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Budesonide And Formoterol Fumarate

FDA Drug Information • Also known as: Breyna

Brand Names
Breyna
Drug Class
Corticosteroid [EPC]
Route
RESPIRATORY (INHALATION)
Dosage Form
AEROSOL, METERED
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION BREYNA 80 mcg/4.5 mcg and BREYNA 160 mcg/4.5 mcg each contain micronized budesonide and micronized formoterol fumarate dihydrate for oral inhalation only. Each BREYNA 80 mcg/4.5 mcg and BREYNA 160 mcg/4.5 mcg canister is formulated as a hydrofluoroalkane (HFA 227; 1,1,1,2,3,3,3-heptafluoropropane)-propelled pressurized metered dose inhaler containing 120 actuations [see Dosage Forms and Strengths (3) and How Supplied/Storage and Handling (16) ] . After priming, each actuation meters either 91/5.1 mcg or 181/5.1 mcg from the valve and delivers either 80/4.5 mcg, or 160/4.5 mcg (budesonide micronized/formoterol fumarate dihydrate micronized) from the actuator. The actual amount of drug delivered to the lung may depend on patient factors, such as the coordination between actuation of the device and inspiration through the delivery system. BREYNA also contains povidone K25 USP as a suspending agent and polyethylene glycol 1000 NF as a lubricant. BREYNA should be primed before using for the first time by releasing two test sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped, prime the inhaler again by shaking well for 5 seconds before each spray and releasing two test sprays into the air away from the face. One active component of BREYNA is budesonide, a corticosteroid designated chemically as (RS)‑11β, 16α, 17,21-Tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. Budesonide is provided as a mixture of two epimers (22R and 22S). The empirical formula of budesonide is C 25 H 34 O 6 and its molecular weight is 430.5. Its structural formula is: Budesonide is a white to off-white, tasteless, odorless powder which is practically insoluble in water and in heptane, sparingly soluble in ethanol, and freely soluble in chloroform. Its partition coefficient between octanol and water at pH 7.4 is 1.6 x 10 3 . The...

What Is Budesonide And Formoterol Fumarate Used For?

1 INDICATIONS AND USAGE BREYNA is a combination product containing a corticosteroid and a long-acting beta 2 -adrenergic agonist indicated for:

  • Treatment of asthma in patients 6 years of age and older. ( 1.1 )
  • Maintenance treatment of airflow obstruction and reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and/or emphysema. ( 1.2 ) Important limitations:
  • Not indicated for the relief of acute bronchospasm. ( 1.1 , 1.2 ) 1.1 Treatment of Asthma BREYNA is indicated for the treatment of asthma in patients 6 years of age and older. BREYNA should be used for patients not adequately controlled on a long-term asthma-control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an inhaled corticosteroid and long-acting beta 2 -adrenergic agonist (LABA). Important Limitations of Use:
  • BREYNA is NOT indicated for the relief of acute bronchospasm. 1.2 Maintenance Treatment of Chronic Obstructive Pulmonary Disease BREYNA 160 mcg/4.5 mcg is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and/or emphysema. BREYNA 160 mcg/4.5 mcg is also indicated to reduce exacerbations of COPD. BREYNA 160 mcg/4.5 mcg is the only strength indicated for the treatment of COPD. Important Limitations of Use:
  • BREYNA is NOT indicated for the relief of acute bronchospasm.

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION For oral inhalation only.

  • Treatment of asthma in patients 12 years and older: 2 inhalations of BREYNA 80 mcg/4.5 mcg or 160 mcg/4.5 mcg twice daily. Starting dosage is based on asthma severity. ( 2.2 )
  • Treatment of asthma in patients aged 6 to less than 12 years: 2 inhalations of BREYNA 80 mcg/4.5 mcg twice daily. ( 2.2 )
  • Maintenance treatment in COPD: 2 inhalations of BREYNA 160 mcg/4.5 mcg twice daily. ( 2.3 ) 2.1 Administration Information BREYNA should be administered as 2 inhalations twice daily (morning and evening, approximately 12 hours apart), every day by the orally inhaled route only. After inhalation, the patient should rinse the mouth with water without swallowing. Prime BREYNA before using for the first time by releasing two test sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped, prime the inhaler again by shaking well before each spray and releasing two test sprays into the air away from the face. More frequent administration or a higher number of inhalations (more than 2 inhalations twice daily) of the prescribed strength of BREYNA is not recommended as some patients are more likely to experience adverse effects with higher doses of formoterol. Patients using BREYNA should not use additional LABA for any reason [see Warnings and Precautions (5.3 , 5.12) ] . 2.2 Asthma If asthma symptoms arise in the period between doses, an inhaled, short-acting beta 2 -agonist should be taken for immediate relief. Adult and Adolescent Patients 12 Years of Age and Older For patients 12 years of age and older, the dosage is 2 inhalations of BREYNA 80 mcg/4.5 mcg or BREYNA 160 mcg/4.5 mcg twice daily. The recommended starting dosages for BREYNA for patients 12 years of age and older are based upon patients’ asthma severity or level of control of asthma symptoms, and risk of exacerbations on current inhaled corticosteroids. The maximum recommended dosage in adult and adolescent patients 12 years and older is BREYNA 160 mcg/4.5 mcg, two inhalations twice daily. Improvement in asthma control following inhaled administration of BREYNA can occur within 15 minutes of beginning treatment, although maximum benefit may not be achieved for 2 weeks or longer after beginning treatment. Individual patients will experience a variable time to onset and degree of symptom relief. For patients who do not respond adequately to the starting dose after 1-2 weeks of therapy with BREYNA 80 mcg/4.5 mcg, replacement with BREYNA 160 mcg/4.5 mcg may provide additional asthma control. If a previously effective dosage regimen of BREYNA fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options, (e.g., replacing the lower strength of BREYNA with the higher strength, adding additional inhaled corticosteroid, or initiating oral corticosteroids) should...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS LABA use may result in the following:

  • Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions (5.1) ] .
  • Cardiovascular and central nervous system effects [see Warnings and Precautions (5.12) ] . Systemic and inhaled corticosteroid use may result in the following:
  • Candida albicans infection [see Warnings and Precautions (5.4) ]
  • Pneumonia or lower respiratory tract infections in patients with COPD [see Warnings and Precautions (5.5) ]
  • Immunosuppression [see Warnings and Precautions (5.6) ]
  • Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8) ]
  • Growth effects in pediatric patients [see Warnings and Precautions (5.14) ]
  • Glaucoma and cataracts [see Warnings and Precautions (5.15) ] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Most common adverse reactions (incidence ≥ 3%) are:
  • Asthma: nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis. ( 6.1 )
  • COPD: nasopharyngitis, oral candidiasis, bronchitis, sinusitis, upper respiratory tract infections. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience in Asthma Adult and Adolescent Patients 12 Years of Age and Older The overall safety data in adults and adolescents are based upon 10 active- and placebo-controlled clinical trials in which 3393 patients ages 12 years and older (2052 females and 1341 males) with asthma of varying severity were treated with budesonide and formoterol fumarate dihydrate inhalation aerosol 80 mcg/4.5 mcg or 160 mcg/4.5 mcg taken 2 inhalations once or twice daily for 12 to 52 weeks. In these trials, the patients on budesonide and formoterol fumarate dihydrate inhalation aerosol had a mean age of 38 years and were predominantly Caucasian (82%). The incidence of common adverse events in Table 2 below is based upon pooled data from three 12‑week, double-blind, placebo-controlled clinical studies in which 401 adult and adolescent patients (148 males and 253 females) age 12 years and older were treated with 2 inhalations of budesonide and formoterol fumarate dihydrate inhalation aerosol 80 mcg/4.5 mcg or budesonide and formoterol fumarate dihydrate inhalation aerosol 160 mcg/4.5 mcg twice daily. The budesonide and formoterol fumarate dihydrate inhalation aerosol group was composed of mostly Caucasian (84%) patients with a mean age of 38 years, and a mean percent predicted FEV 1 at baseline of 76 and 68 for the 80 mcg/4.5 mcg and 160 mcg/4.5 mcg treatment groups, respectively. Control arms for comparison included 2 inhalations of budesonide HFA metered dose inhaler (MDI) 80 mcg or 160 mcg, formoterol dry powder inhaler (DPI) 4.5 mcg, or placebo (MDI and DPI) twice daily. Table 2 includes all adverse events that occurred at an incidence of ≥ 3% in any one budesonide and formoterol fumarate dihydrate inhalation aerosol group and more commonly than in the placebo group with twice-daily dosing. In considering these data, the increased average duration of patient exposure for budesonide and formoterol fumarate dihydrate inhalation aerosol patients should be taken into account, as incidences are not adjusted for an imbalance of treatment duration. Table 2. Adverse Reactions Occurring at an Incidence of ≥ 3% and More Commonly Than Placebo in the Budesonide and Formoterol Fumarate Dihydrate Inhalation Aerosol Groups: Pooled Data from Three 12-week, Double-blind, Placebo-controlled Clinical Asthma Trials in Patients 12 Years and Older Treatment All treatments were administered as 2 inhalations twice...

    • Drug Interactions

    7 DRUG INTERACTIONS In clinical studies, concurrent administration of budesonide and formoterol fumarate dihydrate inhalation aerosol and other drugs, such as short-acting beta 2 -agonists, intranasal corticosteroids, and antihistamines/decongestants has not resulted in an increased frequency of adverse reactions. No formal drug interaction studies have been performed with budesonide and formoterol fumarate dihydrate inhalation aerosol.

  • Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects. ( 7.1 )
  • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of formoterol on vascular system. ( 7.2 )
  • Beta-blockers: Use with caution. May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. ( 7.3 )
  • Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non-potassium-sparing diuretics may worsen with concomitant beta-agonists. ( 7.4 ) 7.1 Inhibitors of Cytochrome P4503A4 The main route of metabolism of corticosteroids, including budesonide, a component of BREYNA, 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 coadministration of BREYNA 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 (5.9) ] . 7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants BREYNA should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of formoterol, a component of BREYNA, on the vascular system may be potentiated by these agents. In clinical trials with budesonide and formoterol fumarate dihydrate inhalation aerosol, a limited number of COPD and asthma patients received tricyclic antidepressants, and, therefore, no clinically meaningful conclusions on adverse events can be made. 7.3 Beta-Adrenergic Receptor Blocking Agents Beta-blockers (including eye drops) may not only block the pulmonary effect of beta-agonists, such as formoterol, a component of BREYNA, but may produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselective beta-blockers could be considered, although they should be administered with...

    • Contraindications

    4 CONTRAINDICATIONS The use of BREYNA is contraindicated in the following conditions:

  • Primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required.
  • Hypersensitivity to any of the ingredients in BREYNA.
  • Primary treatment of status asthmaticus or acute episodes of asthma or COPD requiring intensive measures ( 4 )
  • Hypersensitivity to any of the ingredients in BREYNA ( 4 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of budesonide and formoterol fumarate dihydrate inhalation aerosol or one of its individual components, formoterol fumarate, in pregnant women; however studies are available for the other component budesonide. In animal reproduction studies, budesonide and formoterol fumarate dihydrate, administered by the inhalation route, was teratogenic, embryocidal, and reduced fetal weights in rats at less than the maximum recommended human daily inhalation dose (MRHDID) on a mcg/m 2 basis. Budesonide alone, administered by the subcutaneous route, was teratogenic, embryocidal, and reduced fetal weights in rats and rabbits at less than the MRHDID, but these effects were not seen in rats that received inhaled doses up to 4 times the MRHDID. Studies of pregnant women have not shown that inhaled budesonide alone increases the risk of abnormalities when administered during pregnancy. Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. Formoterol fumarate alone, administered by the oral route, was teratogenic in rats and rabbits at 1600 and 65,000 times the MRHDID, respectively. Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 110 times the MRHDID. These adverse effects generally occurred at large multiples of the MRHDID when formoterol fumarate was administered by the oral route to achieve high systemic exposures. No teratogenic, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 375 times the MRHDID. The estimated background risk of major birth defects and miscarriage of the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical...

    Nursing Mothers The disposition of budesonide when delivered by inhalation from a dry powder inhaler at doses of 200 or 400 mcg twice daily for at least 3 months was studied in eight lactating women with asthma from 1 to 6 months postpartum. Systemic exposure to budesonide in these women appears to be comparable to that in non-lactating women with asthma from other studies. Breast milk obtained over eight hours post-dose revealed that the maximum concentration of budesonide for the 400 and 800 mcg total daily doses was 0.39 and 0.78 nmol/L, respectively, and occurred within 45 minutes after dosing. The estimated oral daily dose of budesonide from breast milk to the infant is approximately 0.007 and 0.014 mcg/kg/day for the two dose regimens used in this study, which represents approximately 0.3% to 1% of the dose inhaled by the mother. Budesonide levels in plasma samples obtained from five infants at about 90 minutes after breastfeeding (and about 140 minutes after drug administration to the mother) were below quantifiable levels (< 0.02 nmol/L in four infants and < 0.04 nmol/L in one infant) [see Use in Specific Populations (8.2) ] .

    Overdosage

    10 OVERDOSAGE BREYNA BREYNA contains both budesonide and formoterol fumarate dihydrate; therefore, the risks associated with overdosage for the individual components described below apply to BREYNA. In pharmacokinetic studies, single doses of 960/54 mcg (12 actuations of budesonide and formoterol fumarate dihydrate inhalation aerosol 80 mcg/4.5 mcg) and 1280/36 mcg (8 actuations of 160 mcg/4.5 mcg), were administered to patients with COPD. A total of 1920/54 mcg (12 actuations of budesonide and formoterol fumarate dihydrate inhalation aerosol 160 mcg/4.5 mcg) was administered as a single dose to both healthy subjects and patients with asthma. In a long-term active-controlled safety study in adolescent and adult asthma patients 12 years of age and older, budesonide and formoterol fumarate dihydrate inhalation aerosol 160 mcg/4.5 mcg was administered for up to 12 months at doses up to twice the highest recommended daily dose. There were no clinically significant adverse reactions observed in any of these studies. Budesonide The potential for acute toxic effects following overdose of budesonide is low. If used at excessive doses for prolonged periods, systemic corticosteroid effects such as hypercorticism may occur [see Warnings and Precautions (5) ] . Budesonide at five times the highest recommended dose (3200 mcg daily) administered to humans for 6 weeks caused a significant reduction (27%) in the plasma cortisol response to a 6-hour infusion of ACTH compared with placebo (+1%). The corresponding effect of 10 mg prednisone daily was a 35% reduction in the plasma cortisol response to ACTH. Formoterol An overdose of formoterol would likely lead to an exaggeration of effects that are typical for beta 2 ‑agonists: seizures, angina, hypertension, hypotension, tachycardia, atrial and ventricular tachyarrhythmias, nervousness, headache, tremor, palpitations, muscle cramps, nausea, dizziness, sleep disturbances, metabolic acidosis, hyperglycemia, hypokalemia. As with all...

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING BREYNA (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol is available in two strengths and is supplied in the following package sizes: Dosage Forms and Strengths Package Size NDC BREYNA Inhalations 80 mcg/4.5 mcg 120 0378-7502-32 BREYNA Inhalations 160 mcg/4.5 mcg 120 0378-7503-32 Each strength is supplied as a pressurized aluminum canister with an attached counting device, a blue plastic actuator body with a blue mouthpiece, and attached grey dust cap. Each 120 inhalation canister has a net fill weight of 10.3 grams. Each canister is packaged in a foil overwrap pouch with desiccant sachet and placed into a carton. Each carton contains one canister and a Patient Information leaflet. The BREYNA canister should only be used with the BREYNA actuator, and the BREYNA actuator should not be used with any other inhalation drug product. The correct amount of medication in each inhalation cannot be ensured after the labeled number of inhalations from the canister have been used, even though the inhaler may not feel completely empty and may continue to operate. The inhaler should be discarded when the labeled number of inhalations have been used or within 3 months after removal from the foil pouch. Never immerse the canister into water to determine the amount remaining in the canister (“float test”). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Store the inhaler with the mouthpiece down. For best results, the canister should be at room temperature before use. Shake well for 5 seconds before using. Keep out of the reach of children. Avoid spraying in eyes. CONTENTS UNDER PRESSURE. Do not puncture or incinerate. Do not store near heat or open flame. Exposure to temperatures over 120ºF may cause bursting. Never throw container into fire or incinerator.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.