Saxagliptin & Concerns of Heart Failure
Post-marketing drug trials of the diabetes drug Saxagliptin have recently led an FDA panel to vote to require new labeling information, warning of the concerns about heart failure, according to Medpage Today. The decision was based on post-marketing trial involving 16,000 patients.
Saxagliptin is currently marketed under two names, Onglyza and Kombiglyze XR.
The FDA announced last year that the agency was involved in an investigation into the connection between incidents of heart failure and the use of Saxagliptin and other type 2 diabetes drugs. One member of the FDA’s review committee, a consumer representative, voted to completely withdraw Saxalgliptin from the market due to the associated risk of heart failure for patients, according to the same article in Medpage Today.
The FDA now requires drug manufacturers applying for FDA approval to prove that their product will not lead to an “unacceptable increase of cardiovascular risk.” Drug manufacturers are now required to engage in post-marketing evaluations of their products, such as the study data recently released in the New England Journal of Medicine (NEJM).
Broad Evaluation of Diabetes Drug Treatments
The FDA reports that they are involved in a broad evaluation of all types of type 2 diabetes drug treatments with regard to cardiovascular risks. A safety notice issued by the agency asks health care providers, as well as diabetes patients currently on the drug, to provide reports of side effects associated with Saxagliptin.
The FDA initiated the investigation into Saxagliptin following the release of a study published in 2013 in the NEJM. This study concluded that there were increased rates of hospitalization for heart failure. The FDA says that the information in this report is considered to be preliminary, and part of a wider investigation into all diabetes drugs with regard to cardiovascular risks.
The manufacturer, AstraZeneca, has already warned patients of various potential side effects, prior to the decision by the FDA. Some of these side effects include pancreatitis, which is potentially fatal, as well as low blood sugar and fluid retention. The FDA panel has voted that this new concern about the risk of heart failure warrants a change in labeling.
Sources:
There is currently no manufacturer warning information available for this drug.
ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. [See Clinical Studies (14).]
ONGLYZA should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings.
ONGLYZA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using ONGLYZA. [See Warnings and Precautions (5.1).]
1.1 Monotherapy and Combination Therapy
ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. [See Clinical Studies (14).]
Saxagliptin is an orally-active inhibitor of the DPP4 enzyme.
Saxagliptin monohydrate is described chemically as (1S,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, monohydrate or (1S,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrate. The empirical formula is C18H25N3O2•H2O and the molecular weight is 333.43. The structural formula is:
Saxagliptin monohydrate is a white to light yellow or light brown, non-hygroscopic, crystalline powder. It is sparingly soluble in water at 24°C ± 3°C, slightly soluble in ethyl acetate, and soluble in methanol, ethanol, isopropyl alcohol, acetonitrile, acetone, and polyethylene glycol 400 (PEG 400). Each film-coated tablet of ONGLYZA for oral use contains either 2.79 mg saxagliptin hydrochloride (anhydrous) equivalent to 2.5 mg saxagliptin or 5.58 mg saxagliptin hydrochloride (anhydrous) equivalent to 5 mg saxagliptin and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, and iron oxides.
