Chemistry:Budesonide

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Short description: Type of corticosteroid medication; group of stereoisomers
Budesonide
Budesonid Grundstruktur V4.svg
Budesonide ball-and-stick.png
Clinical data
Trade namesPulmicort, Rhinocort, Entocort, others
Other namesBUD
AHFS/Drugs.comMonograph
MedlinePlusa608007
License data
Pregnancy
category
  • AU: A / B3
Routes of
administration		By mouth, nasal, tracheal, rectal, inhalation
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability10-20% (first pass effect)
Protein binding85-90%
MetabolismLiver CYP3A4
Elimination half-life2.0-3.6 hours
ExcretionUrine, feces
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
Chemical and physical data
FormulaC25H34O6
Molar mass430.541 g·mol−1
3D model (JSmol)
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Budesonide, sold under the brand name Pulmicort among others, is a medication of the corticosteroid type.[4] It is available as an inhaler, nebulization solution, pill, nasal spray, and rectal forms.[4][5] The inhaled form is used in the long-term management of asthma and chronic obstructive pulmonary disease (COPD).[4][6][7] The nasal spray is used for allergic rhinitis and nasal polyps.[5][8] The pills in a delayed release form and rectal forms may be used for inflammatory bowel disease including Crohn's disease, ulcerative colitis, and microscopic colitis.[9][10][11]

Common side effects with the inhaled form include respiratory infections, cough, and headaches.[4] Common side effects with the pills include feeling tired, vomiting, and joint pains.[4] Serious side effects include an increased risk of infection, loss of bone strength, and cataracts.[4] Long-term use of the pill form may cause adrenal insufficiency.[4] Stopping the pills suddenly following long-term use may therefore be dangerous.[4] The inhaled form is generally safe in pregnancy.[4] Budesonide chiefly acts as a glucocorticoid.[4]

Budesonide was initially patented in 1973.[12] Commercial use as an asthma medication began in 1981.[13] It is on the World Health Organization's List of Essential Medicines.[14] Some forms are available as a generic medication.[15] In 2019, generic budesonide was listed as involved in Teva's price fixing scheme in the United States.[16] In 2020, it was the 207th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[17][18]

Medical uses

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.[19]

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.[20] A Cochrane review found evidence for up to three months (but not longer) of maintenance of remission in Crohn's disease.[21]

Budesonide assists in the induction of remission in people with active ulcerative colitis.[22]

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.[10][23]

Allergic rhinitis

Budesonide in the form of nasal sprays is a treatment for allergic rhinitis.[24]

Eosinophilic esophagitis

Topical budesonide has considerable effects in eosinophilic esophagitis.[25] For this use, it is formulated as a tablet that disperses in the mouth, and sold under the trade name Jorveza.[26]

Berger's disease

Budesonide (Tarpeyo) 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.[2][27]

Side effects

Nasal budesonide inhalers have been associated with a number of side effects.[28][29] These include nose irritation or burning, bleeding or sores in the nose, lightheadedness, upset stomach, cough, hoarseness, dry mouth, rash, sore throat, bad taste in mouth, change in mucus, and blurred vision.[30] Other symptoms which should be reported immediately include difficulty in breathing, swelling of the face, white patches in the throat, mouth, or nose, irregular menstrual periods, severe acne, and on rare occasions, behavioral changes (mostly affecting children)[28]

Contraindications

Budesonide is contraindicated as a primary treatment of status asthmaticus or other acute episode of asthma where intensive measures are required.[31] It is also contraindicated for patients who have hypersensitivity to budesonide.[32]

Interactions

Those taking tablets or capsules orally should avoid grapefruit and grapefruit juice[33][34] and echinacea.[35]:160

  • Grapefruit juice may double bioavailability of oral budesonide.
  • Echinacea diminishes bioavailability.

Also, high-fat meals delay absorption but do not impede absorption.[36]

Pharmacology

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

  • Controls the rate of protein synthesis.[37]
  • Depresses the migration of polymorphonuclear leukocytes and fibroblasts.[38]
  • Reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.
  • Has a potent glucocorticoid activity and weak mineralocorticoid activity.

Pharmacokinetics

  • Onset of action: Nebulization: 2–8 days; Inhalation: 24 hours; Nasal: 10 hours
  • Peak effect: Nebulization: 4–6 weeks; Inhalation: 1–2 weeks
  • Distribution: 2.2-3.9 L/kg
  • Protein binding: 85% to 90%
  • Metabolism: Hepatic via CYP3A4 to two metabolites: 16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide; minor activity
    • Budesonide is extensively metabolized in first pass, resulting in a low bioavailability and systemic effects[39]
    • Bioavailability: Capsule: 9% to 21%; Nebulization: 6%; Inhalation: 6% to 13%
  • Half-life elimination: 2–3.6 hours
  • Time to peak: Capsule: 0.5–10 hours (variable in Crohn's disease); Nebulization: 10–30 minutes; Inhalation: 1–2 hours; Tablet: 7.4-19.2 hours
  • Excretion: urine (60%) and feces as metabolites.

Chemistry

Budesonide, also known as 11β,21-dihydroxy-16α,17α-(butylidenebis(oxy))pregna-1,4-diene-3,20-dione, is a synthetic pregnane steroid and non-halogenated cyclic ketal corticosteroid.[40][41] It is the C16α hydroxyl, C16α,17α cyclic ketal with butyraldehyde derivative of prednisolone (11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione).[40][41]

Stereoisomerism

Budesonide
(2 stereoisomers)
(R)-Budesonid
(22R)-configuration 		(S)-Budesonid
(22S)-configuration

Society and culture

Legal status

On 19 May 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Kinpeygo, intended for the treatment of primary immunoglobulin A nephropathy.[42] The applicant for this medicinal product is Calliditas Therapeutics AB.[42] Kinpeygo is a hybrid medicine of Entocort which has been authorised in the EU since 2 April 1992.[42] Kinpeygo contains the same active substance as Entocort but has a different formulation and a different indication.[42]

Brand names

Inhaler for a powder based on budesonide and formoterol

Aeronide (TH); Aquacort (DE); B Cort (CO); Bronex (PH); Budair (MY); Budecort DP (MY); Budenofalk (DE, GB, HK, KP, PH, SG); Budeson (AR); Budeson Aqua (AR); BudeSpray (TH); Budiair (KP); Budicort Respules (IL); Budinide (KSA); Bunase (TH); Clebudan (CN); Cortiment (CA, GB, AU); Cycortide (HK); Denecort (PH); Duasma (TW); Eltair (MY); Entocort (AR, AT, BE, BR, CH, CZ, DK, FI, FR, GB, HK, IE, IL, IT, KP, NL, NO, PL, PT, SE, TR);[35]:13 Giona Easyhaler (MY, SG, TH); Inflammide (PE); Miflonid (CZ); Miflonide (BE, DE, IL, IT, NZ, PT); Neumocort (PY); Novopulmon (DE, FR); Pulmicon Susp for Nebulizer (KP); Pulmicort (AT, BE, BG, BR, CH, CL, CN, CO, CR, CZ, DE, DK, DO, EE, FI, FR, GB, GR, GT, HN, ID, IN, NI, NL, NO, PA, PK, PL, PT, RU, SE, SV, TR, TW, UY, VE, ZA);[35]:13 Pulmicort Nasal Turbohaler (CL, KE, MU, NG); Pulmicort Turbuhaler (KE, MU, NG); Rafton (FR); Rhinocort (AU); Rhinocort Aqua (HK);[43] Rhinoside (GR); Symbicort (FR, UK, US, ZA) Uceris (US).

Research

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.[44] 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.[45][46] 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.[47][48] The recommendation was withdrawn in December 2021 citing the need for more research.[49][50]

Inhalational budesonide was added to the recommended treatment for cases of COVID-19 in India in April 2021.[51][52]

References

  1. ↑ "Regulatory Decision Summary - Uceris". 23 October 2014. https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?linkID=RDS00675. 
  2. ↑ 2.0 2.1 "Tarpeyo- budesonide capsule, delayed release". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=938cada4-d6bf-4252-836f-dd40f9eadb4d. 
  3. ↑ "Pulmicort Flexhaler- budesonide aerosol, powder". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=54234b7d-3bcc-4809-1881-1d21484856a0. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 "Budesonide". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/budesonide.html. 
  5. ↑ 5.0 5.1 "Budesonide eent". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/budesonide-eent.html. 
  6. ↑ "Tailoring of corticosteroids in COPD management". Current Respiratory Care Reports 3 (3): 121–132. 2014. doi:10.1007/s13665-014-0084-2. PMID 25089228. 
  7. ↑ "Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach". Clinical and Experimental Gastroenterology 9: 125–30. 2016. doi:10.2147/CEG.S80237. PMID 27274301. 
  8. ↑ "Impact of topical nasal steroid therapy on symptoms of nasal polyposis: a meta-analysis". The Laryngoscope 122 (7): 1431–7. July 2012. doi:10.1002/lary.23259. PMID 22410935. 
  9. ↑ "Budesonide in the treatment of inflammatory bowel disease". Expert Review of Clinical Immunology 7 (4): 419–28. July 2011. doi:10.1586/eci.11.34. PMID 21790284. 
  10. ↑ 10.0 10.1 "American Gastroenterological Association Institute Technical Review on the Medical Management of Microscopic Colitis". Gastroenterology 150 (1): 247–274.e11. January 2016. doi:10.1053/j.gastro.2015.11.006. PMID 26584602. 
  11. ↑ British national formulary: BNF 58 (58 ed.). British Medical Association. 2009. pp. 56–57. ISBN 9780857111562. 
  12. ↑ Pharmaceutical patents in Europe. The Hague: Kluwer Law International. 2000. p. 278. ISBN 9789041113481. https://books.google.com/books?id=KZfvZN2WfjcC&pg=PA278. 
  13. ↑ Small Molecule Medicinal Chemistry: Strategies and Technologies. John Wiley & Sons. 2015. p. 390. ISBN 9781118771693. https://books.google.com/books?id=LOudCgAAQBAJ&pg=PA390. 
  14. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  15. ↑ Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. 2015. p. 451. ISBN 9781284057560. 
  16. ↑ "Teva and Other Generic Drugmakers Inflated Prices Up to 1,000%, State Prosecutors Say". The New York Times. 2019-05-11. ISSN 0362-4331. https://www.nytimes.com/2019/05/11/health/teva-price-fixing-lawsuit.html. 
  17. ↑ "The Top 300 of 2020". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  18. ↑ "Budesonide - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/Budesonide. 
  19. ↑ Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GiNA) 2011. Available at https://www.ginasthma.org
  20. ↑ "Management of Crohn's Disease in Adults". Am J Gastroenterol 104 (2): 465–83. 2009. doi:10.1038/ajg.2008.168. PMID 19174807. 
  21. ↑ "Budesonide for maintenance of remission in Crohn's disease.". Cochrane Database Syst Rev 8 (8): CD002913. 2014. doi:10.1002/14651858.CD002913.pub3. PMID 25141071. 
  22. ↑ "Review Article: A Decision-Making Algorithm For the Management of Pregnancy in the Inflammatory Bowel Disease Patient". Aliment Pharmacol Ther 35 (5): 501–15. 2012. doi:10.1111/j.1365-2036.2011.04967.x. PMID 22221203. 
  23. ↑ "European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations". United European Gastroenterology Journal 9 (1): 13–37. February 2021. doi:10.1177/2050640620951905. PMID 33619914. 
  24. ↑ "Once-daily budesonide aqueous nasal spray for allergic rhinitis: a review". Clinical Therapeutics 26 (4): 473–92. April 2004. doi:10.1016/s0149-2918(04)90050-1. PMID 15189745. 
  25. ↑ "Efficacy and Safety of Budesonide in the Treatment of Eosinophilic Esophagitis: Updated Systematic Review and Meta-Analysis of Randomized and Non-Randomized Studies". Drugs in R&D 18 (4): 259–269. December 2018. doi:10.1007/s40268-018-0253-9. PMID 30387081. 
  26. ↑ UK Drug Information
  27. ↑ "FDA approves first drug to decrease urine protein in IgA nephropathy, a rare kidney disease". 17 December 2021. https://www.fda.gov/drugs/fda-approves-first-drug-decrease-urine-protein-iga-nephropathy-rare-kidney-disease.  This article incorporates text from this source, which is in the public domain.
  28. ↑ 28.0 28.1 "GENERIC NAME: BUDESONIDE - NASAL AEROSOL INHALER (byou-DESS-oh-nide)". https://www.emedicinehealth.com/script/main/notfoundstatic.asp?refurl=/budesonide-nasal_aerosol_inhaler/article.htm. 
  29. ↑ "What are the possible side effects of budesonide nasal (Childrens Rhinocort Allergy, Rhinocort Allergy, Rhinocort Aqua)?". https://www.emedicinehealth.com/drug-budesonide_nasal/article_em.htm#sideeffects. 
  30. ↑ "Budesonide: CMDh scientific conclusions and grounds for variation, amendments to the product information and timetable for the implementation - PSUSA/00000449/201604". European Medicines Agency (EMA). 10 March 2017. http://www.ema.europa.eu/docs/en_GB/document_library/Periodic_safety_update_single_assessment/2017/03/WC500223322.pdf. 
  31. ↑ "Acute Adrenal Crisis in Asthmatics Treated With High-Dose Fluticasone Propionate". Eur Respir J 19 (6): 1207–9. 2002. doi:10.1183/09031936.02.00274402. PMID 12108877. 
  32. ↑ "Survey of Adrenal Crisis Associated With Inhaled Corticosteroids in the United Kingdom". Arch Dis Child 87 (6): 457–61. 2002. doi:10.1136/adc.87.6.457. PMID 12456538. 
  33. ↑ "Topically Active Steroid Preparations". Advanced Therapy of Inflammatory Bowel Disease, volume 2: IBD and Crohn's Disease. PMPH-USA. May 2014. p. 651. ISBN 978-1-60795-217-6. https://books.google.com/books?id=-AJri58Yj5EC&q=Budesonide&pg=651. 
  34. ↑ "Grapefruit and Other Fruit Juices Interactions with Medicines". Handbook of drug-nutrient interactions (2nd ed.). New York, NY: Humana Press. 2010. p. 282. ISBN 978-1-60327-362-6. https://www.google.com/books/edition/Handbook_of_Drug_Nutrient_Interactions/6MSRviXlDtAC?gbpv=1&pg=PA282&printsec=frontcover. 
  35. ↑ 35.0 35.1 35.2 Saunders Nursing Drug Handbook 2015 - E-Book. Elsevier Health Sciences. 22 August 2014. p. 160. ISBN 978-0-323-28018-1. https://books.google.com/books?id=qVRTBAAAQBAJ&q=Budesonide+echinacea&pg=160. 
  36. ↑ Pediatric Dosage Handbook; Including Neonatal Dosing, Drug Administration & Extemporaneous Preparations. Lexi-Comp. 2009. ISBN 978-1-59195-267-1. https://www.google.com/books/edition/Pediatric_Dosage_Handbook/ElYtAQAAMAAJ?gbpv=1&bsq=Budesonide+high+fat+meals+absorption&printsec=frontcover. 
  37. ↑ Saunders Nursing Drug Handbook 2019 E-Book. Elsevier Health Sciences. 21 February 2018. p. 160. ISBN 978-0-323-61257-9. https://books.google.com/books?id=eJNNDwAAQBAJ&q=Budesonide+protein+synthesis&pg=160. 
  38. ↑ Mosby's Canadian Nursing Drug Reference - E-Book. Elsevier Health Sciences. 9 July 2020. p. 187. ISBN 978-1-77172-084-7. https://books.google.com/books?id=iS_wDwAAQBAJ&q=Budesonide+fibroblasts+migration&pg=187. 
  39. ↑ "Budesonide for the treatment of ulcerative colitis". Expert Opinion on Pharmacotherapy 17 (11): 1549–1559. August 2016. doi:10.1080/14656566.2016.1183648. PMID 27157244. 
  40. ↑ 40.0 40.1 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 186, 1011. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA186. 
  41. ↑ 41.0 41.1 Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. 2008. pp. 1253–. ISBN 978-0-7817-6879-5. https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1253. 
  42. ↑ 42.0 42.1 42.2 42.3 "Kinpeygo: Pending EC decision". 20 May 2022. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/kinpeygo.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  43. ↑ Complete Guide to Prescription and Nonprescription Drugs 2015; Features an A-Z List of Conditions and the Drugs Most Commonly Used (2015 ed.). Penguin. 2014. ISBN 9780698165519. https://www.google.com/books/edition/Complete_Guide_to_Prescription_and_Nonpr/DHWBAwAAQBAJ?gbpv=1&pg=PA12&printsec=frontcover. 
  44. ↑ "COVID-19 Therapeutic Alert - Inhaled Budesonide for Adults (50 Years and Over) with COVID-19". 12 April 2021. https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103154. 
  45. ↑ "Covid: Asthma drug 'speeds up recovery at home'". 12 April 2021. https://www.bbc.co.uk/news/health-56717486. 
  46. ↑ "Asthma drug Budesonide speeds up Covid recovery times". The Times. 12 April 2021. ISSN 0140-0460. https://www.thetimes.co.uk/article/asthma-drug-speeds-up-covid-recovery-times-t0630b7lp. 
  47. ↑ "Platform trial rules out treatments for COVID-19". NIHR Evidence. https://evidence.nihr.ac.uk/alert/platform-trial-rules-out-covid-treatments/. 
  48. ↑ "Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial". Lancet 398 (10303): 843–855. September 2021. doi:10.1016/S0140-6736(21)01744-X. PMID 34388395. 
  49. ↑ "NICE removes budesonide from recommended COVID-19 treatments" (in en-US). https://pharmaceutical-journal.com/article/news/nice-removes-budesonide-from-recommended-covid-treatments. 
  50. ↑ "Withdrawal of the Recommendation for Consideration of Inhaled Budesonide as a Treatment Option for COVID-19". https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103185. 
  51. ↑ "New guidelines prescribe inhaled steroid 'Budesonide', antiparasitic drug 'Ivermectin' for mild Covid cases". 29 April 2021. https://www.newindianexpress.com/nation/2021/apr/29/new-guidelines-prescribe-inhaled-steroid-budesonide-antiparasitic-drug-ivermectin-for-mild-covid-cases-2296446.html. 
  52. ↑ "Clinical Management Protocol for Covid-19 (in Adults)". 24 May 2021. https://www.mohfw.gov.in/pdf/UpdatedDetailedClinicalManagementProtocolforCOVID19adultsdated24052021.pdf. 

External links



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