Pulmicort Flexhaler

Avoid getting this medicine in your eyes.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using budesonide inhalation.

In the U.S.

• Pulmicort
• Pulmicort Flexhaler
• Pulmicort Respules
• Pulmicort Turbuhaler

In Canada

• Pulmicort Nebuamp
• Rhinocort Turbuhaler

Available Dosage Forms:

• Suspension
• Powder
• Solution
• Aerosol Powder
• Aerosol Liquid

Therapeutic Class: Anti-Inflammatory

Pharmacologic Class: Adrenal Glucocorticoid

Budesonide is used to help prevent the symptoms of asthma. When used regularly every day, inhaled budesonide decreases the number and severity of asthma attacks. However, it will not relieve an asthma attack that has already started.

Budesonide is a corticosteroid or steroid (cortisone-like medicine). It works by preventing inflammation (swelling) in the lungs, which makes the asthma attack less severe. Inhaled budesonide may be used with other asthma medicines such as bronchodilators, which are also used to open up narrowed breathing passages in the lungs.

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

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to use as you have been told by the doctor or read the package insert.
• To gain the most benefit, do not miss doses.
• Keep using Pulmicort Flexhaler as you have been told by your doctor or other health care provider, even if you feel well.
• Rinse out mouth after each use. Do not swallow the rinse water. Spit it out.
• If you are taking more than 1 inhaled drug, talk to your doctor about the best order for taking your drugs.
• For breathing in only.
• Prime puffer (inhaler) before first use by twisting brown grip as far as it will go both ways. Then repeat twisting.
• Have your puffer (inhaler) use checked with your doctor at each visit. Read and follow facts on how to use the puffer. Make sure you use the puffer the right way.
• Do not use a spacer with the puffer (inhaler).
• Put the cap back on after you are done using your dose.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of a weak adrenal gland like a very bad upset stomach or throwing up, very bad dizziness or passing out, muscle weakness, feeling very tired, mood changes, not hungry, or weight loss.
• Signs of Cushing's disease like weight gain in the upper back or belly, moon face, very bad headache, or slow healing.
• Swelling of the ankles.
• Feeling very tired or weak.
• Bone or joint pain.
• Change in eyesight.
• Any unexplained bruising or bleeding.
• Redness or white patches in mouth or throat.
• A burning, numbness, or tingling feeling that is not normal.
• This medicine can cause very bad breathing problems right after you take a dose. Sometimes, this may be life-threatening. If you have trouble breathing, breathing that is worse, wheezing, or coughing after using this medicine, use a rescue inhaler and get medical help right away.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Pulmicort Flexhaler (budesonide inhalation powder), please talk with your doctor, nurse, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Pulmicort Flexhaler. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Pulmicort Flexhaler.

Review Date: October 4, 2017

Local Effects

In clinical studies, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in patients treated with Pulmicort Flexhaler. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral antifungal) therapy while treatment with Pulmicort Flexhaler continues, but at times, therapy with Pulmicort Flexhaler may need to be interrupted. Patients should rinse the mouth after inhalation of Pulmicort Flexhaler.

Deterioration of Asthma or Acute Episodes

Pulmicort Flexhaler is not a bronchodilator and is not indicated for the rapid relief of bronchospasm or other acute episodes of asthma. Patients should be instructed to contact their physician immediately if episodes of asthma not responsive to their usual doses of bronchodilators occur during the course of treatment with Pulmicort Flexhaler. During such episodes, patients may require therapy with oral corticosteroids.

An inhaled short acting beta2-agonist, not Pulmicort Flexhaler, should be used to relieve acute symptoms such as shortness of breath. When prescribing Pulmicort Flexhaler, the physician must also provide the patient with an inhaled, short-acting beta2-agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice-daily (morning and evening) use of Pulmicort Flexhaler.

Hypersensitivity Reactions Including Anaphylaxis

Hypersensitivity reactions including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm have been reported with use of Pulmicort Flexhaler. Discontinue Pulmicort Flexhaler if such reactions occur [see Contraindications (4), Adverse Reactions (6)].

Pulmicort Flexhaler contains small amounts of lactose, which contains trace levels of milk proteins. It is possible that cough, wheezing, or bronchospasm may occur in patients who have a severe milk protein allergy [see Contraindications (4), Adverse Reactions (6.2)].

Immunosuppression

Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox 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 been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects 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 chicken pox, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated (see the respective package inserts for complete VZIG and IG prescribing information). If chicken pox develops, treatment with antiviral agents may be considered. The immune responsiveness to varicella vaccine was evaluated in pediatric patients with asthma ages 12 months to 8 years with budesonide inhalation suspension.

An open-label, nonrandomized clinical study examined the immune responsiveness to varicella vaccine in 243 asthma patients 12 months to 8 years of age who were treated with budesonide inhalation suspension 0.25 mg to 1 mg daily (n=151) or non-corticosteroid asthma therapy (n=92) (i.e., beta2-agonists, leukotriene receptor antagonists, cromones). The percentage of patients developing a seroprotective antibody titer of ≥5.0 (gpELISA value) in response to the vaccination was similar in patients treated with budesonide inhalation suspension (85%), compared to patients treated with non-corticosteroid asthma therapy (90%). No patient treated with budesonide inhalation suspension developed chicken pox as a result of vaccination.

Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract, untreated systemic fungal, bacterial, viral or parasitic infections, or ocular herpes simplex.

Transferring Patients from Systemic Corticosteroid Therapy

Particular care is needed for patients who are transferred from systemically active corticosteroids to Pulmicort Flexhaler because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.

Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn.

During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although Pulmicort Flexhaler may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.

During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.

Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Pulmicort Flexhaler. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with Pulmicort Flexhaler. Lung function (mean forced expiratory volume in 1 second [FEV1] or morning peak expiratory flow [PEF]), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.

Transfer of patients from systemic corticosteroid therapy to Pulmicort Flexhaler may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions). Some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.

Hypercorticism and Adrenal Suppression

Pulmicort Flexhaler will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since budesonide is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of Pulmicort Flexhaler in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing Pulmicort Flexhaler.

Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with Pulmicort Flexhaler should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.

It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients, particularly when budesonide is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of Pulmicort Flexhaler should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma symptoms.

Interactions with Strong Cytochrome P450 3A4 Inhibitors

Caution should be exercised when considering the co-administration of Pulmicort Flexhaler with ketoconazole, and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systemic exposure to budesonide may occur [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Reduction in Bone Mineral Density

Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, post menopausal status, tobacco use, advance age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care.

Effects on Growth

Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving Pulmicort Flexhaler routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including Pulmicort Flexhaler, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration (2.1), Use in Specific Populations (8.4)].

Glaucoma and Cataracts

Glaucoma, increased intraocular pressure, and cataracts have been reported following the long-term administration of inhaled corticosteroids, including budesonide. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.

Paradoxical Bronchospasm and Upper Airway Symptoms

As with other inhaled asthma medications, Pulmicort Flexhaler can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with Pulmicort Flexhaler, it should be treated immediately with an inhaled, short-acting beta2-bronchodilator. Pulmicort Flexhaler should be discontinued immediately, and alternative therapy should be instituted.

Eosinophilic Conditions and Churg-Strauss Syndrome

In rare cases, patients on inhaled corticosteroids may present with systemic eosinophilic conditions. Some of these patients have clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of inhaled corticosteroids. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between budesonide and these underlying conditions has not been established.

Inhibitors of Cytochrome P450 3A4

The main route of metabolism of corticosteroids, including budesonide, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased. Concomitant administration of CYP3A4 may inhibit the metabolism of, and increase the systemic exposure to, budesonide. Caution should be exercised when considering the co-administration of Pulmicort Flexhaler with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.7)].

Pulmicort Flexhaler is available as a dry powder for inhalation containing budesonide in the following 2 strengths: 90 mcg and 180 mcg. Each dosage strength contains 60 or 120 actuations per device. 180 mcg/dose (NDC 0186-0916-12) with a target fill weight of 225 mg (range 200-250), and 90 mcg/dose, 60 dose (NDC 0186-0917-06) with a target fill weight of 165 mg (range 140-190).

Pulmicort Flexhaler consists of a number of assembled plastic details, the main parts being the dosing mechanism, the storage unit for drug substance, and the mouthpiece. The inhaler is protected by a white outer tubular cover screwed onto the inhaler. The body of the inhaler is white and the turning grip is brown. The Pulmicort Flexhaler inhaler cannot be refilled and should be discarded when empty.

The number in the middle of the dose indicator window shows how many doses are left in the inhaler. The inhaler is empty when the number zero (“0”) on the red background reaches the middle of the window. If the unit is used beyond the point at which the zero reaches the middle of the window, the correct amount of medication may not be obtained and the unit should be discarded.

Store in a dry place at controlled room temperature 20-25°C (68-77°F) [see USP] with the cover tightly in place. Keep out of the reach of children.

NDC 0186-0917-06

Pulmicort

Flexhaler™ 90 mcg

(budesonide inhalation

Powder, 90 mcg)

90 mcg

For Oral Inhalation.

60 Metered Doses

Dispense with enclosed Patient

Information and Instructions for Use.

Rx only

AstraZeneca