Fluticasone and salmeterol

Tell your doctor about all the medications you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.  Especially tell your doctor if you take:

• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone
• monoamine oxidase inhibitors such as tranylcypromine (Parnate), phenelzine (Nardil), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), and rasagiline (Azilect)
• tricyclic antidepressants such as trimipramine (Surmontil), amitriptyline (Elavil), nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil), and clomipramine (Anafranil)
• beta blockers such as metoprolol (Toprol XL, Lopressor), carvedilol (Coreg), bisoprolol (Zebeta), betaxolol (Kerlone), nebivolol (Bystolic), propranolol (Inderal)
• non-potassium-sparing diuretics such as bumetanide (Bumex), chlorothiazide (Diuril), chlorthalidone (Thalitone), ethacrynic acid (Edecrin), furosemide (Lasix), hydrochlorothiazide (Microzide, HCTZ), metolazone (Zaroxolyn), torsemide (Demadex)

This is not a complete list of fluticasone/salmeterol drug interactions.  Ask your doctor or pharmacist for more information.

Serious side effects have been reported with fluticasone/salmeterol including the following:

• increased risk of death from asthma problems. People with asthma who take long-acting beta2 adrenergic agonist (LABA) medicines, such as salmeterol (one of the medicines in fluticasone/salmeterol), have an increased risk of death from asthma problems.
• pneumonia. People with COPD have a higher chance of getting pneumonia. Fluticasone/salmeterol may increase the chance of getting pneumonia. Call your healthcare provider if you notice any of the following symptoms: increase in mucus production, change in mucus color, fever, chills, increased cough, and increased breathing problems.
• immunosuppression. Fluticasone/salmeterol may increase the chance of getting infections.
• adrenal insufficiency. Adrenal insufficiency is a condition where the adrenal glands do not make enough steroid hormones.  This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and start taking a medicine containing an inhaled steroid (such as fluticasone/salmeterol). When your body is under stress such as from fever, trauma (such as a car accident), infection, surgery, or worse COPD symptoms, adrenal insufficiency can get worse and may cause death.  Symptoms of adrenal insufficiency include the following: feeling tired, lack of energy, weakness, nausea and vomiting, and low blood pressure.
• thrush. Fluticasone/salmeterol can cause a fungal infection in your mouth or throat.  It is important to rinse your mouth with water without swallowing after using fluticasone/salmeterol to help reduce your chance of getting thrush.
• sudden breathing problems immediately after inhaling your medicine. Call your healthcare provider if breathing problems worsen over time while using fluticasone/salmeterol.
• serious allergic reactions. Call your healthcare provider or get emergency medical care if you get any of the following symptoms of a serious allergic reaction: rash, hives, swelling of your face, mouth, and tongue, and breathing problems.
• effects on the heart. fluticasone/salmeterol can cause increased blood pressure, a fast or irregular heartbeat, and chest pain.
• effects on the nervous system. Fluticasone/salmeterol can cause a tremor and nervousness.
• osteoporosis. Fluticasone/salmeterol can cause bone thinning or weakness.
• slowed growth in children. A child's growth should be checked often.
• glaucoma and cataracts. Fluticasone/salmeterol can cause eye problems. It is important to have regular eye exams while using fluticasone/salmeterol.
• changes in laboratory blood values. Fluticasone/salmeterol can cause changes in your sugar, potassium, and certain types of white blood cells.

Fluticasone/salmeterol can cause drowsiness. Do not drive or operate heavy machinery until you know how fluticasone/salmeterol affects you.

Do not take fluticasone/salmeterol in the following situations:

• are allergic to fluticasone/salmeterol or to any of its ingredients
• have a severe allergy to milk proteins
• treatment of a sudden attack of asthma or COPD

You should not use this medicine if you are allergic to fluticasone, salmeterol, or milk proteins.

Fluticasone and salmeterol is not a rescue medicine. It will not work fast enough to treat an asthma or bronchospasm attack.

Salmeterol may increase the risk of death in people with asthma, but the risk in people with COPD is not known.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

• AirDuo RespiClick
• Fluticasone Propionate and Salmeterol Xinafoate
• Fluticasone/Salmeterol
• Salmeterol and Fluticasone

• Advair Diskus
• Advair HFA
• AirDuo RespiClick

Following administration, rinse mouth with water after use (do not swallow) to reduce risk of oral candidiasis.

Advair Diskus: Dry powder inhaler: After removing from box and foil pouch, write the “Pouch opened” and “Use by” dates on the label on top of the Diskus. The “Use by” date is 1 month from date of opening the pouch. Every time the lever is pushed back, a dose is ready to be inhaled. Do not close or tilt the Diskus after the lever is pushed back. Do not play with the lever or move the lever more than once. The dose indicator tells you how many doses are left. When the numbers 5 to 0 appear in red, only a few doses remain. Discard device 1 month after you remove it from the foil pouch or when the dose counter reads “0” (whichever comes first).

Advair HFA: Metered dose inhaler: Shake well for 5 seconds before each spray. Prime with 4 test sprays (into air and away from face) before using for the first time. If canister is dropped or not used for >4 weeks, prime with 2 sprays. Patient should contact pharmacy for refill when the dose counter reads “020”. Discard device when the dose counter reads “000”. Do not spray in eyes.

AirDuo RespiClick: Dry powder inhaler: Inhaler does not require priming and do not use with a spacer or volume holding chamber. Do not wash or place any part of inhaler in water; if mouthpiece needs cleaning, gently wipe with a dry cloth or tissue. When the number 20 appears in red, only a few doses remain. Discard inhaler 30 days after opening the foil pouch or when the counter reads "0", whichever comes first (device is not reusable).

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Amphotericin B: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cobicistat: May increase the serum concentration of Fluticasone (Oral Inhalation). Avoid combination

Cocaine: May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Salmeterol. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Salmeterol. Avoid combination

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. Avoid combination

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Long-Acting Beta2-Agonists: May enhance the adverse/toxic effect of other Long-Acting Beta2-Agonists. Avoid combination

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loop Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

MAO Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Telaprevir: May increase the serum concentration of Salmeterol. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tipranavir: May increase the serum concentration of Salmeterol. Avoid combination

Tipranavir: May increase the serum concentration of Fluticasone (Oral Inhalation). Avoid combination

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, or pharyngitis. Have patient report immediately to prescriber signs of infection, signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), angina, tachycardia, anxiety, behavioral changes, vision changes, burning or numbness feeling, choking, change in voice, seizures, bone pain, severe dizziness, severe headache, insomnia, severe loss of strength and energy, vaginitis, weight gain, mouth sores, mouth irritation, thrush, or difficulty breathing, wheezing, or coughing after use (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Applies to fluticasone / salmeterol: inhalation aerosol liquid, inhalation aerosol powder, inhalation disk, inhalation powder

Along with its needed effects, fluticasone / salmeterol may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking fluticasone / salmeterol:

• Black, tarry stools
• blindness
• blurred vision
• burning, tingling, numbness, or pain in the hands, arms, feet, or legs
• chills
• cough
• decreased vision
• difficulty with breathing or swallowing
• eye pain
• fast heartbeat
• fever
• headache
• hives or welts, skin itching, rash, or redness
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• nausea or vomiting
• noisy breathing
• painful or difficult urination
• sensation of pins and needles
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stabbing pain in the arms or legs
• swelling of the face, throat, or tongue
• swollen glands
• tearing
• unusual bleeding or bruising

• Abdominal or stomach pain
• backache
• bruising
• darkening of the skin
• decrease in height
• diarrhea
• difficulty with moving
• dizziness
• facial hair growth in females
• fainting
• fast, slow, pounding, or irregular heartbeat or pulse
• flushed, dry skin
• fractures
• fruit-like breath odor
• full or round face, neck, or trunk
• heavy bleeding
• increased hunger
• increased thirst or urination
• irritability
• large, flat, blue, or purplish patches in the skin
• loss of sexual desire or ability
• menstrual irregularities
• mental depression
• muscle pain or stiffness
• muscle wasting
• pain in the back, ribs, arms, or legs
• pain in the joints
• sweating
• troubled breathing
• unexplained weight loss
• unusual tiredness or weakness
• weight gain

Get emergency help immediately if any of the following symptoms of overdose occur while taking fluticasone / salmeterol:

• Chest pain or tightness
• confusion
• convulsions (seizures)
• decreased urine output
• dry mouth
• faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• general feeling of discomfort or illness
• high blood pressure
• loss of appetite
• mood changes
• nervousness
• numbness or tingling in the hands, feet, or lips
• sudden sweating
• tremors
• trouble with sleeping

Some side effects of fluticasone / salmeterol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Body aches or pain
• choking
• congestion
• dryness of the throat
• high-pitched noise when breathing
• hoarseness
• runny nose
• sneezing
• trouble with swallowing
• voice changes

• Cough-producing mucus
• flu-like symptoms
• irritation or inflammation of the eye
• muscle pain
• pain or tenderness around the eyes and cheekbones
• sleep disorders
• stuffy nose
• white patches in the mouth or throat or on the tongue