FDA clears AstraZeneca's SGLT2-metformin combo Xigduo XR
This article was originally published in Scrip
The FDA on 30 October gave its blessing to AstraZeneca to market its once-daily dapagliflozin and metformin combination pill Xigeuo XR as a treatment for adults with type 2 diabetes.
Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), already is sold on the US market as Farxiga – winning that approval in January (scripintelligence.com, 9 January 2014).
Xigduo XR is the first and only once-daily combination tablet of an SGLT2 inhibitor and extended-release metformin, a biguanide, approved in the US.
The drug was previously approved in Australia, and a combination product with dapagliflozin and an immediate-release (IR) form of metformin is approved in the European Union.
The new US combo medicine is indicated as an adjunct therapy to diet and exercise to improve glycemic control in adults with type 2 diabetes when treatment with both dapagliflozin and metformin is appropriate.
Xigduo XR's US labeling came with a black-box warning alerting prescribers and patients about lactic acidosis, a rare, but serious metabolic complication, which can occur due to metformin accumulation during treatment with the combination drug.
AstraZeneca's new medicine is contraindicated in patients with moderate-to-severe renal impairment; a history of a serious hypersensitivity to dapagliflozin or to metformin HCl; or with metabolic acidosis, including diabetic ketoacidosis.
The FDA approved Xigduo in multiple dosage strengths of dapagliflozin and metformin ER: 5mg/500mg, 5mg/1000mg, 10mg/500mg and 10mg/1000mg, respectively.
The labeling advises that a starting dose should be individualized based on each patient's current treatment regimen.
The maximum daily recommended dose is 10mg for dapagliflozin and 2,000mg for metformin.
Xigduo XR is intended to be taken once daily in the morning with food with gradual dose escalation to reduce the risk of adverse gastrointestinal effects due to metformin.
The FDA approved once-daily Xigduo XR based on four Phase III trials, which provided clinical evidence for the efficacy and safety of dapagliflozin and metformin IR or XR tablets in treatment-naïve patients, in patients inadequately controlled on metformin, and compared to glipizide, a sulfonylurea, plus metformin.
But there have been no clinical studies conducted with Xigruo XR combination tablets.
AstraZeneca noted that bioequivalence was demonstrated in healthy adults between XIGDUO XR and dapagliflozin plus metformin XR as separate tablets.