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Beclometasone
View on Wikipediafrom Wikipedia
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| Clinical data | |
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| Trade names | Vanceril, others |
| Other names | Beclometasone dipropionate; beclomethasone dipropionate, beclomethasone (USAN US) |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a681047 |
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| Routes of administration | Inhalation, nasal, topical |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.024.442 |
| Chemical and physical data | |
| Formula | C22H29ClO5 |
| Molar mass | 408.92 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 117 to 120 °C (243 to 248 °F) (dec.) |
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Beclometasone or beclomethasone, sold under the brand name Vanceril among others, is a steroid medication.[5] It is available as an inhaler, cream, pills, and nasal spray.[6] The inhaled form is used in the long-term management of asthma.[5] The cream may be used for dermatitis and psoriasis.[7] The pills have been used to treat ulcerative colitis.[8] The nasal spray is used to treat allergic rhinitis and nasal polyps.[9]
Common side effects with the inhaled form include respiratory infections, headaches, and throat inflammation.[5] Serious side effects include an increased risk of infection, cataracts, Cushing's syndrome, and severe allergic reactions.[5] Long-term use of the pill form may cause adrenal insufficiency.[8] The pills may also cause mood or personality changes.[8] The inhaled form is generally regarded as safe in pregnancy.[10] Beclometasone is a glucocorticoid.[5]
Beclomethasone, as beclomethasone dipropionate, was first patented in 1962 and used medically in 1972.[11] It was approved for medical use in the United States in 1976.[5] It is a therapeutic alternative on the World Health Organization's List of Essential Medicines.[12] In 2023, it was the 351st most commonly prescribed medication in the United States, with more than 51,000 prescriptions.[13]
Medical uses
[edit]Beclometasone is indicated for maintenance treatment of asthma as prophylactic therapy;[2] for the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis;[3] and the relief of the symptoms of seasonal or perennial allergic and nonallergic (vasomotor) rhinitis.[4]
Side effects
[edit]Common side effects with the inhaled form include respiratory infections, headaches, and throat inflammation.[5] Serious side effects include an increased risk of infection, cataracts, Cushing's syndrome, and severe allergic reactions.[5] Long-term use of the pill form may cause adrenal insufficiency.[8] The pills may also cause mood or personality changes.[8] The inhaled form is generally regarded as safe in pregnancy.[10]
Occasionally, it may cause a cough upon inhalation. Deposition on the tongue and throat may promote oral candidiasis, which appears as a white coating, possibly with irritation.[14][15][16]
Nasal corticosteroids may be associated with central serous retinopathy.[17]
Pharmacology
[edit]Beclometasone is a glucocorticoid.[5] Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor[18] that is present in almost every vertebrate animal cell. The activated glucocorticoid receptor-glucocorticoid complex up-regulates the expression of anti-inflammatory proteins in the nucleus (a process known as transactivation) and represses the expression of proinflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus (transrepression).[19]
Society and culture
[edit]Names
[edit]Beclometasone dipropionate is the international nonproprietary name modified and beclomethasone dipropionate is the United States Adopted Name and former British Approved Name. It is a prodrug of the free form, beclometasone (INN). The prodrug beclometasone is marketed in Norway and Russia.[20][21][22][23][24]
Clenil, Qvar, Cortis are brand names for the inhalers; Beconase, Alanase, Vancenase, Qnasl for the nasal spray or aerosol.
References
[edit]- ^ "Therapeutic Goods (Poisons Standard— June 2025) Instrument 2025" (pdf). Therapeutic Goods Administration (TGA). May 2025. Retrieved 31 August 2025.
- ^ a b "Qvar Redihaler- beclomethasone dipropionate hfa aerosol, metered". DailyMed. 20 August 2025. Retrieved 1 September 2025.
- ^ a b "Qnasl- beclomethasone dipropionate aerosol, metered; Qnasl- beclomethasone dipropionate aerosol, metered". DailyMed. 27 September 2022. Retrieved 5 September 2025.
- ^ a b "Beconase- beclomethasone dipropionate monohydrate spray, suspension". DailyMed. 8 September 2010. Retrieved 5 September 2025.
- ^ a b c d e f g h i "Beclomethasone Dipropionate". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 2 December 2015.
- ^ "List of products: Beclometasone dipropionate". MHRA. Archived from the original on 8 December 2015. Retrieved 6 December 2015.
- ^ "Beclometasone dipropionate 0.25 mg/g Cream" (PDF). MHRA. Archived from the original (PDF) on 8 December 2015. Retrieved 6 December 2015.
- ^ a b c d e "Clipper" (PDF). MHRA. Archived from the original (PDF) on 8 December 2015. Retrieved 6 December 2015.
- ^ "Beclomethasone Dipropionate eent". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 2 December 2015.
- ^ a b Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 349. ISBN 9781284057560.
- ^ McPherson EM (2007). "Beclomethasone dipropionate". Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Burlington: Elsevier. p. 539. ISBN 9780815518563. Archived from the original on 8 December 2015.
- ^ World Health Organization (2025). The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization. hdl:10665/382243.
- ^ "Beclomethasone Drug Usage Statistics, United States, 2014 - 2023". ClinCalc. Retrieved 17 August 2025.
- ^ Willey RF, Milne LJ, Crompton GK, Grant IW (January 1976). "Beclomethasone dipropionate aerosol and oropharyngeal candidiasis". British Journal of Diseases of the Chest. 70 (1): 32–38. doi:10.1016/0007-0971(76)90004-8. PMID 1259918.
- ^ Salzman GA, Pyszczynski DR (February 1988). "Oropharyngeal candidiasis in patients treated with beclomethasone dipropionate delivered by metered-dose inhaler alone and with Aerochamber". The Journal of Allergy and Clinical Immunology. 81 (2): 424–428. doi:10.1016/0091-6749(88)90911-6. PMID 3339197.
- ^ Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, et al. (June 2003). "Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone". Annals of Allergy, Asthma & Immunology. 90 (6): 646–651. doi:10.1016/S1081-1206(10)61870-4. PMID 12839324.
- ^ Haimovici R, Gragoudas ES, Duker JS, Sjaarda RN, Eliott D (October 1997). "Central serous chorioretinopathy associated with inhaled or intranasal corticosteroids". Ophthalmology. 104 (10): 1653–1660. doi:10.1016/s0161-6420(97)30082-7. PMID 9331207.
- ^ Pelt AC (2011). Glucocorticoids: effects, action mechanisms, and therapeutic uses. Hauppauge, N.Y.: Nova Science. ISBN 978-1617287589.
- ^ Rhen T, Cidlowski JA (October 2005). "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs". The New England Journal of Medicine. 353 (16): 1711–1723. doi:10.1056/NEJMra050541. PMID 16236742. S2CID 5744727.
- ^ Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 123–. ISBN 978-1-4757-2085-3.
- ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 95–. ISBN 978-3-88763-075-1.
- ^ Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 46–. ISBN 978-94-011-4439-1. Archived from the original on 12 January 2023. Retrieved 17 March 2019.
- ^ Muller NF, Dessing RP, eds. (19 June 1998). European Drug Index: European Drug Registrations (Fourth ed.). CRC Press. pp. 141–. ISBN 978-3-7692-2114-5. Archived from the original on 12 January 2023. Retrieved 17 March 2019.
- ^ "Beclometasone". drugs.com. Archived from the original on 18 January 2018. Retrieved 17 March 2019.
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Beclometasone
View on Grokipediafrom Grokipedia
Medical uses
Respiratory conditions
Beclometasone dipropionate, when administered by inhalation, is primarily utilized as an inhaled corticosteroid for the maintenance therapy of mild to moderate persistent asthma in adults and children aged 4 years and older. This prophylactic approach helps prevent asthma symptoms such as wheezing, chest tightness, and coughing by targeting chronic airway inflammation, rather than providing immediate relief during acute attacks.[11][12] Clinical evidence supports its efficacy in improving lung function and reducing the frequency of exacerbations when used regularly as a controller medication.[13] The Global Initiative for Asthma (GINA) guidelines recommend low-dose inhaled corticosteroids, including beclometasone, as first-line controller therapy for patients with persistent asthma symptoms, emphasizing their role in achieving long-term disease control and minimizing the risk of severe exacerbations.[14] This recommendation is based on extensive evidence showing that regular ICS use markedly reduces asthma-related morbidity compared to short-acting beta-agonists alone.[15] In chronic obstructive pulmonary disease (COPD), inhaled beclometasone is employed for patients with a reversible component to their airflow obstruction, aiding in the prevention of bronchospasm and the reduction of airway inflammation to improve symptoms and pulmonary function.[8] Systematic reviews indicate that, while evidence for monotherapy is limited, beclometasone contributes to better outcomes in selected COPD cases, particularly when combined with bronchodilators.[16] Hydrofluoroalkane (HFA)-propelled formulations of beclometasone, such as Qvar, demonstrate superior lung deposition—approximately 53% of the actuator dose reaching the lungs—compared to chlorofluorocarbon (CFC)-based versions, which achieve only about 4-13% deposition, thereby enhancing therapeutic efficacy at lower nominal doses.[17] This improved delivery profile supports its targeted action on lower respiratory tract inflammation.[18]Nasal conditions
Beclometasone nasal spray is indicated for the treatment of seasonal and perennial allergic rhinitis, where it reduces nasal inflammation, congestion, sneezing, and itching through its glucocorticoid anti-inflammatory effects.[19] Clinical trials have demonstrated significant efficacy, with improvements in reflective total nasal symptom scores (rTNSS) and instantaneous total nasal symptom scores (iTNSS) observed over 30 to 52 weeks compared to placebo, providing clinically meaningful relief starting within 3 days of initiation.[20][21] The recommended starting dose is 1 to 2 sprays (42 mcg each) in each nostril twice daily for adults and children 12 years and older (totaling 168-336 mcg per day), or 2 sprays (80 mcg each) in each nostril once daily (320 mcg per day) for HFA formulations; for children 4 to 11 years, 1 spray (80 mcg) in each nostril once daily (80 mcg per day), with symptom relief often requiring consistent use for up to 2 weeks.[22][21] In the management of nasal polyps in adults, beclometasone nasal spray serves as monotherapy or adjunctive therapy to reduce polyp size and alleviate associated symptoms such as obstruction and rhinorrhea.[19] Randomized controlled trials have shown significant reductions in polyp scores using the Lund-Mackay system and improvements in sino-nasal outcome test-22 (SNOT-22) scores, indicating better nasal airflow and quality of life after 6 months of treatment at doses around 200 mcg daily in specific studies.[23] The starting dose is typically 1 to 2 sprays (42-84 mcg each) in each nostril twice daily, totaling 168-336 mcg per day, with treatment often continued for several weeks to achieve and maintain benefits, particularly post-surgically to prevent recurrence.[24][19]Dermatological uses
Beclomethasone dipropionate is formulated as a topical cream or ointment at a concentration of 0.025% w/w for treating inflammatory skin disorders, including eczema, psoriasis, and dermatitis, where it effectively alleviates itching, redness, and scaling through its anti-inflammatory action.[25][26] Classified as a potent corticosteroid (potency class II in UK guidelines), it exhibits strong vasoconstrictive activity, approximately 50-100 times that of hydrocortisone in human skin tests, making it suitable for moderate to severe lesions but requiring cautious use to prevent adverse effects like skin atrophy.[27][25][28] Treatment is intended for short-term application, generally limited to up to 4 weeks on the body or 1-2 weeks on sensitive areas like the face, with discontinuation or tapering upon symptom improvement to avoid prolonged exposure.[29][30] A thin layer of the cream or ointment should be applied to the affected areas 1 to 3 times daily, gently massaged in until absorbed, depending on lesion severity; patients are advised to monitor response, typically visible within days, and consult a healthcare provider if no improvement occurs after 7-14 days.[25][26] Clinical evidence from dermatology studies underscores its efficacy in atopic dermatitis; for instance, a 1984 trial involving children with atopic eczema found beclomethasone dipropionate cream produced significant symptom reduction comparable to other potent corticosteroids, with good tolerability.[31]Other uses
Beclometasone dipropionate in oral tablet form has been utilized for managing flare-ups of mild to moderate ulcerative colitis, leveraging its localized anti-inflammatory effects in the gastrointestinal tract while minimizing systemic exposure due to its topical action.[32] Clinical studies have demonstrated its efficacy in inducing remission and clinical improvement, often as an add-on therapy or alternative to other treatments, with a favorable safety profile compared to systemic corticosteroids.[33][34] Off-label applications of beclometasone extend to other inflammatory bowel diseases, such as Crohn's ileitis, where it has shown potential in reducing relapse rates post-remission through its gut-targeted anti-inflammatory properties.[35] In broader inflammatory bowel disease management, it is prescribed off-label in approximately 12% of cases, particularly when systemic effects need to be limited. Additionally, beclometasone inhaler, used off-label as an oral spray, serves as a first-line topical treatment option for oral lichen planus, helping to alleviate mucosal inflammation and symptoms in primary care settings.[37][38] Limited evidence supports the use of swallowed beclomethasone (typically from inhalers) for eosinophilic esophagitis, where pilot studies indicate it reduces esophageal eosinophilia and inflammatory markers like mast cell tryptase and interleukin-13, positioning it as a potential topical corticosteroid option.[39][40] Oral administration of beclometasone remains relatively uncommon overall, primarily due to concerns over potential systemic absorption and associated corticosteroid risks, though its formulation aims to mitigate these issues.[41]Administration and dosage
Inhalation
Beclometasone dipropionate is administered via oral inhalation for maintenance therapy in asthma, using devices such as metered-dose inhalers (MDIs) or breath-actuated inhalers.[11] The starting dose for adults with no prior inhaled corticosteroid (ICS) use is typically 40 to 80 mcg twice daily, while those previously on ICS may require 40 to 160 mcg twice daily, titrated based on asthma control.[42] For severe cases, doses up to 320 mcg twice daily may be used, with the goal of stepping down to the lowest effective dose after stability is achieved.[43] In children aged 4 to 11 years, the initial dose is 40 mcg twice daily, which can be increased to 80 mcg twice daily after 2 weeks if response is inadequate, not exceeding 160 mcg daily.[42][13] Administration techniques vary by device type. For standard MDIs, the inhaler should be shaken vigorously for 5 to 10 seconds before each use to ensure proper mixing of the suspension, followed by actuation during a slow, deep inhalation.[44] Breath-actuated inhalers, such as the Qvar RediHaler, do not require shaking or manual pressing; instead, the patient opens the cap, exhales fully away from the device, seals lips around the mouthpiece, and inhales forcefully to trigger release.[45] Regardless of device, patients should rinse their mouth with water and spit after each use to minimize the risk of oral candidiasis (thrush).[46] Dose adjustments are necessary when switching between formulations due to differences in particle size and lung deposition. Extrafine particle formulations like Qvar (with particles <2 μm) achieve higher lung deposition, requiring approximately half the nominal dose of standard particle beclometasone (e.g., 100 mcg extrafine equivalent to 200 mcg standard) for comparable efficacy.[47] This equivalence supports lower overall exposure while maintaining therapeutic benefits in respiratory conditions such as asthma.[48]Nasal administration
Beclometasone nasal spray is administered intranasally to deliver the medication directly to the nasal mucosa. For adults treating rhinitis, the recommended dose is 1 to 2 sprays (typically 40 to 80 mcg per spray, depending on the formulation) per nostril once or twice daily, with a maximum total daily dose of 400 mcg.[49][50] For children 6 to 12 years, the starting dose is 1 spray (42 mcg) per nostril twice daily (total 168 mcg/day); this may be increased to 2 sprays per nostril twice daily (total 336 mcg/day) if inadequate response, then reduced to the lowest effective dose once controlled.[51] For nasal polyps, the dose may be increased up to 336 mcg daily as adjunctive therapy, with tapering to the lowest effective dose once symptoms are controlled.[50][51][24] Proper administration begins with gently shaking the bottle to ensure even suspension of the medication. The pump should be primed by actuating it several times (usually 5 to 6 times for new bottles or after prolonged non-use) until a fine mist is produced, directing the spray away from the face. To apply, the user gently blows their nose to clear the nostrils, tilts their head slightly forward, inserts the nozzle into one nostril while closing the other with a finger, and aims the spray toward the outer wall of the nostril (away from the septum) to minimize irritation. While breathing in gently through the nose, the pump is pressed firmly to release the spray, followed by breathing out through the mouth; this process is repeated for the second spray if required, then for the other nostril. The nozzle should be wiped clean and the cap replaced after use.[49][50] Treatment duration for perennial rhinitis involves continuous use as needed to maintain symptom control, often for several months, while for seasonal rhinitis, it is adjusted based on allergen exposure, typically starting 1 to 2 weeks before symptoms and continuing up to 3 months or until symptoms resolve. Beclometasone nasal spray has demonstrated efficacy in reducing inflammation associated with rhinitis when used as directed.[49][50]Topical application
Beclometasone dipropionate is applied topically as a cream or ointment to treat inflammatory skin conditions. The recommended dose is to apply a thin film to the affected area 1 to 2 times daily, without exceeding 30% of the body surface area to reduce the risk of systemic effects.[52][26] Ointments are typically selected for dry or scaly skin because their thicker, greasier base provides better occlusion and moisture retention, whereas creams are more appropriate for moist or weeping lesions due to their lighter, water-based formulation that absorbs quickly.[53][54] For resistant cases, occlusion techniques—such as covering the treated area with plastic film or dressings after application—may be employed intermittently to enhance drug absorption, but only as directed by a healthcare provider to avoid excessive exposure.[26][54] Ongoing monitoring is essential, with weekly reassessment recommended to evaluate response, adjust treatment if needed, and limit duration to the shortest effective period.[26][54]Oral use
Oral beclometasone dipropionate is administered orally for the management of mild to moderate ulcerative colitis, particularly as adjunctive therapy to 5-aminosalicylic acid agents in cases unresponsive to monotherapy.[55] The formulation consists of enteric-coated tablets designed to resist gastric acid and release the active drug primarily in the distal ileum and colon, thereby maximizing local anti-inflammatory effects while minimizing systemic absorption.[56] For mild to moderate active disease, the standard dosing is 5 mg once daily for 4 to 8 weeks, with tapering as needed. In refractory cases unresponsive to standard doses, higher regimens such as 5 mg three times daily (totaling 15 mg daily) for 4 weeks may be used, followed by gradual tapering to prevent relapse and reduce potential systemic risks.[57][34] Tablets should be taken with food to help mitigate gastrointestinal upset.[34] Treatment is restricted to short courses, generally 4 to 8 weeks, owing to the risk of systemic corticosteroid adverse effects such as hypothalamic-pituitary-adrenal axis suppression, despite the drug's low bioavailability.[58]Contraindications and precautions
Absolute contraindications
Beclometasone is absolutely contraindicated in individuals with a known hypersensitivity to the active ingredient or any excipients in the formulation, as this can precipitate severe allergic reactions including anaphylaxis.[13][19] The drug must not be employed as the primary therapy for status asthmaticus or other acute asthma exacerbations that demand intensive interventions, such as systemic corticosteroids, oxygen, or parenteral bronchodilators, since inhaled or topical beclometasone lacks the rapid onset required for such emergencies.[59][60] Untreated systemic infections, including fungal, bacterial, or viral etiologies such as active tuberculosis, represent an absolute contraindication, as beclometasone's immunosuppressive effects can worsen the infection and promote dissemination, particularly in cases of significant systemic absorption.[61][62] In patients receiving high doses of beclometasone, recent administration of live virus vaccines is contraindicated due to the heightened risk of vaccine-related disseminated infections stemming from impaired immune response.[63][62]Relative precautions
Beclometasone, particularly when administered via inhalation or intranasally, should be used with caution in patients with active or quiescent tuberculosis infections of the respiratory tract, and only if appropriate anti-tuberculosis therapy is in place to mitigate risks of exacerbation.[64][19] In patients with hepatic impairment, beclometasone metabolism may be altered, leading to increased systemic exposure; such individuals require close monitoring for signs of enhanced glucocorticoid or mineralocorticoid effects, with dose reduction considered if necessary.[65][64] Individuals at risk for osteoporosis, such as those with prolonged immobilization, family history, or postmenopausal status, should undergo regular monitoring of bone mineral density during long-term beclometasone therapy to detect any corticosteroid-induced decreases.[64] Similarly, patients with a history of glaucoma or increased intraocular pressure warrant periodic ophthalmologic evaluation to monitor for potential elevations in pressure or disease progression.[19][64] There are no adequate and well-controlled studies of beclomethasone in pregnant women. Animal reproduction studies have shown adverse developmental effects at doses approximately 0.75 times the maximum recommended human daily inhalation dose or greater. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus, with monitoring of fetal growth recommended during prolonged exposure.[13][66] Due to variable systemic absorption depending on the route and formulation, precautions are heightened in these scenarios to minimize potential impacts.[64] There are no available data on the presence of beclomethasone in human milk. Other inhaled corticosteroids have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for beclomethasone and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.[13]Side effects
Local effects
Local effects of beclometasone primarily manifest at the site of administration and are generally mild to moderate, often related to the drug's corticosteroid properties that can alter mucosal or skin integrity with prolonged use.[59] When administered via inhalation for asthma management, common local adverse reactions include oral candidiasis (thrush), characterized by white patches and soreness in the mouth or throat, occurring in less than 1% of patients in clinical trials. Hoarseness or dysphonia affects less than 1% of users, while cough is reported in 1-3% of cases, typically mild and transient. These effects arise from deposition of the aerosol in the oropharynx, and their incidence may increase with higher doses or improper technique; rinsing the mouth with water after each use significantly reduces the risk of oral candidiasis by removing residual drug.[59][59][67] For nasal administration in allergic rhinitis, epistaxis (nosebleeds) is a frequent local effect, with incidences of 1.9% to 11% in adults during short- and long-term trials, often mild but occasionally requiring intervention. Nasal discomfort, including dryness and irritation, occurs in about 5% of users, while septal perforation is rare, reported in fewer than 1% of cases and typically linked to extended high-dose use or pre-existing nasal damage. Proper technique, such as aiming the spray away from the septum, and periodic evaluation can help mitigate these risks.[21][21][21] For oral administration in ulcerative colitis, uncommon local effects include nausea and abdominal pain.[68] Topical application for dermatoses like eczema can lead to site-specific reactions such as skin atrophy (thinning), telangiectasia (visible small blood vessels), and acneiform eruptions, particularly with prolonged or occlusive use, though exact frequencies are not well-established from available data and are considered uncommon when used as directed. These effects result from local suppression of collagen synthesis and vascular changes; mitigation involves limiting treatment duration, avoiding occlusion, and using the lowest effective potency, especially on sensitive areas like the face.[26][26][26]Systemic effects
Systemic effects of beclometasone, a glucocorticoid primarily administered via inhalation, nasal spray, or topical application, arise from its absorption into the bloodstream and are generally minimized due to its low oral bioavailability of less than 1%, which limits systemic exposure.[4] These effects are rare at standard low doses but can occur with prolonged high-dose use or oral administration, potentially impacting multiple organ systems. Long-term use may also decrease bone mineral density, increasing the risk of osteoporosis, particularly at higher doses.[69] Immunosuppression is a notable systemic risk, particularly increasing susceptibility to infections such as pneumonia in patients with chronic obstructive pulmonary disease (COPD) or asthma. For instance, use of inhaled beclometasone has been associated with an adjusted odds ratio of 1.09 for pneumonia or lower respiratory tract infections.[70] Adrenal suppression, manifesting as reduced cortisol production, is uncommon with low-dose inhalation (e.g., ≤400 μg/day) but more frequent at high doses (≥1000 μg/day) or with oral forms, where doses exceeding 2000 μg/day have shown cortisol levels below normal in up to 36% of patients.[71][72] Ocular effects, including cataracts and glaucoma, may develop with long-term use, though the risk remains low. Inhaled beclometasone has been linked to a modest increase in cataract risk, with an adjusted odds ratio of 1.05 (95% CI 0.95–1.16), particularly in elderly patients on prolonged therapy.[70] Metabolic disturbances, such as iatrogenic Cushing's syndrome characterized by weight gain, hypertension, and moon facies, are infrequent but reported in cases of high-dose or combined use, often alongside adrenal suppression.[73] In children, high doses (e.g., 400 μg/day) can lead to growth retardation, with studies showing an average linear growth reduction of 1.54 cm per year during the first year of treatment.[74]Pharmacology
Mechanism of action
Beclometasone dipropionate is a prodrug that undergoes rapid hydrolysis by esterases, primarily in the lung epithelium, to form its active metabolite, 17-beclomethasone monopropionate (17-BMP).[12] This activation step is crucial, as beclometasone dipropionate itself exhibits weak binding affinity to the glucocorticoid receptor, whereas 17-BMP demonstrates high potency with an in vitro affinity approximately 13 times that of dexamethasone and 25 times that of the parent compound.[75][12] Upon activation, 17-BMP binds to the cytoplasmic glucocorticoid receptor (GR), inducing a conformational change that leads to receptor dimerization and translocation to the nucleus. There, the 17-BMP-GR complex interacts with glucocorticoid response elements (GREs) on DNA, modulating gene transcription. A key aspect of its anti-inflammatory action involves the inhibition of pro-inflammatory transcription factors such as nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1), which prevents the activation of inflammatory genes; this also promotes histone deacetylation via recruitment of histone deacetylase complexes, further suppressing transcription.[12] This molecular mechanism results in the downregulation of multiple inflammatory mediators, including cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α), as well as enzymes like phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2). For instance, increased expression of lipocortin-1 (annexin-1), an anti-inflammatory protein induced by the GR complex, inhibits PLA2 activity, thereby reducing arachidonic acid release and subsequent production of prostaglandins and leukotrienes.[12][76] The topical potency of beclometasone dipropionate stems from 17-BMP's high GR affinity, which enables effective local anti-inflammatory effects at low doses, while its low systemic activity is attributed to rapid further metabolism by esterases to the inactive metabolite beclomethasone (BOH), minimizing unwanted glucocorticoid effects elsewhere in the body.[12][76]Pharmacokinetics
Beclometasone dipropionate (BDP), a prodrug, exhibits low systemic absorption following inhalation, with less than 2% bioavailability of the parent compound due to extensive presystemic metabolism in the lungs via esterase hydrolysis to its active metabolite, beclomethasone-17-monopropionate (17-BMP).[4] In contrast, nasal and topical administration result in higher systemic bioavailability of 17-BMP, up to approximately 44%, primarily from the swallowed fraction undergoing gastrointestinal absorption.[12][4] Following absorption, 17-BMP demonstrates high plasma protein binding of 94-96%, with a steady-state volume of distribution of approximately 424 L (~6 L/kg).[4][12][77] BDP is rapidly metabolized in the lungs and liver, initially by esterases to the active 17-BMP, followed by hepatic cytochrome P450 3A4 (CYP3A4) oxidation to inactive metabolites such as beclomethasone-21-monopropionate (less active) and beclomethasone (BOH).[78][12] The elimination half-life of 17-BMP is approximately 2.8 hours after inhaled administration and 7-9 hours after oral administration.[12][77] Excretion of BDP and its metabolites occurs primarily via the fecal route, with less than 10% eliminated in the urine, and no significant accumulation with repeated dosing due to its clearance profile.[77][24]Chemistry
Chemical structure and properties
Beclometasone, also known as beclomethasone, is a synthetic glucocorticoid with the chemical name 9-chloro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione.[79] Its molecular formula is C22H29ClO5, and the molecular weight is 408.92 g/mol.[79] The chlorine atom at the 9α position is a key structural modification that enhances its glucocorticoid potency compared to cortisol by increasing receptor binding affinity and metabolic stability.[80] The commonly used form is beclometasone dipropionate, the di-ester prodrug with the chemical name 9-chloro-11β-hydroxy-16β-methyl-3,20-dioxopregna-1,4-diene-17,21-diyl dipropanoate.[81] This esterification adds two propionyl groups, resulting in the molecular formula C28H37ClO7 and a molecular weight of 521.05 g/mol.[81] The dipropionate form improves lipophilicity, facilitating better pulmonary deposition and local activation in the lungs while minimizing systemic exposure.[81] Beclometasone dipropionate appears as a white to off-white crystalline powder. It has a melting point of approximately 210°C and an octanol-water partition coefficient (logP) of 3.49, indicating moderate lipophilicity.[81] The compound is sparingly soluble in water, with solubility below 0.1 mg/mL at neutral pH, which contributes to its suitability for aerosol and topical formulations.[81]Synthesis
Beclometasone dipropionate, the diester form commonly used in pharmaceuticals, was originally synthesized in the 1960s by researchers at Allen & Hanburys using steroidal precursors derived from natural corticosteroids.[32] One established pathway begins with 16β-methylprednisolone, a key intermediate that undergoes formation of the 9,11-epoxide (known as DB-11). This epoxide is then opened via reaction with hydrochloric acid, introducing a chlorine atom at the C9 position while yielding a hydroxyl group at C11, thereby establishing the core structure of beclometasone.[82][83] Subsequent steps focus on selective esterification of the hydroxyl groups at the C17 and C21 positions using propionic anhydride, often in the presence of triethyl orthopropionate to enhance regioselectivity and minimize over-esterification at C11. This acylation step is critical for forming the dipropionate ester, which improves the compound's lipophilicity and delivery properties.[82][84] A practical and scalable industrial route, refined in recent years, starts directly from the readily available DB-11 epoxide and incorporates the epoxide-opening chlorination followed by the targeted propionylation. The process concludes with alkaline hydrolysis to remove any excess esters and rigorous purification via recrystallization or chromatography, achieving yields of approximately 82% overall and purity exceeding 99% without relying on hazardous reagents like toxic solvents or unstable intermediates. This approach supports kilogram-scale production suitable for pharmaceutical manufacturing.[82]History
Development
Beclometasone dipropionate was first patented in 1962 and developed in the mid-1960s by researchers at Allen & Hanburys, a division of Glaxo Laboratories (now GlaxoSmithKline), during a systematic search for corticosteroids exhibiting potent topical anti-inflammatory activity suitable for inhalation. The compound, patented as a 9-chloro derivative of betamethasone 17,21-dipropionate (US Patent 3,312,590), was engineered to prioritize localized effects in the airways while minimizing absorption into the systemic circulation.[85] In preclinical development, beclometasone was specifically designed for enhanced lung retention and reduced systemic bioavailability, distinguishing it as the first chlorinated steroid optimized for inhaled delivery. This structural modification, involving chlorination at the 9α position, aimed to boost glucocorticoid potency at the site of action while limiting hypothalamic-pituitary-adrenal (HPA) axis suppression, a common issue with earlier systemic corticosteroids. Animal studies confirmed its high topical-to-systemic activity ratio, supporting its potential for safe long-term use in respiratory conditions like asthma.[86] Early clinical trials in the 1970s validated these properties, demonstrating beclometasone's superior efficacy over oral steroids for asthma control without inducing significant HPA suppression. A landmark 1975 double-blind study involving 75 steroid-dependent patients found that inhaled beclometasone dipropionate (400 μg/day) maintained asthma stability equivalently to oral prednisone (14 mg/day) but allowed greater reduction in systemic steroid doses and avoided adrenal insufficiency. Additional trials corroborated these findings, showing improved lung function, reduced symptoms, and minimal systemic side effects compared to oral alternatives.[87] A pivotal milestone occurred in 1972 with the launch of Becotide metered-dose inhaler (MDI) in the United Kingdom by Allen & Hanburys, introducing beclometasone as the first inhaled corticosteroid available for clinical use and transforming asthma management by enabling targeted therapy.[88]Regulatory approvals
Beclometasone dipropionate was first approved for medical use in the United Kingdom in 1972 for inhalation therapy in asthma management, with the Medicines and Healthcare products Regulatory Agency (MHRA) granting initial marketing authorization on 10 October 1972 for the Becotide 50 mcg inhaler developed by Allen & Hanburys (now part of GlaxoSmithKline).[89] In the United States, the Food and Drug Administration (FDA) approved beclometasone dipropionate in 1976 as Vanceril, a chlorofluorocarbon (CFC)-propelled metered-dose inhaler for the maintenance treatment of asthma in patients aged 12 years and older.[90] This approval marked the introduction of the drug for oral inhalation in the US market. Subsequent formulations addressed environmental concerns over ozone-depleting CFCs; the FDA mandated a phase-out of CFC-based metered-dose inhalers by 2010 under the Montreal Protocol, leading to the discontinuation of Vanceril in 2009 and the transition to hydrofluoroalkane (HFA)-propelled alternatives.[91] The first HFA version, Qvar inhalation aerosol, received FDA approval on 15 September 2000 for asthma prophylaxis in adults and children aged 12 years and older, with pediatric indications extended to children aged 5 to 11 years in May 2002 based on safety and efficacy data extrapolated from adult studies.[92][93] Further US approvals expanded beclometasone's applications and delivery options. The nasal aerosol formulation QNASL was approved by the FDA on 23 March 2012 for treating allergic rhinitis in adults and adolescents aged 12 years and older, with an extension to pediatric patients aged 4 to 11 years approved on 17 December 2014 following clinical trials demonstrating efficacy in seasonal and perennial allergic rhinitis.[94][95] In 2017, the FDA approved Qvar RediHaler, a breath-actuated HFA inhalation aerosol, on 16 August 2017 for asthma maintenance therapy in patients aged 4 years and older, providing an alternative to traditional press-and-breathe inhalers and including pediatric labeling based on pharmacokinetic bridging to the original Qvar.[13][96] In October 2025, the FDA granted tentative approval to Amneal Pharmaceuticals for a generic version of beclomethasone dipropionate HFA inhalation aerosol, pending final review.[97] Beclometasone has been recognized internationally for its role in essential asthma care. It was first included on the World Health Organization's Model List of Essential Medicines in 1979 as an inhalation aerosol (50 micrograms dipropionate per dose) for asthma treatment, serving as a therapeutic alternative to other inhaled corticosteroids.[98] The listing has been maintained in subsequent updates, emphasizing its accessibility in low- and middle-income countries for prophylactic asthma management.Society and culture
Brand names and formulations
Beclometasone, also known as beclomethasone dipropionate, is marketed under several brand names across different formulations for respiratory, nasal, topical, and limited oral uses.[12]Inhalation Formulations
Inhalation products are primarily used for asthma management and include metered-dose inhalers. Major brands include Qvar (manufactured by Teva Pharmaceuticals), which delivers beclometasone dipropionate via hydrofluoroalkane (HFA) propellant in doses such as 40 mcg and 80 mcg per actuation. Clenil, produced by Chiesi Farmaceutici, is another common inhaler formulation available in strengths like 50 mcg, 100 mcg, 200 mcg, and 250 mcg per puff, often in pressurized metered-dose inhalers. Becloforte, an older brand, was formulated as a dry powder inhaler but has been largely phased out in favor of HFA-based options.Nasal Formulations
Nasal sprays target allergic rhinitis and related conditions. Beconase AQ, approved by the FDA, is an aqueous suspension containing 42 mcg of beclometasone dipropionate per spray, delivered via a metered-dose pump.[50] QNASL, also FDA-approved, provides 80 mcg per actuation in an HFA nasal aerosol for once-daily use in adults and children.Topical Formulations
Topical applications for skin conditions such as eczema and dermatitis are available as creams and ointments. Becloderm is a 0.025% cream or ointment formulation of beclometasone dipropionate, applied directly to affected areas for anti-inflammatory effects.Oral Formulations
Oral use is limited and primarily for gastrointestinal indications like ulcerative colitis. Clipper tablets contain 5 mg of beclometasone dipropionate each, designed for gut-targeted release to minimize systemic absorption. Generic versions of beclometasone dipropionate in various formulations have been widely available since the expiration of original patents in the 1980s, enabling cost-effective alternatives to branded products.[99]Availability and legal status
Beclometasone is classified as a prescription-only medication in most countries worldwide, requiring a physician's authorization for dispensing due to its corticosteroid properties and potential for systemic side effects when used inappropriately. In the United States, it is available solely by prescription from the Food and Drug Administration (FDA), applicable to inhalation, nasal, and topical formulations.[69] In the European Union, regulatory approvals through the European Medicines Agency (EMA) designate it as a prescription medicine for asthma and allergic rhinitis management, with national variations in supply conditions but generally requiring medical oversight.[7] In India, beclometasone falls under Schedule H of the Drugs and Cosmetics Rules, mandating prescription and record-keeping by pharmacists to prevent misuse.[100] The drug is widely accessible in developed countries through pharmacies and healthcare systems, supported by both branded and generic versions that have improved affordability. Generic beclometasone inhalers, such as those equivalent to Qvar, are available in the US market following FDA approvals, with monthly costs typically ranging from $50 to $100 without insurance as of 2024, though patient assistance programs and recent price caps can lower this further.[101] In Europe and other high-income regions, generics contribute to broader availability, often covered under national health insurance schemes. For low- and middle-income settings, the World Health Organization (WHO) includes beclometasone on its Model List of Essential Medicines as an inhalation aerosol (50–250 mcg per dose), facilitating procurement and distribution through prequalified suppliers to enhance access in resource-limited areas.[98] There are no major global bans on beclometasone, though certain fixed-dose combinations containing it have been restricted in countries like India for safety reasons. Topical corticosteroids of low potency, such as hydrocortisone, are available over-the-counter in parts of Europe for short-term use, but beclometasone topical formulations require a prescription.References
- https://pubmed.ncbi.nlm.nih.gov/30908719/