Fluticasone and Salmeterol Oral Inhalation

Fluticasone and salmeterol oral inhalation is a maintenance combination therapy used across several branded products for lung conditions — it is not interchangeable between all forms for all uses.

• Treats asthma in patients aged 4 and older (inhalation powder) who are not adequately controlled on an inhaled corticosteroid (ICS) alone, or whose condition warrants treatment with both an ICS and a long-acting beta-agonist (LABA)
• Provides maintenance treatment of COPD (chronic obstructive pulmonary disease), including chronic bronchitis and emphysema, in adults — inhalation powder only
• Reduces the frequency of COPD flare-ups (exacerbations) in adults with a history of exacerbations — inhalation powder only
• Not indicated for the relief of sudden (acute) bronchospasm or acute asthma or COPD attacks
• Advair HFA (inhaler form) is used in asthma treatment; always follow the specific product's approved indication

This inhaler delivers two medicines that work in different but complementary ways. Fluticasone propionate is a corticosteroid that reduces inflammation in the airways — the swelling and irritation that make breathing difficult in asthma and COPD. Salmeterol is a long-acting beta-agonist (LABA) that latches onto receptors in the smooth muscle surrounding the airways, causing those muscles to relax and the airways to widen (bronchodilation) for up to 12 hours per dose.

Together, controlling both inflammation and airway tightness leads to better day-to-day breathing, fewer flare-ups, and reduced need for rescue medications. Because salmeterol works locally in the lungs, blood levels of the drug do not predict how well it is working.

Both forms are inhaled by mouth twice daily, roughly 12 hours apart — they are not swallowed. The inhalation powder is taken as one inhalation of the prescribed strength twice daily; the appropriate strength for asthma is chosen based on disease severity and prior therapy. For COPD, only one specific strength of the inhalation powder is approved. After each use, rinse your mouth with water and spit — do not swallow — to reduce the risk of a fungal mouth infection.

• Do not take more than one inhalation twice daily of your prescribed strength
• Do not use this inhaler as a rescue inhaler — always have a short-acting bronchodilator (like albuterol) available for sudden symptoms
• If you miss a dose, follow your prescriber's guidance; do not double up to make up for a missed dose
• Do not use another long-acting beta-agonist inhaler at the same time as this product

The most common side effects reported in clinical trials include:

• Upper respiratory tract infections (colds, congestion)
• Sore throat (pharyngitis)
• Hoarseness or voice changes (dysphonia)
• Oral thrush — a fungal infection of the mouth (oral candidiasis)
• Headache
• Cough
• Nausea and vomiting (in asthma patients)
• Pneumonia, throat irritation, and musculoskeletal pain (more common in COPD patients)

Serious reactions to act on immediately include sudden severe breathing difficulty (paradoxical bronchospasm), chest pain or fast/irregular heartbeat, signs of a severe allergic reaction, and white patches in the mouth that don't go away with rinsing. Call your doctor or seek emergency care right away if any of these occur.

• LABA risk in asthma: Using a long-acting beta-agonist alone (without a corticosteroid) increases the risk of serious asthma-related events, including death. This combination product includes the corticosteroid to reduce that risk — never use this medicine as your sole asthma treatment, and never add a separate LABA inhaler.
• Not for acute attacks: This is a maintenance inhaler only. Do not use it to treat sudden breathing problems. Serious and sometimes fatal events have been reported when salmeterol was started in patients with rapidly worsening asthma.
• Pneumonia in COPD: Patients with COPD have a higher risk of pneumonia with inhaled corticosteroids; older patients are at greatest risk. Watch for fever, increased mucus, or worsening cough.
• Adrenal suppression: Long-term or high-dose corticosteroid use can suppress the adrenal glands (which produce natural stress hormones). This is especially important when switching from oral corticosteroids — taper slowly under medical supervision.
• Bone density, eyes, and growth: Long-term inhaled corticosteroid use can reduce bone mineral density, increase the risk of cataracts and glaucoma, and may slow growth in children. Periodic monitoring is recommended.
• Infections: Corticosteroids can reduce the immune response, making infections like chickenpox or measles potentially more serious. Avoid exposure to these illnesses if you have not been immunized.

Several medicines and drug classes can interact meaningfully with fluticasone and salmeterol:

• Strong CYP3A4 inhibitors (ritonavir, ketoconazole, itraconazole, clarithromycin, and others) — can dramatically increase blood levels of fluticasone and salmeterol, raising the risk of serious side effects including abnormal heart rhythms and adrenal suppression; avoid combining
• MAO inhibitors and tricyclic antidepressants — can intensify salmeterol's cardiovascular effects; avoid use within 2 weeks of stopping these medicines
• Beta-blockers (metoprolol, atenolol, propranolol, etc.) — can block the airway-opening effect of salmeterol and may trigger severe bronchospasm in patients with asthma or COPD
• Non-potassium-sparing diuretics (loop and thiazide diuretics such as furosemide or hydrochlorothiazide) — can worsen low potassium levels and abnormal heart rhythms when combined with salmeterol
• Other LABA-containing inhalers — using two LABA products together can cause an overdose; do not combine

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not use if you have a severe allergy to milk proteins, fluticasone propionate, salmeterol, or any inactive ingredients in the product
• Do not use as the primary treatment during a severe asthma attack or acute COPD episode requiring emergency care
• Tell your doctor if you have heart disease, abnormal heart rhythms, or high blood pressure — salmeterol can have cardiovascular effects
• Tell your doctor if you have seizure disorders, thyroid problems, diabetes, or low potassium — these conditions may be affected by this medicine
• If you are pregnant: poorly controlled asthma in pregnancy carries real risks for both mother and baby; discuss the benefit-risk balance with your doctor
• If you are breastfeeding: it is not known whether these medicines pass into human milk; discuss with your doctor
• Children's height and growth should be monitored regularly during long-term treatment
• Older adults with COPD have a higher risk of pneumonia with this medicine — ensure your doctor is aware
• If you have liver problems: your body may clear these medicines more slowly; your doctor should monitor you for signs of increased drug exposure

Too much of the salmeterol component can cause signs of excessive stimulation: fast or irregular heartbeat, chest pain (angina), tremor, headache, dizziness, muscle cramps, nausea, low potassium, high blood sugar, and in serious cases, dangerous heart rhythm abnormalities or cardiac arrest. Too much of the fluticasone component over time can cause signs of excess corticosteroid effects (hypercorticism), such as weight gain or easy bruising. If an overdose is suspected, stop using the inhaler and seek medical attention right away — cardiac monitoring is recommended.

At recommended doses, salmeterol's effects on heart rate, blood pressure, blood potassium, and blood sugar are not significantly different whether it is given as part of the combination product or alone. Clinical studies in people with asthma showed no significant abnormal heart rhythms on continuous heart monitoring. The corticosteroid component (fluticasone) can affect the body's cortisol production at high doses, but at recommended doses, most patients retain the ability to produce a normal stress response. The two medicines do not meaningfully alter each other's systemic (whole-body) effects when inhaled together.

Both fluticasone and salmeterol act locally in the lungs, so blood levels do not reflect how well they are working. Fluticasone is very poorly absorbed when swallowed (less than 1% bioavailability) because the gut and liver break it down quickly; most of what reaches the body comes from the lungs. Peak plasma levels of fluticasone are reached within 1 to 2 hours after inhalation, and salmeterol peaks in about 5 minutes. Because of the small doses inhaled, salmeterol blood levels are often low or undetectable at recommended doses. Both medicines are broken down primarily through the CYP3A4 enzyme system in the liver, which is why strong inhibitors of that enzyme can significantly raise drug levels and cause side effects.

Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) . Store in a dry place away from direct heat or sunlight. Keep out of reach of children.