interaction is not clear, use caution. Use Caution/Monitor.ziprasidoneMonitor Closely (4)glycopyrrolate inhaled decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor. ziprasidone increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. glycopyrrolate inhaled decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. 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 (2)glycopyrrolate inhaled decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. glycopyrrolate inhaled decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. 1-10% Cough (4%) Urinary tract infection (2.6%) Arthralgia (<2%) Chest pain (<2%) Tooth abscess (<2%) Muscle spasms (<2%) Headache (<2%) Oropharyngeal pain (<2%) Vomiting (<2%) Pain in extremity (<2%) Dizziness (<2%) Anxiety (<2%) Dry mouth (<2%) Fall (<2%) Influenza (<2%) Fatigue (<2%) Acute sinusitis (<2%) Contusion (<2%) Frequency Not Defined Formoterol Hypersensitivity reactions Hyperglycemia Sleep disturbance Agitation Restlessness Tremor Nausea Tachycardia Palpitations Cardiac arrhythmias Contraindications Hypersensitivity All LABAs are contraindicated in patients with asthma without use of a long-term asthma control medication; not indicated for the treatment of asthma Cautions Do not use more often than recommended, at higher doses than recommended, or in combination with additional therapy containing a LABA because of risk of overdose; clinically significant cardiovascular effects and fatalities reported in association with excessive use of inhaled sympathomimetic medicines; patients using drug should not use another medicine containing a LABA for any reason Can produce paradoxical bronchospasm that may be life-threatening; treat immediately with an inhaled, short-acting bronchodilator, discontinue therapy, and institute alternative therapy Immediate hypersensitivity reactions have been reported after administration of formoterol or glycopyrrolate; if signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of tongue, lips, and face), urticaria, or skin rash, therapy should be stopped at once and alternative treatment considered Therapy should be used with caution in patients with narrow-angle glaucoma; prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (eg, eye pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival congestion and corneal edema); instruct patients to consult a physician immediately should any of these signs or symptoms develop Therapy should be used with caution in patients with urinary retention; prescribers and patients should be alert for signs and symptoms of urinary retention (eg, difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder neck obstruction; instruct patients to consult a physician immediately should any of these signs or symptoms develop Like all medications containing sympathomimetic amines, this medication should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines Beta2-agonist medicines may produce transient hyperglycemia in some patients; clinical significance unknown LABAs can produce clinically significant cardiovascular effects, including increases in pulse rate or systolic or diastolic blood pressure; if such effects occur, therapy may need to be discontinued; beta-agonists have also been reported to produce electrocardiographic changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression; clinical significance of these findings is unknown; the drug should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension Doses of the related beta2-agonist albuterol, when administered IV, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis owing to transient hyperglycemia; use caution LABAs may produce significant hypokalemia, which has the potential to produce adverse cardiovascular effect; in patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility for cardiac arrhythmias; the decrease in serum potassium is usually transient, not requiring supplementation Asthma-related events The safety and efficacy in patients with asthma not established; not indicated for the treatment of asthma Use of LABA as monotherapy, without inhaled corticosteroids (ICS), for asthma associated with increased risk of asthma-related death Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases risk of asthma-related hospitalization in pediatric and adolescent patients; these findings are considered a class effect of LABA monotherapy When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone No trial adequate to determine whether rate of asthma-related deaths is increased in patients treated with this drug combination has been conducted Available data do not suggest an increased risk of death with use of LABA in patients with COPD Deterioration of disease and acute episodes Therapy should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition; this drug has not been studied in patients with acutely deteriorating COPD; using the drug inthis setting is inappropriate Therapy should not be used for relief of acute symptoms, eg, as rescue therapy for treatment of acute episodes of bronchospasm; the drug has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose; acute symptoms should be treated with an inhaled short-acting beta2-agonist When initiating therapy, patients who have been taking inhaled, short-acting beta2-agonists on a regular basis (eg, four times a day) should be instructed to discontinue the regular use of these medicines and use them only for symptomatic relief of acute respiratory symptoms When prescribing the drug, the healthcare provider should also prescribe an inhaled, short-acting beta2-agonist and instruct the patient on how it should be used; increasing inhaled beta2-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated COPD may deteriorate acutely over a period of hours or chronically over several days or longer; if the drug no longer controls the symptoms of bronchoconstriction, or the patient’s inhaled, short-acting beta2-agonist becomes less effective, or the patient needs more inhalations of short-acting beta2-agonist than usual, these may be markers of deterioration of disease; in this setting, a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once; increasing the daily dosage beyond the recommended dose is not appropriate in this situation Pregnancy There are no well-controlled human trials that have investigated the effects on preterm labor or labor at term; because beta 2 agonists may potentially interfere with uterine contractility, drug should be used during labor only if potential benefit justifies potential risk Single-dose studies in humans found that a very small amount of glycopyrrolate passed the placental barrier Animal studies Glycopyrrolate Administered by the subcutaneous route in rats and rabbits, there were no structural abnormalities or a decrease in fetal survival at exposures approximately 2700 and 5400 times from the maximum recommended human daily inhalation dose (MRHDID), respectively; it had no effects on physical, functional, and behavioral development of rat pups with exposures up to 2700 times the MRHDID Formoterol fumarate Formoterol fumarate alone, administered by the oral route in rats and rabbits, caused structural abnormalities at 1500 and 61,000 times the MRHDID, respectively Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 110 times the MRHDID The adverse effects generally occurred at large multiples of the MRHDID when formoterol fumarate was administered by oral route to achieve high systemic exposures No structural abnormalities, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 350 times the MRHDID Lactation There are no available data on effects of glycopyrrolate, or formoterol fumarate on breastfed child or milk production There are no available data on presence of glycopyrrolate or formoterol fumarate in human milk Formoterol fumarate and glycopyrrolate have been detected in plasma of undosed rat pups suckling from exposed dams; the developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breast-fed child from drug or from underlying maternal conditionPregnancy 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 Glycopyrronium: Long-acting muscarinic antagonist (LAMA); often referred to as an anticholinergic; produces bronchodilation by inhibiting acetylcholine’s effect on muscarinic receptors in the airway smooth muscle Formoterol: Long-acting beta2-agonist (LABA) with a rapid onset of action; stimulates intracellular adenyl cyclase, causing conversion of ATP to cyclic AMP; increased cyclic AMP levels cause relaxation of bronchial smooth muscle Absorption Peak plasma concentration: 5 min (glycopyrrolate); 20-60 min (formoterol) Steady-state achieved: 2-3 days Extent of systemic exposure increases at steady state compared to first dose; 2.3 x higher (glycopyrrolate) and 1.5 x higher (formoterol) Distribution Protein bound: 46-58% (formoterol) Vd (central compartment): 951 L (glycopyrrolate); 948 L (formoterol) Vd (peripheral compartment): 2019 L (glycopyrrolate); 434 L (formoterol) Metabolism Glycopyrrolate: metabolism plays a minor role in the overall elimination of glycopyrrolate Formoterol Primary metabolism of formoterol is by direct glucuronidation and by O-demethylation followed by conjugation to inactive metabolites Secondary metabolic pathways include deformylation and sulfate conjugation CYP2D6 and CYP2C have been identified as being primarily responsible for O-demethylation Elimination Half-life: 11.8 hr (glycopyrrolate); 11.8 hr (formoterol) Elimination Glycopyrrolate: 85% urine; small amount in bile Formoterol: 62% in urine; 24% in feces Orally Inhaled Administration Shake well before each use Do not exceed 2 inhalations twice daily Canister contains 120 inhalations and has an attached dose indicator, which indicates how many inhalations remain The dose indicator display will move after every tenth actuation When nearing the end of the usable inhalations, the color behind the number in the dose indicator display window changes to red Discarded when the dose indicator display window shows zero Prime device Prime the inhaler to ensure appropriate drug content in each actuation Prime before using for the first time To prime, release 4 sprays into the air away from the face, shaking well before each spray Must be reprimed when the inhaler has not been used for >7 days; to reprime, release 2 sprays into the air away from the face; shake canister well before each spray Storage Store at controlled room temperature 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) 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 other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand