Generic Name

Empagliflozin + Linagliptin

Precaution

Not to be used in patients w/ type 1 diabetes. Immediately assess for ketoacidosis if symptoms eg, nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness occur. Discontinue treatment if ketoacidosis, necrotizing fasciitis of the perineum (Fournier's gangrene), pancreatitis, bullous pemphigoid is suspected or in clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or surgery). Higher risk of ketoacidosis in patients on a very low carbohydrate diet, w/ an acute illness, pancreatic disorders suggesting insulin deficiency (eg, type 1 diabetes, history of pancreatitis or pancreatic surgery), insulin dose reduction (including insulin pump failure), alcohol abuse, severe dehydration & history of ketoacidosis. Evaluate for necrotizing fasciitis in patients who present w/ pain or tenderness, erythema, swelling in the genital or perineal area, fever, malaise. Combination w/ sulphonylurea or insulin. Patients for whom an empagliflozin-induced decrease in BP could pose a risk eg, patients w/ known CV disease, on antihypertensive therapy w/ history of hypotension or patients ≥75 yr. Monitor carefully vol status (eg, physical exam, BP measurements, laboratory tests including haematocrit) & electrolytes in conditions that may lead to fluid loss (eg, GI illness). Complicated UTI including pyelonephritis & urosepsis. Cardiac failure (NYHA class I-IV). Positive test result for glucose in urine. Not to be used in patients w/ eGFR <60 mL/min/1.73 m2 or CrCl <60 mL/min. Assess renal function prior to treatment initiation & periodically during treatment; & prior to initiation of any concomitant medicines that may have negative impact on renal function. Avoid use during pregnancy. Discontinue breast feeding during treatment. Not recommended for use in childn <18 yr. Not recommended in elderly >85 yr.

Indication

Type 2 Diabetes Mellitus

Contra Indication

Severe renal impairment, end-stage renal disease, or dialysis Hypersensitivity to empagliflozin, linagliptin, or excipients (eg, anaphylaxis, angioedema, exfoliative skin conditions, urticaria, bronchial hyperreactivity)

Dose

N/A

Side Effect

>10% Urinary tract infection (11.4-12.5%) 1-10% Upper respiratory tract infection (7%) Nasopharyngitis (5.9-6.6%) Increased LDL-C (4.6-6.5%) Hypoglycemia (2.2-3.6%) Increased hematocrit (2.8%)

Pregnancy Category

Mode of Action

First combination approved by the FDA of a sodium glucose cotransporter-2 (SGLT2) inhibitor and a dipeptidyl peptidase-4 (DPP-4) inhibitor Empagliflozin: SGLT2 inhibitor; SGLT2 is expressed in the proximal renal tubules and is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion Linagliptin: DPP-4 inhibitor; increases and prolongs incretin hormone activity, which is inactivated by DPP-4 enzyme; incretins regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and reducing glucagon secretion from pancreatic alpha cells

Interaction

May increase risk of hypoglycemia w/ insulin & sulphonylureas. Interference w/ 1,5-anhydroglucitol (1,5-AG) assay. Empagliflozin: May add to the diuretic effect of thiazide & loop diuretics & may increase risk of dehydration & hypotension. Risk of decreased efficacy w/ UGT enzyme inducers. Linagliptin: Decreased exposure w/ rifampicin & reduced efficacy w/ strong P-gp or CYP450 isozyme CYP3A4 inducer.

Pregnancy Category Note

Pregnancy Based on animal data showing adverse renal effects from empagliflozin, it is not recommended during the second and third trimesters of pregnancy There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy; an alternate diabetic therapy appropriate for pregnant women should be initiated Animal data In animal studies, empagliflozin, a component of the drug combination, resulted in adverse renal changes in rats when administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy Doses approximately 13-times maximum clinical dose caused renal pelvic and tubule dilatations that were reversible No adverse developmental effects were observed when the combination of linagliptin and empagliflozin was administered to pregnant rats Lactation There is no information regarding presence in human milk, effects on breastfed infant, or effects on milk production; since potential for serious adverse reactions, including potential for empagliflozin to affect postnatal renal development, in a breastfed infant, advise patients that therapy is not recommended while breastfeeding; a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother should be initiated

Adult Dose

Type 2 Diabetes Mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes when both empagliflozin and linagliptin are appropriate treatments. 10 mg/5 mg once daily in the morning. Dose may be increased to 25 mg/5 mg once daily if needed and tolerated. Hepatic impairment: No dose adjustment required

Child Dose

N/A

Renal Dose

Renal impairment eGFR >45 mL/min/1.73 m2: No dose adjustment required eGFR 30-45 mL/min/1.73 m2: Do not initiate drug eGFR < 30 mL/min/1.73 m2, end-stage renal disease (ESRD), or dialysis: Contraindicated Discontinued if eGFR is persistently drops to <45 mL/min/1.73 m2

Administration

May be taken with or without food