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How does Advair Diskus work?

Advair Diskus includes two drugs: fluticasone propionate and salmeterol. The mechanisms of each of these components are described below.

Fluticasone propionate: Fluticasone propionate is a synthetic corticosteroid with anti-inflammatory properties. In vitro, fluticasone propionate demonstrates an affinity for the glucocorticoid receptor in humans. As a corticosteroid, fluticasone propionate exhibits activity on multiple inflammatory cells and mediators. This is an important mechanism in treating the inflammation pathways implicated in asthma and COPD.

Salmeterol: Salmeterol belongs to the LABA class and is a selective LABA. Research demonstrates that salmeterol is 50 times more selective for beta2-adrenoreceptors compared with albuterol. Salmeterol’s effect on these adrenoreceptors contributes to increased cyclic AMP levels, causing the bronchial smooth muscle to relax and the inhibition of mediator release.

Side Effects

Side effects of Advair Diskus include:

• Headaches
• Upper respiratory tract infections (URTIs)
• Dizziness
• Nausea
• Vomiting
• Diarrhea
• Stomach Upset
• Oral thrush
• Sore throat
• Dry mouth, throat, and nose
• Stuffy nose
• Cough
• Sinus pain
• Deep or hoarse voice
• Musculoskeletal pain

Warnings & Precautions

Severe Asthma-Related Hospitalizations, Intubations, and Death

Using a LABA alone (without a concomitant ICS) for asthma treatment has shown to increase an individual’s risk of asthma-related death. This was demonstrated in the Salmeterol Multicenter Asthma Research Trial (SMART). Research also indicates that LABA monotherapy elevates one’s risk of asthma-related hospitalization in adolescent and pediatric patients. This is seen across all LABAs, and therefore, is thought to be a class effect when used without an ICS. When a LABA is used in a fixed-dose combination with an ICS, there is not an elevated chance of serious asthma-related events compared with ICS alone.

Deterioration of Disease and Acute Episodes

Advair Diskus has not been evaluated in individuals with acutely deteriorating asthma or COPD. Therefore, it should not be used in individuals that have quickly deteriorating or potentially life-threatening asthma or COPD events.

Excessive Use of Advair Diskus and Concomitant Use with other LABAs

Advair Diskus should not be taken more frequently than is recommended. Additionally, it should not be taken at doses higher than what is recommended or with other medications that contain a LABA. Research indicates that excessive administration of inhaled sympathomimetic drugs is associated with serious cardiovascular events and death. Therefore, individuals taking Advair Diskus should not take another LABA-containing medication (e.g., formoterol fumarate, salmeterol, arformoterol tartrate, etc.).

Local Effects of Inhaled Corticosteroids

Studies demonstrate that Advair Diskus can cause localized Candida albicans infections in the pharynx or mouth. In these cases, providers should treat patients with local or systemic antifungal therapy. Advair Diskus usually should not be interrupted while treating infection. Patients should rinse their mouths with water after inhalation to lessen the risk of developing candidiasis infection.

Pneumonia

Patients with COPD taking inhaled corticosteroids, such as fluticasone propionate, have developed lower respiratory tract infections like pneumonia. Providers should monitor COPD patients for signs and symptoms of pneumonia. This is important to assess, as exacerbations and pneumonia share similar clinical characteristics.

Immunosuppression

Individuals on immunosuppressive drugs are at higher risk of developing an infection. Corticosteroids, for example, have caused increased susceptibility to measles or chickenpox in both children and adults. Providers should use caution when prescribing Advair Diskus to patients who are not immunized against these diseases or who have not previously had these diseases.

If an individual is exposed to chickenpox, the provider may consider initiating prophylaxis with the varicella zoster immune globulin (VZIG). If the patient develops chickenpox, they should be treated with appropriate antiviral agents. If an individual is exposed to measles, the provider may consider prophylaxis with pooled intramuscular immunoglobulin (IG). Additionally, patients with tuberculosis of the respiratory tract, ocular herpes simplex, and other systemic infections should use caution when an ICS and potentially avoid taking an ICS.

Transferring Individuals from Systemic Corticosteroid Therapy

Individuals previously on systemically active corticosteroids but transferring to an ICS need to use caution. There have been cases of death due to adrenal insufficiency in those that have made this transition. Therefore, patients may require a washout period lasting a few months to recover their hypothalamic-pituitary-adrenal (HPA) function after systemic corticosteroid discontinuation.

Hypercorticism and Adrenal Suppression

Sensitive patients may demonstrate systemic corticosteroid effects while on Advair Diskus, such as adrenal suppression and hypercorticism. If this happens, the Advair Diskus dose should be decreased slowly as one would decrease systemic corticosteroids. Other treatment options for asthma symptoms should then be explored.

Strong Cytochrome P450 3A4 Inhibitor Drug Interactions

Advair Diskus should not be used with strong cytochrome P450 3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole, ritonavir, etc.). Concomitant use can cause elevated systemic corticosteroid and cardiovascular effects may occur.

Paradoxical Bronchospasm and Upper Airway Symptoms

Advair Diskus can cause paradoxical bronchospasm like other inhaled medications. This event can be life-threatening. If this happens, patients should be administered an inhaled, short-acting bronchodilator immediately. Stop Advair Diskus right away and consider and start a different therapy. Advair Diskus has been shown to cause upper airway symptoms such as laryngeal spasm, swelling, irritation, and choking.

Immediate Hypersensitivity Reactions

Advair Diskus has been shown to cause hypersensitivity events such as rash, angioedema, hypotension, and bronchospasm. Additionally, anaphylactic reactions have been reported in those with a serious milk protein allergy. This is because the inhalation powder contains lactose. Individuals that have milk protein allergies, therefore, should not use Advair Diskus.

Drug Interactions

Strong Cytochrome P450 3A4 Inhibitor Drug Interactions

Advair Diskus should not be used with strong cytochrome P450 3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole, ritonavir, etc.). Concomitant use can cause elevated systemic corticosteroid, and cardiovascular effects may occur.

Tricyclic Antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs)

Providers should use caution when prescribing Advair Diskus with MAOIs or TCAs. Salmeterol’s effect on the vascular system can be increased by these types of medications.

Beta-adrenergic Receptor Blocking Agents

Beta-blockers stop the beta-agonist effects on the pulmonary system. Additionally, they may cause serious bronchospasm in those with COPD or asthma. Any patients with COPD or asthma should avoid beta-blockers. If necessary, providers can consider cardio-selective beta-blockers but should still use caution.

Non-Potassium-Sparing Diuretics

Beta-agonists, such as salmeterol, can worsen hypokalemia and/or ECG changes caused by non-potassium-sparing diuretics like thiazide or loop diuretics. Providers should use caution when prescribing Advair Diskus in patients on these types of diuretics.

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