Fluticasone, Umeclidinium, and Vilanterol

• Fluticasone Furoate, Umeclidinium, and Vilanterol
• Umeclidinium, Fluticasone, and Vilanterol
• Vilanterol, Umeclidinium, and Fluticasone

Chronic obstructive pulmonary disease: Maintenance treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, in patients who are on a fixed-dose combination of fluticasone and vilanterol for airflow obstruction and reducing exacerbations in whom additional treatment of airflow obstruction is desired or for patients who are already receiving umeclidinium and a fixed-dose combination of fluticasone and vilanterol.

Limitations of use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma

Concerns related to adverse effects:

• Adrenal suppression: Fluticasone may cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, including adrenal crisis, in patients sensitive to these effects. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled corticosteroids; deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic steroids to a less systemically available inhaled corticosteroid. Patients receiving ≥20 mg/day of prednisone (or equivalent) may be most susceptible. Fluticasone/vilanterol does not provide the systemic steroid dose needed to treat patients having trauma, surgery, or infections. Do not use this product to transfer patients from oral corticosteroid therapy. Observe patients 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. If systemic corticosteroid withdrawal effects occur (eg, fatigue, lassitude, weakness, nausea, vomiting, hypotension), taper fluticasone/vilanterol slowly and other treatments for management of COPD symptoms should be considered.

• Asthma-related deaths: [US Boxed Warning]: Long-acting beta-2 adrenergic agonists (LABAs), such as vilanterol, increase the risk of asthma-related death. Data from a placebo-controlled trial that compared the safety of another LABA (salmeterol) with placebo added to asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol; this finding is considered a class effect of LABAs. Data are not available to determine if the addition of an inhaled corticosteroid lessens this increased risk of death associated with LABA use; however, current guidelines recommend the use of an inhaled corticosteroid before adding a LABA (GINA 2015; NIH/NHLBI 2007). In a more recent multicenter, randomized, double-blinded trial, the use of salmeterol and an inhaled corticosteroid (ie, fluticasone) combined in a single inhaler in a large number of children, adolescent, and adult patients with persistent asthma (non-life threatening and stable) did not increase the risk of serious asthma-related events compared with fluticasone alone; in addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). A similar increase in the risk of death associated with LABAs has not been demonstrated in patients with COPD. Not indicated for treatment of asthma.

• Bronchospasm: Can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, discontinue immediately and alternative therapy should be instituted.

• Hypersensitivity: Severe hypersensitivity, including anaphylaxis, angioedema, rash and urticaria may occur; discontinue if a hypersensitivity reaction occurs. Immunosuppression: Use increases susceptibility to infections (eg, chickenpox and measles, sometimes more serious or even fatal, in susceptible children or adults using corticosteroids). Avoid exposure in such patients who have not had these diseases or been properly immunized. Use with caution (if at all) in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

• Lower respiratory infections: An increase in the incidence of pneumonia and other lower respiratory tract infections (some fatal) have been reported in patients with COPD following use; monitor COPD patients closely since pneumonia symptoms may overlap symptoms of exacerbations.

• Oral candidiasis: Infections with Candida albicans in the mouth and throat (thrush) have been reported with use.

Disease-related concerns:

• Bone mineral density: Use with caution in 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 (eg, anticonvulsants or oral corticosteroids); long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease, especially coronary insufficiency, arrhythmias, and hypertension; beta-agonists may cause elevation in blood pressure, heart rate, and increase risk of arrhythmias (eg, supraventricular tachycardia, extrasystoles); may also cause ECG changes (eg, flattening of the T wave, QTc prolongation, ST segment depression).

• Diabetes: Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.

• Hepatic impairment: Fluticasone exposure may be increased up to threefold in patients with hepatic impairment; use with caution in patients with moderate or severe impairment and monitor closely.

• Hypokalemia: Use with caution in patients with hypokalemia; beta2-agonists may decrease serum potassium.

• Ocular disease: Use with caution in patients with increased intraocular pressure, cataracts and/or glaucoma; increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use of inhaled corticosteroids. Consider routine eye exams in chronic users.

• Prostatic hyperplasia/bladder neck obstruction: Umeclidinium may worsen the symptoms of prostatic hyperplasia and/or bladder neck obstruction (eg, painful urination, difficulty passing urine); use with caution.

• Seizure disorders: Use with caution in patients with seizure disorders.

• Thyrotoxicosis: Use with caution in patients with thyrotoxicosis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Lactose: May contain lactose; anaphylactic reactions have been reported in patients with severe milk protein allergy using other lactose-containing powder products.

Other warnings/precautions:

• Appropriate use: Do not use for acute episodes of COPD. Do not initiate in patients with significantly worsening, potentially life-threatening, or acutely deteriorating COPD. Do not exceed the recommended dose. Do not use with other long-acting beta2-agonists; clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

• Discontinuation of systemic corticosteroids: Withdraw systemic corticosteroid therapy with gradual tapering of dose (eg, patients on prednisone may decrease dose by 2.5 mg weekly during inhaled corticosteroid therapy). Monitor lung function, beta-agonist use, and COPD symptoms, and for signs and symptoms of adrenal insufficiency (fatigue, lassitude, weakness, nausea and vomiting, hypotension) during withdrawal. Allergic conditions (eg, eosinophilic conditions, rhinitis, eczema, arthritis, conjunctivitis) may be unmasked when transitioning from systemic to inhaled corticosteroid therapy.

• Patient information: Patients must be instructed to use short-acting beta2-agonists (eg, albuterol) for acute COPD symptoms and to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of inhaled short-acting beta2-agonists may indicate deterioration of COPD, and medical evaluation to assess treatment regimen must not be delayed.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Call your doctor right away if your breathing problems get worse, if your rescue inhaler does not work as well, or if you need to use your rescue inhaler more often.
• Have your blood pressure checked often. Talk with your doctor.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Do not take more of fluticasone, umeclidinium, and vilanterol or use it more often than you have been told. Deaths have happened when too much of this type of drug has been taken. Talk with your doctor.
• When changing from an oral steroid to another form of a steroid, there may be very bad and sometimes deadly side effects. Signs like weakness, feeling tired, dizziness, upset stomach, throwing up, not thinking clearly, or low blood sugar may happen. Call your doctor right away if you have any of these signs. If you have a bad injury, have surgery, or any type of infection, you may need extra doses of oral steroids. These extra steroids will help your body deal with these stresses. Carry a warning card saying that there may be times when you may need extra steroids.
• Some people who take this medicine may have a higher chance of getting pneumonia. The chance of having to go to the hospital for pneumonia may also be higher. Some cases have been deadly. Talk with the doctor.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• Chickenpox and measles can be very bad or even deadly in some people taking steroid drugs like fluticasone, umeclidinium, and vilanterol. Avoid being near anyone with chickenpox or measles if you have not had these health problems before. If you have been exposed to chickenpox or measles, talk with your doctor.
• Long-term use may raise the chance of cataracts or glaucoma. Talk with the doctor.
• Have an eye exam as you have been told by your doctor.
• This medicine may cause weak bones (osteoporosis) with long-term use. Talk with your doctor to see if you have a higher chance of weak bones or if you have any questions.
• This medicine is not approved for use in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Back pain.
• Change in taste.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Cough.
• Throat pain.
• Mouth pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.