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 albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.triazolamMonitor Closely (1)triazolam increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.triclabendazoleMonitor Closely (1)albuterol and triclabendazole both increase QTc interval. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trifluoperazineMonitor Closely (1)trifluoperazine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trimipramineMonitor Closely (2)albuterol and trimipramine both increase QTc interval. Use Caution/Monitor. trimipramine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine, albuterol. 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 albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.triptorelinMonitor Closely (1)albuterol and triptorelin both increase QTc interval. Use Caution/Monitor.valbenazineMonitor Closely (1)valbenazine and albuterol both increase QTc interval. Use Caution/Monitor.vandetanibMonitor Closely (1)albuterol and vandetanib both increase QTc interval. Use Caution/Monitor.vardenafilMonitor Closely (1)albuterol and vardenafil both increase QTc interval. Use Caution/Monitor.vemurafenibMonitor Closely (1)albuterol and vemurafenib both increase QTc interval. Use Caution/Monitor.voclosporinMonitor Closely (1)albuterol and voclosporin both increase QTc interval. Use Caution/Monitor.voriconazoleMonitor Closely (1)albuterol and voriconazole both increase QTc interval. Use Caution/Monitor.vorinostatMonitor Closely (1)albuterol and vorinostat both increase QTc interval. Use Caution/Monitor.xylometazolineMonitor Closely (2)albuterol and xylometazoline both decrease sedation. Use Caution/Monitor. albuterol and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.yohimbineMonitor Closely (2)albuterol and yohimbine both decrease sedation. Use Caution/Monitor. albuterol and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.ziconotideMonitor Closely (1)ziconotide increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziprasidoneMonitor Closely (2)ziprasidone increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. albuterol and ziprasidone both increase QTc interval. Use Caution/Monitor. 1-10% Headache (4.3%) Oral candidiasis (1.3%) Cough (1%) Postmarketing Reports Cardiovascular disorders: Myocardial ischemia, tremor, tachycardia, palpitations, extrasystoles, arrhythmias (eg, atrial fibrillation, supraventricular tachycardia), syncope, hypertension, peripheral vasodilatation Endocrine disorders: Signs or symptoms of systemic glucocorticoid effect (eg, hypofunction of the adrenal gland and reduction of growth rate) Eye disorders: Cataracts, glaucoma, increased intraocular pressure Immune system disorders: Immediate and delayed hypersensitivity reactions (eg, anaphylactic reaction, angioedema, bronchospasm, rash, contact dermatitis and urticaria) General disorders: Fever, weight gain, taste perversion, flu syndrome Gastrointestinal disorders: Nausea, vomiting, dyspepsia, diarrhea Infections: Sinusitis, pharyngitis, respiratory tract infection, nasopharyngitis, gastroenteritis, otitis media, laryngitis Metabolic disorders: Hypokalemia, metabolic acidosis Musculoskeletal disorders: Hypertonia, musculoskeletal pain, myalgia, asthenia, arthralgia, muscle cramps, fracture Neurological or psychiatric system disorders: Migraine, dizziness, central nervous system stimulation, insomnia, hyperactivity, psychiatric symptoms (eg, psychosis, depression, aggressive reactions, irritability, nervousness, restlessness, behavioral disturbances and anxiety) Respiratory, thoracic, and mediastinal disorders: Rhinitis, nasal congestion, throat irritation, oropharyngeal edema, upper respiratory inflammation, drying or irritation of the oropharynx Skin and subcutaneous tissue disorders: Skin bruising, ecchymosis Contraindications Hypersensitivity to albuterol, budesonide, or any of the excipients Cautions Hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, oropharyngeal edema, rash, urticaria) reported; discontinue if such reactions occur Use sympathomimetic amines cautiously in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines Beta-adrenergic agonists may cause hypokalemia in some patients, possibly through intracellular shunting, and thereby potential for adverse cardiovascular effects may occur; decreased serum potassium is usually transeint, not requiring supplementation Orally inhaled corticosteroids may reduce growth velocity when administered to pediatric patients; safety and effectiveness of albuterol/budesonide have not been established in pediatric patients, and is not indicated for use in this population Deterioration of asthma Asthma may deteriorate acutely over several hours or chronically over several days or longer If symptoms continue after using albuterol/budesonide or requires more doses than usual, evaluate patient and treatment regimen Paradoxical bronchospasm Treatment may produce paradoxical bronchospasm, which may be life threatening If paradoxical bronchospasm occurs following, discontinue immediately, and initiate alternant therapy Paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister Cardiovascular effects Beta2-adrenergic agonists can produce clinically significant cardiovascular (CV) effects (eg, increased pulse rate, blood pressure), ECG changes (flattening of T wave, QT prolongation, ST-segment depression), and/or other symptoms If such effects occur, albuterol/budesonide may need to be discontinued Caution in patients with CV disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension Maximum daily dose Exceeding maximum dose may result in overdose Clinically significant CV effects and fatalities reported in association with excessive use of inhaled sympathomimetic drugs Immunosuppression and risk of infections Unknown, how the dose, route, and duration of corticosteroid administration affect risk of developing a disseminated infection Patients taking immunosuppressants are more susceptible to infection; chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients using corticosteroids Review patient's immunization history and administer necessary vaccinations Immune globulins (eg, VZIG, IG) may be needed if exposure occurs and active infection occurs; consider antiviral agents if chickenpox develops Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent TB infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex Oropharyngeal candidiasis Inhaled corticosteroid (ICS) may increase risk for localized infections of the mouth and pharynx with Candida albicans Advise patient to rinse their mouth with water, if available, without swallowing following administration to help reduce risk If oropharyngeal candidiasis develops, treat with appropriate local or systemic (ie, oral) antifungal therapy while treatment with albuterol/budesonide continues For some patients, albuterol/budesonide treatment may need to be interrupted Hypercorticism and adrenal suppression Orally inhaled budesonide often helps control asthma symptoms with less suppression of hypothalamic-pituitary-adrenal (HPA) function than therapeutically equivalent oral doses of prednisone Since budesonide 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 Reduced bone mineral density Decreases in bone mineral density (BMD) observed with long-term administration of ICS Clinical significance of small changes in BMD with regard to long-term consequences (eg, fracture) is unknown Patients with major risk factors for decreased bone mineral content (eg, prolonged immobilization, family history of osteoporosis, post-menopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass [eg, anticonvulsants, oral corticosteroids]) should be monitored and treated with established standards of care Glaucoma and cataracts Glaucoma, increased intraocular pressure, and cataracts reported following the long-term administration of ICS Consider referral to an ophthalmologist in patients who develop ocular symptoms Drug interaction overview Budesonide is a CYP3A4 substrate (major) Strong CYP3A4 inhibitors Caution Strong CYP3A4 inhibitors may increase adverse effects owing to increased budesonide systemic exposure Other short-acting bronchodilators Use judiciously to prevent beta-agonist overdose Additive effects of albuterol with other bronchodilators may occur Beta-blockers Caution Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists (eg, albuterol, but may also produce severe bronchospasm in patients with asthma Therefore, patients with asthma should not normally be treated with beta-blockers However, under certain circumstances (eg, prophylaxis after MI), no acceptable alternatives may be available in these patients In this setting, consider cardioselective beta-blockers, although they should be administered with caution Diuretics Caution; consider monitoring potassium levels ECG changes and/or hypokalemia resulting from nonpotassium sparing diuretics (eg, loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially if beta-agonist dose exceeded Digoxin Monitor serum digoxin levels if coadministered Mean decreases in serum digoxin levels of 16% and 22% demonstrated after single-dose IV and oral albuterol, respectively, to normal volunteers who had received digoxin for 10 days Clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is unclear MAOIs or TCAs Caution Monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants (TCAs) may enhance adverse effects of beta2-agonists Administer albuterol/budesonide with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents Pregnancy Albuterol or budesonide: Available data from epidemiological studies and postmarketing case reports of pregnancy outcomes following inhaled albuterol or inhaled budesonide use do not consistently demonstrate a risk of major birth defects or miscarriage Pregnancy Exposure Registry Registry monitors pregnancy outcomes in women exposed to asthma medications during pregnancy For more information, contact the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists at 1-877-311-8972 or visit https://mothertobaby.org/ongoing-study/asthma/ Clinical considerations In females with poorly or moderately controlled asthma, risk is increased for several perinatal adverse outcomes (eg, preeclampsia in the mother; prematurity, low birth weight, and small for gestational age in the neonate) Closely monitor pregnant women with asthma and adjust medication as necessary to maintain optimal asthma control Labor or delivery 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 Serious adverse reactions, including pulmonary edema, reported during or following treatment of premature labor with beta2-agonists, including albuterol Lactation Data are unavailable on the effects of albuterol/budesonide on breastfed children or on milk production Budesonide, like other inhaled corticosteroids, is present in human milkPregnancy 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 Albuterol: Short-acting beta2-adrenergic bronchodilator; increases cyclic AMP which leads to protein kinase A activation, which inhibits myosin phosphorylation and lowers intracellular ionic calcium concentrations; these actions result in bronchial smooth muscle relaxation Budesonide: Anti-inflammatory corticosteroid; has potent glucocorticoid activity and weak mineralocorticoid activity; inflammation is an important component in the pathogenesis of asthma Absorption Albuterol (healthy subjects) Peak plasma time: 1 hr Peak plasma concentration: 472.2 pg/mL Budesonide (healthy subjects) Peak plasma time: 0.33 hr Peak plasma concentration: 272.8 pg/mL Distribution Albuterol (healthy subjects) Vd: 565.7 L Budesonide (healthy subjects) Protein bound: 85-90% Vd: 1002 L Metabolism Albuterol: Primarily metabolized by SULTIA3 (sulfotransferase) Budesonide: Rapidly and extensively metabolized by CYP3A4 to metabolites with <1% activity of that of the parent compound Elimination Excretion Albuterol: Primarily renal excretion Budesonide: Urine ~60% as metabolites Inhaler Priming and Care Write “use by date” (12 months after opening foil pouch) on actuator label using permanent ink Rinse white actuator weekly and let dry Priming inhaler Primer inhaler before first use Remove mouthpiece cover, shake, and spray test puff into air facing away from user; repeat for a total of 4 test puffs Re-priming inhaler Re-prime if not used for >7 days, if inhaler dropped, or after rinsing white actuator Remove mouthpiece cover, shake and spray test puff; repeat for a total of 2 test puffs Oral Inhalation Shake inhaler and remove cap Breathe out fully Place mouthpiece into mouth and close lips around mouthpiece Start to breathe in deeply and slowly while spraying 1 puff; continue breathing as tolerated Remove mouthpiece and hold breath for as long as you can (up to 10 seconds) Repeat above steps for 2nd inhalation Rinse mouth with water (if available) after inhalation to decrease risk of oral/laryngeal fungal infection (thrush) Canister has attached dose indicator showing how many inhalations remain Storage Store at room temperature at 68-77ºF (20-25ºC) Keep in dry (nonhumid) place away from heat and sunlight 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