Jardiance Duo Special Precautions

General: JARDIANCE DUO should not be used in patients with type 1 diabetes.
Diabetic ketoacidosis: Cases of diabetic ketoacidosis (DKA), a serious life-threatening condition requiring urgent hospitalisation, have been reported in patients treated with empagliflozin, including fatal cases. In a number of reported cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/l (250mg/dl).
The risk of diabetic ketoacidosis must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness.
Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level. If ketoacidosis is suspected, JARDIANCE DUO should be discontinued, patient should be evaluated and prompt treatment should be instituted.
Patients who may be at higher risk of DKA while taking JARDIANCE DUO include patients on a very low carbohydrate diet (as the combination may further increase ketone body production), patients with an acute illness, pancreatic disorders suggesting insulin deficiency (e.g. type I diabetes, history of pancreatitis or pancreatic surgery), insulin dose reduction (including insulin pump failure), alcohol abuse, severe dehydration and patients with the history of ketoacidosis. JARDIANCE DUO should be used with caution in these patients. When reducing the insulin dose caution should be taken (see Dosage & Administration). In patients treated with JARDIANCE DUO consider monitoring for ketoacidosis and temporarily discontinuing JARDIANCE DUO in clinical situations known to predispose to ketoacidosis (e.g. prolong fasting due to acute illness or surgery). In these situations, consider monitoring of ketones, even if JARDIANCE DUO treatment has been interrupted.
Lactic acidosis: Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.
In case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake), metformin should be temporarily discontinued and contact with a health care professional is recommended.
Medicinal products that can acutely impair renal function (such as antihypertensive, diuretics and NSAIDs) should be initiated with caution in metformin-treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequate controlled diabetes, ketosis, prolonged fasting, and any condition associated with hypoxia as well as concomitant use of medicinal products that may cause lactic acidosis (see Contraindications and Interactions).
Patient and/ or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention.
Diagnostic laboratory findings are decreased blood pH (< 7.35), increased plasma lactate levels (> 5 mmol/L), and an increased anion gap and lactate/pyruvate ratio.
Necrotizing fasciitis of the perineum (Fournier's gangrene): Postmarketing cases of necrotizing fasciitis of the perineum (also known as Fournier's gangrene), a rare, but serious and life-threatening necrotizing infection, have been reported in female and male patients with diabetes mellitus treated with SGLT2 inhibitors, including empagliflozin. Serious outcomes have included hospitalization, multiple surgeries, and death.
Patients treated with JARDIANCE DUO who present with pain or tenderness, erythema, swelling in the genital or perineal area, fever, malaise should be evaluated for necrotizing fasciitis. If suspected, JARDIANCE DUO should be discontinued and prompt treatment should be instituted (including broad-spectrum antibiotics and surgical debridement if necessary).
Use in patients with renal impairment: Due to the mechanism of action, the efficacy of empagliflozin is dependent on renal function.
GFR should be assessed before treatment initiation and regularly thereafter (see Dosage & Administration). JARDIANCE DUO is contraindicated in patients with eGFR persistently <45 ml/min/1.73m² and should be temporarily discontinued in the presence of conditions that alter renal function (see Contraindications).
Cardiac function: Patients with heart failure are more at risk of hypoxia and renal insufficiency. In patients with stable chronic heart failure, JARDIANCE DUO may be used with a regular monitoring of cardiac and renal function.
For patients with acute and unstable heart failure, JARDIANCE DUO is contraindicated due to the metformin component (see Contraindications).
Hepatic injury: Cases of hepatic injury have been reported with empagliflozin in clinical trials. A causal relationship between empagliflozin and hepatic injury has not been established.
Use in patients at risk for volume depletion: Based on the mode of action of SGLT2 inhibitors, osmotic diuresis accompanying therapeutic glucosuria may lead to a modest decrease in blood pressure. Therefore, caution should be exercised in patients for whom an empagliflozin-induced drop in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or patients aged 75 years and older.
In case of conditions that may lead to fluid loss (e.g. gastrointestinal illness), careful monitoring of volume status (e.g. physical examination, blood pressure measurements, laboratory tests including haematocrit) and electrolytes is recommended for patients receiving empagliflozin. Temporary interruption of treatment with JARDIANCE DUO should be considered until the fluid loss is corrected.
Urosepsis and Pyelonephritis: There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalisation in patients receiving SGLT2 inhibitors, including empagliflozin. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated (see Adverse Reactions).
Discontinuation of JARDIANCE DUO 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 another SGLT2 inhibitor. It is unknown whether this constitutes a class effect. Like for all diabetic patients it is important to counsel patients on routine preventive foot care.
Combination with glucagon like peptide (GLP-1) analogues: Empagliflozin has not been studied in combination with glucagon like peptide 1 (GLP-1) analogues.
Administration of iodinated contrast agent: Intravascular administration of iodinated contrast media may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis. Metformin should be discontinued prior to or at the time of the imaging procedure and not restarted until 48 hours afterwards, provided that renal function has been re-evaluated and found to be stable (see Interactions).
Surgery: JARDIANCE DUO must be discontinued at the time of surgery under general, spinal or epidural anaesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and provided that renal function has been re-evaluated and found to be stable.
Vitamin B12 levels: The risk of low vitamin B12 levels increases with increasing metformin dose, treatment duration, and/or in patients with risk factors known to cause vitamin B12 deficiency. In case of suspicion of vitamin B12 deficiency (such as anaemia or neuropathy), vitamin B12 serum levels should be monitored. Periodic vitamin B12 monitoring could be necessary in patients with risk factors for vitamin B12 deficiency. Metformin therapy should be continued for as long as it is tolerated and not contra-indicated and appropriate corrective treatment for vitamin B12 deficiency in line with current guidelines.
Effect on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.
Use in Children: Safety and effectiveness of JARDIANCE DUO in paediatric patients under 18 years have not been established.
Use in the elderly: Patient aged 75 years and older may be at an increased risk of volume depletion, therefore, JARDIANCE DUO should be prescribed with caution in these patients (see Adverse Reactions).
As metformin is extracted by the kidney, JARDIANCE DUO should be used with caution as age increase. Monitoring of renal function is necessary to aid in prevention of metformin associated lactic acidosis, particularly in elderly patients.