Aclidinium Bromide+ Formoterol Fumarate inhaler

Aclidinium Bromide+ Formoterol Fumarate inhaler is used for: Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease Indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD) 1 inhalation PO BID Not to exceed 1 inhalation BID

Severe hypersensitivity to milk proteins Hypersensitivity to aclidinium bromide, formoterol fumarate, or any product component Not indicated for asthma; use of long-acting beta2-adrenergic agonists (LABAs), including formoterol fumarate, without an inhaled corticosteroid is contraindicated in patients with asthma

Safety and efficacy not established for patients with asthma; not indicated for asthma; use of LABA as monotherapy (without inhaled corticosteroids) for asthma associated with increase asthma-related deaths; available data do not suggest increased risk of death with LABAs in patients with COPD Do not initiate in acutely deteriorating COPD, which may be a life-threatening condition; aclidinium/formoterol is intended as maintenance treatment and should not be used for relief of acute symptoms (ie, rescue therapy for acute bronchospasm) May cause paradoxical bronchospasm, which may be life threatening; if paradoxical bronchospasm occurs, treat immediately with an inhaled short-acting bronchodilator; discontinue aclidinium/formoterol and institute alternant therapy Immediate hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, rash, bronchospasm, or itching, reported; discontinue aclidinium/formoterol and institute alternant therapy if this occurs Beta-agonists can produce clinically significant cardiovascular effects as measured by increases in pulse rate, systolic or diastolic or blood pressure, or symptoms; additionally, may cause ECG changes (eg, flattening of the T wave, prolongation of the QTc interval, and ST-segment depression), although clinical significance is unknown Caution with using sympathomimetic amines in patients with convulsive disorders, thyrotoxicosis, and in those who are unusually responsive to sympathomimetic amines; doses of the related beta-agonist albuterol, when administered IV, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis Caution with narrow-angle glaucoma; monitor for signs and symptoms of acute narrow-angle glaucoma (eg, eye pain or discomfort, blurred vision, visual halos, colored images in association with red eyes from conjunctival congestion and corneal edema) May worsen urinary retention or bladder neck obstruction; monitor for signs and symptoms (eg, difficulty passing urine, painful urination)

Pregnancy There are no adequate and well-controlled studies of aclidinium/formoterol or its individual components in pregnant women to assess drug-associated risks Animal studies No adverse developmental effects were seen with inhalation administration of aclidinium bromide to pregnant rats and rabbits during organogenesis at 15 or 20 times, respectively, the maximum recommended human daily inhaled dose (MRHDID) Formoterol fumarate alone, administered by the oral route, was teratogenic in rats and rabbits at 1,200 and 49,000 times the MRHDID, respectively Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 85 times the MRHDID Labor or delivery No well-controlled human studies Because of the potential for beta-agonist interference with uterine contractility, use of during labor should be restricted to those patients in whom the benefits clearly outweigh the risk Lactation There are no available data on the breastfed child or on milk production or presence in human milk Both aclidinium bromide and formoterol fumarate are present in rat milk; when a drug is present in animal milk, it is likely that the drug will be present in human milk Animal studies Aclidinium bromide reduced pup weights when pregnant rats continued inhalation administration through lactation at 5 times the MRHDID Formoterol fumarate increased pup loss at birth and during lactation, and decreased pup weight in rats at 85 times the MRHDID

Caution with coadministration with additional adrenergic drugs, by any administration route, because additive sympathetic effects Concomitant treatment with xanthine derivatives or steroids may potentiate any hypokalemic effect of beta-adrenergic agonists Caution if coadministered with other drugs that cause hypokalemia (eg, loop or thiazide diuretics) Caution if beta2-agonists are coadministered with MAO inhibitors, tricyclic antidepressants, or other drugs known to prolong the QTc interval, because the action of adrenergic agonists on the cardiovascular system may be potentiated by these agents Formoterol and beta-blockers may inhibit the effect of each other if coadministered; patients with COPD are not typically treated with beta-blockers; however, under certain circumstances (eg, prophylaxis after MI), there may be no acceptable alternatives to the use of beta-blockers in patients with COPD; if needed, consider cautious use of cardioselective beta-blockers Avoid coadministration of other anticholinergic medications with aclidinium, owing to additive effects

Side effects of Aclidinium Bromide+ Formoterol Fumarate inhaler : 1-10% Upper respiratory tract infection (8.9%) Headache (6.3%) Back pain (3.8%) Cough (1-3%) Sinusitis (1-3%) Influenza (1-3%) Tooth abscess (1-3%) Insomnia (1-3%) Dizziness (1-3%) Dry mouth (1-3%) Oropharyngeal pain (1-3%) Muscle spasms (1-3%) Musculoskeletal pain (1-3%) Arthralgia (1-3%) Pain in extremity (1-3%) Urinary tract infection (1-3%) Blood creatine phosphokinase increased (1-3%)

Aclidinium: Long-acting muscarinic antagonist (LAMA), often referred to as an anticholinergic, has specificity for muscarinic receptors with affinity for the M3 (subscript) receptor in the airways; produces bronchodilation by inhibiting acetylcholine’s effect on muscarinic receptors in the airway smooth muscle Formoterol: Long-acting selective beta-2 agonist (LABA); elicits bronchial smooth muscle relaxation by stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP); increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibit release of mediators of immediate hypersensitivity from cells, especially from mast cells