Arformoterol

Uses

Arformoterol tartrate is a salt of Arformoterol, the (R,R)-enantiomer of formoterol. Arformoterol is a selective beta 2-adrenergic bronchodilator. It has two-fold greater potency than racemic formoterol which contains both the (S,S) and (R,R)-enantiomers. The (S,S)-enantiomer is about 1,000-fold less potent as a beta2-agonist than the (R,R)-enantiomer. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung.

Arformoterol is also used to associated treatment for these conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD)

How Arformoterol works

While it is recognized that β2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and β1-receptors are the predominant receptors in the heart, data indicate that there are also β2-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective β2-agonists may have cardiac effects. The pharmacologic effects of β2-adrenoceptor agonist drugs, including arformoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (cyclic AMP). Increased intracellular cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of proinflammatory mediators from cells, especially from mast cells. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Arformoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-response.

Dosage

Arformoterol dosage

The recommended dose of Arformoterol nebuliser solution is one 15 mcg unit-dose ampoule administered twice daily (morning and evening) by nebulization. A total daily dose of greater than 30 mcg (15 mcg twice daily) is not recommended.Pediatric Use: COPD does not occur in children. The safety and efficacy of Arformoterol nebuliser solution in pediatric patients have not been established

Side Effects

Most common adverse reactions are pain, chest pain, back pain, diarrhea, sinusitis, leg cramps, dyspnea, rash, flu syndrome, peripheral edema and lung disorder. Arformoterol can cause serious side effects, including: People with asthma, who take LABA medicines, have an increased risk of death from asthma problems. Patient should get emergency medical care if:• Breathing problems worsen quickly• After the use of rescue inhaler medicine, it does not relieve breathing problems

Toxicity

A death was reported in dogs after a single oral dose of 5 mg/kg (approximately 4500 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose.

Precaution

Arformoterol nebuliser should not be initiated in acutely deteriorating patients. It should be used with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs. Life-threatening paradoxical bronchospasm can occur.

Food Interaction

Arformoterol Hypertension interaction

[Moderate] Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression).

Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol.

However, beta-2-selectivity is not absolute and can be lost with larger doses.

High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias.

Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and

The recommended dosages should not be exceeded.

Arformoterol Drug Interaction

Moderate: fluticasone / salmeterol, fluticasone / salmeterol, fluticasone / vilanterol, fluticasone / vilanterol, albuterol / ipratropium, albuterol / ipratropium, albuterol / ipratropium, albuterol / ipratropium, metoprolol, metoprololUnknown: zolpidem, zolpidem, roflumilast, roflumilast, tiotropium, tiotropium, cholecalciferol, cholecalciferol, revefenacin, revefenacin

Arformoterol Disease Interaction

Major: asthmaModerate: hepatic impairment, cardiovascular, diabetes, hypokalemia, seizures

Half Life

In COPD patients given 15 mcg inhaled arformoterol twice a day for 14 days, the mean terminal half-life of arformoterol was 26 hours.

Clearance

• renal cl=8.9 L/hr [Healthy male subjects]

Elimination Route

After administration of a single oral dose of radiolabeled arformoterol to eight healthy male subjects, 63% of the total radioactive dose was recovered in urine and 11% in feces within 48 hours. Direct glucuronidation of arformoterol is mediated by several UGT enzymes and is the primary elimination route.

Pregnancy & Breastfeeding use

Pregnancy Category C. Arformoterol nebuliser solution should be used during pregnancy, only if the potential benefit justifies the potential risk to the fetus. It is not known whether arformoterol is excreted in human milk.

Acute Overdose

As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of Arformoterol nebuliser solution.

Interaction with other Medicine

Other adrenergic drugs may potentiate effect. Xanthine derivatives, steroids, diuretics, or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes. MAO inhibitors, tricyclic antidepressants and drugs that prolong the QTc interval may potentiate effect on the cardiovascular system. Beta-blockers may decrease effectiveness.

Storage Condition

Arformoterol nebuliser solution should be stored at 2-8°c, protected from light and excessive heat. Do not freeze. Keep out of the reach of children

Innovators Monograph

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