Clinical data | |
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Trade names | Pulmicort, Rhinocort, Entocort, others |
Other names | BUD |
AHFS/Drugs.com | Monograph |
MedlinePlus | a608007 |
License data |
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Pregnancy category |
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Routes of administration | By mouth, nasal, tracheal, rectal, inhalation |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | 10-20% (first pass effect) |
Protein binding | 85-90% |
Metabolism | Liver CYP3A4 |
Elimination half-life | 2.0-3.6 hours |
Excretion | Urine, feces |
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CAS Number | |
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DrugBank | |
ChemSpider | |
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ChEMBL | |
PDB ligand | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.051.927 |
Chemical and physical data | |
Formula | C25H34O6 |
Molar mass | 430.541 g·mol−1 |
3D model (JSmol) | |
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Budesonide, sold under the brand name Pulmicort, among others, is a steroid medication. [8] It is available as an inhaler, nebulization solution, pill, nasal spray, and rectal forms. [8] [9] The inhaled form is used in the long-term management of asthma and chronic obstructive pulmonary disease (COPD). [8] [10] [11] The nasal spray is used for allergic rhinitis and nasal polyps. [9] [12] Modified-release pills or capsules and rectal forms may be used for inflammatory bowel disease including Crohn's disease, ulcerative colitis, and microscopic colitis. [13] [14] [15]
Common side effects with the inhaled form include respiratory infections, cough, and headaches. [16] Common side effects with the pills include feeling tired, vomiting, and joint pains. [16] Serious side effects include an increased risk of infection, loss of bone strength, and cataracts. [16] Long-term use of the pill form may cause adrenal insufficiency. [16] Stopping the pills suddenly following long-term use may therefore be dangerous. [16] The inhaled form is generally safe in pregnancy. [16] Budesonide chiefly acts as a glucocorticoid. [16]
Budesonide was initially patented in 1973. [17] Commercial use as an asthma medication began in 1981. [18] It is on the World Health Organization's List of Essential Medicines. [19] Some forms are available as a generic medication. [20] [21] In 2022, it was the 177th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [22] [23]
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. [24]
Formulations of delayed-release budesonide are an effective treatment for mild-to-moderately active Crohn's disease involving the ileum and/or ascending colon. [25] 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. [26]
Budesonide assists in the induction of remission in people with active ulcerative colitis. [27]
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. [28] [29]
Budesonide in the form of nasal sprays is a treatment for allergic rhinitis. [30]
Topical budesonide has considerable effects in eosinophilic esophagitis. [31] For this use, it is formulated as a tablet that disperses in the mouth, and sold under the brand name Jorveza. [32]
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] [33] [7]
Nasal budesonide inhalers have been associated with a number of side effects. [34] [35] 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. [36] 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). [34]
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 can cause systemic toxicity that manifests as hypercortisolism. [37] 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. [38] [39]
Budesonide is contraindicated in people with:
In Canada, there are additional contraindications labeled for Budesonide for people with:
Budesonide is mainly metabolized in the liver by the enzyme CYP3A4. [37] [42] Drugs that are CYP3A4 inhibitors such as ketoconazole, clarithromycin, ritonavir, and nefazodone, among many others, may inhibit the metabolism of Budesonide, prolonging its elimination and leading to possible increased rates of corticosteroid adverse effects due to unwanted drug accumulation. [37] [43] Grapefruit is also a potent inhibitor of CYP3A4, and therefore its consumption is not recommended while on budesonide treatment. [37] [44]
Budesonide is an agonist of glucocorticoid receptors. Among its effects are:
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. [48] 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. [49] 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. [49] [50] When nebulized, budesonide has an bioavailability of 6% and reaches Cmax within 1–3 hours. [50] [49] When formulated as a rectal foam, budesonide has an bioavailability of 3% to 27% and reaches Cmax around 1.5 hours. [51]
The plasma protein binding of budesonide is around 85-90%, with an apparent volume of distribution of 2.2-3.9L/kg. [49] [48] 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. [49] 60% of budesonide is excreted is through the urine as its metabolites, no unchanged budesonide is detectable in urine. [49] The average elimination half-life in plasma is between 2-3.6 hours. [49]
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. [52] [53] It is the C16α hydroxyl, C16α,17α cyclic ketal with butyraldehyde derivative of prednisolone (11β,17α,21-trihydroxypregna-1,4-diene-3,20-dione). [52] [53]
Budesonide (2 stereoisomers) | |
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(22R)-configuration | (22S)-configuration |
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. [54] [55]
Systemic (oral pills): Tarpeyo, Uceris, Eohilia, Cortiment, Entocort Jorveza. [56] [55]
Nasal: MYLAN-Budesonide AQ, Rhinocort Aqua, Formancis. [57] [55]
In 2019, 44 US states filed a lawsuit claiming that leading drug companies including Teva, Pfizer, Novartis and Mylan conspired to inflate the prices of over a hundred generic drugs, including budesonide, as much as tenfold. [59]
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, [60] was approved for medical use in the European Union in July 2022. [7] [61]
The FDA granted the application breakthrough therapy designation. [62]
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. [63] 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. [64] [65] 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. [66] [67] Inhalational budesonide was added to the recommended treatment for cases of COVID-19 in India in April 2021. [68] [69] The NIH recommendation was withdrawn in December 2021 citing the need for more research. [70] [71]
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.
Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist that causes relaxation of airway smooth muscle. It is used to treat asthma, including asthma attacks and exercise-induced bronchoconstriction, as well as chronic obstructive pulmonary disease (COPD). It may also be used to treat high blood potassium levels. Salbutamol is usually used with an inhaler or nebulizer, but it is also available in a pill, liquid, and intravenous solution. Onset of action of the inhaled version is typically within 15 minutes and lasts for two to six hours.
Ipratropium bromide, sold under the brand name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.
Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting tobacco smoking by about 55%. Often it is used along with other behavioral techniques. NRT has also been used to treat ulcerative colitis. Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler. The use of multiple types of NRT at a time may increase effectiveness.
Salmeterol is a long-acting β2 adrenergic receptor agonist (LABA) used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms. Symptoms of bronchospasm include shortness of breath, wheezing, coughing and chest tightness. It is also used to prevent breathing difficulties during exercise.
Budesonide/formoterol, sold under the brand name Symbicort among others, is a fixed-dose combination medication used in the management of asthma or chronic obstructive pulmonary disease (COPD). It contains budesonide, a steroid; and formoterol, a long-acting β2-agonist (LABA). The product monograph does not support its use for sudden worsening or treatment of active bronchospasm. However, a 2020 review of the literature does support such use. It is used by breathing in the medication.
Formoterol, also known as eformoterol, is a long-acting β2 agonist (LABA) used as a bronchodilator in the management of asthma and chronic obstructive pulmonary disease (COPD). Formoterol has an extended duration of action compared to short-acting β2 agonists such as salbutamol (albuterol), which are effective for 4 h to 6 h. Formoterol has a relatively rapid onset of action compared to other LABAs, and is effective within 2-3 minutes. The 2022 Global Initiative for Asthma report recommends a combination formoterol/inhaled corticosteroid inhaler as both a preventer and reliever treatment for asthma in adults. In children, a short-acting β2 adrenergic agonist is still recommended.
Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate, or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the release of inflammatory chemicals such as histamine from mast cells.
An inhaler is a medical device used for delivering medicines into the lungs through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which provides the ability for targeted medical treatment to this specific region of the body, as well as a reduction in the side effects of oral medications. There are a wide variety of inhalers, and they are commonly used to treat numerous medical conditions with asthma and chronic obstructive pulmonary disease (COPD) being among the most notable.
Glycopyrronium bromide is a medication of the muscarinic anticholinergic group. It does not cross the blood–brain barrier and consequently has few to no central effects. It is given by mouth, via intravenous injection, on the skin, and via inhalation. It is a synthetic quaternary ammonium compound. The cation, which is the active moiety, is called glycopyrronium (INN) or glycopyrrolate (USAN).
Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.
Fluticasone propionate, sold under the brand names Flovent and Flonase among others, is a glucocorticoid steroid medication. When inhaled it is used for the long term management of asthma and COPD. In the nose it is used for hay fever and nasal polyps. It can also be used for mouth ulcers. It works by decreasing inflammation.
A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs in the form of a short burst of aerosolized medicine that is usually self-administered by the patient via inhalation. It is the most commonly used delivery system for treating asthma, chronic obstructive pulmonary disease (COPD) and other respiratory diseases. The medication in a metered dose inhaler is most commonly a bronchodilator, corticosteroid or a combination of both for treating asthma and COPD. Other medications less commonly used but also administered by MDI are mast cell stabilizers, such as cromoglicate or nedocromil.
Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol or salbutamol-levosalbutamol combinations, though levosalbutamol is believed to have a better safety profile due to its more selective binding to β2 receptors versus β1.
Azelastine, sold under the brand name Astelin among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis. Other uses may include asthma and skin rashes for which it is taken by mouth. Onset of effects is within minutes when used in the eyes and within an hour when used in the nose. Effects last for up to 12 hours.
Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD). It is delivered as an aerosol formulation through a dry powder inhaler.
Fluticasone furoate, sold under the brand name Flonase Sensimist among others, is a corticosteroid for the treatment of non-allergic and allergic rhinitis administered by a nasal spray. It is also available as an inhaled corticosteroid to help prevent and control symptoms of asthma. It is derived from cortisol. Unlike fluticasone propionate, which is only approved for children four years and older, fluticasone furoate is approved in children as young as two years of age when used for allergies.
Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator used in the management of chronic obstructive pulmonary disease (COPD) and asthma. Specifically it is used during periods of breathing difficulty to prevent them from getting worse, rather than to prevent them from happening. It is used by inhalation through the mouth. Onset typically begins within half an hour and lasts for 24 hours.
Fluticasone furoate/umeclidinium bromide/vilanterol, sold under the brand name Trelegy Ellipta among others, is a fixed-dose combination inhaled medication that is used for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The medications work in different ways: fluticasone furoate is an inhaled corticosteroid (ICS), umeclidinium is a long-acting muscarinic antagonist (LAMA), and vilanterol is a long-acting beta-agonist (LABA).
Salbutamol/budesonide, sold under the brand name Airsupra, is a fixed-dose combination medication for the treatment of bronchoconstriction and asthma. It is a combination of salbutamol sulfate, a short-acting beta2-adrenergic agonist, and budesonide, an inhaled corticosteroid. It is inhaled using a pressurized metered-dose inhaler.