Dapagliflozin

Dapagliflozin

Haworth projection (bottom)
Clinical data
Pronunciation	/ˌdæpəɡlᵻˈfloʊzɪn/ DAP-ə-glif-LOH-zin
Trade names	Forxiga, Farxiga
AHFS/Drugs.com	UK Drug Information
License data	EU EMA: Forxiga US FDA: Dapagliflozin
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	By mouth (tablets)
ATC code	A10BK01 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	78% (after 10 mg dose)
Protein binding	~91%
Metabolism	UGT1A9 (major), (minor)
Metabolites	Dapagliflozin 3-O-glucuronide (inactive)
Biological half-life	~12.9 hours
Excretion	Urine (75%), feces (21%)
Identifiers
IUPAC name (2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
Synonyms	BMS-512148; (1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-D-glucitol
CAS Number	461432-26-8 N
PubChem CID	9887712
IUPHAR/BPS	4594
DrugBank	DB06292 N
ChemSpider	8063384 Y
UNII	1ULL0QJ8UC
KEGG	D08897 N
ChEBI	CHEBI:85078 N
ChEMBL	CHEMBL429910 Y
ECHA InfoCard	100.167.331
Chemical and physical data
Formula	C21H25ClO6
Molar mass	408.873 g/mol
3D model (Jmol)	Interactive image
SMILES Clc1ccc(cc1Cc2ccc(OCC)cc2)[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O
InChI InChI=1S/C21H25ClO6/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21/h3-8,10,17-21,23-26H,2,9,11H2,1H3/t17-,18-,19+,20-,21+/m1/s1 Y Key:JVHXJTBJCFBINQ-ADAARDCZSA-N Y
NY (what is this?)

Dapagliflozin (INN,USAN, trade name Farxiga /fɑːrˈsiːɡə/ far-SEE-gə in the U.S. and Forxiga in the EU and Russia) is a drug of the gliflozin class, used to treat type 2 diabetes. It was developed by Bristol-Myers Squibb in partnership with AstraZeneca.

In July 2011 a U.S. Food and Drug Administration (FDA) endocrinologic and metabolic drugs advisory committee recommended against approval until more data were available.

The FDA approved dapagliflozin on January 8, 2014 for glycemic control, along with diet and exercise, in adults with type 2 diabetes.

In 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a positive opinion on the drug. It is now marketed in a number of European countries.

The FDA approved the combination product dapagliflozin and metformin hydrochloride extended-release, called Xigduo XR, in October 2014.

In Feb 2017 the FDA approved a once-daily combination of dapagliflozin 10 mg and saxagliptin 5 mg, as Qtern.

Since dapagliflozin leads to heavy glycosuria (sometimes up to about 70 grams per day) it can lead to rapid weight loss and tiredness. The glucose acts as an osmotic diuretic (this effect is the cause of polyuria in diabetes) which can lead to dehydration. The increased amount of glucose in the urine can also worsen the infections already associated with diabetes, particularly urinary tract infections and thrush (candidiasis). Dapagliflozin is also associated with hypotensive reactions. There are concerns it may increase the risk of diabetic ketoacidosis.