Dapagliflozin/Metformin

Dapagliflozin/metformin is a prescription medication used for treating type 2 Diabetes Mellitus. 

• Dapagliflozin/metformin is available under the following different brand names: Xigduo XR. 

Adult dosage

Tablet, extended-release

• 2.5mg/1000mg
• 5mg/500mg
• 5mg/1000mg
• 10mg/500mg
• 10mg/1000mg

Type 2 Diabetes Mellitus

Adult dosage

• Improve glycemic control
• Individualize the starting dose based upon the patient’s current regimen
• Not already taking dapagliflozin: Initiate dapagliflozin at 5 mg orally once daily

Reduce the risk of hospitalization for heart failure

• Dapagliflozin is 10 mg once daily

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Dapagliflozin/Metformin include:

• muscle aches,
• sore throat,
• stuffy or runny nose,
• back pain,
• body aches or pain,
• difficulty having a bowel movement,
• tender, swollen glands in the neck, and
• voice changes

Serious side effects of Dapagliflozin/Metformin include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• bladder pain,
• bloody urine,
• cloudy urine,
• change in color, amount, or odor of vaginal discharge,
• burning or painful urination,
• frequent urge to urinate,
• lower back or side pain,
• decreased appetite,
• diarrhea,
• fast or shallow breathing,
• general ill feeling,
• muscle pain or cramping,
• nausea,
• sleepiness,
• stomach pain,
• unusual tiredness or weakness,
• anxiety,
• blurred vision,
• chills,
• clay-colored stools,
• cold sweats,
• pale skin,
• depression,
• lightheadedness,
• fast heartbeat,
• fever,
• headache,
• itches,
• dizziness,
• hoarseness,
• increased appetite,
• irritation,
• joint pain, stiffness, or swelling,
• loss of appetite,
• loss of consciousness,
• nightmares,
• pain, tenderness, redness, or swelling of the area between the anus and genitals,
• redness of the skin,
• seizures,
• tremors,
• shakiness,
• slurred speech,
• sweating,
• tightness in the chest,
• difficulty swallowing,
• unpleasant breath odor,
• vomiting blood, and
• yellowing of the skin or eyes (jaundice)

Rare side effects of Dapagliflozin/Metformin include:

• none 

If your medical doctor is using this medicine to treat your pain, 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/Metformin has severe interactions with no other drugs
• Dapagliflozin/Metformin has serious interactions with at least 12 other drugs.
• Dapagliflozin/Metformin has moderate interactions with at least 188 other drugs.
• Dapagliflozin/Metformin has minor interactions with at least 82 drugs:

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs 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.

Contraindications

• Severe renal impairment (e.g., eGFR less than 30 ml/min/1.73 m2), end-stage renal disease, or patients on dialysis, which may also result from conditions such as shock, acute MI, and septicemia
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis
• Hypersensitivity

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dapagliflozin/Metformin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dapagliflozin/Metformin?”

Cautions

• Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), increased lactate: pyruvate ratio
• Lactic acidosis: risk increases with the degree of renal dysfunction and age
• Before initiating therapy, assess volume status and correct hypovolemia in the elderly, in patients with renal impairment or low systolic blood pressure, and patients on diuretics, monitor for signs and symptoms during therapy
• Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk; metformin use in patients with impaired hepatic function has been associated with some cases of lactic acidosis; generally, avoid in patients with hepatic impairment
• Alcohol is known to potentiate the effect of metformin on lactate metabolism; warn patients against excessive alcohol intake while receiving therapy
• The shock from various causes (e.g., acute CHF, acute MI, and other conditions characterized by hypoxemia) is associated with lactic acidosis and may also cause prerenal azotemia
• In diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to 170 mL/minute under good hemodynamic conditions)
• Closely monitor patients taking drugs that may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation (e.g., cationic drugs)
• Elderly patients and patients with impaired renal function may be more susceptible to increases in serum creatinine and decreased eGFR; renal function should be evaluated before initiation of therapy and monitored periodically thereafter
• Elderly patients have a greater likelihood of having hepatic or cardiac impairment than younger patients; the risk of metformin-associated lactic acidosis increases with patient’s age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients
• Metformin is known to be substantially excreted by the kidney and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment; before initiating therapy, obtain an estimated glomerular filtration rate (eGFR)
• Dapagliflozin increases the risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated
• Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level; consider risk factors for ketoacidosis before initiating therapy; patients may require temporary discontinuation of therapy in clinical situations that may predispose to ketoacidosis
• Cases of metformin-associated lactic acidosis reported in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia); cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; discontinue therapy when such events occur
• Dapagliflozin increases the risk for genital mycotic infections
• Before initiating therapy, obtain estimated glomerular filtration rate (eGFR); obtain an eGFR at least annually in all patients receiving therapy; in patients at increased risk for development of renal impairment (e.g., the elderly), renal function should be assessed more frequently
• Metformin associated with a decrease to subnormal levels of previously normal serum vitamin B-12 levels, without clinical manifestations; measure hematological parameters annually and vitamin B12 at 2- to 3-year intervals and manage any abnormalities
• Bone fractures were reported in 30 patients with eGFR 30 to less than 60 mL/min/1.73 m2 for treatment durations up to 104 weeks compared with none receiving a placebo

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 before 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
• Necrotizing fascitis of 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, closely monitor blood glucose levels, and provide an appropriate alternative therapy for glycemic control; start broad-spectrum antibiotics immediately and surgical debridement if necessary

Hypoglycemia

• Dapagliflozin can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue; a lower dose of insulin or insulin secretagogue may be required
• Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (e.g., sulfonylureas, insulin) or ethanol

Hypotension and acute renal injury

• Dapagliflozin causes intravascular volume contraction
• Symptomatic hypotension and/or acute renal injury can occur after initiating, particularly with eGFR less than 60 mL/min/1.73 m2, in elderly patients, with coadministration with diuretics, or medications that interfere with the renin-angiotensin-aldosterone system (e.g., ACE inhibitors, angiotensin receptor blockers), or in patients with low systolic blood pressure
• Consider temporarily discontinuing therapy in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (gastrointestinal illness or excessive heat exposure), monitor patients for signs and symptoms of acute kidney injury
• Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment; if acute kidney injury occurs, discontinue therapy promptly and institute treatment; temporarily discontinue therapy while patients have restricted food and fluid intake.

Pregnancy and Lactation

• Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy
• Limited data in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage
• Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk
• There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
• Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women
• Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications; poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
• There is no information regarding the presence of human milk, the effects on the breastfed infant, or the effects on milk production
• Limited published studies report that metformin is present in human milk
• However, there is insufficient information on the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production
• Dapagliflozin is present in the milk of lactating rats
• Because of the potential for serious adverse reactions in breastfed infants, advise women that use is not recommended while breastfeeding.