neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .trazodoneMonitor Closely (1)trazodone increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trazodone, salmeterol. 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 salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.triazolamMonitor Closely (1)triazolam increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trifluoperazineMonitor Closely (1)trifluoperazine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trimipramineMonitor Closely (1)trimipramine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine, salmeterol. 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 salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valbenazineMonitor Closely (1)valbenazine and salmeterol both increase QTc interval. Use Caution/Monitor.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase fluticasone systemic exposureSerious - Use Alternative (1)voriconazole will increase the level or effect of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xylometazolineMonitor Closely (2)salmeterol and xylometazoline both decrease sedation. Use Caution/Monitor. salmeterol and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.yohimbineMonitor Closely (2)salmeterol and yohimbine both decrease sedation. Use Caution/Monitor. salmeterol and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.ziconotideMonitor Closely (1)ziconotide increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziprasidoneMonitor Closely (1)ziprasidone increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. >10% Upper respiratory tract infection (21-27%) Headache (12-21%) Pharyngitis (10-13%) 1-10% Candidiasis, nonspecific site (0-10%) Throat irritation (7-9%) Musculoskeletal pain (2-9%) Bronchitis (2-8%) Upper respiratory inflammation (4-7%) Viral respiratory infections (4-6%) Nausea or vomiting (4-6%) Cough (3-6%) Sinusitis (4-5%) Hoarseness or dysphonia (2-5%) Fever (3-4%) Diarrhea (2-4%) Gastrointestinal (GI) discomfort or pain (1-4%) Oral candidiasis (1-4%) Muscle cramps or spasms (3%) Malaise or fatigue (2-3%) Viral GI infections (0-3%) Postmarketing Reports Cardiac: Arrhythmias, ventricular tachycardia Endocrine: Cushing syndrome, cushingoid features, growth velocity reduction in children and adolescents, hyperadrenocorticism Eye: Glaucoma, cataracts, blurred vision, and central serous chorioretinopathy GI: Abdominal pain, dyspepsia, xerostomia Immunologic: Immediate and delayed hypersensitivity reaction, anaphylactic reaction in patients with severe milk protein allergy (very rare) Metabolic: Hyperglycemia, weight gain Musculoskeletal: Arthralgia, cramps, myositis, osteoporosis Neurologic: Paresthesia, restlessness Psychiatric: Agitation, aggression, depression, behavioral changes (eg, hyperactivity, irritability; rare and occurring primarily in children) Reproductive: Dysmenorrhea Respiratory: Congestion, tightness, dyspnea, facial and oropharyngeal edema, immediate bronchospasm, paradoxical bronchospasm, tracheitis, wheezing, upper respiratory symptoms (eg, laryngeal spasm, irritation, or swelling, such as stridor or choking) Dermatologic: Ecchymoses, photodermatitis Vascular: Pallor Contraindications Primary treatment of status asthmaticus or acute episodes of asthma or COPD requiring intensive measures Severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone propionate, salmeterol, or any of the excipients Cautions Risk of LABAs used as monotherapy Use of LABAs as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death Data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patient 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 Dosing frequency should not exceed q12hr Aerosol not recommended when patient is being switched from PO to inhaled corticosteroids Risk of localized Candida albicans infections in mouth and pharynx in some patients; when such an infection develops, it should be treated with appropriate local or systemic (ie, oral) antifungal therapy while treatment continues, but at times therapy may need to be interrupted; mouth must be rinsed after dosing to reduce risk Monitor COPD patients for signs and symptoms of pneumonia and lung infection Risk of more serious or fatal course of chickenpox or measles in susceptible patients (eg, unvaccinated or immunologically unexposed individuals); care must be taken to avoid exposure Particular care is needed in switching patients from systemic to inhaled corticosteroids; potentially fatal adrenal insufficiency may occur before or afterward; taper withdrawal gradually by reducing daily prednisone dose by 2.5 mg on weekly basis During stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should resume PO corticosteroids immediately Risk of paradoxical bronchospasm, which may be life-threatening; discontinue, and treat immediately with inhaled SABA Cardiovascular and central nervous system (CNS) effects may occur as consequences of excess beta-adrenergic stimulation; may result in asthma-related death; caution is advised in patients with cardiovascular or convulsive disorders or thyrotoxicosis Bone mineral density may decrease after long-term administration of corticosteroids; monitor patients at risk Should not be used for relief of acute symptoms, like, rescue therapy for treatment of acute episodes of bronchospasm; acute symptoms should be treated with inhaled, short-acting beta2-agonist May decrease growth velocity in children; monitor Risk of cataracts, glaucoma, and increased intraocular pressure Rare cases of vasculitis (Churg-Strauss syndrome) or other systemic eosinophilic conditions may occur Use caution in patients with diabetes mellitus; beta2 agonists may increase glucose levels Use caution in patients with hepatic impairment; may lead to accumulation of fluticasone in plasma; monitor closely; glaucoma: consider eye exams in chronic users Use caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation Changes in thyroid status may require dosage adjustments; hyperthyroidism may increase corticosteroids clearance while it may decrease in hypothyroidism Prolonged corticosteroid use may increase incidence of secondary infection, mask acute infection, prolong or exacerbate viral infections, or limit response to vaccines Corticosteroids may cause psychiatric manifestations, including depression, euphoria, insomnia, mood swings, and personality changes; may also exacerbate preexisting psychiatric conditions Laryngeal spasm, irritation and swelling (choking) may occur Risk of transient hypokalemia; supplementation may not be required Long-acting beta-agonist (LABA) monotherapy increases risk of serious asthma-related events Not for use in acutely deteriorating asthma or COPD; not for treatment of acute symptoms Potential worsening of infections (eg, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; ocular herpes simplex); use caution in patients with these infections Should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) as an overdose may result; clinically significant cardiovascular effects and fatalities reported in association with excessive use of inhaled sympathomimetic drugs; patients receiving therapy should not use another medicine containing a LABA for any reason Immunosuppression and risk of infections Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible adolescents or adults using corticosteroids; in such patients who have not had these diseases or who have not been properly immunized, particular care should be taken to avoid exposure How the dose, route and duration of corticosteroid administration affect risk of developing a disseminated infection is not known The contribution of the underlying disease and/or prior corticosteroid treatment to risk is also not known; if a patient is exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) may be indicated If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered; inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex Transferring patients from systemic corticosteroid therapy Particular care needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function Patients who have been previously maintained on 20 mg or more of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss Although treatment may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does not provide the mineralocorticoid activity that is necessary for coping with these emergencies During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physician for further instruction These patients should also be instructed to carry a medical identification warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack Patients requiring systemic corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to aerosol formulation or inhaler, Lung function (mean forced expiratory volume in 1 second [FEV1] or morning peak expiratory flow [AM PEF]), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of systemic corticosteroids In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension Unmasking of allergic conditions resulting from systemic corticosteroid suppression Transfer of patients from systemic corticosteroid therapy may unmask allergic conditions previously suppressed by systemic corticosteroid therapy (eg, rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions) Corticosteroid withdrawal symptoms During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (eg, joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function Hypercorticism and adrenal suppression Fluticasone propionate, a component of the aerosol and inhaler formulations, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing the drug combinaton Because of possibility of significant systemic absorption of inhaled corticosteroids, patients treated with the combination drug should be observed carefully for any evidence of systemic corticosteroid effects Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients