Axinat25 mcg/puff

Established (FDA-approved) uses

• Maintenance treatment of asthma in patients 4 years of age and older. Axinat must always be given together with an inhaled corticosteroid (ICS) - it must never be used alone (as monotherapy) for asthma, per its boxed warning.
• Prevention of exercise-induced bronchospasm (EIB) in patients 4 years of age and older.
• Long-term, twice-daily maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Important limitation of use

Axinat is not a rescue medicine. It does not relieve acute asthma or COPD symptoms and must not be used to treat acute bronchospasm or status asthmaticus. A separate fast-acting (short-acting beta-agonist) inhaler must always be available for acute symptoms.

Salmeterol Xinafoate is available as a metered-dose inhaler (MDI) or dry powder inhaler (DPI). Each actuation/blister delivers a fixed microgram dose of salmeterol base (as the xinafoate salt), commonly 25 mcg/puff (MDI) or 50 mcg/blister (DPI), depending on the marketed brand and device. It is also available combined with an inhaled corticosteroid (fluticasone propionate) in fixed-dose combination products, which are considered separately from single-ingredient Salmeterol Xinafoate.

Axinat is the xinafoate (1-hydroxy-2-naphthoic acid) salt of salmeterol, a selective, long-acting beta-2 adrenergic receptor agonist (LABA). It is delivered by oral inhalation for the long-term, twice-daily maintenance treatment of asthma and chronic obstructive pulmonary disease (COPD). Unlike short-acting bronchodilators, Axinat has a slow onset of action (about 10-20 minutes) but a prolonged bronchodilator effect lasting approximately 12 hours, which is why it is dosed twice daily rather than used for immediate symptom relief.

Long-acting beta-2 adrenergic agonist (LABA) bronchodilator

Pharmacodynamics

Salmeterol Xinafoate selectively stimulates beta-2 adrenergic receptors on bronchial smooth muscle, producing bronchodilation. Its long lipophilic side chain anchors it near the receptor, giving a sustained duration of bronchodilator action of approximately 12 hours per dose, in contrast to short-acting beta-agonists.

Pharmacokinetics

• Absorption: Most of an inhaled dose is swallowed, but therapeutic effect results from local deposition in the lung; plasma concentrations are very low and are not useful for predicting therapeutic effect.
• Metabolism: Extensively metabolized in the liver, mainly via hydroxylation by CYP3A4, to alpha-hydroxysalmeterol.
• Excretion: Primarily eliminated in feces, with a smaller amount in urine.

• Axinat is for oral inhalation only and must not be swallowed, injected, or used in a nebulizer unless a specific nebulizer solution is prescribed.
• For a metered-dose inhaler, shake well, prime if new or unused for several days, exhale fully, form a tight seal around the mouthpiece, inhale slowly and deeply while actuating the device, then hold the breath for about 10 seconds.
• For a dry powder inhaler (Diskus-type device), load the dose per the device instructions, exhale away from the device, then inhale forcefully and deeply through the mouthpiece.
• Rinse the mouth with water after use (without swallowing) if the product also contains an inhaled corticosteroid, to reduce the risk of oral thrush.
• Doses should be evenly spaced approximately 12 hours apart, once in the morning and once in the evening.

• Strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin): can significantly increase systemic salmeterol exposure and the risk of QT prolongation and cardiovascular adverse effects; concurrent use is not recommended.
• Other long-acting beta-agonist (LABA)-containing medicines: must not be used together with Axinat, as this increases the risk of additive beta-agonist toxicity (tachycardia, arrhythmia, tremor).
• Beta-blockers (including cardioselective agents and ophthalmic beta-blockers): may blunt or block the bronchodilator effect of Axinat and can cause severe bronchospasm in patients with reactive airway disease; avoid unless there are compelling reasons and use with caution if unavoidable.
• Non-potassium-sparing diuretics (e.g. loop or thiazide diuretics): may worsen ECG changes and hypokalemia caused by beta-agonists; use with caution and monitor potassium.
• Monoamine oxidase inhibitors and tricyclic antidepressants: may potentiate the cardiovascular effects of Axinat (e.g. QT prolongation); use with caution.

Common (asthma)

Headache, influenza-like symptoms, nasal and sinus congestion, pharyngitis, rhinitis, tracheitis/bronchitis.

Common (COPD)

Cough, headache, musculoskeletal pain, throat irritation, viral upper respiratory infection.

Less common but clinically important

• Tachycardia, palpitations, tremor (see Precautions and Warnings for cardiovascular risk)
• Paradoxical bronchospasm (see Precautions and Warnings)
• Hypokalemia and hyperglycemia, particularly at higher than recommended doses
• Hypersensitivity reactions including urticaria, angioedema, rash, and rarely anaphylaxis
• Oropharyngeal candidiasis (mainly with combination ICS/LABA products)

Pregnancy

Data on Axinat use in human pregnancy are limited. As with other medicines, Axinat should be used during pregnancy only if the potential benefit to the mother (maintaining asthma/COPD control) justifies the potential risk to the fetus, and only under a physician's guidance. Uncontrolled asthma during pregnancy itself carries risks to both mother and fetus, so treatment should generally not be stopped without medical advice.

Lactation

It is not known whether salmeterol passes into human breast milk in clinically significant amounts. Because systemic absorption after inhalation is very low, risk to a breastfed infant is expected to be minimal, but a physician should be consulted before using Axinat while breastfeeding, weighing the mother's clinical need against any potential infant exposure.

Boxed warning: asthma-related death

Long-acting beta-2 adrenergic agonists, including Axinat, increase the risk of asthma-related death when used as monotherapy for asthma. Axinat must always be used together with an inhaled corticosteroid for asthma; it must never be used alone for this indication.

Other precautions

• Not for acute symptoms: Axinat does not replace a fast-acting rescue inhaler and should not be initiated in patients with rapidly deteriorating or potentially life-threatening asthma/COPD.
• Do not combine with other LABAs: concurrent use of other medicines containing a long-acting beta-agonist should be avoided due to additive toxicity risk.
• Cardiovascular effects: beta-agonists can produce tachycardia, palpitations, tremor, and rarely significant blood pressure changes or ECG changes (including QT prolongation); use with caution in patients with cardiovascular disease, arrhythmias, or hypertension.
• Paradoxical bronchospasm: if it occurs, discontinue Axinat immediately and treat with an alternative fast-acting bronchodilator.
• Metabolic effects: may cause hypokalemia (increased risk with concurrent diuretics) and transient hyperglycemia; monitor in susceptible patients.
• Use with caution in patients with convulsive disorders, thyrotoxicosis, or diabetes mellitus, and in those unusually responsive to sympathomimetic amines.
• Not a substitute for oral or inhaled corticosteroids; corticosteroid therapy should not be stopped or reduced abruptly upon starting Axinat.

Overdose with Axinat is expected to produce exaggerated beta-adrenergic effects, which may include tachycardia, palpitations, tremor, headache, muscle cramps, dry mouth, hypertension or hypotension, seizures, hypokalemia, hyperglycemia, and, rarely, serious arrhythmias or cardiac arrest.

If an overdose is suspected, seek immediate medical attention or contact emergency services/a poison control center. Treatment is supportive; the drug should be discontinued and cardiac monitoring performed as directed by a physician. Do not attempt to manage a suspected overdose at home with additional inhaler doses.

Store at room temperature (below 30°C), away from direct sunlight, heat, and freezing temperatures. Do not puncture, break, crush, or burn the canister/inhaler, even when it appears empty. Keep out of reach of children.

• Pediatric: see Pediatric Uses.
• Geriatric: no dosage adjustment is generally required based on age alone; use with caution given a higher likelihood of concurrent cardiovascular disease.
• Hepatic impairment: Axinat is extensively metabolized by the liver; patients with hepatic impairment should be monitored closely for systemic beta-agonist effects, as drug exposure may be increased.
• Renal impairment: no specific dose adjustment is established; limited data are available, so use with routine clinical monitoring.
• Pregnancy and lactation: see Pregnancy and Lactation.

Axinat is intended for long-term, regular maintenance use, not short-term or as-needed treatment. It should be continued at the prescribed twice-daily schedule for as long as the treating physician determines it is needed to control asthma or COPD symptoms, with periodic reassessment of asthma control, and, when appropriate, stepping down of the inhaled corticosteroid/LABA combination once control is well maintained, under medical supervision. Do not stop treatment abruptly without consulting a physician.

Bronchodilators; Long-acting beta-2 adrenergic agonists (LABA); Anti-asthmatic and anti-COPD agents

Salmeterol Xinafoate acts by selectively binding to and stimulating beta-2 adrenergic receptors located on airway smooth muscle. Receptor activation stimulates adenylyl cyclase, raising intracellular cyclic AMP (cAMP), which activates protein kinase A and leads to relaxation of bronchial smooth muscle and bronchodilation. The long lipophilic side chain of the salmeterol molecule allows it to remain anchored near the beta-2 receptor, producing a sustained bronchodilator effect of about 12 hours, distinguishing it from short-acting beta-agonists.

C

Axinat is approved for the maintenance treatment of asthma (with a concurrent inhaled corticosteroid) and for prevention of exercise-induced bronchospasm in children 4 years of age and older. Safety and efficacy in children younger than 4 years have not been established, and Axinat should not be used in this age group. In pediatric and adolescent patients, a fixed-dose combination inhaler containing both an inhaled corticosteroid and salmeterol is generally preferred over separate inhalers to help ensure salmeterol is not used without concurrent corticosteroid therapy.