The future of asthma management with objective data from the Digihaler system^1-3

IMPORTANT SAFETY INFORMATION: AIRDUO® DIGIHALER® (fluticasone propionate and salmeterol) AND ARMONAIR® DIGIHALER® (fluticasone propionate and salmeterol):

• Contraindications: ArmonAir Digihaler and AirDuo Digihaler are contraindicated in:
  • Primary treatment of status asthmaticus or other acute episodes of asthma requiring intensive measures
  • Patients with known severe hypersensitivity to milk proteins or any ingredients of ArmonAir Digihaler or AirDuo Digihaler
  • Serious Asthma-Related Events – Hospitalizations, Intubations, Death: Use of LABA as monotherapy (without an ICS) for asthma is associated with an increased rish of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are use din fixed-dose combination with ICS (such as AirDuo Digihaler), data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hosplitalizations, intubaitons, death) compared with ICS alone
• Deterioration of Disease and Acute Episodes: AirDuo Digihaler should not be initiated in patiends during rapidlly deteriorating or potetially life-threatening episodes of asthma. ArmonAir Digihaler and AirDuo Digihaler are not indicated for releif of acute bronchospasm. An inhaled, short-acting beta2-agonist, not ArmonAir Digihaler or AirDuo Digihaler, should not be used to relieve acute symptoms such as shortness of breath.
• Avoid Excessive Use and Avoid Use with Other Long acting Beta2-agonists: AirDuo Digihaler should not be used more often than recommended, at higher doses that recommended, ori n conjunction with other medicines containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sypathomimetic drugs.
  Patients using AirDuo Digihaler should not use another medicine containing a LABA (e.g. salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason
• Oropharyngeal Candidiasis has occured in patients treated with ArmonAir Digihaler and AirDuo Digihaler. Advise patients to rinse the mouth with water without swallowing following inhalatiom
• Immunosuppression and Risks of Infections: Patients who use corticosteroids, such are found in AirDuo Digihaler and ArmonAir Digihaler are at risk for potential wosening of existing tuberculosis; fungal, bacterials, viral or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpoy or measles may occur in susceptible patients. Use with cauion in patients with the above because of the potential for worsening of these infections
• Transferring Patients from Systemic Corticosteroid Therapy: Particilar care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occured in patients with asthma during and after transfer from systemic corticosteroids to less sistemically available ICS. Taper patients slowly from systemic corticosteroids if transferring to ArmonAir Digihaler or AirDuo Digihaler
• Hypoercorticism and Adrenal Suppression may occur with high doses of ICS, including fluticasone propionate, or at the recommended dose in susceptible individuals. If such changes occur, discontinue ArmonAir Digihaler or AirDuo Digihaler slowly
• Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors: The use of strong cytochromeP450 3A4 (CYP3A4) inhibitors (e.g. ritonavir, ketoconazole) with ArmonAir Digihaler or AirDuo Digihaler is not recommended because increased systemic croticosteroid adverse effects may also occur with AirDuo Digihaler
• Paradoxical Bronchospasm and Upper Airway Symptoms: Paradoxical Bronchospasm may occur. If bronchospasm occurs treat immediately with an inhaled, short-acting bronchodilator. Discontinue AirDuo Digihaler or ArmonAir Digihaler and institute alternative therapy
• Hypersensitivity Reactions, Including Anaphylaxis: Immediate hypersensitivity reactions (e.g. urticatia, angiodema, rash, bronchospasm, hypotension), including anaphylaxis, may occus aftr administration of ArmonAir Digihaler or AirDuo Digihaler. Discontinue ArmonAir Digihaler or AirDuo Digihaler if such reactions occur
• Cardiovasular and Central Nervous System Effects: The salmeterol component of AirDuo Digihaler, can be associated with excessive beta-adreneric stimulation which could present as the following symptoms: seizures, angina, hypertension or hypotension, tachycardia with rate sup to 200 beats/min, arrhythmias, nevousness, headache, tremor, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Use with caution in ptients with cardiac arrhythmias, hypertension, coronary insufficiency. Drug may need to be discontinued in certain patients.
• Reduction in Bone Mineral Density (BMD): Decreases in BMD have been observed with long-term administration of products containing ICS. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, 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 when using ArmonAir Digihaler and AirDuo Digihaler
• Effect on Growth: ICS may cause a reduction in growth velocity. Patients should be maintained on the lowest dose of inhaled corticosteroid that effectively controls their asthma. Monitor growth of pediatric patients receiving ArmonAir Digihaler or AirDuo Digihaler.
• Glaucoma and Cataracts: Long-term use of ICS, includinf fluticasone propionate, a component of ArmonAir Digihaler and AirDuo Digihaler, may increase the rish for cataracts or glaucoma. Regular eye exams should be considered
• Eosinophilic Conditions and Churg-Strauss Syndrome: Systemic eosinophilic conditions, such as Churg- Strauss syndrome, may occur when using ArmonAir Digihaler or AirDuo Digihaler. Be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy
• Coexisting conditions: Use AirDuo Digihaler with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympatomimetic amines
• Hypolaemia and Hyperglycemia: Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. Decrease in serum potassium are usually transient, not requiring supplementation. Be alert to hypokalemia and hyperglycemia in patients using AirDuo Digihaler
• Adverse Reactions with ArmonAir Digihaler: Most common adverse reactions (greater then or equal to 3%) are: upper respiratory tract infection, nasopharyngitis, oral candidiasis, headache and cough
• Adverse Reactions with AirDuo Digihaler: Most common adverse reactions (greater then or equal to 3%) include nasopharyngitis, oral candidiasis, headache, cough and back pain

INDICATION

ArmonAir Digihaler inhalation powder is indicated for the maintenance treatment of asthma as prophylactic therapy in patients 12 years of age and older.

Limitation of Use: ArmonAir Digihaler is not indicated for the relief acute bronchospasm.

AirDuo Digihaler inhalation powder is indicated for the treatment of asthma in patients aged 12 years and older. AirDuo Digihaler is only for patients uncontrolled on an inhaled corticosteroid (ICS) or whose disease severity clearly warrants an ICS/Long-acting beta2-agonist (LABA).

Limitation of Use: AirDuo Digihaler is not indicated for the relief acute bronchospasm.

ArmonAir Digihaler and AirDuo Digihaler contain a built-in electronic module which detects, records and stores data on inhaler events for transmission to mobile App. Use of the mobile App is not required for administration of medication to the patient.

Devices comply with part 15 of the FCC Rules. Operation is subject to the following two contidions: (1) These devices may not cause harmful interference, and (2) these devices must accept any interference received, including interference that may cause undesired operation. Changes or modifications not expressly approved by Teva could void the user's authority to operate the equipment.

Please see full Prescribing information for ArmonAir Digihaler and AirDuo Digihaler.

IMPORTANT SAFETY INFORMATION ABOUT PROAIR® DIGIHALER® (albuterol sulfate)

• Contraindications: ProAir Digihaler (albuterol sulfate) Inhalation Powder is contraindicated in patients with hypersensitivity to albuterol or patients with a severe hypersensiticity to milk proteins. Rare cases of hypersensitivity reactions, including urticatia, angioedema and rash have been reported after the use of albuterol sulfate. There have been reports of anaphylactic reactions in patients using inhaladion therapies containing lactose
• Paradoxical Bronhcospasm: ProAir Digihaler can produce paradoxical bronchospasm that may be life-threatening. Discountinue ProAir Digihaler and institute alternative therapy if paradoxical bronchospasm occurs
• Deterioration of Asthma: Need for more doses of ProAir Digihaler than usual may be a marker of acute or chronic deterioration of asthma and requires reevaluation of treatment, such as possible need for anti-inflammatory treatment, e.g. corticosteroids
• Use of Anti-Inflammatory Agents: ProAir Digihaler alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids
• Cardiovascular Effects: ProAir Digihaler, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by heart rate, blood pressure, and/or symptoms. If such effects occur, the drug may need to be discontinued. ProAir Digihaler, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhytmias, and hypertension
• Do Not Exceed Recommended Dose: Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma
• Hypersensitivity Reactions Including Anaphylaxis: Immediate hypersensitivity reactions may occur after administration of albuterol sulfate, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Hypersensitivity reactions including anaphylaxis, angioedema, pruritus, and rash have been reported with the use of therapies containing lactose, and inactive ingredient in ProAir Digihaler.
• Coexisting Conditions: ProAir Digihaler, like all sypathomimetic amines, hould be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines.
• Hypokalemia: As with other beta-agonists, ProAir Digihaler may produce significant hypokalemia in some patients. The decrease is usually transient, not requiring supplementation
• Most common adverse reactions (≥1% and >placebo) are back pain, pain, gastroenteritis viral, sinus headache, urinary tract infection, nasopharyngitis, oropharyngeal pain and vomiting
• Drug interactions: other short-acting sypathomimetic bronchodilators should not be used concomitantly with ProAir Digihaler
  • Beta-Blockers: Beta-adrenergic-receptor blocking agents not only block the pulmonary effect of beta-agonists, such as ProAir Digihaler, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers
  • Diuretics: Caution is advised in the coadministration of beta.agonists with non-potassium sparing diuretics (such as loop or thiazide diuretics). Consider monitoring potassium levels
  • Digoxin: Carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and ProAir Digihaler
  • Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: ProAir Digihaler should be administered with extreme caution to patients being treated with these agents, or within 2 weeks of discontinuation of these agents, bacause the action of albuterol on the cardiovascular system may be potentiated. Consider alternative therapy

INDICATION

ProAirDigihaler Inhalation Powder is indicated in patients ≥4 years of age for the treatment or prevention of bronchospasm with reversible obstructive airway disease and in patients ≥4 years of age for the prevention of excercise-induced bronnchospasm.

ProAir Digihaler contains a built-in electronic module that detects, records and stores inhaler event informaiton. ProAir Digihaler may be used with, and transmits informaiton to, a mobile app. Use of the mobile app is not required for administration of medication to the patient.

Please see full Prescribing information for ProAir Digihaler.

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