Respiratory infection (8% to 11%), sinusitis (8%), and viral infection (6%) have been reported in adult patients during clinical trials with oral budesonide. Ear infection (unspecified), bronchitis, abscess, rhinitis, dyspnea, and pharynx disorder were reported in less than 5% of adult patients receiving oral budesonide.[34979] [64318] [67192] Respiratory tract infection (including acute sinusitis, sinusitis, nasopharyngitis, respiratory tract infection, viral respiratory infection, upper respiratory tract infection, viral upper respiratory tract infection, and rhinitis) were reported in 13% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Throat irritation/oropharyngeal pain (3%) and nasal congestion (less than 2%) were reported in patients receiving oral budesonide suspension for EoE.[70334] Nasal or respiratory adverse events reported during treatment with nasal budesonide include cough (2%), epistaxis (8%), pharyngitis (4%), nasal irritation (2%), sinusitis (3% or more), and bronchospasm (2%).[31824] Respiratory infection (3% to 38%), rhinitis (7% to 12%), cough (5% to 9%), nasopharyngitis (9%), nasal congestion (3%), pharyngitis (3%), allergic rhinitis (2%), viral upper respiratory tract infection (2%), otitis media (1% to 12%), ear infection (2% to 5%), epistaxis (2% to 4%) and viral infection (2% to 5%) were reported by patients receiving budesonide inhalation powder or budesonide inhalation suspension. Chest pain, dysphonia, stridor, otalgia, external ear infection, voice alteration, and cervical lymphadenopathy were also reported in 1% to less than 3% of patients.[33486][34376] Throat irritation and bronchitis has also been reported during postmarketing use of budesonide inhalation powder and suspension.[31824] [33486] [34376] [34979] [52910] [58166] [64318] [70334] Nasal septum perforation, anosmia, pharynx disorders (throat irritation, throat pain, swollen throat, burning throat, itchy throat), and wheezing have been reported with intranasal budesonide during postmarketing experience.[31824]

Headache (10% to 21%), dizziness (7%), fatigue (2% to 5%), mood changes (2.5% to 6.5%), and insomnia (up to 6.5%) were reported during clinical trials in adult patients with oral budesonide. Agitation, amnesia, confusion, hyperkinesis, nervousness, paresthesias, sleep changes, somnolence or drowsiness, tremor, and vertigo have been reported in less than 5% of adult patients receiving oral budesonide.[34979] [52910] [64318] [67192] Headache/migraine (5%) were reported in adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Fatigue, feeling abnormal, depression, irritability, restlessness, and tremor were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for EoE.[70334] Insomnia, sleep disorder, and depression were reported in less than 1% of adult patients using budesonide rectal foam.[58166] In pediatric patients (age 12 months to 8 years), hyperkinesia (restlessness), fatigue, and emotional lability was reported in 1% to less than 3% of patients receiving budesonide inhalation suspension.[33486] Headache (3% or more) and migraine (1% to 3%) have been reported in with budesonide inhalation powder and suspension. Psychosis, emotional lability, depression, aggressive reactions, irritability, nervousness, restlessness, anxiety, and headache have been reported in postmarketing experience with budesonide inhalation powder and suspension.[34376] [33486] Mood swings, agitation, confusion, insomnia, nervousness, dizziness, and sleep disorder have been reported in postmarketing experience with oral budesonide.[34979] [64318] Mood swings and dizziness have been reported in postmarketing experience with rectal budesonide.[52910]

Dermatitis (6% or less) was reported in adult patients receiving oral budesonide. Alopecia, eczema (atopic dermatitis), skin disorder, hyperhidrosis, and purpura were reported in less than 5% of adult patients receiving oral budesonide during clinical trials.[34979][64318][67192] Ecchymosis (8%) has been reported in patients receiving nasal budesonide in clinical trials.[31824] In pediatric patients, rash was reported in up to 4% of patients receiving budesonide inhalation suspension (age 12 months to 8 years). Allergic reaction, contact dermatitis, ecchymosis, eczema, pustular rash, pruritus, and purpura occurred in 1% to less than 3% of patients receiving inhaled budesonide power or suspension.[33486] [34376] Anaphylactic reactions, angioedema, bronchospasm, dermatitis, rash, ecchymosis, urticaria, and facial skin irritation have been reported with postmarketing use of budesonide inhalation powder, inhalation suspension, and intranasal budesonide.[33486] [34376] Wheezing or bronchospasm in patients with severe milk protein hypersensitivity has been reported in postmarketing experience with budesonide inhalation powder use.[34376] Anaphylactoid reactions, maculopapular rash, and allergic dermatitis have been reported with oral and rectal budesonide during postmarketing use.[34979] [52910] [58166] [64318] [70334] Discontinue budesonide if such reactions occur.

Budesonide therapy, just like any corticosteroid, has been associated with the development of cataracts, increased ocular pressure or ocular hypertension, and glaucoma. Long-term use of inhaled corticosteroids may increase the risk of these eye problems. Regular eye examinations should be done.[33486] Eye abnormality and abnormal vision/visual impairment was reported in less than 5% of adult patients receiving oral budesonide during clinical trials.[34979] [64318]  In pediatric patients (age: 12 months to 8 years), conjunctivitis (less than 1% to 4%) and ocular infection (unspecified) (1% to less than 3%) were reported in patients receiving budesonide inhalation suspension.[33486] Cataracts, glaucoma, and increased intraocular pressure have been reported during postmarketing experience with budesonide inhalation powder, inhalation suspension, and intranasal budesonide.[31824] [33486] [34376]

Pharmacologic doses of corticosteroids administered for prolonged periods can result in hypothalamic-pituitary-adrenal (HPA) suppression. Adrenocortical insufficiency was reported in 1% more of adult patients taking oral budesonide.[34979] [64318] In a study looking at response to ACTH stimulation in patients receiving oral budesonide 9 mg once daily, the proportion of patient with an abnormal response was 47% at 4 weeks and 79% at 8 weeks.[52910] Adrenal suppression, including adrenal insufficiency, was reported in 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE).[70334] A decrease in blood cortisol (17%) and adrenal insufficiency (4%) has been reported in adult patients using budesonide rectal foam.[58166] Adrenal insufficiency and withdrawal symptoms may occur after treatment discontinuation or when transitioning from systemic corticosteroids to inhaled corticosteroids. Patients should taper slowly if discontinuing corticosteroids or when transitioning from systemic corticosteroids to inhaled budesonide suspension or dry powder inhaler.[33486] [34376] Symptoms of adrenal insufficiency include tiredness, weakness, nausea and vomiting, and low blood pressure. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Use of inhaled corticosteroids with systemic corticosteroids could increase the likelihood of HPA suppression as compared with a therapeutic dose of either alone.[31824] [33486] [34376] [34979] [52910] [58166] [64318] [70334] Symptoms of hypocorticism and hypercorticism have been reported during postmarketing experience with budesonide inhaled suspension.[33486]

Corticosteroids may cause growth inhibition in pediatric subjects. Data regarding effects on growth are conflicting; the lowest effective dose of any corticosteroid dosage form should be utilized and growth should be routinely monitored during use.[66299] 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 children. With orally inhaled corticosteroids, the mean reduction in growth velocity is approximately 1 centimeter/year (range 0.3 to 1.8 centimeter/year) and appears to be related to the dose and duration of exposure. In a study, children 5 to 12 years of age with asthma receiving inhaled budesonide experienced a 1.1 centimeter reduction in growth compared to the placebo group by the end of 1 year. By the end of 4 years, the growth velocities of both groups were similar.[33486] In general, the benefits of regular inhaled corticosteroid use outweigh the potential risk of relatively small and non-cumulative growth suppression in children with asthma; however, growth should be monitored.[57670] 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, titrate to the lowest effective dose.[34376] [33486] [34979] [52910] [57670] [58166] [64318] [70334] Growth suppression has been reported with postmarketing experience with budesonide inhalation suspension.[33486]

Arthralgia (2% to 6%) and arthritis (less than 5%) was reported in adult patients receiving oral budesonide.[34979][52910] [64318] [67192] Arthralgia was reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE).[70334] Arthralgia was reported in adult patients receiving budesonide via a dry powder inhaler.[34376] Fracture was reported in 1% to less than 3% of pediatric patients (age 12 months to 8 years) receiving budesonide inhalation suspension during clinical trials.[33486] Prolonged use (e.g., more than 1 year) of high doses of inhaled corticosteroids, such as budesonide, especially when used in combination with frequent courses of systemic corticosteroids, may be associated with skeletal changes and reduced bone mineral density (BMD), which may increase the risk of osteopenia and osteoporosis. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown. Avascular necrosis of the femoral head and osteoporosis were reported with postmarketing experience with budesonide inhalation suspension.[33486]

Signs and symptoms of hypercorticism (Cushing's syndrome) have been reported in adult patients receiving oral budesonide and included: flushing (less than 5%), acne vulgaris (1% to 15%), bruising easily (5% to 15%), moon face or Cushingoid features (1% to 11%), swollen ankles (2% to 7%), hirsutism (0% to 5%), buffalo hump (1%), skin striae (2% or less), fluid retention (1% to 2%), and face edema (8% or less).[34979] [52910] [64318] [67192] Hirsutism and dermatitis acneiform were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE).[70334] Acne (less than 1%) and hyperglycemia (less than 1%) has been reported in adult patients receiving budesonide rectal foam.[58166] Benign increased intracranial pressure has been reported during postmarketing experience with budesonide.[34979] [52910] [58166]

Nausea (5% to 11%), diarrhea (10%), dyspepsia (6% to 7%), abdominal pain (6%), upper abdominal pain (3% to 4%), abdominal distension (2%), flatulence (2% to 6%), constipation (2% or less), vomiting (6%), and weight gain (7% or less) were reported in adult patients receiving oral budesonide during clinical trials. Anus disorder, enteritis, epigastric pain, gastrointestinal fistula, glossitis, hemorrhoids, GI obstruction, tongue edema, tooth disorder, and appetite stimulation were reported in less than 5% of patients.[34979] [52910] [64318] [67192] Gastroenteritis (3%) and erosive esophagitis (2%) were reported in adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Xerostomia, dysgeusia, dyspepsia, erosive duodenitis, gastrointestinal motility disorder, esophageal food impaction, and palatal swelling were all reported in less than 2% of patients receiving oral budesonide suspension for EoE.[70334] Nausea (2%) was reported in adult patients using budesonide rectal foam.[58166] Nausea (2%), viral gastroenteritis (2%), dry mouth (1% to less than 3%), and taste perversion/dysgeusia (1% to less than 3%) were reported in adult and pediatric patients receiving budesonide inhalation powder (age 6 years and older).[34376] Gastroenteritis (5%), vomiting (2% to 4%), diarrhea (2% to 4%), abdominal pain (2% to 3%), and anorexia (1% to less than 3%) were reported in pediatric patients receiving budesonide inhalation suspension.[33486] Rectal GI bleeding has been reported during postmarketing experience with oral budesonide tablets.[52910] Pancreatitis has also been reported during postmarketing experience for budesonide.[58166]

Peripheral edema (17%) and hypertension (12% or less) have been reported during clinical trials in adult patients receiving oral budesonide. Palpitations, sinus tachycardia, dependent edema, and chest pain (unspecified) were reported in less than 5% of adult patients receiving oral budesonide during clinical trials.[34979] [64318] [67192] Palpitations, hypertension, and syncope were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE).[70334] In pediatric patients, chest pain has been reported in 1% to less than 3% of patient receiving budesonide inhalation suspension.[33486] Syncope has been reported in 1% to less than 3% of pediatric patients using budesonide inhalation powder.[34376] An increase in blood pressure has been reported during postmarketing experience with budesonide.[52910]

In rare cases, persons receiving inhaled budesonide may present with eosinophilia and clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition often treated with systemic corticosteroids. These events have happened most commonly in association with systemic corticosteroid withdrawal in conjunction with the introduction of inhaled corticosteroid therapy. Persons presenting with eosinophilia, vasculitis with granulomas, worsening pulmonary symptoms, and/or neuropathy may have this condition, which may be severe. Similar cases have been reported with the use of other inhaled corticosteroids. A causal relationship to budesonide has not yet been established.[33486] [34376]

Asthenia, influenza or flu-like disorder, malaise, and fever occurred in less than 5% of adult patients receiving oral budesonide during clinical trials.[34979] [64318] Fever was reported in 3% or more of patients using inhaled budesonide via a dry power inhaler.[34376] Fatigue and flu-like disorder were reported in 1% to less than 3% of pediatric patients (age 12 months to 8 years) receiving budesonide inhalation suspension during clinical trials.[33486] Fever has been reported during postmarketing experience with oral, rectal, and inhaled budesonide.[33486] [58166]

Leukocytosis (increased white blood cell count) was reported in 1% to 6% in adult patients receiving oral budesonide.[67192] [34979] Hypokalemia was reported in less than 5% of patients receiving one oral capsule formulation at incidences greater than with placebo, and greater than 1% of patients receiving other oral formulations.[34979] [64318] Anemia, hematuria, pyuria, increased erythrocyte sedimentation rate, increased alkaline phosphatase, atypical neutrophils, increased c-reactive protein, and adrenal insufficiency where reported in 1% or more of adult patients taking oral budesonide.[34979] [64318] Hyperkalemia, elevated hepatic enzymes (transaminases increased), and dyslipidemia were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE).[70334]

Gastrointestinal mucosal candidiasis (including esophageal candidiasis, oropharyngeal candidiasis, oral candidiasis) was reported in 8% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Fungal skin infection, paronychia, pneumonia, sepsis, and bronchitis were reported in less than 2% of patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE).[70334] Urinary tract infection and thrush have occurred in less than 5% of adult patients receiving oral budesonide during clinical trials.[34979] [52910] [64318] In clinical studies with intranasal budesonide, the development of localized infections of the nose and pharynx with Candida albicans has occurred.[31824] Oral candidiasis infection was reported in 1% of adult and pediatric patients receiving budesonide inhalation powder (age 6 years and older). Rinsing the mouth after use of budesonide inhalation powder may minimize the incidence of oropharyngeal thrush.[34376] Moniliasis (3% to 4%) was reported in pediatric patients (age 12 months to 8 years) receiving budesonide inhalation suspension during clinical trials. Herpes simplex and infection (unspecified) were reported in 1% to less than 3% of pediatric patients.[33486] Monitor patients on long-term budesonide therapy for signs of infection. Discontinuation of budesonide may be required.[33486] [34376] [34979] [52910] [58166] [64318] [67192] [70334]

Dysuria, increased urinary frequency (micturition frequency), and nocturia were reported in less than 5% of adult patients receiving oral budesonide during clinical trials.[34979] [64318]

Vaginal bleeding (intermenstrual bleeding) and menstrual irregularity/menstrual disorder has been reported in less than 5% of adult patients receiving oral budesonide during clinical trials.[34979] [64318]

Inhaled budesonide is contraindicated as primary therapy for patients with status asthmaticus or other types of acute bronchospasm for which intensive therapy is warranted. Patients should be advised that budesonide is not to be used as a bronchodilator and is not indicated for relief of acute bronchospasm.[33486] [34376]

Systemic corticosteroids, including budesonide, may cause immunosuppression and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: 1) Reduce resistance to new infections, 2) Exacerbate existing infections, 3) Increase the risk of disseminated infections, 4) Increase the risk of reactivation or exacerbation of latent infections 5) Mask some signs of infection. Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider corticosteroid withdrawal or dosage reduction as needed. If budesonide is used to treat a condition in patients with latent tuberculosis (TB) or tuberculin reactivity, reactivation of TB may occur. Closely monitor such patients for TB reactivation. During prolonged budesonide therapy, patients with latent TB or tuberculin reactivity should receive chemoprophylaxis. Viral infection, such as varicella zoster (chickenpox or shingles) and measles can have a serious or even fatal course in non-immune patients taking corticosteroids; other herpes infection (herpes simplex) may also disseminate in immunosuppressed individuals. Corticosteroids should be used with caution, if at all, in patients with ocular herpes simplex. In corticosteroid-treated patients who have not had these diseases or are nonimmune, avoid exposure of these people to these viral infections. If a corticosteroid-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If varicella develops, consider treatment with antiviral. If a corticosteroid-treated patient is exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. Hepatitis B exacerbation/reactivation can occur in patients who are hepatitis B virus carriers treated with immunosuppressive dosages of corticosteroids, including budesonide. Reactivation can also occur infrequently in corticosteroid-treated people who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with systemic corticosteroids. For individuals who show evidence of hepatitis B infection, consult providers with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Systemic budesonide use is contraindicated in the presence of a systemic fungal infection. Corticosteroids, including budesonide, may exacerbate systemic fungal infections; therefore, avoid corticosteroid use in the presence of a fungal infection unless a corticosteroid is needed to control drug reactions. If a fungal infection develops during chronic corticosteroid therapy, corticosteroid withdrawal or dosage reduction is recommended. Corticosteroids, including budesonide, may activate latent amebiasis. Latent or active amebiasis should be ruled out before initiating budesonide in people who have spent time in the tropics or have unexplained diarrhea. Corticosteroids, including budesonide, should be used with great care in the presence of known or suspected Strongyloides (threadworm) helminth infection. Corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. In selected patients from strongyloidiasis endemic areas who need systemic corticosteroids, consider administering prophylactic treatment. Also avoid corticosteroids, including budesonide, in people with cerebral malaria.[52910] [70334] [67192] These precautions and considerations also apply to budesonide rectal foam and inhalational product use.[58166] [33486] [34376] Administration via the nasal route generally minimizes systemic infection risk. Localized fungal infection of the nose, mouth, and pharynx with Candida albicans has been reported with inhalational or nasal corticosteroid use. Instruct patients to rinse mouth after each use of nasal or inhaled budesonide to minimize risk.[31824] [33486] [34376] Patients using budesonide nasal spray for extended periods (i.e., months) should be examined periodically for evidence of infection or other adverse effects on the nasal mucosa.[31824]

Corticosteroids may cause growth inhibition in infants, children, and adolescents. Data regarding effects on growth are conflicting; the lowest effective dose of any corticosteroid dosage form should be utilized and growth should be routinely monitored during use.[66299] Controlled clinical studies have shown that inhaled corticosteroids (ICS) may cause a dose-dependent effect on growth. 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. Controlled clinical studies have shown that ICS may cause a mean reduction in growth velocity of approximately 1 centimeter (cm) per year (range: 0.3 to 1.8 cm/year) and that this reduction appears to depend on dose and duration of exposure. Pediatric patients receiving any formulation of budesonide should be monitored closely for growth inhibition.[33486] [34376] [31824] [34979] [52910] [57670]

Studies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy.[31824] [33486] [34376] [46711] A review of Swedish registries of more than 2,000 births indicated that no increased risk for congenital malformations during early pregnancy with budesonide inhalation powder or solution.[46713] Despite adverse effects in animal studies, fetal harm appears remote. Corticosteroid treatment may not be necessary during pregnancy due to a natural increase in corticosteroid production; however, poorly controlled maternal asthma also poses risk to the mother and the fetus. Low-dose inhaled corticosteroids are considered first-line therapy for control of mild persistent asthma during pregnancy according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group; of the inhaled corticosteroids, more data are available for budesonide use in pregnancy. Data on the use of medium- to high-dose inhaled corticosteroid use during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. However, there are no data to indicate safety concerns with other inhaled corticosteroids, and maintaining a previously established treatment regimen may be more beneficial to the patient.[31822] Selection of any pharmacologic treatment for asthma control during pregnancy should include the specific needs of the patient, based on an individual evaluation, and consideration of the potential benefits or risks to the fetus. A position statement by the American College of Allergy, Asthma and Immunology also considers budesonide a good choice for pregnant women requiring high doses of inhaled steroids for effective asthma management.[46717] Limited published studies report on the use of oral budesonide in pregnant patients; however, the data are insufficient to inform a drug-associated risk of major birth defects and miscarriage. Oral budesonide products (e.g., Entocort EC, Ortikos, Uceris, Tarpeyo) have been teratogenic and embryocidal in animal studies. At subcutaneous budesonide doses that were 0.3 to 0.5 or 0.03 to 0.05 times the maximum recommended human dose (MRHD) in pregnant rats and rabbits, respectively, fetal loss, decreased pup weights, and skeletal anomalies occurred. There is a natural increase in endogenous corticosteroid production during pregnancy, and many women will require a lower exogenous dose or no corticosteroid treatment at all during pregnancy. Oral budesonide (e.g., Entocort EC, Ortikos, Uceris, Eohilia, Tarpeyo) products should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Some studies show an association of adverse pregnancy outcomes in women with Crohn's disease with increased disease activity (increased stool activity and abdominal pain) which can lead to preterm birth and low birth weight infants. Counsel the patients about the importance of controlling the disease.[34979] [64318] IgA nephropathy in pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including stillbirth and low birth weight. Hypoadrenalism may occur in an infant born to a mother receiving corticosteroids during pregnancy, and the infant should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting.[34979] [52910] [64318] [67192] [70334]

Oral, nasal, rectal, and inhaled forms of budesonide are compatible with breast-feeding. The amount of infant exposure from use of inhaled budesonide by the breast-feeding parent is negligible. Budesonide is excreted into breast milk in small amounts with a relative infant dose (RID) of 0.3%. In addition, budesonide has an oral bioavailability of 10.7%, further limiting total infant exposure.[70364] [70365] Based on data from a small number (n = 8) of breast-feeding women taking inhaled dry powder budesonide 200 to 400 mcg twice daily, approximately 0.3% to 1% of the dose inhaled by the mother is available via breast milk to an exclusively breast-fed infant. Budesonide plasma concentrations obtained in five of the infants in this study about 140 minutes after maternal drug administration and 90 minutes after breast-feeding were below quantifiable levels.[33725] Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. Due to greater availability of data, budesonide is considered the preferred agent in this population.[31822] Reviewers and an expert panel consider all inhaled corticosteroids acceptable to use during breast-feeding.[33723] [33724] [31822] Single- and repeated-dose pharmacokinetic studies have shown that maximum plasma budesonide concentrations after a 9 mg oral daily dose are up to 10-times greater than the concentrations measured after inhaled doses of 400 to 800 mcg/day. Assuming that the coefficient of extrapolation between inhaled and oral doses is constant across all doses, it is possible that budesonide exposure to breast-feeding infants after maternal oral ingestion may be up to 10-times higher than exposure to infants after maternally inhaled budesonide.[34979] [52910]

When budesonide is used chronically, systemic effects such as hypercorticism and adrenal axis suppression may occur.  Pediatric patients with Crohn's disease and patients with moderate to severe hepatic impairment (Child-Pugh Class B and C) could be at increased risk due to increased systemic exposure of oral budesonide.[34979] [64318] [67192] Hypothalamic-pituitary-adrenal (HPA) axis suppression can occur with any budesonide formulation, including budesonide inhalation. Corticosteroids can reduce the response of the HPA axis to stress. Observe patients during periods of stress e.g., trauma, surgery, infection) for evidence of inadequate adrenal response. Patients may require systemic corticosteroids during periods of physiologic stress.[33486] [34376] [34979] [52910] [58166] [67192] When discontinuing therapy or switching between corticosteroids, monitor for signs of adrenal axis suppression, benign increased intracranial pressure, and withdrawal of steroid therapy. Adrenocortical function monitoring may be required in these patients.[52910] [58166] [67192] Transferring a patient from systemic corticosteroids to inhaled budesonide should be done with care to avoid symptoms of HPA suppression.[34376] [34979] Avoid abrupt discontinuation in systemic corticosteroid to reduce symptoms of acute corticosteroid withdrawal. Deaths due to adrenal insufficiency have been reported in asthma patients during and after such a change. After withdrawal from systemic therapy, a number of months are required for recovery of HPA-axis function. Patients previously maintained on doses equivalent to 20 mg/day or more of prednisone may be at increased risk.[34376] Use of budesonide inhalation suspension should be used concurrently with patient's maintenance dose of systemic corticosteroid. After a week, gradually reduce the systemic corticosteroid dose (not more than 25% of the prednisone dose or its equivalent). Further reductions in the systemic corticosteroid dose maybe be made every 1 or 2 weeks. When transferring from systemic corticosteroids to a budesonide inhaler, reduce the daily prednisone dose (or equivalent steroid dose) by 2.5 mg per week. The transfer from systemic corticosteroid therapy to budesonide may also result in unmasking of allergies or other immunologic conditions, such as rhinitis, eczema, eosinophilia, conjunctivitis, or arthritis, that were previously controlled by treatment with systemic corticosteroids.[34376] [34979] [58166] [64318] [70334]

Glucocorticoids, such as budesonide, should be avoided in patients with Cushing's disease since they can produce or aggravate Cushing's syndrome. It is possible that systemic corticosteroid effects such as hypercortisolism may appear in a small number of patients receiving inhaled budesonide, particularly at higher doses. If features consistent with hypercorticism or Cushing's disease occur, the steroid should be reduced slowly, consistent with accepted procedures for management of symptoms and for tapering of systemic steroids.

Due to the inhibitory effects of glucocorticoids on wound healing, intranasal budesonide should be avoided in patients with a recent history of oral surgery or nasal surgery, nasal trauma, or nasal septal ulcers until their condition has healed. Intranasal budesonide overuse, improper use, or chronic use might lead to nasal septal perforation; patients who experience recurrent episodes of epistaxis (nosebleeds) or nasal septum discomfort while taking this medication should contact their prescriber for evaluation. If perforation occurs, the drug should be discontinued until healing is complete.[31824]

Corticosteroids, including inhaled budesonide, can decrease bone mineral density (BMD). The clinical significance of these small changes in BMD with regard to long-term outcomes is unknown. Monitor patients, especially those with risk factors, such as preexisting osteopenia, prolonged immobilization, family history of osteoporosis, tobacco smoking, malnutrition, post menopausal status, advanced age, or chronic use of other medications that may reduce bone mass.[33486] [34376] [34979] [52910] [64318] [67192]

Although oral budesonide has weak mineralocorticoid properties, hypertension due to edema and electrolyte imbalance may occur. Prolonged administration of systemic glucocorticoids also can result in edema and hypertension. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups.[24362]

Monitor patient at risk for diabetes, have diabetes mellitus, have a family history of diabetes, or have peptic ulcer disease. Budesonide may exacerbate these conditions (increase in blood sugar/hyperglycemia or GI perforation).[34979] [52910] [58166] [64318] [67192]

Budesonide undergoes extensive hepatic metabolism. Patients who have moderate to severe hepatic impairment may be at an increased risk of hypercorticism and adrenal axis suppression due to increased budesonide systemic exposure. No dosage adjustment is suggested for nasal, inhaled, or rectal budesonide. In patients with mild hepatic impairment, no dosage adjustments for oral formulations are recommended; however, avoidance or dosage adjustment is product specific in patients with moderate to severe hepatic disease receiving oral formulations. Monitor all patients on any form of budesonide for signs and symptoms of hypercorticism. Consider discontinuing budesonide if hypercorticism is observed.[34979] [52910] [58166] [64318] [67192] [70334]

Prolonged use of systemic corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure or glaucoma. Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled or intranasal administration of corticosteroids. Therefore, close monitoring is warranted in patients with a history of these conditions, a change in vision, or with prolonged corticosteroid use.[31824] [34376] [33486] [34979] [52910] [67192] [70334]

Systemic glucocorticoids, like budesonide, should be used with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents. Muscle weakness may be transiently increased during the initiation of systemic glucocorticoid therapy in patients with myasthenia gravis, necessitating respiratory support.[34979] [52910] [64318]

Budesonide treatment is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of the product chosen for use. Anaphylactic reactions have occurred with some budesonide formulations.[52910] [67192] [70334] [31824] [59312] [34376] [33486] Budesonide inhalation powder contains small amounts of lactose, which contain trace levels of milk protein. Patients with a severe milk protein hypersensitivity may experience an allergic reaction to this product.[34376] True corticosteroid hypersensitivity is rare. 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.[27616] [27642]

There is no special precaution needed for the dosage of inhaled, rectal, or nasal budesonide in older adults.[34376] [59312] [58166] In general, oral budesonide dose selection for a geriatric adult should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy, particularly with chronic use.[34979] [52910] [64318] [67192] According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium; avoid when possible in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. Oral corticosteroids may be required for chronic conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.[63923]

Erosive esophagitis (2%) has been reported in patients receiving oral budesonide suspension. These patients had no erosions present at baseline esophagogastroduodenoscopy (EGD). After 12 weeks of treatment with oral budesonide suspension, 2 subjects had Los Angeles (LA) classification grade A, 1 subject had LA grade B, and 1 subject had LA grade C erosive esophagitis. All but 1 of the 4 patients developed erosive esophagitis while receiving concomitant therapy with a PPI. Advise patients and caregivers to report new or worsening signs of symptoms of erosive esophagitis to their healthcare provider. Consider endoscopic evaluation as appropriate.[70334]

Kaposi's sarcoma has been reported with systemic corticosteroid use, most often for chronic conditions. Use with budesonide orally with caution. Discontinuation of the systemic corticosteroid may result in clinical improvement of Kaposi's sarcoma.[52910] [67192][70334]

As with other inhaled asthma medications, paradoxical bronchospasm can occur with an immediate increase in wheezing after administration of inhaled budesonide. If bronchospasm occurs after inhalation, treat immediately with an inhaled, short-acting bronchodilator, discontinue budesonide, and institute alternative therapy.[33486] [34376]