Glyhart Special Precautions

Diabetic Ketoacidosis in Patients with Diabetes: The use of SGLT2 inhibitors in patients with type 2 diabetes mellitus may lead to diabetic ketoacidosis (DKA) requiring hospitalization. Fatal cases of diabetic ketoacidosis have been reported in patients receiving dapagliflozin. DKA associated with the use of SGLT2 inhibitors may be present without markedly elevated blood glucose values [e.g., below than 13.9 mmol/L (250 mg/dL)].
DKA must be considered in the event of non-specific symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, anorexia, excessive thirst, and unusual fatigue or sleepiness. If DKA is suspected, regardless of blood glucose level, patients should discontinue dapagliflozin treatment and be assessed for DKA immediately.
Treatment of ketoacidosis generally requires insulin, fluid, potassium and carbohydrate replacement.
Restarting SGLT2 inhibitor treatment in patients with previous DKA while on SGLT2 inhibitor treatment is not recommended unless another clear precipitating factor is identified and resolved.
Before initiating dapagliflozin, consider factors in the patient history that may predispose to ketoacidosis.
Factors that predispose patients to ketoacidosis include insulin deficiency from any cause (including insulin pump failure, history of pancreatitis or pancreatic surgery), insulin dose reduction, reduced caloric intake or increased insulin requirements due to infections, low carbohydrate diet, acute illness, surgery, a previous ketoacidosis, dehydration and alcohol abuse. Dapagliflozin should be used with caution in these patients. Consider monitoring patients for ketoacidosis and temporarily discontinuing dapagliflozin in clinical situations known to predispose to ketoacidosis.
For patients who will undergo scheduled surgery, consider temporarily discontinuing dapagliflozin for at least 3 days prior to surgery. Treatment with dapagliflozin may be restarted once the patient's condition has stabilized and oral intake is normal.
Volume Depletion and/or Hypotension: Dapagliflozin may cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Following initiation of dapagliflozin, symptomatic hypotension can occur, particularly in patients with impaired renal function (eGFR <60 mL/min/1.73 m²), elderly patients, or patients receiving loop diuretics. Prior to initiating dapagliflozin in such patients, volume status should be assessed and corrected. Monitor for signs and symptoms of hypotension and renal function after initiating dapagliflozin therapy.
In case of intercurrent conditions that may lead to volume depletion (e.g., gastrointestinal illness), careful monitoring of volume status (e.g., physical examination, blood pressure measurements, laboratory tests including hematocrit and electrolytes) is recommended. Temporary interruption of treatment with dapagliflozin is recommended for patients who develop volume depletion until the depletion is corrected.
Renal Effects: Dapagliflozin may cause intravascular volume depletion and renal impairment. Dapagliflozin may increase serum creatinine and decrease eGFR; elderly patients and patients with impaired renal function may be more susceptible to these changes. Renal function should be evaluated prior to initiation of dapagliflozin and periodically thereafter.
Monitoring of renal function is recommended as follows: prior to initiation of dapagliflozin and at least yearly thereafter; prior to initiation of concomitant medicines that may reduce renal function and periodically thereafter; for renal function approaching eGFR 45 mL/min/1.73 m², at least 2 to 4 times per year. If renal function falls persistently below eGFR <45 mL/min/1.73 m², treatment with dapagliflozin should be discontinued.
Before initiating dapagliflozin, also consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications [diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs)]. Consider temporarily discontinuing dapagliflozin in any setting of reduced oral intake (e.g., acute illness or fasting) or fluid losses (e.g., gastrointestinal illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue dapagliflozin promptly and institute treatment.
Concomitant Therapy with Hypoglycemic Agents: Insulin and insulin secretagogues (e.g., sulfonylureas) are known to cause hypoglycemia. The use of dapagliflozin in combination with insulin or an insulin secretagogue may increase the risk of hypoglycemia. Reduction in the dose of insulin or the insulin secretagogue may be necessary to reduce the risk of hypoglycemia when used in combination with dapagliflozin.
Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): There have been postmarketing reports of necrotizing fasciitis of the perineum (Fournier's gangrene), a rare but serious or life-threatening bacterial infection, requiring urgent surgical intervention, in men and women with type 2 diabetes mellitus receiving an SGLT2 inhibitor, including dapagliflozin. Serious outcomes have included hospitalization, multiple surgeries, and death.
Patients receiving dapagliflozin who develop pain or tenderness, erythema, or swelling in the genital or perineal area, with or without to fever or malaise, should be assessed for necrotizing fasciitis. If suspected, dapagliflozin should be discontinued and prompt treatment should be initiated with broad-spectrum antibiotics; surgical debridement should be performed if necessary. Closely monitor blood glucose levels and provide appropriate alternative therapy for glycemic control.
Genital Mycotic Infections: Dapagliflozin may increase the risk of genital mycotic infections in males (e.g., balanitis) and females (e.g., vulvovaginal mycotic infection). In clinical trials, patients with a history of genital mycotic infections were more likely to develop such infections. Patients should be monitored for genital mycotic infections and appropriate treatment should be instituted if these infections occur.
Urinary Tract Infections (including Urosepsis and Pyelonephritis): Dapagliflozin may increase the risk for urinary tract infections. There have been postmarketing reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients treated with dapagliflozin. Assess patients for signs and symptoms of urinary tract infections and treat promptly, if indicated. Temporary interruption of dapagliflozin should be considered when treating pyelonephritis or urosepsis. Discontinuation of dapagliflozin may be considered in cases of recurrent urinary tract infections.
Lower Limb Amputations: An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term clinical studies with SGLT2 inhibitors. However, it is unknown whether this constitutes a class effect. It is important to regularly examine the feet and advise all patients with diabetes on routine preventative foot care.
Laboratory Test Interferences: SGLT2 inhibitors such as dapagliflozin increase urinary glucose excretion and will result in positive urine glucose tests. Monitoring glycemic control with 1,5-anhydroglucitol (1,5-AG) assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.
Lactose Intolerance: Dapagliflozin tablet contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this drug product.
Effects on Ability to Drive and Use Machines: There were no studies on the effects on the ability to drive and use machines have been performed with dapagliflozin. Patients should be warned about driving a vehicle or operating machinery under conditions where risk of hypoglycemia is present.
Use in Children: The safety and efficacy of dapagliflozin have not been established in pediatric patients <18 years of age. Therefore, dapagliflozin is not recommended in these patients.
Use in the Elderly: Elderly patients may be at a greater risk for volume depletion and are more likely to be treated with diuretics. They are also more likely to have impaired renal function, and/or to be treated with antihypertensives that may cause changes in renal function (e.g., ACE inhibitors, and ARBs). Caution should be exercised in elderly patients.