Jardiance Duo

/ Boehringer Ingelheim

Recommended Dosage:
1. In patients with volume depletion not previously treated with empagliflozin, correct this condition before initiating this formulation.
2. Individualize the starting dose of this formulation based on the patient’s current regimen:
– In patients on metformin hydrochloride, switch to this combined formulaion containing empagliflozin 5 mg  with a similar total daily dose of metformin hydrochloride;
– In patients already treated with empagliflozin and metformin hydrochloride, switch to this combined formulation containing the same total daily doses of each component.
3. Take combined formulation twice daily with meals; with gradual dose escalation to reduce the gastrointestinal side effects due to metformin.
4. Adjust dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of metformin hydrochloride 2000 mg and empagliflozin 25 mg.
Recommended Dosage in Patients with Renal Impairment:
1. Assess renal function prior to initiation of this combined formulaion and periodically, thereafter.
2. This combined formulaion is contraindicated in patients with an eGFR less than 45 mL/min/1.73 m².
Discontinuation for Iodinated Contrast Imaging Procedures:
Discontinue this formulation at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 45 and 60 mL/min/1.73 m²; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after the imaging procedure; restart this formulation if renal function is stable. 

Indicated in adults aged 18 years and older with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control
1. in patients inadequately controlled on their maximally tolerated dose of metformin alone.
2. in patients inadequately controlled with metformin in combination with other glucose-lowering medicinal products, including insulin.
3. in patients already being treated with the combination of empagliflozin and metformin as separate tablets.

This product is contraindicated in patients with:
1. Moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m²), end stage renal disease, or dialysis.
2. Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin.
3. Hypersensitivity reaction to empagliflozin, metformin, or any of the excipients.

This formulation is not indicated for patients with type 1 diabetes.
Lactic acidosis: Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Ketoacidosis: Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization have been identified in postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors, including empagliflozin. Fatal cases of ketoacidosis have been reported in patients taking empagliflozin. This formulation is not indicated for the treatment of patients with type 1 diabetes mellitus.
Volume Depletion: Empagliflozin can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including empagliflozin. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. In patients with volume depletion, correct this condition before initiating this medicinal product. Monitor for signs and symptoms of volume depletion and renal function after initiating therapy.
Urosepsis and Pyelonephritis: There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including empagliflozin.
Hypoglycemia: Insulin and insulin secretagogues are known to cause hypoglycemia. The risk of hypoglycemia is increased when empagliflozin is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Reports of necrotizing fasciitis of the perineum (Fournier’s gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including empagliflozin. Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death.
Patients treated with JARDIANCE DUO presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue this drug, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
Genital Mycotic Infections: Empagliflozin increases the risk for genital mycotic infections. Patients with a history of chronic or recurrent genital mycotic infections were more likely to develop genital mycotic infections. Monitor and treat as appropriate.
Lower Limb Amputation: In some clinical studies with SGLT2 inhibitors an imbalance in the incidence of lower limb amputation has been observed.
this medicinal product is not indicated for the treatment of chronic kidney disease.
Peripheral artery disease, and diabetic foot infection (including osteomyelitis), were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of diabetic foot, peripheral artery disease (including previous amputation) or diabetes.
Counsel patients about the importance of routine preventative foot care. Monitor patients for signs and symptoms of diabetic foot infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions, (e.g., angioedema) in patients treated with empagliflozin, one of the components of this formula. If a hypersensitivity reaction occurs, discontinue this product; treat promptly per standard of care, and monitor until signs and symptoms resolve. This product is contraindicated in patients with a previous serious hypersensitivity reaction to empagliflozin or any of the excipients in this formula.
Vitamin B12 Levels: In controlled, 29-week clinical trials of metformin, a decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of metformin-treated patients.
Effects on ability to drive and use machines: this medicinal product has minor influence on the ability to drive and use machines. Patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines, in particular when this drug is used in combination with a sulphonylurea and/or insulin.
See prescribing information for full details.

Lactic Acidosis, ketoacidosis, volume depletion, urosepsis and pyelonephritis ,hypoglycemia, necrotizing fasciitis of the perineum, genital mycotic infections, hypersensitivity Reactions, vitamin B₁₂ deficiency, lower limb amputation.
See prescribing information for full details.

Drug Interactions with Empagliflozin: 
Diuretics: Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.
Insulin or Insulin Secretagogues: Coadministration of empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia.
Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control.
Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 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.
Drug Interactions with Metformin Hydrochloride:
Drugs that Reduce Metformin Clearance: Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal
elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use.
Carbonic Anhydrase Inhibitors: Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide)
frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with this product may increase the risk of lactic acidosis. Consider more frequent monitoring of these patients.
Drugs Affecting Glycemic Control: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include
the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving this product, the patient should be closely observed to maintain adequate glycemic control. When such drugs are withdrawn from a patient receiving this product, the patient should be observed closely for hypoglycemia.
Alcohol: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving this product.

Pregnancy: Based on animal data showing adverse renal effects, this formulation is not recommended during the second and third trimesters of pregnancy.
Lactation: There is no information regarding the presence of this formulation or empagliflozin in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed infant, including the potential for empagliflozin to affect postnatal renal development, advise women that use of this product is not recommended while breastfeeding.
See prescribing information for full details.

Employ the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive treatment) as dictated by the patient’s clinical status. Removal of empagliflozin by hemodialysis has not been studied. However, metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful partly for removal of accumulated metformin from patients in whom this formulation overdosage is suspected.
Metformin hydrochloride: Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams.
Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases.

Storage: Store below 25°C.