Pulmonary – Combination Products

Drug UPDATES:  BEVESPI AEROSPHERE ™ (glycopyrrolate and formoterol fumarate ) inhalation aerosol [Drug information ]     REVIEW PACKAGE INSERT FOR POSSIBLE UPDATES PACKAGE INSERT -Dosing:  Click (+) next to Dosage and Administration section (drug info link) BOXED WARNING: WARNING: ASTHMA-RELATED DEATH Long-acting beta2-adrenergic agonists (LABAs) increase the risk of asthma-related death. Data from a large placebo-controlled US trial that compared the safety of another LABA (salmeterol) with placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol. This finding with salmeterol is considered a class effect of all LABAs, including formoterol fumarate, one of the active ingredients in BEVESPI AEROSPHERE. The safety and efficacy of BEVESPI AEROSPHERE in patients with asthma have not been established. BEVESPI AEROSPHERE is not indicated for the treatment of asthma. Initial U.S. Approval:  2016 Mechanism of Action: BEVESPI AEROSPHERE contains both glycopyrrolate and formoterol fumarate. The mechanism of action described below for the individual components apply to BEVESPI AEROSPHERE. These drugs represent two different classes of medications (a long-acting muscarinic antagonist and a long-acting selective beta2-adrenoceptor agonist) that have different effects on clinical and physiological indices. Glycopyrrolate Glycopyrrolate is a long-acting antimuscarinic agent which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of the M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methylcholine and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted more than 12 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of glycopyrrolate is predominantly a site-specific effect. Formoterol Fumarate Formoterol fumarate is a long-acting selective beta2-adrenergic agonist (beta2-agonist) with a rapid onset of action. Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1-receptors. The in vitro binding selectivity to beta2- over beta1-adrenoceptors is higher for formoterol than for albuterol (5 times), whereas salmeterol has a higher (3 times) beta2-selectivity ratio than formoterol. Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol fumarate, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that formoterol fumarate is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Formoterol fumarate also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown. INDICATIONS AND USAGE: BEVESPI AEROSPHERE is a combination of glycopyrrolate, an anticholinergic, and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA) indicated for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). (1) Limitation of Use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma. DOSAGE AND ADMINISTRATION: For oral inhalation only. Maintenance treatment of COPD: 2 inhalations of BEVESPI AEROSPHERE twice daily. CONTRAINDICATIONS All LABAs are contraindicated in patients with asthma without use of a long-term asthma controller medication. (4) BEVESPI AEROSPHERE is not indicated for the treatment of asthma. (1) Hypersensitivity to glycopyrrolate, formoterol fumarate, or to any component of this product. HOW SUPPLIED: Inhalation aerosol: Pressurized metered dose inhaler containing a combination of glycopyrrolate (9 mcg) and formoterol fumarate (4.8 mcg) as an inhalation aerosol. Two inhalations equal one dose. BEVESPI AEROSPHERE Inhalation Aerosol is supplied as a pressurized aluminum canister with an attached dose indicator, a white plastic actuator and mouthpiece, and an orange dust cap. Each 120 inhalation canister has a net fill weight of 10.7 grams. Each canister is packaged in a foil pouch with desiccant sachet and is placed into a carton. Each carton contains one canister and a Medication Guide (NDC 0310-4600-12). The BEVESPI AEROSPHERE canister should only be used with the BEVESPI AEROSPHERE actuator, and the BEVESPI AEROSPHERE actuator should not be used with any other inhalation drug product. The correct amount of medication in each inhalation cannot be assured after the label number of inhalations from the canister have been used, when the dose indicator display window shows zero, even though the canister may not feel completely empty. BEVESPI AEROSPHERE should be discarded when the dose indicator display window shows zero or 3 months after removal from the foil pouch, whichever comes first. Never immerse the canister into water to determine the amount remaining in the canister (“float test”). Store at controlled room temperature 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP].

COMBIVENT® RESPIMAT®

INDICATIONS AND USAGE
COMBIVENT RESPIMAT Inhalation Spray is a combination of an anticholinergic and beta-adrenergic indicated for:

Patients with chronic obstructive pulmonary disease (COPD) on a regular aerosol bronchodilator who continue to have evidence of bronchospasm and who require a second bronchodilator

DOSAGE AND ADMINISTRATION
For oral inhalation only

One inhalation four times a day, not to exceed six inhalations in 24 hours

DOSAGE FORMS AND STRENGTHS
Inhalation spray: 20 mcg ipratropium bromide (monohydrate) and 100 mcg albuterol (equivalent to 120 mcg albuterol sulfate) per actuation with the COMBIVENT RESPIMAT inhaler.
COMBIVENT RESPIMAT inhaler delivers 120 metered actuations.

WARNINGS AND PRECAUTIONS

• Paradoxical bronchospasm: Discontinue COMBIVENT RESPIMAT immediately and treat with alternative therapy if paradoxical bronchospasm occurs
• Patients with cardiovascular system disorders: Use with caution because of beta-adrenergic stimulation
• Ocular effects: Advise patients to avoid spraying into eyes and to contact a physician if blurred vision, halos, or other visual disturbances occur. Monitor patients with narrow-angle glaucoma.
• Urinary retention: Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction
• Hypersensitivity reactions including anaphylaxis: Discontinue COMBIVENT RESPIMAT and institute alternative therapy if immediate hypersensitivity reactions such as urticaria, angioedema, rash, bronchospasm, anaphylaxis, or oropharyngeal edema occur
• Coexisting conditions: Use with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus

====Previous formulation==========
Combivent ® - albuterol + ipratropium
INDICATIONS AND USAGE
COMBIVENT Inhalation Aerosol is indicated for use in patients with chronic obstructive pulmonary disease (COPD) on a regular aerosol bronchodilator who continue to have evidence of bronchospasm and who require a second bronchodilator.

CONTRAINDICATIONS
COMBIVENT Inhalation Aerosol is contraindicated in patients with a history of hypersensitivity to soya lecithin or related food products such as soybean and peanut. COMBIVENT Inhalation Aerosol is also contraindicated in patients hypersensitive to any other components of the drug product or to atropine or its derivatives.

DOSAGE AND ADMINISTRATION
The dose of COMBIVENT® Inhalation Aerosol is two inhalations four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours. Safety and efficacy of additional doses of COMBIVENT Inhalation Aerosol beyond 12 puffs/24 hours have not been studied. Also, safety and efficacy of extra doses of ipratropium or albuterol in addition to the recommended doses of Combivent® (ipratropium bromide and albuterol sulfate) Inhalation Aerosol have not been studied. It is recommended to “test-spray” three times before using for the first time and in cases where the aerosol has not been used for more than 24 hours. Avoid spraying into eyes.

HOW SUPPLIED
COMBIVENT Inhalation Aerosol is supplied as a metered-dose inhaler with a white mouthpiece that has a clear, colorless sleeve and an orange protective cap. The COMBIVENT Inhalation Aerosol canister is to be used only with the COMBIVENT Inhalation Aerosol mouthpiece and not with other mouthpieces. This mouthpiece should not be used with other aerosol medications. Each actuation meters 21 mcg of ipratropium bromide and 120 mcg of albuterol sulfate from the valve and delivers 18 mcg of ipratropium bromide and 103 mcg of albuterol sulfate (equivalent to 90 mcg albuterol base) from the mouthpiece.

Each 14.7 gram canister provides sufficient medication for 200 actuations (NDC 0597-0013-14).

WARNING: ASTHMA-RELATED DEATH
See full prescribing information for complete boxed warning.

Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in ANORO ELLIPTA, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths in subjects receiving salmeterol. This finding with salmeterol is considered a class effect of all LABA, including vilanterol.

The safety and efficacy of ANORO ELLIPTA in patients with asthma have not been established. ANORO ELLIPTA is not indicated for the treatment of asthma.

ANORO ELLIPTA is an inhalation powder drug product for delivery of a combination of umeclidinium (an anticholinergic) and vilanterol (a LABA) to patients by oral inhalation.

INDICATIONS AND USAGE:
ANORO ELLIPTA is a combination of umeclidinium, an anticholinergic, and vilanterol, a long-acting beta2-adrenergic agonist (LABA), indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).

Important limitations: Not indicated for the relief of acute bronchospasm or for the treatment of asthma.

DOSAGE AND ADMINISTRATION:
For oral inhalation only.
Maintenance treatment of COPD: 1 inhalation of ANORO ELLIPTA once daily.

ANORO ELLIPTA should be taken at the same time every day. Do not use ANORO ELLIPTA more than 1 time every 24 hours.

No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment

DOSAGE FORMS AND STRENGTHS:
Inhalation Powder. Inhaler containing 2 double-foil blister strips of powder formulation for oral inhalation. One strip contains umeclidinium 62.5 mcg per blister and the other contains vilanterol 25 mcg per blister.

Drug UPDATES:  STIOLTO™ RESPIMAT ® (tiotropium bromide and olodaterol) inhalation spray, for oral inhalation use [Drug information  ]     Click link for the latest monograph Dosing:  Click (+) next to Dosage and Administration section (drug info link) Initial U.S. Approval:  2015 Mechanism of Action: STIOLTO RESPIMAT- STIOLTO RESPIMAT contains both tiotropium and olodaterol. The properties described below for the individual components apply to STIOLTO RESPIMAT. These drugs represent 2 different classes of medication (an anticholinergic and a beta-agonist) that have different effects on clinical and physiological indices. Tiotropium: Tiotropium is a long-acting, muscarinic antagonist which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methacholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site-specific effect. Olodaterol: Olodaterol is a long-acting beta2-adrenergic agonist (LABA). The compound exerts its pharmacological effects by binding and activation of beta2-adrenoceptors after topical administration by inhalation. Activation of these receptors in the airways results in a stimulation of intracellular adenyl cyclase, an enzyme that mediates the synthesis of cyclic-3’, 5’ adenosine monophosphate (cAMP). Elevated levels of cAMP induce bronchodilation by relaxation of airway smooth muscle cells. In vitro studies have shown that olodaterol has 241-fold greater agonist activity at beta2-adrenoceptors compared to beta1-adrenoceptors and 2299-fold greater agonist activity compared to beta3-adrenoceptors. The clinical significance of these findings is unknown. Beta-adrenoceptors are divided into three subtypes: beta1-adrenoceptors predominantly expressed on cardiac muscle, beta2-adrenoceptors predominantly expressed on airway smooth muscle, and beta3-adrenoceptors predominantly expressed on adipose tissue. Beta2-agonists cause bronchodilation. Although the beta2-adrenoceptor is the predominant adrenergic receptor in the airway smooth muscle, it is also present on the surface of a variety of other cells, including lung epithelial and endothelial cells and in the heart. The precise function of beta2-receptors in the heart is not known, but their presence raises the possibility that even highly selective beta2-agonists may have cardiac effects. INDICATIONS AND USAGE: 1.1 Maintenance Treatment of COPD STIOLTO RESPIMAT is a combination of tiotropium and olodaterol indicated for long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Important Limitations of Use STIOLTO RESPIMAT is not indicated to treat acute deteriorations of COPD [See Warnings and Precautions (5.2)]. STIOLTO RESPIMAT is not indicated to treat asthma. The safety and effectiveness of STIOLTO RESPIMAT in asthma have not been established. HOW SUPPLIED:  Inhalation spray: Each actuation from the mouthpiece contains 3.124 mcg tiotropium bromide monohydrate, equivalent to 2.5 mcg tiotropium, and 2.736 mcg olodaterol hydrochloride, equivalent to 2.5 mcg olodaterol. Two actuations equal one dose.

Drug UPDATES:  UTIBRONTM NEOHALER® (indacaterol and glycopyrrolate) inhalation powder, for oral inhalation use [Drug information ]     Click link for the latest monograph Dosing:  Click (+) next to Dosage and Administration section (drug info link) Initial U.S. Approval:  2015 Mechanism of Action: UTIBRON NEOHALER contains both indacaterol and glycopyrrolate. The mechanisms of action described below for the individual components apply to UTIBRON NEOHALER. These drugs represent 2 different classes of medications (a LABA and an anticholinergic) that have different and additive effects on clinical and physiological indices. Indacaterol: Indacaterol is a long-acting beta2-adrenergic agonist (LABA). When inhaled, indacaterol acts locally in the lung as a bronchodilator. Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-adrenergic receptors in the human heart comprising 10% to 50% of the total adrenergic receptors. The precise function of these receptors is not known, but their presence raises the possibility that even highly selective beta2-adrenergic agonists may have cardiac effects. The pharmacological effects of beta2-adrenoceptor agonist drugs, including indacaterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3’, 5’-adenosine monophosphate (cyclic monophosphate). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro studies have shown that indacaterol has more than 24-fold greater agonist activity at beta2-receptors compared to beta1-receptors and 20-fold greater agonist activity compared to beta3-receptors. The clinical significance of these findings is unknown. Glycopyrrolate: Glycopyrrolate is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methacholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of glycopyrrolate is predominantly a site-specific effect. INDICATIONS AND USAGE: UTIBRON NEOHALER is a combination of indacaterol, a long-acting beta2-adrenergic agonist (LABA), and glycopyrrolate, an anticholinergic, indicated for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD) (1) Limitations of Use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma. HOW SUPPLIED: Inhalation powder: UTIBRON capsules contain 27.5 mcg of indacaterol and 15.6 mcg glycopyrrolate inhalation powder for use with the NEOHALER device.

WARNING: ASTHMA-RELATED DEATH
Long-acting beta2-adrenergic agonists (LABAs), such as salmeterol, one of the active ingredients in ADVAIR DISKUS®, increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of salmeterol (SEREVENT®showed an increase in asthma-related deaths in patients receiving salmeterol (13 deaths out of 13,176 patients treated for 28 weeks on salmeterol versus 3 o Inhalation Aerosol) or placebo added to usual asthma therapy ut of 13,179 patients on placebo). Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABAs. Available data from controlled clinical trials suggest that LABAs increase the risk of asthma-related hospitalization in pediatric and adolescent patients.

Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue ADVAIR DISKUS) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use ADVAIR DISKUS for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

INDICATIONS AND USAGE
ADVAIR DISKUS is a combination product containing a corticosteroid and a LABA indicated for:
Treatment of asthma in patients aged 4 years and older.
Maintenance treatment of airflow obstruction and reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD).

Important limitation:
Not indicated for the relief of acute bronchospasm.

DOSAGE AND ADMINISTRATION
For oral inhalation only.

Treatment of asthma in patients ≥12 years: 1 inhalation of ADVAIR DISKUS 100/50, 250/50, or 500/50 twice daily. Starting dosage is based on asthma severity.

Treatment of asthma in patients aged 4 to 11 years: 1 inhalation of ADVAIR DISKUS 100/50 twice daily.

Maintenance treatment of COPD: 1 inhalation of ADVAIR DISKUS 250/50 twice daily.

CONTRAINDICATIONS
Primary treatment of status asthmaticus or acute episodes of asthma or COPD requiring intensive measures.
Severe hypersensitivity to milk proteins.

DOSAGE FORMS AND STRENGTHS
DISKUS device containing a combination of fluticasone propionate (100, 250, or 500 mcg) and salmeterol (50 mcg) as an oral inhalation powder.

WARNINGS AND PRECAUTIONS

• Asthma-related death: LABAs increase the risk. Prescribe only for recommended patient populations.
• Deterioration of disease and acute episodes: Do not initiate in acutely deteriorating asthma or to treat acute symptoms.
• Use with additional LABA: Do not use in combination because of risk of overdose.
• Localized infections: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically for signs of adverse effects on the oral cavity. Advise patients to rinse the mouth following inhalation.
• Pneumonia: Increased risk in patients with COPD. Monitor patients for signs and symptoms of pneumonia.
• Immunosuppression: Potential worsening of infections (e.g., existing tuberculosis, fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.
• Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from oral steroids. Taper patients slowly from systemic corticosteroids if transferring to ADVAIR DISKUS.
• Hypercorticism and adrenal suppression: May occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue ADVAIR DISKUS slowly.
• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid and cardiovascular effects. Use not recommended with ADVAIR DISKUS.
• Paradoxical bronchospasm: Discontinue ADVAIR DISKUS and institute alternative therapy if paradoxical bronchospasm occurs.
• Patients with cardiovascular or central nervous system disorders: Use with caution because of beta-adrenergic stimulation.
• Decreases in bone mineral density: Assess bone mineral density initially and periodically thereafter.
• Effects on growth: Monitor growth of pediatric patients.
• Glaucoma and cataracts: Close monitoring is warranted.
• Metabolic effects: Be alert to eosinophilic conditions, hypokalemia, and hyperglycemia.
• Coexisting conditions: Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.

Indications and usage:
BREO ELLIPTA is a combination of fluticasone furoate, an inhaled corticosteroid (ICS), and vilanterol, a long-acting beta2-adrenergic agonist (LABA), indicated for long-term, once-daily, maintenance treatment of airflow obstruction and for reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD).

Important limitations: Not indicated for relief of acute bronchospasm or for treatment of asthma.

Dosage and administration:
For oral inhalation only.
Maintenance treatment of COPD:
BREO ELLIPTA 100 mcg/25 mcg should be administered as 1 inhalation once daily by the orally inhaled route only. After inhalation, the patient should rinse his/her mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis.

BREO ELLIPTA should be taken at the same time every day. Do not use BREO ELLIPTA more than 1 time every 24 hours.

No dosage adjustment is required for geriatric patients, patients with hepatic impairment, or renally impaired patients

Additional information

INDICATIONS AND USAGE
DULERA is a combination product containing a corticosteroid and a long-acting beta2-adrenergic agonist indicated for:
Treatment of asthma in patients 12 years of age and older.

Important limitations:
Not indicated for the relief of acute bronchospasm.

USE IN SPECIFIC POPULATIONS
Hepatic impairment: Monitor patients for signs of increased drug exposure.

DOSAGE AND ADMINISTRATION
For oral inhalation only.
Treatment of asthma in patients ≥12 years: 2 inhalations twice daily of DULERA 100 mcg/5 mcg or 200 mcg/5 mcg. Starting dosage is based on prior asthma therapy.

2.1 General
DULERA should be administered only by the orally inhaled route (see Instructions for Using DULERA in the Medication Guide). After each dose, the patient should be advised to rinse his/her mouth with water without swallowing.

DULERA should be primed before using for the first time by releasing 4 test sprays into the air, away from the face, shaking well before each spray. In cases where the inhaler has not been used for more than 5 days, prime the inhaler again by releasing 4 test sprays into the air, away from the face, shaking well before each spray.

The DULERA canister should only be used with the DULERA actuator. The DULERA actuator should not be used with any other inhalation drug product. Actuators from other products should not be used with the DULERA canister.

2.2 Dosing
DULERA should be administered as two inhalations twice daily every day (morning and evening) by the orally inhaled route.

Shake well prior to each inhalation.

The recommended starting dosages for DULERA treatment are based on prior asthma therapy.
Table 1: Recommended Dosages for DULERA

Previous Therapy	Recommended Dose	Maximum Recommended Daily Dose
Inhaled medium dose corticosteroids	DULERA 100 mcg/5 mcg, 2 inhalations twice daily	400 mcg/20 mcg
Inhaled high dose corticosteroids	DULERA 200 mcg/5 mcg, 2 inhalations twice daily	800 mcg/20 mcg

The maximum daily recommended dose is two inhalations of DULERA 200 mcg/5 mcg twice daily. Do not use more than two inhalations twice daily of the prescribed strength of DULERA as some patients are more likely to experience adverse effects with higher doses of formoterol. If symptoms arise between doses, an inhaled short-acting beta2-agonist should be taken for immediate relief.

If a previously effective dosage regimen of DULERA fails to provide adequate control of asthma, the therapeutic regimen should be reevaluated and additional therapeutic options, e.g., replacing the current strength of DULERA with a higher strength, adding additional inhaled corticosteroid, or initiating oral corticosteroids, should be considered.

The maximum benefit may not be achieved for 1 week or longer after beginning treatment. Individual patients may experience a variable time to onset and degree of symptom relief. For patients ≥12 years of age who do not respond adequately after 2 weeks of therapy, higher strength may provide additional asthma control.

HOW SUPPLIED
DULERA is available in two strengths and supplied in the following package sizes:
Package NDC
------------------------------------------------------------------------------
DULERA 100 mcg/5 mcg
120 inhalations 0085-7206-01

DULERA 100 mcg/5 mcg
60 inhalations (institutional pack) 0085-7206-07

DULERA 200 mcg/5 mcg
120 inhalations 0085-4610-01

DULERA 200 mcg/5 mcg
60 inhalations (institutional pack) 0085-4610-05

Adult (usual):  DOSAGE AND ADMINISTRATION

SYMBICORT should be administered twice daily every day by the orally inhaled route only. After inhalation, the patient should rinse the mouth with water without swallowing.

Prime SYMBICORT 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 SYMBICORT is not recommended as some patients are more likely to experience adverse effects with higher doses of formoterol. Patients using SYMBICORT should not use additional long-acting beta2-agonists for any reason.

Asthma
If asthma symptoms arise in the period between doses, an inhaled, short-acting beta2-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 twice daily (morning and evening, approximately 12 hours apart).

The recommended starting dosages for SYMBICORT for patients 12 years of age and older are based upon patients' asthma severity.

The maximum recommended dosage is SYMBICORT 160/4.5 mcg twice daily.

Improvement in asthma control following inhaled administration of SYMBICORT 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 SYMBICORT 80/4.5, replacement with SYMBICORT 160/4.5 may provide additional asthma control.

If a previously effective dosage regimen of SYMBICORT 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 SYMBICORT with the higher strength, adding additional inhaled corticosteroid, or initiating oral corticosteroids) should be considered.

Chronic Obstructive Pulmonary Disease (COPD)
For patients with COPD the recommended dose is SYMBICORT 160/4.5, two inhalations twice daily.

If shortness of breath occurs in the period between doses, an inhaled, short-acting beta2-agonist should be taken for immediate relief.

DOSAGE FORMS AND STRENGTHS
SYMBICORT is available as a metered-dose inhaler containing a combination of budesonide (80 or 160 mcg) and formoterol (4.5 mcg) as an inhalation aerosol in the following two strengths: 80/4.5 and 160/4.5. Each dosage strength contains 60 or 120 actuations per/canister. Each strength of SYMBICORT is supplied with a red plastic actuator with a gray dust cap.