QTERN

QTERN- dapagliflozin and saxagliptin hydrochloride tablet, film coated
AstraZeneca Pharmaceuticals LP

1 INDICATIONS AND USAGE

QTERN (dapagliflozin and saxagliptin) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Limitations of Use

QTERN is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

2 DOSAGE AND ADMINISTRATION

2.1 Prior to Initiation of QTERN

Assess renal function prior to initiation of QTERN therapy and periodically thereafter [see WARNINGS AND PRECAUTIONS (5.5)].

In patients with volume depletion, correct this condition prior to initiation of QTERN [see WARNINGS AND PRECAUTIONS (5.3) and USE IN SPECIFIC POPULATIONS (8.5, 8.6)].

2.2 Dosage

For patients not already taking dapagliflozin, the recommended starting dose of QTERN is a 5 mg dapagliflozin/5 mg saxagliptin tablet taken orally once daily in the morning with or without food.

In patients tolerating 5 mg dapagliflozin and 5 mg saxagliptin once daily who require additional glycemic control, the QTERN dose can be increased to 10 mg dapagliflozin/5 mg saxagliptin tablet once daily in the morning with or without food.

Swallow whole. Do not crush, cut or chew QTERN tablets.

2.3 Patients with Renal Impairment

No dose adjustment is needed in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 45 mL/min/1.73 m2.

QTERN is contraindicated in patients with an eGFR less than 45 mL/min/1.73 m2 [ see CONTRAINDICATIONS (4) and USE IN SPECIFIC POPULATIONS (8.6)].

2.4 Use with Strong CYP3A4/5 Inhibitors

Do not coadminister QTERN with strong cytochrome P450 3A4/5 inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin) [see DRUG INTERACTIONS (7)].

3 DOSAGE FORMS AND STRENGTHS

Tablets:

5 mg dapagliflozin/5 mg saxagliptin as light purple to reddish purple, biconvex, round, film-coated tablet, with “1120” printed on both sides, in blue ink.
10 mg dapagliflozin/5 mg saxagliptin as light brown to brown, biconvex, round, film-coated tablet, with “1122” printed on both sides, in blue ink.

4 CONTRAINDICATIONS

QTERN is contraindicated in patients with:

History of a serious hypersensitivity reaction to dapagliflozin or to saxagliptin, including anaphylactic reactions, angioedema or exfoliative skin conditions [see WARNINGS AND PRECAUTIONS (5.9) and ADVERSE REACTIONS (6.1)].
Moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m2), end-stage renal disease (ESRD), or patients on dialysis [see USE IN SPECIFIC POPULATIONS (8.6)].

5 WARNINGS AND PRECAUTIONS

5.1 Pancreatitis

There have been postmarketing reports of acute pancreatitis in patients taking saxagliptin. In a cardiovascular outcomes trial enrolling participants with established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (SAVOR trial), cases of definite acute pancreatitis were confirmed in 17 of 8240 (0.2%) patients receiving saxagliptin compared to 9 of 8173 (0.1%) receiving placebo. Pre-existing risk factors for pancreatitis were identified in 88% (15/17) of those patients receiving saxagliptin and in 100% (9/9) of those patients receiving placebo.

After initiation of QTERN, observe patients for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue QTERN and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using QTERN.

5.2 Heart Failure

In a cardiovascular outcomes trial enrolling participants with established ASCVD or multiple risk factors for ASCVD (SAVOR trial), more patients randomized to saxagliptin (289/8280, 3.5%) were hospitalized for heart failure compared to patients randomized to placebo (228/8212, 2.8%). In a time-to-first-event analysis the risk of hospitalization for heart failure was higher in the saxagliptin group (estimated Hazard Ratio: 1.27; 95% CI: 1.07, 1.51). Subjects with a prior history of heart failure and subjects with renal impairment had a higher risk for hospitalization for heart failure, irrespective of treatment assignment.

Consider the risks and benefits of QTERN prior to initiating treatment in patients at a higher risk of heart failure. Observe patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of QTERN.

5.3 Hypotension

Dapagliflozin causes intravascular volume contraction. Symptomatic hypotension can occur after initiating QTERN [see ADVERSE REACTIONS (6.1)] particularly in patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics. Before initiating QTERN volume status should be assessed and corrected. QTERN is contraindicated in patients with an eGFR <45 mL/min/1.73 m2. Monitor for signs and symptoms of hypotension after initiating therapy.

5.4 Ketoacidosis

Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, have been identified in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose cotransporter-2 (SGLT2) inhibitors, including dapagliflozin. Fatal cases of ketoacidosis have been reported in patients taking dapagliflozin. QTERN is not indicated for the treatment of patients with type 1 diabetes mellitus [see INDICATIONS AND USAGE (1) ].

Patients treated with QTERN who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels as ketoacidosis associated with QTERN may be present even if blood glucose levels are less than 250 mg/dL. If ketoacidosis is suspected, QTERN should be discontinued, the patient should be evaluated and prompt treatment should be instituted. Treatment of ketoacidosis may require insulin, fluid, and carbohydrate replacement.

In many of the postmarketing reports for dapagliflozin, and particularly in patients with type 1 diabetes, the presence of ketoacidosis was not immediately recognized, and the institution of treatment was delayed because the presenting blood glucose levels were below those typically expected for diabetic ketoacidosis (often less than 250 mg/dL). Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. In some but not all cases, factors predisposing to ketoacidosis, such as insulin dose reduction, acute febrile illness, reduced caloric intake, surgery, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse were identified.

Before initiating QTERN, consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse.

For patients who undergo elective surgery, consider temporarily discontinuing QTERN for at least 3 days prior to surgery [see Clinical Pharmacology (12.2, 12.3)].

Consider monitoring for ketoacidosis and temporarily discontinuing QTERN in other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post surgery) [see ADVERSE REACTIONS (6.2)]. Ensure risk factors for ketoacidosis are resolved prior to restarting QTERN.

Educate patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue QTERN and seek medical attention immediately if signs and symptoms occur.

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