CONTRAINDICATIONS

• WIXELA INHUB is contraindicated for primary treatment of status asthmaticus or other acute episodes of asthma or chronic obstructive pulmonary disease (COPD) where intensive measures are required.
• WIXELA INHUB is contraindicated in patients with severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone propionate, salmeterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

• LABA monotherapy for asthma increases the risk of asthma-related death, and in pediatric and adolescent patients, available data also suggest an increased risk of asthma-related hospitalization. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.
• WIXELA INHUB should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD.
• WIXELA INHUB should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short-acting beta₂-agonist, not WIXELA INHUB, should be used to relieve acute symptoms such as shortness of breath.
• WIXELA INHUB should not be used more often than recommended, at higher doses than recommended, or in 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 sympathomimetic drugs. Patients using WIXELA INHUB should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.
• Candida albicans has occurred in patients treated with fluticasone propionate and salmeterol inhalation powder. Advise patients to rinse the mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.
• There is an increased risk of pneumonia with WIXELA INHUB in patients with COPD. Monitor patients for signs and symptoms of pneumonia.
• Patients who use corticosteroids are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections.
• Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. Slowly taper the dose of systemic corticosteroids if transferring patients to WIXELA INHUB.
• Hypercorticism and adrenal suppression may occur with high doses of inhaled corticosteroids, including fluticasone propionate, or at the recommended dose in susceptible individuals. If such effects occur, discontinue WIXELA INHUB slowly.
• If paradoxical bronchospasm occurs, discontinue WIXELA INHUB immediately and institute alternative therapy.
• Salmeterol, a component of WIXELA INHUB, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. If such effects occur, WIXELA INHUB may need to be discontinued. WIXELA INHUB should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
• Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced 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. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating WIXELA INHUB and periodically thereafter.
• Orally inhaled corticosteroids, as well as poorly controlled asthma, may cause a reduction in growth velocity, and the long-term effect on final adult height is unknown. Patients should be maintained on the lowest dose of inhaled corticosteroid that effectively controls their asthma. Monitor growth of pediatric patients.
• Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with asthma and COPD following the long‐term administration of inhaled corticosteroids, including fluticasone propionate, a component of WIXELA INHUB. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use WIXELA INHUB long term.
• Be alert to hypokalemia, hyperglycemia, and systemic eosinophilic conditions, such as Churg-Strauss syndrome.
• Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 3%) include:
Asthma: Upper respiratory tract infection or inflammation, pharyngitis, dysphonia, oral candidiasis, bronchitis, cough, headaches, nausea and vomiting.
COPD: Pneumonia, oral candidiasis, throat irritation, dysphonia, viral respiratory infections, musculoskeletal pain.

DRUG INTERACTIONS

• The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with WIXELA INHUB is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur.
• WIXELA INHUB should be administered with extreme 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 salmeterol, a component of WIXELA INHUB, on the vascular system may be potentiated by these agents.
• Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as salmeterol, a component of WIXELA INHUB, but may also produce severe bronchospasm in patients with asthma or COPD.
• Use WIXELA INHUB with caution in patients taking non–potassium-sparing diuretics (such as loop or thiazide diuretics), as electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with coadministration with beta-agonists, such as salmeterol.

USE IN SPECIFIC POPULATIONS

• Fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism. Impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma. Therefore, patients with hepatic disease should be closely monitored.