and spit it out. Do not swallow.

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

If you switched to ciclesonide from another steroid medicine, do not stop using the other steroid suddenly or you may have unpleasant withdrawal symptoms. Talk with your doctor about tapering your steroid dose before stopping completely.

Ciclesonide nasal is usually used once per day. The usual dose of Omnaris is 2 sprays in each nostril once daily. The usual dose of Zetonna is 1 spray in each nostril once daily. Carefully follow your doctor's dosing instructions.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Shake the Omnaris bottle well just before each use.

To use the nasal spray:

• Blow your nose gently. Keep your head upright and insert the tip of bottle into one nostril. Press your other nostril closed with your finger. Breathe in quickly and gently spray the medicine into your nose. Then use the spray in your other nostril.

• Do not blow your nose for at least a few minutes after using the nasal spray.

• Do not use the nasal spray more than once in a 24-hour period.

• If the spray gets in your eyes or mouth or on your skin, rinse with water.

It may take up 2 to 5 weeks before your symptoms improve. Call your doctor if your symptoms do not improve, or if they get worse.

If you use this medicine long-term, you may need frequent eye exams.

Store this medicine in an upright position at room temperature, away from moisture and heat. Do not allow the medicine to freeze. Keep the spray bottle clean and dry.

Keep the Zetonna canister away from open flame or high heat, such as in a car on a hot day. The canister may explode if it gets too hot. Do not puncture or burn an empty canister.

Throw away the Omnaris nasal spray after you have used 120 sprays or 4 months after removing the bottle from the foil pouch, even if there is still medicine left in the bottle.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Zetonna™ in children 12 years of age and older with seasonal and perennial allergic rhinitis. However, safety and efficacy have not been established in children younger than 12 years of age.

Appropriate studies have not been performed on the relationship of age to the effects of Omnaris™ in children younger than 6 years of age with seasonal allergic rhinitis, and in children younger than 12 years of age with perennial allergic rhinitis. Safety and efficacy have not been established in these age groups.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ciclesonide nasal spray in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution in patients receiving ciclesonide nasal spray.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Desmopressin

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bemiparin
• Nadroparin
• Pixantrone

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Cataracts, history of or
• Glaucoma, history of—Use with caution. May make these conditions worse.

• Chicken pox (includes recent exposure) or
• Herpes simplex infection of the eye or
• Infections (bacteria, fungus, virus, or parasite), active or untreated or
• Measles (includes recent exposure) or
• Tuberculosis, active or history of—Can reduce the body's ability to fight infections.

• Injury to the nose or
• Nose surgery, recent or
• Sores or ulcers in the nose, recent—May prevent proper healing of these conditions.

It is very important that your doctor check the progress of you or your child at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you or your child should continue to use it.

If your or your child's symptoms do not improve within a few days or if they become worse, check with your doctor.

This medicine may increase your risk of having some unwanted effects in the nose. Check with your doctor right away if you or your child have bloody mucus, sores inside the nose, unexplained nosebleeds, or a whistling sound when you breathe while you are using this medicine.

You may get infections more easily while you are using this medicine. Avoid being around people who are sick or have infections such as chickenpox or measles or if you have never had these infections. This is especially important for children. Tell your doctor right away if you think you have been exposed to chickenpox or measles.

This medicine may cause thrush (a type of fungus infection) in the nose or throat. Tell your doctor right away if you or your child have white patches in the throat, or pain when you eat or swallow.

This medicine can cause a serious allergic reaction called angioedema. Call your doctor right away if you start to have swelling of your face, lips, tongue, throat, arms, or legs, or if you are having trouble swallowing or breathing while you are using this medicine.

This medicine may cause children to grow more slowly than normal. This would cause a child not to gain weight or get taller. Talk with your doctor if you think your child is not growing properly or if you have any questions about this.

This medicine may increase your risk of having an adrenal gland that is less active than normal. The adrenal gland makes steroids for your body. This is more likely for people who use steroids for a long time or use high doses. Check with your doctor right away if you or your child have any of the following symptoms: darkening of the skin, diarrhea, dizziness, fainting, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting. Rarely, menstrual cycle changes, acne, pimples, or weight gain (fat deposits) around the face, neck, and trunk may occur while taking this medicine.

Check with your doctor immediately if blurred vision, difficulty in reading, or any other change in vision occurs during or after treatment. Your doctor may want you or your child to have your eyes checked by an ophthalmologist (eye doctor).

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloody nose
• fever
• headache
• muscle aches
• nasal discomfort
• sore throat
• stuffy or runny nose
• unusual tiredness or weakness

• Acne or pimples
• blindness
• blistering, burning, crusting, dryness, or flaking of the skin
• bloody mucus or unexplained nosebleeds
• blurred vision
• change in vision
• darkening of the skin
• decreased vision
• diarrhea
• difficulty with breathing or troubled breathing
• difficulty with swallowing
• dizziness
• eye pain
• fainting
• hives
• itching, scaling, severe redness, soreness, or swelling of the skin
• loss of appetite
• loss of consciousness
• loss of vision
• menstrual changes
• mental depression
• nausea
• reddening of the skin, especially around the ears
• skin rash
• swelling of the eyes, eyelids, face, or inside of the nose
• tearing
• tightness in the chest
• vomiting
• weight gain around the face, neck, and trunk
• wheezing
• white patches inside the nose or throat

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Ear pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Treatment of Allergic Rhinitis

Zetonna® (ciclesonide) Nasal Aerosol is indicated for the treatment of symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older.

Zetonna Nasal Aerosol is provided at strength of 37 mcg per actuation strength containing 60 actuations per canister.

In vitro studies and clinical pharmacology studies suggested that des-ciclesonide has no potential for metabolic drug interactions or protein binding-based drug interactions [see Clinical Pharmacology (12.3)]. In a drug interaction study, co-administration of orally inhaled ciclesonide and oral ketoconazole, a potent inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of des-ciclesonide by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. Erythromycin, a moderate inhibitor of cytochrome P450 3A4, had no effect on the pharmacokinetics of either des-ciclesonide or erythromycin following oral inhalation of ciclesonide [see Clinical Pharmacology (12.3)].

Pregnancy

Teratogenic Effects: Pregnancy Category C.

There are no adequate and well-controlled trials in pregnant women. Zetonna should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to physiologic, doses suggests that rodents are more prone to teratogenic effects from corticosteroids than humans.

Oral administration of ciclesonide in rats at approximately 120 times the maximum recommended human daily intranasal dose (MRHDID) in adults (on a mcg/m2 basis at a maternal dose of 900 mcg/kg/day) produced no teratogenicity or other fetal effects. However, subcutaneous administration of ciclesonide in rabbits at similar to MRHDID (on a mcg/m2 basis at a maternal dose of 5 mcg/kg/day) produced fetal toxicity. This included fetal loss, reduced fetal weight, cleft palate, skeletal abnormalities including incomplete ossifications, and skin effects. No toxicity was observed at ¼ of the MRHDID in adults (on a mcg/m2 basis at a maternal dose of 1 mcg/kg/day).

Nonteratogenic Effects: Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.

Nursing Mothers

It is not known if ciclesonide is excreted in human milk. However, other corticosteroids are excreted in human milk. In a study with lactating rats, minimal but detectable levels of radiolabeled ciclesonide were recovered in milk. Caution should be used when Zetonna is administered to nursing women.

Pediatric Use

The safety and effectiveness for seasonal and perennial allergic rhinitis in children 12 years of age and older have been established. The safety and efficacy of Zetonna for treatment of the symptoms of seasonal and perennial allergic rhinitis in patients 11 years of age and younger have not been established.

The safety and efficacy of Zetonna in pediatric patients 6-11 years of age were evaluated in two randomized, double blind, parallel placebo-controlled clinical trials in 1693 pediatric patients with allergic rhinitis. Of the two trials, one was 2 weeks in duration and evaluated the efficacy of two doses of Zetonna (37 mcg and 74 mcg once daily) in 847 patients with seasonal allergic rhinitis. The second clinical trial was 12 weeks in duration and evaluated the efficacy of two doses of Zetonna (37 mcg and 74 mcg once daily) in 846 patients with perennial allergic rhinitis. The trials were similar in design to the trials conducted in adolescents and adults. The primary efficacy endpoint was the difference from placebo in the change from baseline of the average morning and evening reflective total nasal symptom scores (rTNSS) averaged over 2 weeks of treatment in the seasonal allergic rhinitis trial and over the first 6 weeks of treatment in the perennial allergic rhinitis trial. In the 2-week trial in patients with seasonal allergic rhinitis, treatment with Zetonna at either dose failed to demonstrate efficacy. In the 12-week trial in patients with perennial allergic rhinitis, Zetonna 37 mcg and 74 mcg once daily both demonstrated significant improvement in rTNSS compared to placebo with treatment differences of 0.59 (95% CI: 0.23, 0.95) and 0.47 (95% CI: 0.11, 0.83), respectively. The safety profile observed in children 6 to 11 years of age with seasonal or perennial allergic rhinitis was similar to the adverse reactions observed in the clinical trial population of patients 12 year of age and older [see Adverse Reactions (6.1)].

The effect of Zetonna on the HPA axis was evaluated in one placebo-controlled clinical study of 6 weeks in duration in children 6 to11 years of age with perennial allergic rhinitis [see Clinical Pharmacology (12.2)].

Studies in children under 6 years of age have not been conducted.

Controlled clinical trials have shown that intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA)-axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA-axis function. The long-term effects of this reduction in growth velocity associated with intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with intranasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving intranasal corticosteroids, including Zetonna, should be monitored routinely (e.g., via stadiometry). A 52-week, multi-center, double-blind, randomized, placebo-controlled parallel-group trial was conducted to assess the effect of orally inhaled ciclesonide (ALVESCO® Inhalation Aerosol) on growth rate in 609 pediatric patients with mild persistent asthma, aged 5 to 8.5 years. Treatment groups included orally inhaled ciclesonide 40 mcg or 160 mcg or placebo given once daily. Growth was measured by stadiometer height during the baseline, treatment and follow-up periods. The primary comparison was the difference in growth rates between ciclesonide 40 and 160 mcg and placebo groups. Conclusions cannot be drawn from this trial because compliance could not be assured. Ciclesonide blood levels were also not measured during the one-year treatment period. There was no difference in efficacy measures between the placebo and the orally inhaled ciclesonide (ALVESCO® Inhalation Aerosol) groups.

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 minimize the systemic effects of intranasal corticosteroids, each patient should be titrated to the lowest dose that effectively controls his/her symptoms.

The potential for Zetonna to cause growth suppression in susceptible patients or when given at higher than recommended dosages cannot be ruled out.

Geriatric Use

Clinical trials of Zetonna did not include sufficient numbers of patients age 65 and over to determine whether they responded differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

You should not use Zetonna if you are allergic to ciclesonide.

To make sure Zetonna is safe for you, tell your doctor if you have:

• asthma, tuberculosis, or other lung problems;

• any type of infection caused by bacteria, virus, fungus, or parasites;

• glaucoma, cataracts, or herpes infection of the eyes;

• a sore inside your nose that has not yet healed;

• a recent nose injury or surgery; or

• if you have recently used any other steroid medicine (methylprednisolone, prednisone, beclomethasone, fluticasone, dexamethasone, and others).

It is not known whether Zetonna will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether ciclesonide nasal passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Steroid medicine can affect growth in children. Tell your doctor if your child is not growing at a normal rate while using Zetonna.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Applies to ciclesonide nasal: nasal aerosol liquid, nasal spray

Along with its needed effects, ciclesonide nasal (the active ingredient contained in Zetonna) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ciclesonide nasal:

• Bloody nose
• fever
• headache
• muscle aches
• nasal discomfort
• sore throat
• stuffy or runny nose
• unusual tiredness or weakness

• Acne or pimples
• blindness
• blistering, burning, crusting, dryness, or flaking of the skin
• bloody mucus or unexplained nosebleeds
• blurred vision
• change in vision
• darkening of the skin
• decreased vision
• diarrhea
• difficulty with breathing or troubled breathing
• difficulty with swallowing
• dizziness
• eye pain
• fainting
• hives
• itching, scaling, severe redness, soreness, or swelling of the skin
• loss of appetite
• loss of consciousness
• loss of vision
• menstrual changes
• mental depression
• nausea
• reddening of the skin, especially around the ears
• skin rash
• swelling of the eyes, eyelids, face, or inside of the nose
• tearing
• tightness in the chest
• vomiting
• weight gain around the face, neck, and trunk
• wheezing
• white patches inside the nose or throat

Some side effects of ciclesonide nasal may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Ear pain