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Mechanism of Action
US Drug Names
2 oral inhalations of either 80/4.5 (80 mcg budesonide with 4.5 mcg formoterol per actuation) or 160/4.5 (160 mcg budesonide with 4.5 mcg formoterol per actuation) twice daily, morning and evening, at the same times each day. Choose dose based on asthma severity and previous therapy. Max: 2 oral inhalations of 160/4.5 twice daily (640 mcg budesonide with 18 mcg formoterol per day).
2 oral inhalations of 80/4.5 (80 mcg budesonide with 4.5 mcg formoterol per actuation) twice daily is the recommended and max dosage (Max: 320 mcg budesonide with 18 mcg formoterol per day).
1 or 2 oral inhalations (for a total per dose of 160 to 320 mcg budesonide with 9 mcg formoterol) given once or twice daily (depending on asthma severity and ICS dose in the ICS-formoterol preparation). When this combination is used as both a controller and a reliever therapy, the maximum total dosage for formoterol per NAEPP is 54 mcg/day or 12 oral inhalations of a product containing 4.5 mcg/actuation of formoterol.
100 mcg budesonide/6 mcg formoterol (1 oral inhalation) or 200 mcg budesonide/6 mcg formoterol (1 oral inhalation) twice daily. Some patients may require increased controller dosage, up to 800 mcg budesonide/24 mcg formoterol via oral inhalation twice daily. When this combination is used as both a controller and a reliever therapy, the maximum total dosage for formoterol per GINA is 72 mcg/day (12 oral inhalations of a formoterol 6 mcg/actuation product per day). The Symbicort Turbohaler is an approved drug in the UK for maintenance and reliever therapy, and thus maximum dosages and product strengths vary from U.S. available products. 
100 mcg budesonide/6 mcg formoterol (1 oral inhalation) or 200 mcg budesonide/6 mcg formoterol (1 oral inhalation) twice daily. Some patients may require increased controller dosage, up to 400 mcg budesonide/12 mcg formoterol twice daily. When this combination is used as both a controller and a reliever therapy, the maximum total dosage per GINA for formoterol is 72 mcg/day (12 oral inhalations of a formoterol 6 mcg/actuation product per day). The Symbicort Turbohaler is an approved drug in the UK for maintenance and reliever therapy, and thus maximum dosages and product strengths vary from U.S. available products. 
80 mcg budesonide/4.5 mcg formoterol (1 oral inhalation) once daily as a controller dose, with additional inhalations allowed "as needed", has been used per the SMART dosing strategy. Max: 8 oral inhalations/day (Max formoterol: 36 mcg/day). Data are limited for "as needed" use in this age group.  Symbicort Turbohaler is approved in the UK for maintenance therapy for children 6 to 11 years of age; the recommended dose for that product is 2 oral inhalations of 100/6 (100 mcg budesonide/6 mcg formoterol per actuation) twice daily; however, the product is not labeled for reliever therapy for this age group.
1 or 2 oral inhalations (for a total per dose of 160 to 320 mcg budesonide with 9 mcg formoterol) as needed in addition to daily maintenance dosing; may repeat dose after 5 minutes if needed. The maximum total dosage for formoterol per NAEPP is 54 mcg/day or 12 oral inhalations of a product containing 4.5 mcg/actuation of formoterol.
100 mcg budesonide/6 mcg formoterol (1 oral inhalation) or 200 mcg budesonide/6 mcg formoterol (1 oral inhalation) as needed in addition to a daily maintenance dose; may repeat after 5 minutes. GINA Max: 12 oral inhalations/day (do not exceed formoterol 72 mcg/day). Dosing for reliever therapy is based on a product not available in U.S.
80 mcg budesonide/4.5 mcg formoterol (1 oral inhalation) has been used "as needed" in addition to a daily maintenance dose per the SMART dosing strategy. Max: 8 oral inhalations total/day (Max formoterol: 36 mcg/day). Per guidelines, data are limited for "as needed" use in this age group due to varying doses and protocols in studies.  Symbicort Turbohaler is approved in the UK for asthma controller therapy for children 6 to 11 years of age; however, the product is not labeled for reliever therapy for this age group.
1 oral inhalation of 160/4.5 (160 mcg budesonide with 4.5 mcg formoterol per actuation) 5 to 20 minutes prior to exercise has been used in a clinical trial and was efficacious. FDA-approved Max: 2 oral inhalations of 160/4.5 twice daily (640 mcg budesonide with 18 mcg formoterol per day). Regular ICS controller therapy is also known to reduce the incidence of EIB.   
2 oral inhalations of 160/4.5 (160 mcg of budesonide with 4.5 mcg of formoterol per actuation) twice daily, approximately 12 hours apart, is the recommended and max dosage (max: 640 mcg budesonide with 18 mcg formoterol per day). Not indicated for the relief of acute bronchospasm. Use an inhaled short-acting beta-2 agonist (SABA) for immediate relief of acute symptoms. Do not use other long-acting beta-agonists (LABAs) concurrently. If on oral corticosteroids, wean the OCS slowly after transferring to budesonide; formoterol by reducing the daily dose by 2.5 mg prednisone or equivalent on a weekly basis. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, budesonide; formoterol may be used as initial therapy in group D (those with a high risk of exacerbation). At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a long-acting muscarinic antagonist (LAMA), a long-acting beta-2 agonist (LABA), and an inhaled corticosteroid (ICS).
640 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day regardless of strength of Symbicort is 4.
12 years: 640 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day regardless of strength of Symbicort is 4.
6 to 11 years: 320 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day of Symbicort is 4.
1 to 5 years: Safety and efficacy have not been established.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Budesonide; formoterol is a combination of an inhaled corticosteroid (ICS), budesonide, and a long-acting beta-2 agonist (LABA), formoterol. It is administered by oral inhalation twice daily. The combination is indicated for the maintenance treatment of asthma in adult and pediatric patients 6 years and older. Budesonide; formoterol is also indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults and to reduce the risk of exacerbations of COPD. According to the FDA-approved label, budesonide; formoterol is not recommended for acute bronchospasm or acute asthmatic attacks ; however, guidelines promote the use of "SMART" (single maintenance and reliever therapy) inhaler dosing strategies for daily and "as-needed" formoterol-ICS as the preferred combined controller and reliever regimen in adults and adolescents 12 years and older with mild to moderate asthma. For children 4 to 11 years of age, NAEPP additionally recommends maintenance and "as-needed" ICS-formoterol "SMART" regimens as an option for those needing step 3 (moderate) and step 4 (moderate to severe) level persistent asthma treatment. GINA recommends that in children 6 to 11 years with moderate to severe asthma, an ICS in combination with LABA is the preferred controller regimen and is used with an as-needed short-acting beta-agonist (SABA) as the preferred reliever. Budesonide; formoterol is approved as both a reliever and controller asthma therapy in other countries. Clinical trials have demonstrated the beneficial effects of the concurrent use of budesonide; formoterol on lung function and the subsequent reduction of asthma symptoms. Budesonide; formoterol may be used as initial therapy in patients with a high risk of COPD exacerbation. An ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD; however clinical trials failed to demonstrate a statistically significant effect on survival.
For storage information, see the specific product information within the How Supplied section.
NOTE: Patients should be instructed to never use budesonide; formoterol to treat acute bronchospasm. If any patient who uses budesonide; formoterol experiences wheezing that worsens and cannot be relieved during an acute asthma attack, they should be instructed to seek immediate medical attention.
The safety of orally inhaled budesonide; formoterol for asthma was studied in patients 12 years or older in three 12-week controlled clinical trials. Studies included 277 and 124 patients receiving the two available strengths of budesonide; formoterol 80/4.5 mcg and 160/4.5 mcg, respectively. The most commonly reported adverse reactions (occurring at an incidence of 3% or more) in the two dosing groups are listed regardless of causality and at increased incidence vs. placebo: back pain (3.2%, 1.6%), headache (6.5%, 11.3%), influenza (3.2%, 2.4%), nasal congestion (2.5%, 3.2%), naso-pharyngitis (10.5%, 9.7%), vomiting (1.4%, 3.2%), pharyngo-laryngeal pain (6.1%, 8.9%), sinusitis (5.8%, 4.8%), stomach discomfort (1.1%, 6.5%), and upper respiratory tract infection (7.6%, 10.5%). The safety profile in pediatric patients 6 to 11 years old with asthma was similar to that of older patients. Reactions occurring in 3% or more included upper respiratory tract infection, pharyngitis, headache, and rhinitis. In clinical trials for COPD, 771 patients received budesonide; formoterol 160/4.5 mcg for an average duration of 255.2 days. The most commonly reported adverse reactions (occurring at an incidence of 3% or more) relative to placebo included naso-pharyngitis (7.3%), bronchitis (5.4%), sinusitis (3.5%), and viral respiratory tract infection (3.5%). Lung infections other than pneumonia (mostly bronchitis) occurred in 7.9% of patients receiving active drug. Other adverse reactions reported with budesonide; formoterol use include nausea, muscle cramps, tremor, dizziness, dysphonia, cough, and throat irritation.
Budesonide; formoterol, like other products containing inhaled beta-2 agonists, can produce life-threatening paradoxical bronchospasm. In the event of a paradoxical bronchospasm, discontinue budesonide; formoterol immediately and initiate an alternative therapy.
An increase in the need for rescue inhaler use and/or worsening wheezing may occur during therapy with budesonide; formoterol and are symptoms of a deterioration of the underlying respiratory condition, a potentially life-threatening condition. Advise patients not to exceed recommended doses of this medicine, but instead, seek immediate medical attention if such symptoms occur. When long-acting beta agonists (LABAs) such as formoterol 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. The use of a LABA as monotherapy to treat asthma, without inhaled corticosteroids [ICS], is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients.  These findings are considered a class effect of LABA monotherapy. In most cases, serious acute respiratory events have occurred in patients with severe asthma and/or in patients in whom asthma has been acutely deteriorating, but such events have also occurred in patients with less severe asthma. These findings pertain only to patients who have asthma.
Immediate and delayed hypersensitivity reactions, including anaphylactoid reactions, angioedema, bronchospasm, urticaria, exanthema, dermatitis, and pruritus have been reported with budesonide; formoterol use.
As with other beta-2 agonists, a number of metabolic disturbances can develop including hyperglycemia and hypokalemia; these events were seen infrequently during clinical studies in patients receiving inhaled budesonide; formoterol at recommended dosages but have been reported with postmarketing use. Beta-agonist-induced hypokalemia may increase the risk of cardiac arrhythmia exacerbation in predisposed patients. Angina pectoris, sinus tachycardia, atrial tachycardia, ventricular tachycardia, atrial fibrillation, extrasystoles, palpitations, hypotension, and hypertension have been reported with postmarketing use of budesonide; formoterol. Treatment with long-acting beta-agonists, like formoterol, has been reported to produce clinically significant QT prolongation, which can lead to ventricular arrhythmias. Excessive beta-adrenergic stimulation has been associated with angina, hypertension or hypotension, tachycardia, arrhythmias, and palpitations.
Orally inhaled budesonide; formoterol has a relatively low risk of hypothalamic-pituitary-adrenal (HPA) suppression when used at recommended doses. Pharmacologic doses of budesonide administered for prolonged periods may, however, result in adrenocortical insufficiency. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of orally inhaled steroids in pediatric patients. Local immunosuppression associated with inhaled budesonide use may be manifested as an overgrowth of fungus in the nose, mouth, and throat. Oral candidiasis (thrush) is a well-known adverse reaction of oral inhalation steroid therapy and occurred in 1.4% to 6% of adult patients receiving inhaled budesonide; formoterol during clinical trials.
Growth inhibition has been observed in some children following therapy with orally inhaled corticosteroids including budesonide. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients. With orally inhaled corticosteroids, the mean reduction in growth velocity is approximately one centimeter per year (range 0.3 to 1.8 cm per year) and appears to be related to the dose and duration of exposure. In general, the benefits of regular inhaled corticosteroid (ICS) use outweigh the potential risk of relatively small and non-cumulative growth suppression in children with asthma; however, growth should be monitored. Further study is needed to determine the long-term effects of growth velocity reduction in children, including the impact on final adult height. To minimize the effects of inhaled corticosteroids, each patient should be titrated to the lowest effective dose.
Corticosteroids, even orally inhaled doses like budesonide, can induce cataracts and have the potential to induce or worsen ocular hypertension (glaucoma). Although rarely reported during treatment with budesonide; formoterol, patients are encouraged to keep up with routine ophthalmological exams.
Behavior disturbances, sleep disturbances, agitation, depression, nervousness, restlessness, and skin bruising (ecchymosis) have been reported with postmarketing use of budesonide; formoterol.
Prolonged use (e.g., more than 1 year) of high doses of inhaled corticosteroids, like budesonide, especially when used in combination with frequent courses of systemic corticosteroids, may be associated with reduced bone mineral density (BMD), which may increase the risk of osteopenia or osteoporosis. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown.
NOTE: This monograph discusses the use of budesonide; formoterol combination product for treating asthma. Clinicians may wish to consult the individual monographs for more information about the specific contraindications and precautions for each agent.
Do not exceed recommended dosages of beta-agonists; fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest after an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.
Hypersensitivity to any of the ingredients in budesonide; formoterol contraindicates its use. Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to budesonide should not receive any form of budesonide. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid. Immediate hypersensitivity reactions may also occur after the administration of budesonide; formoterol, as demonstrated by rare cases of urticaria, angioedema, rash, and bronchospasm.
Budesonide; formoterol use is contraindicated as a primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required. Do not initiate during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD. Long-acting beta-2 agonists (LABAs), when used alone, have been associated with increased risk of severe asthma exacerbation and asthma-related death; this is considered a class effect. When a LABA is used in fixed-dose combination with an inhaled corticosteroid (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. Available data do not suggest an increased risk of death with the use of LABAs in patients with COPD.   Budesonide; formoterol should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD; this product has not been studied in patients with these acutely deteriorating conditions. Do not use budesonide; formoterol for the relief of acute symptoms (i.e., as rescue therapy for the treatment of acute bronchospasm). Acute symptoms should be treated with an inhaled, short-acting beta-agonist (SABA). When initiating treatment with budesonide; formoterol, patients who have been taking oral or inhaled SABAs on a regular basis should be instructed to discontinue the regular use of these drugs and to use them only for symptomatic relief of acute respiratory symptoms. Prescribe an inhaled SABA, such as albuterol, for rescue treatment of an acute asthma or COPD attack and inform patients that increased use of an inhaled SABA is a signal of deteriorating disease. Loss of symptom control with budesonide; formoterol is also a marker of deterioration of disease; in this setting, a re-evaluation of the patient and the asthma or COPD treatment regimen should be undertaken at once, giving special consideration to the possible need for replacing the current strength of budesonide; formoterol with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids. Patients should not use budesonide; formoterol more often than recommended, at higher doses than recommended, or in conjunction with other LABAs as this would be considered duplicative therapy and may lead to additive untoward effects. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma.
Discontinue the regular use of short acting beta-2 agonists (i.e., four times daily) upon budesonide; formoterol initiation; however, short acting beta-2 agonists can be continued for symptomatic relief of acute asthma symptoms, often referred to as rescue inhalers. Furthermore, patients should not use budesonide; formoterol in conjunction with other long acting beta-2 agonists or other inhaled corticosteroid therapy as this would be considered duplicative therapy and may lead to additive untoward effects.
Budesonide; formoterol should be used with caution in patients with cardiovascular disorders, particularly coronary insufficiency, cardiac arrhythmias (including tachycardia), and hypertension. Formoterol, like other beta-2 agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or cardiac symptoms. If such effects occur, the inhaler may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression, although the clinical significance of these findings is unknown. Use budesonide; formoterol with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, cardiac disease, cardiac arrhythmias, coronary artery disease, hypertension, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.     Correct pre-existing hypokalemia and use with caution in patients at risk for developing hypokalemia. Formoterol, like all beta-agonists, may produce significant hypokalemia and related CV adverse effects in some patients, possibly through intracellular shunting (the decrease is usually transient, not requiring supplementation). In patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility for cardiac arrhythmias.
Budesonide; formoterol should be used with caution in patients with diabetes mellitus. Inhalation of high doses of beta-2 agonists may cause transient, but clinically relevant, hyperglycemia in some patients. Corticosteroids are also associated with increases in blood glucose in some patients. Such increases in blood glucose are most relevant for patients with diabetes mellitus.
Budesonide; formoterol should be used cautiously in patients with hyperthyroidism or thyrotoxicosis, unusual responsiveness to sympathomimetic amines, pheochromocytoma, or a seizure disorder.
Budesonide; formoterol should be administered with extreme caution to patients being treated with MAOI therapy (see Drug Interactions).
Budesonide; formoterol should be used cautiously in patients with glaucoma or other visual disturbance or with a family history of glaucoma. Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids, including budesonide. Patients receiving corticosteroids chronically should be periodically assessed for cataract formation.
Although the risk of developing hypothalamic-pituitary-adrenal (HPA) suppression is very low with inhaled budesonide; formoterol, patients should, nevertheless, be monitored for this possibility. Particular care is needed for patients who are transferred from systemic to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic to less systemically absorbed inhaled corticosteroids. Patients previously maintained on doses equivalent to 20 mg/day or more of prednisone may be at increased risk. After withdrawal from systemic corticosteroids, a number of months are required for recovery of HPA-axis function.
Although inhaled budesonide; formoterol is absorbed systemically to a lesser extent than other corticosteroids, significant amounts can be absorbed when large doses are administered. This can increase the risk for infection. In general, inhaled corticosteroid therapy used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; untreated systemic fungal infection, bacterial infection, viral infection, or a parasitic infection, especially those not adequately controlled by anti-infective agents. Inhaled corticosteroids should be used cautiously, if at all, in patients with an active herpes infection (including ocular herpes simplex). If a patient on immunosuppressant doses of corticosteroids is exposed to chickenpox, therapy with varicella-zoster immune globulin or pooled intramuscular immunoglobulin may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin may be indicated. Budesonide oral inhalation has been associated with the development of localized infection with Candida albicans in the nose, mouth, and pharynx. If this develops, discontinuation of inhaled budesonide is warranted, and appropriate local therapy should be instituted. Patients who are on long-term budesonide inhalation therapy should receive a periodic evaluation for Candida infection or other adverse effects.
Long-term use of orally inhaled corticosteroids, such as budesonide, may affect normal bone metabolism resulting in a loss of bone mineral density or osteopenia. Use budesonide; formoterol with caution in patients with risk factors for decreased bone mineral content, including tobacco use, advanced age, sedentary lifestyle, poor nutrition, family history of osteoporosis, or chronic use of drugs that decrease bone mass.
Formal pharmacokinetic studies using budesonide; formoterol inhalation have not been conducted in patients with hepatic impairment. However, since budesonide and formoterol are predominantly cleared by hepatic metabolism, impairment of liver function may lead to increased exposure of budesonide and formoterol. Therefore, patients with severe hepatic disease should be closely monitored.
The safety and efficacy of budesonide; formoterol have not been established in neonates, infants, or children younger than 6 years. For pediatric patients with persistent asthma, limit use to those who have asthma that is not adequately controlled with a long-term asthma control medication, such as an inhaled corticosteroid. When long-acting beta-agonists (LABAs) are used in fixed-dose combination with inhaled corticosteroids (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. Available data from clinical trials suggest that asthma treatment with LABA monotherapy, without an inhaled corticosteroid, increases the risk of asthma-related hospitalization and death in children and adolescents.  Pediatric patients may be more susceptible to developing systemic toxicity from corticosteroids. Growth inhibition has been observed in some children following therapy with corticosteroids, including inhaled budesonide therapy. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of orally inhaled corticosteroid formulations in young patients. To minimize the effects of orally inhaled corticosteroids, each patient should be titrated to the lowest effective dose. The growth of pediatric patients should be monitored regularly.
There are no adequate and well-controlled studies of budesonide; formoterol during human pregnancy; however, studies of pregnant women taking inhaled budesonide alone have not shown increases in the risk of abnormalities when given during pregnancy. In animal studies, formoterol fumarate has only shown adverse effects when administered systemically at high systemic exposures greatly exceeding the maximum recommended human daily inhalational dose (MRHDID). No teratogenic, embryocidal, or developmental effects were seen in rats that received formoterol inhalation doses up to 375 times the MRHDID. Women with asthma who become pregnant while stabilized on budesonide; formoterol therapy should discuss their asthma management with a qualified health care professional. A review of Swedish registries indicated that in over 2,000 births there was no increased risk for congenital malformations during early pregnancy with budesonide inhalation powder or solution. It is known that improved maternal and perinatal outcomes are achieved with optimal control of asthma during pregnancy. Large studies of women with asthma have confirmed the lack of relationship between the use of inhaled beta-2 agonists and adverse maternal or fetal outcomes; however, less data are available for long-acting beta agonists (LABAs) such as formoterol vs. short-acting beta agonists (SABAs). However, most inhaled beta-2 agonists, as well as inhaled budesonide, are considered acceptable for use during pregnancy because of the low bioavailability and maternal serum levels after use.   According to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group, long-acting beta-2 agonists (LABAs), in combination with inhaled corticosteroids (ICS), are one of the preferred treatment options for the long-term control of moderate asthma during pregnancy and lactation; use of medium dose ICS is also a preferred option. Although a preferred LABA is not recommended, the guideline states that more experience is available with salmeterol. Due to the availability of safety information during pregnancy, budesonide is preferred over other ICS. Infants born to mothers taking substantial corticosteroid doses during pregnancy should be monitored for signs of hypoadrenalism. There are no well-controlled human studies that have investigated the effects of budesonide; formoterol on preterm labor or labor at term. Because of the potential for beta-2 agonist interference with uterine contractility, use of budesonide; formoterol should be restricted to those patients in whom the benefits clearly outweigh the risks.
There are no well-controlled human studies that have investigated the effects of budesonide; formoterol during breast-feeding. Formoterol was excreted in milk in reproductive studies in rats; however, it is unknown whether formoterol is excreted in human milk. Glucocorticoids, such as budesonide, are excreted into human breast milk. Data from a small number (n = 8) of lactating women showed an estimated oral daily dose of budesonide available to the nursing infants which was approximately 0.3% to 1% of the dose inhaled by the mothers. Budesonide plasma concentrations obtained in five of the infants at about 140 minutes after drug administration to the mother and 90 minutes after breast-feeding were below quantifiable levels. The amount of inhaled budesonide excreted in breast-milk is minute, and infant exposure is negligible. While not measured, the amount of formoterol absorbed into the maternal bloodstream and excreted into breast-milk after inhalation is expected to be very low; therefore, it is unlikely that nursing infants would be exposed to clinically significant amounts of formoterol via breast milk. Most inhaled bronchodilators are considered acceptable for use during the postpartum period and breast-feeding because of the low bioavailability and maternal serum levels after use.  The 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group consider a combination of inhaled corticosteroids with long-acting inhaled beta-2 agonists (LABAs) a preferred treatment option for moderate asthma in pregnancy and lactation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Similar to other inhaled beta-agonists, budesonide; formoterol can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, it should be treated immediately with a short-acting, inhaled bronchodilator, and budesonide; formoterol should be discontinued immediately and alternative therapy instituted.
Budesonide is an antiinflammatory corticosteroid; formoterol is a long-acting, selective beta-agonist; when used together, the combination is more effective than either drug alone.
•Budesonide: In the treatment of asthma, orally inhaled corticosteroids are believed to reduce the immediate and late-phase allergic responses associated with allergies and chronic bronchial asthma. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV1, peak-flow rate, and respiratory symptoms.
•Formoterol: Similar to other beta-2 agonists, formoterols mechanism of action involves stimulation of adenyl cyclase leading to the production of cyclic adenosine monophosphate (cAMP) via adenosine triphosphate (ATP). Increased levels of cAMP result in relaxation of the bronchial smooth muscle.Formoterol, like salmeterol, is highly lipophilic. It enters the plasma cell membrane in the form of a depot and is gradually released into the aqueous phase to react with the beta-2 receptor, resulting in a long duration of action. The aqueous phase activity, not demonstrated by salmeterol, is responsible for the rapid onset of action of formoterol. Formoterol has more than a 200-fold greater agonist activity at beta-2 receptors (primarily in the lung) than at beta-1 receptors (primarily in the heart). However, 10% to 50% of the beta receptors in the heart are beta-2 receptors and raise the possibility that even highly selective beta-2 receptor agonists may have adverse cardiovascular effects, such as tachycardia, palpitations, and ischemia (see Adverse Reactions). As with other beta-2 agonists, formoterol may possess antiinflammatory activity, but the clinical significance of this effect is unknown.In vitro studies have demonstrated inhibition of mast cell mediators such as histamine and leukotrienes. Monotherapy with formoterol is inappropriate due to lack of proven antiinflammatory and disease-modifying properties.
Budesonide; formoterol is administered via oral inhalation.
The median time to onset of clinically significant bronchodilation (>15% improvement in FEV1), following administration from metered-dose inhaler (MDI) of formoterol, is seen within 15 minutes. Maximum improvement in FEV1 occurs within 3 hours, and clinically significant improvement is maintained over 12 hours.
No data is available regarding use of budesonide; formoterol in patients with hepatic impairment. Because formoterol is primarily eliminated via hepatic metabolism, an increased exposure can be expected in patients with severe hepatic impairment.
No data are available regarding use of budesonide; formoterol in patients with renal impairment. Although budesonide metabolites are renally excreted, their activity is negligible.
No differences in the pharmacokinetics of pediatric patients between the age of 6 and 12 years have been identified. Limited data are available in patients less than 12 years; in a single dose study in patients ages 6—11 years, peak plasma concentrations of budesonide were similar to adult patients and approximately 3.5% of the delivered formoterol dose was recovered in the urine as unchanged formoterol.
Pharmacokinetic parameters in geriatric patients have not been assessed.
No gender differences have been noted.
No race differences have been noted.
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