BECLOMETHASONE DIPROPIONATE MONOHYDRATE

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H37ClO7.H2O
Molecular Weight	539.057
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of BECLOMETHASONE DIPROPIONATE MONOHYDRATE

Structure Search

SMILES

O.[H][C@@]12C[C@H](C)[C@](OC(=O)CC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]3(Cl)[C@@]2([H])CCC4=CC(=O)C=C[C@]34C

InChI

InChIKey=QHQJZIXSVLFOHD-LYRZEVDOSA-N

InChI=1S/C28H37ClO7.H2O/c1-6-23(33)35-15-22(32)28(36-24(34)7-2)16(3)12-20-19-9-8-17-13-18(30)10-11-25(17,4)27(19,29)21(31)14-26(20,28)5;/h10-11,13,16,19-21,31H,6-9,12,14-15H2,1-5H3;1H2/t16-,19-,20-,21-,25-,26-,27-,28-;/m0./s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020911s025lbl.pdf
Curator's Comment: description was created based on several sources, including http://reference.medscape.com/drug/qvar-beclomethasone-inhaled-343427

Beclometasone dipropionate or beclomethasone dipropionate is sold under the brand name Qvar among others. Beclomethasone dipropionate is a corticosteroid demonstrating potent anti-inflammatory activity. The precise mechanism of corticosteroid action on asthma is not known. Corticosteroids have been shown to have multiple anti-inflammatory effects, inhibiting both inflammatory cells (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and release of inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines). These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma. Beclomethasone dipropionate is a prodrug that is rapidly activated by hydrolysis to the active monoester, 17 monopropionate (17-BMP). Beclomethasone 17 monopropionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor, which is approximately 13 times that of dexamethasone, 6 times that of triamcinolone acetonide, 1.5 times that of budesonide and 25 times that of beclomethasone dipropionate. The clinical significance of these findings is unknown. Studies in patients with asthma have shown a favorable ratio between topical anti-inflammatory activity and systemic corticosteroid effects with recommended doses of QVAR. Beclometasone dipropionate was first patented in 1962 and used medically in 1972. Common side effects with the inhaled form include respiratory infections, headaches, and throat inflammation. Serious side effects include an increased risk of infection, cataracts, Cushing’s syndrome, and severe allergic reactions. Long term use of the pill form may cause adrenal insufficiency. The pills may also cause mood or personality changes. The inhaled form is generally regarded as safe in pregnancy. Beclometasone is mainly a glucocorticoid.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16507850	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Asthma 241 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020911s025lbl.pdf	Palliative		Approved 8429	QVAR® 40 Approved Use QVAR is indicated in the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older. QVAR is also indicated for asthma patients who require systemic corticosteroid administration, where adding QVAR may reduce or eliminate the need for the systemic corticosteroids. Launch Date 2000

C_max

Value	Dose	Analyte	Population
3103.4 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28937845	160 μg single, respiratory dose: 160 μg route of administration: Respiratory experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6635.1 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28937845	320 μg single, respiratory dose: 320 μg route of administration: Respiratory experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
181.95 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202813Orig1s000MedR.pdf	320 μg single, nasal dose: 320 μg route of administration: Nasal experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
262.65 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202813Orig1s000MedR.pdf	320 μg single, nasal dose: 320 μg route of administration: Nasal experiment type: SINGLE co-administered:	BECLOMETHASONE 17-MONOPROPIONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
88 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020911s029s030lbl.pdf	320 μg single, respiratory dose: 320 μg route of administration: Respiratory experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
283.5 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28937845	160 μg single, respiratory dose: 160 μg route of administration: Respiratory experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
623.6 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28937845	320 μg single, respiratory dose: 320 μg route of administration: Respiratory experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
88.23 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202813Orig1s000MedR.pdf	320 μg single, nasal dose: 320 μg route of administration: Nasal experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1661.53 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202813Orig1s000MedR.pdf	320 μg single, nasal dose: 320 μg route of administration: Nasal experiment type: SINGLE co-administered:	BECLOMETHASONE 17-MONOPROPIONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28937845	160 μg single, respiratory dose: 160 μg route of administration: Respiratory experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.92 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28937845	320 μg single, respiratory dose: 320 μg route of administration: Respiratory experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.278 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202813Orig1s000MedR.pdf	320 μg single, nasal dose: 320 μg route of administration: Nasal experiment type: SINGLE co-administered:	BECLOMETHASONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.457 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202813Orig1s000MedR.pdf	320 μg single, nasal dose: 320 μg route of administration: Nasal experiment type: SINGLE co-administered:	BECLOMETHASONE 17-MONOPROPIONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
13% OTHER GOV https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Beconase_AQ/pdf/BECONASE-PI-PIL.PDF			BECLOMETHASONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
320 ug single, respiratory Highest studied dose Dose: 320 ug Route: respiratory Route: single Dose: 320 ug Sources: https://pubmed.ncbi.nlm.nih.gov/28937845/	healthy, 18 - 45 years n = 66 Health Status: healthy Age Group: 18 - 45 years Sex: M Population Size: 66 Sources: https://pubmed.ncbi.nlm.nih.gov/28937845/	Disc. AE: Presyncope... Other AEs: Headache, Nausea... AEs leading to discontinuation/dose reduction: Presyncope (1 patient) Other AEs: Headache (2 patients) Nausea (1 patient) Tonsillar hypertrophy (1 patient) Cerumen impaction (1 patient) Oropharyngeal pain (1 patient) Anxiety (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/28937845/
40 ug 2 times / day steady, respiratory Recommended Dose: 40 ug, 2 times / day Route: respiratory Route: steady Dose: 40 ug, 2 times / day Co-administed with:: albuterol(360 ug) Sources: https://pubmed.ncbi.nlm.nih.gov/21324520/	unhealthy, 5-18 years n = 71 Health Status: unhealthy Condition: asthma Age Group: 5-18 years Sex: M+F Population Size: 71 Sources: https://pubmed.ncbi.nlm.nih.gov/21324520/	Sources: https://pubmed.ncbi.nlm.nih.gov/21324520/
40 ug 2 times / day steady, respiratory Recommended Dose: 40 ug, 2 times / day Route: respiratory Route: steady Dose: 40 ug, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21324520/	unhealthy, 5-18 years n = 72 Health Status: unhealthy Condition: asthma Age Group: 5-18 years Sex: M+F Population Size: 72 Sources: https://pubmed.ncbi.nlm.nih.gov/21324520/	Sources: https://pubmed.ncbi.nlm.nih.gov/21324520/
320 ug 2 times / day steady, respiratory Highest studied dose Dose: 320 ug, 2 times / day Route: respiratory Route: steady Dose: 320 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020911s029s030lbl.pdf	unhealthy, adult n = 56 Health Status: unhealthy Condition: asthma Age Group: adult Sex: unknown Population Size: 56 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020911s029s030lbl.pdf	Other AEs: Headache, Pain... Other AEs: Headache (25%) Pain (5%) Back pain (4%) Dysphonia (4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020911s029s030lbl.pdf
320 ug 1 times / day steady, respiratory Dose: 320 ug, 1 times / day Route: respiratory Route: steady Dose: 320 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26653155/	unhealthy, adults and children n = 219 Health Status: unhealthy Condition: allergic rhinitis Age Group: adults and children Sex: unknown Population Size: 219 Sources: https://pubmed.ncbi.nlm.nih.gov/26653155/	Disc. AE: Nasal mucosal disorder NOS... AEs leading to discontinuation/dose reduction: Nasal mucosal disorder NOS (17 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/26653155/
80 ug 1 times / day steady, respiratory Dose: 80 ug, 1 times / day Route: respiratory Route: steady Dose: 80 ug, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01697956	unhealthy, child n = 67 Health Status: unhealthy Condition: Perennial Allergic Rhinitis Age Group: child Population Size: 67 Sources: https://clinicaltrials.gov/ct2/show/NCT01697956	Other AEs: Epistaxis, Pyrexia... Other AEs: Epistaxis (below serious, 5 patients) Pyrexia (below serious, 5 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01697956
80 ug 1 times / day steady, respiratory Dose: 80 ug, 1 times / day Route: respiratory Route: steady Dose: 80 ug, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01783548	unhealthy, child n = 362 Health Status: unhealthy Condition: Perennial Allergic Rhinitis Age Group: child Population Size: 362 Sources: https://clinicaltrials.gov/ct2/show/NCT01783548	Other AEs: Epistaxis... Other AEs: Epistaxis (below serious, 18 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01783548

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781	inducer 389

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 OATP1B1 788 OATP1B3 706	CYP3A5 395 CYP3A7 110 esterase 72 P-gp 1537	UGT2B10 2 UGT2B17 2 CYP1A2 701 UGT1A 2 P-gp 257 MRP1 48 MRP2 111

Drug as perpetrator

Target	Modality	Activity
OATP1B3 715	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864424/	yes [IC50 1.4 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864424/	yes [IC50 6.7 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15365089/	yes [Inhibition 40.4 uM]
CYP1A2 1692	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
CYP2C9 1819	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
CYP3A4 1925	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
MRP1 172	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
MRP2 475	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
P-gp 1650	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
UGT1A 5	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
UGT2B10 27	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes
UGT2B17 20	inducer 1573 Sources: https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1080/10258140412331286946 Page: 3.0	yes

Drug as victim

Target	Modality	Activity
CYP3A7 110	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629798/	no
CYP3A4 1737	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629798/	yes
CYP3A5 395	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629798/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22464980/ Page: 6.0	yes
esterase 72	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629798/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3001	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3001
ChemicalBook	CB7694093	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7694093
MolPort	MolPort-003-844-701	https://www.molport.com/shop/molecule-link/MolPort-003-844-701
ZINC	ZINC000004097285	http://zinc15.docking.org/substances/ZINC000004097285
eMolecules	31224812	https://www.emolecules.com/cgi-bin/more?vid=31224812

PubMed

Title	Date	PubMed
Comparison of hydrofluoroalkane-beclomethasone dipropionate Autohaler with budesonide Turbuhaler in asthma control.	2001	11694816
Effects of inhaled corticosteroids on cough threshold in patients with bronchial asthma.	2001	11162417
Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.	2001 Aug	11527250
Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction.	2001 Aug 1	11500334
Effects of theophylline withdrawal in well-controlled asthmatics treated with inhaled corticosteroid.	2001 Dec	11758890
Inhaled corticosteroids reduce growth. Or do they?	2001 Feb	11334133
Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate.	2001 Feb	11258691
Influence of water on the solubility of two steroid drugs in hydrofluoroalkane (HFA) propellants.	2001 Jan	11247538
Therapeutic equivalence study of two formulations (innovator v. generic) of beclomethasone dipropionate in adult asthmatic patients.	2001 Jan	11236299
Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease.	2001 Jan	11208630
e-NO peak versus e-NO plateau values in evaluating e-NO production in steroid-naive and in steroid-treated asthmatic children and in detecting response to inhaled steroid treatment.	2001 Jan	11180673
Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years.	2001 Jan	11167954
The topical glucocorticoids beclomethasone dipropionate and fluticasone propionate inhibit human T-cell allergen-induced production of IL-5, IL-3 and GM-CSF mRNA and protein.	2001 Jan	11167953
Step-down and step-up therapy in moderate persistent asthma.	2001 Jan-Mar	11307032
[Tracheobronchopathia osteochondroplastica].	2001 Jul	11802998
Treatment update: nonallergic rhinitis.	2001 Jul-Aug	11552668
A comparison of clinical use of fluticasone propionate and beclomethasone dipropionate in pediatric asthma.	2001 Jun	11559968
Preliminary results of a pilot study investigating the potential of salivary cortisol measurements to detect occult adrenal suppression secondary to steroid nose drops.	2001 Jun	11437848
Effect of the long-term use of inhaled corticosteroids on bone mineral density in asthmatic women.	2001 Jun	11422892
Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older.	2001 Jun	11422148
Leukotriene receptor antagonists in the treatment of asthma.	2001 Mar	11253866
The risk of cataract among users of inhaled steroids.	2001 Mar	11246585
[Stabilization of two patients with brittle asthma by inhaled beclomethasone dipropionate with small particle size].	2001 May	11449610
Churg-Strauss syndrome after reduction of inhaled corticosteroid in a patient treated with pranlukast for asthma.	2001 May	11393418
Dose-response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients.	2001 May	11348935
Effects of glucocorticoids on endogenous and transcellular metabolism of eicosanoids in asthma.	2001 May	11344349
The linear relationship between changes in childhood growth velocity and topical glucocorticoid dose.	2001 May-Jun	11424876
Effects of 2 inhaled corticosteroids on growth: results of a randomized controlled trial.	2001 Nov	11695935
Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate.	2001 Sep	11555383
Effect of seasonal allergen exposure on mucosal IL-16 and CD4+ cells in patients with allergic rhinitis.	2001 Sep	11551252
Inhaled steroids for children's acute asthma exacerbations?	2002 Jan	11814283

Patents

Sample Use Guides

In Vivo Use Guide

Administer QVAR (beclomethasone dipropionate HFA 40 ug) by the orally inhaled route only. Patients should prime QVAR by actuating into the air twice before using for the first time or if QVAR has not been used for over 10 days.

Route of Administration: Other

In Vitro Use Guide

Incubation of challenged rings (bronchial rings from nonatopic humans) for 3 h with 3 x 10(-6) M beclomethasone dipropionate (BDP) restored the relaxant effect, suggesting reversal of beta(2)-AR pathway dysfunction.

Name

Type

Language

BECLOMETHASONE DIPROPIONATE MONOHYDRATE

Common Name

English

BECLOMETASONE DIPROPIONATE MONOHYDRATE [EP IMPURITY]

Common Name

English

BECLOMETASONE DIPROPIONATE MONOHYDRATE

Common Name

English

BECLOMETASONE DIPROPIONATE MONOHYDRATE [EP MONOGRAPH]

Common Name

English

Beclometasone dipropionate monohydrate [WHO-DD]

Common Name

English

BECLOMETHASONE DIPROPIONATE MONOHYDRATE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C521