Budesonide/formoterol

Budesonide/formoterol
Combination of
BudesonideGlucocorticoid
FormoterolLong-acting beta-adrenoceptor agonist
Names
Trade namesSymbicort, DuoResp Spiromax, BiResp Spiromax, others
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B3[1]
  • US: N (Not classified yet)[1]
    Routes of
    use    		Inhaled[2]
    Defined daily dosenot established[3]
    External links
    AHFS/Drugs.comProfessional Drug Facts
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only) [4]
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Chemical and physical data
    FormulaC44H58N2O10
    Molar mass774.952 g·mol−1
    3D model (JSmol)
    SMILES
    • CCCC1OC2CC3C4CCC5=CC(=O)C=CC5(C4C(CC3(C2(O1)C(=O)CO)C)O)C.CC(CC1=CC=C(C=C1)OC)NCC(C2=CC(=C(C=C2)O)NC=O)O
    InChI
    • InChI=1S/C25H34O6.C19H24N2O4/c1-4-5-21-30-20-11-17-16-7-6-14-10-15(27)8-9-23(14,2)22(16)18(28)12-24(17,3)25(20,31-21)19(29)13-26;1-13(9-14-3-6-16(25-2)7-4-14)20-11-19(24)15-5-8-18(23)17(10-15)21-12-22/h8-10,16-18,20-22,26,28H,4-7,11-13H2,1-3H3;3-8,10,12-13,19-20,23-24H,9,11H2,1-2H3,(H,21,22)/t16-,17-,18-,20+,21?,22+,23-,24-,25+;13-,19+/m00/s1
    • Key:PJFHZKIDENOSJB-JIVDDGRNSA-N

    Budesonide/formoterol, sold under the brand name Symbicort among others, is a combination medication used in the management of asthma or chronic obstructive pulmonary disease (COPD).[2] It contains budesonide, a steroid and formoterol, a long-acting β2-agonist (LABA).[2] The product monograph does not support its use for sudden worsening or treatment of active bronchospasm.[2] However, a 2020 review of the literature does support such use.[5] It is used by breathing in the medication.[2]

    Common side effects include throat pain, influenza, runny nose, and a yeast infection of the mouth.[2] There were concerns that the LABA component increases the risk of death in children with asthma, however these concerns were removed in 2017.[6] Therefore, this combination is only recommended in those who are not controlled on an inhaled steroid alone.[2] There is tentative evidence that typical doses of inhaled steroids and LABAs are safe in pregnancy.[7] Both formoterol and budesonide are excreted in breast-milk.[1]

    Budesonide/formoterol was approved for medical use in the United States in 2006.[8][2] It is on the World Health Organization's List of Essential Medicines.[9] In the United States, as of 2017, the wholesale cost of an inhaler is about US$30.[10] In the United Kingdom, the cost as of 2015, was about GB£35 for a unit with 120 doses.[11] In 2017, it was the 74th most commonly prescribed medication in the United States, with more than ten million prescriptions.[12][13]

    Medical uses

    Maintenance

    Budesonide/formoterol has shown efficacy to prevent asthma attacks.[5] It is unclear if budesonide/formoterol differs from fluticasone and salmeterol in chronic asthma.[14]

    Exacerbation

    The combination is approved in the United States only as a maintenance medication in asthma and chronic obstructive pulmonary disease (COPD).[2] However, a 2020 review of the literature does support use as needed during acute worsening in those with mild disease, and as maintenance followed by extra doses during worsening.[5]

    Use for both maintenance and as needed treatment is also known as single maintenance and reliever therapy ( SMART) and is a well-established treatment.[15][16] It has been shown to reduce asthma exacerbations that require oral corticosteroids, hospital visits better than maintenance inhaled corticosteroids alone at a higher dose, or inhaled corticosteroid at the same or higher dose with a long acting bronchodilator (LABA)), with a short-acting bronchodilator (SABA) as a reliever.[15][16] More studies using budesonide/formoterol SMART in children are needed.[16]

    Dosage

    The defined daily dose is not established.[3]

    Side effects

    Common (up to 1 in 10 people)

    Often mild, and usually disappear as the medication continues to be used:

    Uncommon (up to 1 in 100 people)

    Rare (up to 1 in 1,000 people)

    • Rash
    • Itchiness
    • Bronchospasm (tightening of the muscles in the airways causing wheezing immediately after use of the medication, which is possibly sign of an allergic reaction and should be met with immediate medical attention)
    • Hypokalemia (low levels of potassium in the blood)
    • Heart arrhythmia

    Very rare (up to 1 in 10,000 people)

    Other

    With high doses for a long period of time.

    Allergic reaction

    • Angioedema (swelling of the face, mouth, tongue, and/or throat. Difficulty swallowing. Hives. Difficulty breathing. Feeling of faintness)
    • Bronchospasm (sudden acute wheezing or shortness of breath immediately after use of medication. The patient should use their reliever medication immediately.)[17]

    Society and culture

    Cost

    In the United States, as of 2017, the wholesale cost of an inhaler is about US$30.[10] In the United Kingdom, the cost as of 2015, was about GB£35 for a unit with 120 doses.[11] In 2017, it was the 74th most commonly prescribed medication in the United States, with more than ten million prescriptions.[12][13]

    • Costs (US)
      Costs (US)
    • Prescriptions (US)
      Prescriptions (US)

    Formulations

    Unopened Symbicort Turbuhaler (left) and opened (middle and right)

    Symbicort in the United States is a metered-dose inhaler and is available in 160/4.5mcg and 80/4.5mcg per actuation.

    In the European Union, Australia, Canada, Israel, Saudi Arabia and elsewhere the combination is available as a dry powder inhaler in the following doses: 50/3 (40/2.25), 100/3 (80/2.25), 100/6 (80/4.5), 200/6 (160/4.5) and 400/12 (320/9), where the larger number is the dose per actuation of budesonide (in micrograms) and the lower number the dose of formoterol (also in micrograms).

    Market

    Budesonide/formoterol formulation was introduced in Sweden in 2000. It was approved for use in the United States in July 2006.[8][18] It is now approved for use in at least 70 countries, yielding global sales in excess of $1 billion in 2005, and now approximately $3.7 billion per annum.

    Budesonide/formoterol was approved for use in the European Union in April 2014.[19][20]

    There are several patents related to the drug; some of them are already expired.[21] It was initially marketed by AstraZeneca.

    References

    1. 1 2 3 "Budesonide / formoterol (Symbicort) Use During Pregnancy". Drugs.com. 28 August 2019. Archived from the original on 18 December 2019. Retrieved 13 April 2020.
    2. 1 2 3 4 5 6 7 8 9 "Symbicort- budesonide and formoterol fumarate dihydrate aerosol". DailyMed. 24 July 2019. Archived from the original on 24 November 2020. Retrieved 29 April 2020.
    3. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 1 July 2021. Retrieved 11 September 2020.
    4. ↑ "Symbicort Turbohaler 200/6 Inhalation powder - Summary of Product Characteristics (SmPC)". (emc). 30 August 2019. Archived from the original on 6 August 2020. Retrieved 13 April 2020.
    5. 1 2 3 Jenkins, CR; Bateman, ED; Sears, MR; O'Byrne, PM (31 March 2020). "What have we learnt about asthma control from trials of budesonide/formoterol as maintenance and reliever?". Respirology (Carlton, Vic.). doi:10.1111/resp.13804. PMID 32237004.
    6. ↑ "Safety Alerts for Human Medical Products - Long-Acting Beta agonists (LABAs) and Inhaled Corticosteroids (ICS): Drug Safety Communication - Boxed Warning About Asthma-Related Death Removed". FDA. Archived from the original on 25 April 2018. Retrieved 23 December 2017.
    7. ↑ "Global Strategy for Asthma Management and Prevention" (PDF). Ginasthma.org. 2020. p. 90. Archived (PDF) from the original on 19 May 2020. Retrieved 9 May 2020. evidence for safety of usual doses of ICS and LABA
    8. 1 2 "Drug Approval Package: Symbicort (budesonide/formoterol fumarate dihydrate) NDA #021929". U.S. Food and Drug Administration (FDA). 30 October 2008. Archived from the original on 13 April 2021. Retrieved 29 April 2020.
    9. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    10. 1 2 "NADAC as of 2017-12-13". Centers for Medicare and Medicaid Services. Archived from the original on 14 December 2017. Retrieved 13 December 2017.
    11. 1 2 British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 202. ISBN 9780857111562.
    12. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on 12 February 2021. Retrieved 11 April 2020.
    13. 1 2 "Budesonide; Formoterol - Drug Usage Statistics". ClinCalc. Archived from the original on 11 April 2020. Retrieved 11 April 2020.
    14. ↑ Lasserson, Toby J; Ferrara, Giovanni; Casali, Lucio (7 December 2011). Cochrane Airways Group (ed.). "Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children". Cochrane Database of Systematic Reviews (12): CD004106. doi:10.1002/14651858.CD004106.pub4. PMID 22161385.
    15. 1 2 Kew KM, Karner C, Mindus SM, Ferrara G, et al. (Cochrane Airways Group) (December 2013). "Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children". The Cochrane Database of Systematic Reviews (12): CD009019. doi:10.1002/14651858.CD009019.pub2. PMID 24343671.
    16. 1 2 3 Sobieraj DM, Weeda ER, Nguyen E, Coleman CI, White CM, Lazarus SC, et al. (April 2018). "Association of Inhaled Corticosteroids and Long-Acting β-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma: A Systematic Review and Meta-analysis". JAMA. 319 (14): 1485–1496. doi:10.1001/jama.2018.2769. PMC 5876810. PMID 29554195.
    17. ↑ "PACKAGE LEAFLET:INFORMATION FOR THE USER Symbicort® Turbohaler® 200 micrograms/6 micrograms/inhalation, inhalation powder budesonide, formoterol fumarate dihydrate" (PDF). hpra.ie - Health Products Regulatory Authority (Irish state agency). July 2015. Archived (PDF) from the original on 9 August 2018.
    18. ↑ Haber, Gary (19 November 2006). "AstraZeneca banking on asthma inhaler". Delaware News-Journal (delawareonline). Archived from the original on 30 September 2007. Retrieved 9 July 2020.
    19. ↑ "BiResp Spiromax EPAR". European Medicines Agency (EMA). Archived from the original on 12 August 2020. Retrieved 29 April 2020.
    20. ↑ "DuoResp Spiromax EPAR". European Medicines Agency (EMA). Archived from the original on 12 November 2020. Retrieved 29 April 2020.
    21. ↑ "Has a generic version of Symbicort been approved?". Drugs.com. Archived from the original on 18 December 2019. Retrieved 23 January 2018.
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