use caution. Use Caution/Monitor. aclidinium and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.Serious - Use Alternative (2)trazodone and formoterol both increase QTc interval. Avoid or Use Alternate Drug. trazodone, formoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.triamtereneMonitor Closely (1)triamterene increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.triazolamMonitor Closely (1)triazolam increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trifluoperazineMonitor Closely (3)trifluoperazine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. aclidinium decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor. trifluoperazine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Serious - Use Alternative (1)trifluoperazine and formoterol both increase QTc interval. Avoid or Use Alternate Drug.trihexyphenidylMonitor Closely (1)aclidinium and trihexyphenidyl both decrease cholinergic effects/transmission. Use Caution/Monitor.trimethoprimMonitor Closely (1)formoterol and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.trimipramineMonitor Closely (2)trimipramine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. aclidinium and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.Serious - Use Alternative (2)trimipramine and formoterol both increase QTc interval. Avoid or Use Alternate Drug. trimipramine, formoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.triprolidineMonitor Closely (1)triprolidine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.triptorelinMonitor Closely (1)triptorelin increases levels of formoterol by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.tropisetronMonitor Closely (1)formoterol and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.trospium chlorideMonitor Closely (1)aclidinium and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.umeclidinium bromideMonitor Closely (1)umeclidinium bromide and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor. If possible, avoid coadministration of additional anticholinergic agentsumeclidinium bromide/vilanterol inhaledContraindicated (1)aclidinium, umeclidinium bromide/vilanterol inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Duplicate therapy.Serious - Use Alternative (1)formoterol increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.vecuroniumMonitor Closely (1)aclidinium and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.venlafaxineMonitor Closely (1)formoterol and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.vilanterol/fluticasone furoate inhaledSerious - Use Alternative (1)formoterol increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.voriconazoleMonitor Closely (1)formoterol and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.xylometazolineMonitor Closely (2)formoterol and xylometazoline both decrease sedation. Use Caution/Monitor. formoterol and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.yohimbineMonitor Closely (2)formoterol and yohimbine both decrease sedation. Use Caution/Monitor. formoterol and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.ziconotideMonitor Closely (1)ziconotide increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziprasidoneMonitor Closely (3)aclidinium decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor. ziprasidone increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. ziprasidone increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)formoterol and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zotepineMonitor Closely (1)aclidinium decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. 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%) Contraindications 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 Cautions 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) Instruct patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (eg, 4x/day) to discontinue the regular use of these drugs and use them only for symptomatic relief of acute respiratory symptoms As with other inhaled drugs containing beta-agonists, do not use more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result; clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs 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) Hypokalemia and hyperglycemia Beta-agonists may produce significant hypokalemia, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects; this decrease is usually transient, not requiring potassium supplementation Beta-agonist medications may produce transient hyperglycemia Clinical trials of aclidinium/formoterol over 24-52 weeks' duration did not show evidence of an effect on serum glucose or potassium Drug interaction overview 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 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 Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action 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 Absorption Peak plasma time: Within 5 minutes after inhalation Peak plasma concentration: 128 pg/mL (aclidinium); 17 pg/mL (formoterol) Steady-state achieved within 5 days Distribution Vd (aclidinium; 400 mcg IV): 300 L Protein bound (formoterol; 54 mcg inhaled): 46% (RR enantiomer); 58% (SS enantiomer) Metabolism Aclidinium Major metabolic route is hydrolysis, both chemically and enzymatically by esterases Rapidly and extensively hydrolyzed in plasma to alcohol and dithienylglycolic acid derivatives, neither of which binds to muscarinic receptors and are devoid of pharmacologic activity Owing to the low plasma levels achieved at the clinically relevant doses, aclidinium and its metabolites are not expected to alter the disposition of drugs metabolized by the human CYP450 enzymes Formoterol Primarily by direct glucuronidation and by O-demethylation, followed by conjugation to inactive metabolites Secondary metabolic pathways include deformylation and sulfate conjugation; CYP2D6 and CYP2C identified as being primarily responsible for O-demethylation Elimination Half-life: ~12 hr (aclidinium) Total clearance: ~170 L/hr (aclidinium IV) Excretion Aclidinium: 54-65% urine; 20-33% feces; <1% excreted as unchanged drug Formoterol: 62% urine; 24% feces Oral Inhalation Administration Not for relief of acute symptoms; extra doses should not be used for that purpose Do not use additional LABAs while taking this combination inhaler Breath-actuated inhaler; counsel patients with instructions and images included with inhaler Missed dose: Instruct patient to take the next dose at the usual time; do not take 2 doses at one time Storage Unopened: Store inside the sealed bag and only open immediately before use; discard bag and desiccant sachet Opened: Store in dry place at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) Do not store inhaler on a vibrating surface No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to