Dapagliflozin/Saxagliptin

Dapagliflozin/saxagliptin is used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin.

Dapagliflozin/saxagliptin is available under the following different brand names: Qtern.

Dosages of Dapagliflozin/Saxagliptin:

Dosage Forms and Strengths

Tablet

• 10mg/5mg

Dosage Considerations – Should be Given as Follows:

Type 2 Diabetes Mellitus

• Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin
• 1 tablet (i.e., 10mg/5mg) orally once daily in the morning with or without food

Dosage Modifications

Renal impairment

• eGFR less than 60 mL/minute/1.73 m²: Do not initiate
• Discontinue if eGFR persistently falls to less than 60 mL/minute/1.73 m²
• eGFR less than 45 mL/minute/1.73 m²: Contraindicated

Hepatic impairment

• May be administered with hepatic impairment
• Severe hepatic impairment: Individually assess benefit-risk

Coadministration with strong CYP3A4/5 inhibitors

• Do not co-administer with strong CYP3A4/5 inhibitors
• Examples include ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir,
• ritonavir, saquinavir, and telithromycin

Dosing Considerations

• In patients with volume depletion, correct this condition before initiating drug
• Assess renal function before initiating and periodically thereafter

Limitations of use

• Not indicated for type 1 diabetes mellitus or diabetic ketoacidosis
• Should only be used in patients who tolerate dapagliflozin 10 mg
• Safety and efficacy not established in pediatric patients

Common side effects of dapagliflozin/saxagliptin include:

• Upper respiratory tract infection
• Urinary tract infection (UTI)
• Abnormal amount of fats in the blood (dyslipidemia)
• Headache
• Diarrhea
• Back pain
• Genital infection
• Joint pain
• Renal impairment
• Increased serum inorganic phosphorus
• Low blood sugar (hypoglycemia)
• Increased hematocrit
• Elevated creatine kinase

Less common side effects of dapagliflozin/saxagliptin include:

• Volume depletion (hypotension, dehydration, hypovolemia)
• Acute pancreatitis
• Decreased lymphocyte count
• Newly diagnosed bladder cancer

Postmarketing side effects of dapagliflozin/saxagliptin reported include:

Saxagliptin

• Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions
• Pancreatitis
• Severe and disabling joint pain
• Bullous pemphigoid
• Muscle wasting (rhabdomyolysis)

Dapagliflozin

• Ketoacidosis
• Acute kidney injury and impaired renal function
• Urosepsis and pyelonephritis
• Rash

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Dapagliflozin/saxagliptin has no listed severe interactions with other drugs.
 

Serious interactions of dapagliflozin/saxagliptin include:

• apalutamide
• erdafitinib
• ethanol
• idelalisib
• ivosidenib
• lasmiditan
• voxelotor

Dapagliflozin/saxagliptin has moderate interactions with at least 104 different drugs.

Dapagliflozin/saxagliptin has mild interactions with at least 113 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings
This medication contains dapagliflozin/saxagliptin. Do not take Qtern if you are allergic to dapagliflozin/saxagliptin or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• History of hypersensitivity to dapagliflozin or saxagliptin, including anaphylaxis, angioedema, or exfoliative skin conditions
• Moderate-to-severe renal impairment (eGFR less than 45 mL/minute/1.73 m²), end-stage renal disease, or patients on dialysis

Effects of Drug Abuse

• No information is available

Short-Term Effects

• See "What Are Side Effects Associated with Using Dapagliflozin/Saxagliptin?”

Long-Term Effects

• See "What Are Side Effects Associated with Using Dapagliflozin/Saxagliptin?”

Cautions

• Acute pancreatitis reported; after initiating drug, monitor for signs and symptoms of pancreatitis; if suspected, promptly discontinue dapagliflozin/saxagliptin and initiate appropriate management
• Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary
• May increase the risk for developing heart failure (HF) or exacerbation of existing HR; observe patients for signs and symptoms of HF
• Dapagliflozin causes intravascular volume contraction; symptomatic hypotension and acute kidney injury can occur, particularly with impaired renal function, elderly patients, chronic renal insufficiency, congestive HF, or coadministration of certain drugs [e.g., diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs)]; before initiating, volume status should be assessed and corrected; do not initiate if eGFR is less than 60 mL/minute/1.73 m²
• Evaluate renal function before initiation of therapy and monitor periodically thereafter; contraindicated in patients with an eGFR less than 45 mL/minute/1.73 m²
• Low blood sugar (hypoglycemia) risk increased with insulin and insulin secretagogues; adjust the dose
• Genital mycotic infections may occur; patients with a history of genital mycotic infections and uncircumcised males are more susceptible
• Increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate for signs and symptoms of UTIs and treat promptly, if indicated
• Dose-related increases in LDL-C reported with dapagliflozin
• Across 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 10 (0.17%)/6045 patients treated with dapagliflozin and 1 (0.03%)/3512 patients treated with placebo/comparator; bladder cancer risk factors and hematuria (a potential indicator of preexisting tumors) were balanced between treatment arms at baseline and there were too few cases to determine whether the emergence of these events is related to dapagliflozin
• Do not administer to patients with active bladder cancer and should be administered with caution in patients with a prior history of bladder cancer
• No conclusive evidence of macrovascular risk reduction with dapagliflozin or any other antidiabetic agent
• GLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests; use alternative methods to monitor glycemic control
• Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
• Serious hypersensitivity reactions with saxagliptin were reported (typically within the first 3 months of therapy)
• Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use; patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor

Ketoacidosis

• Before initiating therapy, consider factors inpatient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
• Consider temporarily discontinuing therapy for at least 3 days for patients who undergo scheduled surgery
• Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved prior to restart therapy
• Educate patients on signs and symptoms of ketoacidosis and instruct patients to discontinue therapy and seek medical attention immediately if signs and symptoms occur

Pregnancy and Lactation

• Dapagliflozin/saxagliptin is not recommended during the second and third trimesters of pregnancy. Adverse renal effects have been shown in animal studies. Consult your doctor
• It is unknown if dapagliflozin/saxagliptin is distributed in human breast milk. Because of the potential for serious adverse reactions in a breastfed infant, dapagliflozin/saxagliptin is not recommended for use while breastfeeding.