Budesonide

Asthma

Budesonide is given by metered-dose inhaler or nebulizer for maintenance and prophylactic treatment of asthma, including patients who require oral corticosteroids and those who may benefit from a systemic dose reduction.[22]

Inflammatory bowel disease

Formulations of delayed-release budesonide are an effective treatment for mild-to-moderately active Crohn's disease involving the ileum and/or ascending colon.[23] A Cochrane review found evidence for up to three months (but not longer) of maintenance of remission in Crohn's disease, concluding that budesonide is not effective for maintenance of remission in CD.[24]

Budesonide assists in the induction of remission in people with active ulcerative colitis.[25]

Budesonide is highly effective and recommended as the drug of choice in microscopic colitis, for induction and maintenance of remission, and for both the lymphocytic colitis and collagenous colitis forms.[13][26]

Allergic rhinitis

Budesonide in the form of nasal sprays is a treatment for allergic rhinitis.[27]

Eosinophilic esophagitis

Topical budesonide has considerable effects in eosinophilic esophagitis.[28] For this use, it is formulated as a tablet that disperses in the mouth, and sold under the brand name Jorveza.[29]

Berger's disease

Budesonide (Tarpeyo (US); Kinpeygo (EU, UK)) is indicated to reduce proteinuria (increased protein levels in the urine) in adults with primary immunoglobulin A (IgA) nephropathy (Berger's disease) at risk of rapid disease progression.[3][30]

Overdose

Acute toxicity from an overdose of budesonide is significantly more rare than an overdosing of budesonide over a prolonged period of therapy, however both can cause systemic toxicity that manifests as hypercortisolism.[34] Symptoms of an overdose include more specific symptoms such as darkening and thinning of the skin, changes in body fat around the face, neck, back, and waist, increased acne or facial hair, menstrual problems, impotence, or loss of interest in sex, as well as some less specific symptoms such as diarrhea, dizziness, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.[35][36]

Mechanism of action

Budesonide is an agonist of glucocorticoid receptors. Among its effects are:

• Controls the rate of protein synthesis.[42]
• Depresses the migration of polymorphonuclear leukocytes and fibroblasts.[43]
• Reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.[42]
• Has a potent glucocorticoid activity and weak mineralocorticoid activity.[44]

Pharmacokinetics

Different pharmacokinetic proprieties can be seen in the absorption of budesonide depending on how it is formulated. When taken as an extended-release oral capsule, budesonide has an oral bioavailability of 9–21% and reaches peak plasma concentrations (Cmax) within 2–8 hours.[45] A high fat meal when taken with the capsule can lengthen the time it takes to reach Cmax by another 2.3 hours, but will not have any other affects on the pharmacokinetics properties of budesonide.[46] When inhaled through an metered dose inhaler, 34% of budesonide is deposited in the lung with a bioavailability of 39% and reaches Cmax within 10 minutes.[46][39] When nebulized, budesonide has an bioavailability of 6% and reaches Cmax within 1–3 hours.[39][46] When formulated as a rectal foam, budesonide has an bioavailability of 3% to 27% and reaches Cmax around 1.5 hours.[47]

The plasma protein binding of budesonide is around 85-90%, with an apparent volume of distribution of 2.2-3.9L/kg.[46][45] Budesonide is 80-90% metabolized at first pass in the liver by the hepatocytic cytochrome P450 isoenzyme 3A4 (CYP3A4) into two metabolites: 16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide. Both of these metabolites have a negligible glucocorticoid activity of less than 1% compared to the parent compound budesonide.[46] 60% of budesonide is excreted through urine as its metabolites, no unchanged budesonide is detectable in urine.[46] The average elimination half-life in plasma is between 2–3.6 hours.[46]

Stereoisomerism

Brand names

Budesonide is marketed under various brand and generic names internationally. Notable examples for each formulation include:

Inhalation: Pulmicort, Pulmicort Flexhaler, Pulmicort Nebuamp, Pulmicort Turbuhaler, TARO-Budesonide, TEVA-Budesonide, Novolizer budesonid meda, Budenova.[39][46]

Systemic (oral pills): Tarpeyo, Uceris, Eohilia, Cortiment, Entocort Jorveza.[45][46]

Nasal: MYLAN-Budesonide AQ, Rhinocort Aqua, Formancis.[50][46]

Topical: Entocort, Uceris, Budenofalk.[47][46]

Legal status

Kinpeygo, a hybrid medicine of Entocort (which has been authorised in the EU since 2 April 1992) that contains the same active substance as Entocort but has a different formulation and a different indication,[52] was approved for medical use in the European Union in July 2022.[53][54]

The FDA granted the application breakthrough therapy designation.[55]

COVID-19

Budesonide was recommended in April 2021 by the UK's NHS to treat COVID-19 on a case-by-case basis for those aged 50 years of age and older.[56] After a University of Oxford research team found in a trial with 1,700 patients that budesonide could benefit many people over 50 with COVID-19 symptoms, it was recommended from 12 April 2021, by the National Health Service in the UK for general practitioners (GPs) to treat COVID-19 on a case-by-case basis.[57][58] Results of a large-scale trial published in August 2021 suggest that inhaled budesonide improves the time of recovery and people's well-being during the recovery process.[59][60] Inhalational budesonide was added to the recommended treatment for cases of COVID-19 in India in April 2021.[61][62] The NIH recommendation was withdrawn in December 2021 citing the need for more research.[63][64]