Budesonide

Budesonide belongs to the group of synthetic, non-halogenated glucocorticoids and is mainly used for the local treatment of diseases of the respiratory and gastrointestinal tract.

Budesonide has a primary anti-inflammatory effect by binding to glucocorticoid receptors (GCC). In the cytosol, the binding of the glucorticoid to the receptor leads to a glucocorticoid-receptor complex. The binding affinity of budesonide to the receptor is about 18 times stronger than that of prednisolone and 70 times stronger than that of cortisol (hydrocortisone). Budesonide affects numerous cell types such as mast cells, eosinophils, neutrophils, macrophages and lymphocytes. In addition, the active substance inhibits (depending on application and site of action) the antigen-stimulated release of numerous pro-inflammatory signal molecules such as interleukins, RANTES, TNF-α, IFN-γ and GM-CSF or eotaxin-3. As a result, there is a significant decrease in the inflammation-related infiltration of the mucous membranes of the stomach, intestine, oesophagus or respiratory tract.

The pharmacokinetics of budesonide depend on the type and form of application (e.g. as aerosol, rectal foam, nasal spray, melting tablet or enteric-coated hard capsule) of the drug. In principle, the active ingredient binds to a high degree to plasma proteins and is well distributed in the tissue. After oral administration the systemic availability is about 10 percent. Budesonide is mainly metabolised via the cytochrome P-450 system. The average terminal elimination half-life after oral administration is about 3 to 4 hours, the average half-life is about 2.8 h

Modified release dosage forms for oral use:

Crohn's disease and collagenous colitis in adults (over 18 years): The recommended daily dose is 9 mg of budesonide once a day in the morning, about half an hour before breakfast. The full effect is achieved after 2 - 4 weeks and the application period is usually 8 weeks.

Acute microscopic colitis: The recommended dose is 9 mg budesonide once daily. The duration of use is generally 8 weeks.

Autoimmune hepatitis in adults (>18 years): the recommended daily dose is 3 mg budesonide 3 times a day. After achieving remission, a daily dose of 3 mg budesonide twice daily, morning and evening, is recommended. In patients who tolerate azathioprine, budesonide should be combined with azathioprine.

Eosinophilic esophagitis in adults (over 18 years): The recommended daily dose is 2 mg of budesonide as a 1-mg oral tablet morning and evening. Children and adolescents: Budesonide should not be given to children under 12 years of age due to the limited experience and possibly increased risk of adrenal suppression in this age group. Dosage recommendations are not given.

Patients with kidney disease: As budesonide is not excreted via the kidneys, patients with mild to moderate kidney dysfunction may be treated with caution without reducing the dose. Use in patients with severe renal insufficiency is not recommended.

Patients with liver disease: Caution is advised in patients with mild to moderate liver dysfunction. Control of liver function values.

Stop: Treatment with budesonide should not be stopped abruptly. At the end of treatment budesonide should be given at extended dose intervals for up to two weeks. After that the treatment can be stopped.

Rectal use: A rectal foam and a rectal suspension with the same indication are commercially available. Before use, the different methods of application should be considered.

Acute treatment of ulcerative colitis in adults, limited to the rectum and sigmoid colon: 2 mg of budesonide should be administered once daily via the rectal suspension rectally in the evening before going to bed, while 2 mg of budesonide can be administered once daily rectally in the morning or evening via the rectal foam. The duration of application depends on the clinical picture. As a rule, the full effect is achieved after 2 - 4 weeks.

Inhalative application (powder for inhalation and compressed gas inhalation):

Bronchial asthma: Basically, budesonide is part of the long-term treatment of bronchial asthma. In stable patients with mild to moderate asthma, the dosage can be changed from twice a day to once a day.

Adults and children/young people over 12 years of age: 200 - 400 µg once or twice daily. The maximum recommended dose is 800 µg twice a day.

Children from 6 - 12 years: 200 µg twice or 200 - 400 µg once a day. The maximum recommended dose is 400 µg twice a day. The once daily dose should be inhaled in the evening.

Chronic obstructive pulmonary disease (COPD): adults: 200 - 400 µg budesonide twice a day.

Bronchial asthma: Infants from 6 months of age, infants and children up to 12 years of age: 0.5 - 1 mg budesonide twice daily. Adults and adolescents over 12 years of age: 1 - 2 mg of budesonide twice a day. Maintenance dose: The maintenance dose should be adjusted individually and to the lowest dose that will keep the patient free of symptoms.

Pseudocroup: In infants and children with pseudocroup, the usual dose is 2 mg budesonide in suspension and is used either as a single dose or in two 1 mg doses at 30-minute intervals. The application may be repeated every 12 hours for a maximum of 36 hours or until clinical improvement.

Nasal use: Nasal sprays of 50 µg, 32 µg and 64 µg of budesonide per spray are commercially available. The corresponding application areas must be observed.

Rhinitis allergica: Adults and children from 6 years of age: The standard dose is 50 µg or 64 µg budesonide twice daily or 128 µg budesonide once daily per nostril. Children should be treated under the supervision of their parents.

Nasal polyps: Adults and children from 6 years of age: The standard dose is 64 µg budesonide twice daily per nostril or 128 µg budesonide once daily per nostril.

Pregnancy: In animal studies, high doses of budesonide caused abnormalities in fetal development. The clinical relevance for humans is unclear. Use of oral and rectal budesonide during pregnancy should be avoided unless there are convincing reasons for treatment. There are few data on the outcome of pregnancy when oral budesonide is used in humans, but bioavailability after oral administration is low.

The data on the inhaled use of budesonide in a very large number of exposed pregnancies did not indicate an increased risk of side effects for the fetus and newborn. Adequate asthma therapy during pregnancy is very important for both the fetus and the mother. However, before using budesonide during pregnancy, a risk-benefit assessment is necessary. Inhalation should be as short as possible and the lowest effective dose of budesonide should be used. Nasal budesonide should only be used during pregnancy, especially in the first trimester, and only on the doctor's instructions.

Lactation: Budesonide passes into breast milk. Inhaled maintenance therapy with budesonide in nursing women with asthma leads to negligible systemic exposure of breastfed infants. However, the plasma sample concentrations of budesonide in infants were all below the limit of determination. Based on data on inhaled budesonide and the fact that budesonide exhibits linear pharmacokinetic properties within the therapeutic dose intervals after nasal, inhalation, oral and rectal administration, low infant exposure to therapeutic doses of budesonide is expected. The decision to breastfeed or wean or not to use budesonide must be carefully weighed against the benefits of breastfeeding for the infant and the benefits of therapy for the mother.

The side effects of budesonide depend on the type and site of application. Oral, inhalation or nasal application often results in local oral and oropharyngeal candidiasis.

Very common: Cushing's syndrome, for example with full moon face, truncal obesity, decreased glucose tolerance, diabetes mellitus, hypertension, sodium retention with oedema formation, increased potassium excretion, inactivity or atrophy of the adrenal cortex, striae cutis distensae, steroid acne and disturbance of sex hormone secretion such as amenorrhoea, hirsutism and/or impotence.

Frequent: Dyspepsia, increase in risk of infection, muscle and joint pain, muscle weakness and twitching, osteoporosis, headache, depression, irritability, euphoria, petechiae, delayed wound healing, skin atrophy.

Occasional: ventriculic ulcer, dodenic ulcer, psychomotor hyperactivity, anxiety.

Rare: glaucoma, cataract, blurred vision, pancreatitis, osteonecrosis, aggression, ecchymosis.

Very rare: growth retardation in children, constipation, pseudotumor cerebri including papilledema in adolescents, increase in risk of thrombosis, vasculitis (withdrawal syndrome after long-term therapy),fatigue, malaise.

Budesonide can increase the glycoside effect by a hypokalemic effect when heart glycosides are administered together. Simultaneous administration of saluretics may increase the risk of increased potassium excretion.

Simultaneous treatment with CYP3A inhibitors may increase the risk of systemic side effects.

The simultaneous oral administration of 200 mg of ketoconazole once daily may increase the plasma concentrations of budesonide by a factor of 6. When ketoconazole was taken about 12 hours after budesonide intake, increased concentrations of budesonide were observed by about 3 times. The data do not yet allow a dosage recommendation. Therefore this combination is not recommended.

Probably other strong CYP3A4 inhibitors such as ritonavir, itraconazole, clarithromycin and grapefruit juice can also increase the plasma concentration of budesonide. Simultaneous application should therefore be avoided.

CYP3A4 inducers: CYP3A4 inducers such as carbamazepine and rifampicin can reduce both the systemic and local availability of budesonide. Sometimes the budesonide dosage must be adjusted.

Steroid-binding resins: Interactions with steroid-binding resins such as colestyramine and with antacids cannot be excluded. If budesonide is taken at the same time, its effect may be reduced. Therefore, these preparations should not be taken simultaneously. A time interval of at least 2 hours is recommended.

Estrogens: In women who have taken estrogens or oral contraceptives at the same time, increased plasma levels and an increased effect of glucocorticoids such as budesonide are possible.

Budesonide must not be used in cases of hypersensitivity to the active substance. Depending on the form of application, it is also prohibited to use in cases of severe liver dysfunction such as cirrhosis of the liver.

Measles: Patients with a budesonide-impaired immune system who have been exposed to measles should receive post-exposure normal immunoglobulin as soon as possible.

Vaccines: Patients receiving budesonide permanently should not be given live vaccines. Antibody production after administration of other vaccines may be reduced.

Liver dysfunction: In patients with primary biliary cirrhosis (PBC) in the late stage (with liver cirrhosis) and in patients with severely impaired liver function, increased systemic availability of budesonide must be expected. The recommendation of treatment must be carefully considered.

Visual impairment: Local or systemic use of glucocorticoids such as budesonide may cause visual impairment. In case of symptoms such as blurred vision or other visual disturbances, the patient should be referred to an ophthamologist to evaluate possible causes. These include cataract, glaucoma or rare conditions such as central serous chorioretinopathy (CSC), which may occur after the use of systemic or topical glucocorticoids.

• Aquacort® 50 micrograms nasal spray
• Budenobronch® 0.5 mg/2 ml suspension for one nebuliser
• InfectoPharm Medicines and Consilium GmbH
• Budenobronch® 1.0 mg/2 ml suspension for one nebuliser
• Budenofalk® 3 mg 2care4 gastric juice resistant hard capsules

Roadworthiness and operation of machinery: Budesonide nasal or inhaled has no or negligible influence on roadworthiness and the ability to operate machinery. When applied orally or rectally, it should be taken into account that fatigue may occasionally occur.