Glyxambi

/ Boehringer Ingelheim

The recommended dose of this drug is 10 mg empagliflozin/5 mg linagliptin once daily in the morning, taken with or without food. In patients tolerating this formulation, the dose may be increased to 25 mg empagliflozin/5 mg linagliptin once daily.
In patients with volume depletion, correcting this condition prior to initiation of this formulation is recommended.
No studies have been performed specifically examining the safety and efficacy of this drug  in patients previously treated with other oral antihyperglycemic agents and switched to this formulation.  Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.
Patients with Renal Impairment: Assessment of renal function is recommended prior to initiation of this drug and periodically thereafter. This formulation should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m2. No dose adjustment is needed in patients with an eGFR greater than or equal to 45 mL/min/1.73 m2. This drug should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m2.
Hepatic impairment: may be used in patients with hepatic impairment.
See prescribing information for full details.

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both empagliflozin and linagliptin is appropriate.
Limitations of Use: This drug is not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
This formulation has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using this drug.

Severe renal impairment, end-stage renal disease, or dialysis.
Serious hypersensitivity reaction to empagliflozin, linagliptin, or any of the excipients in this product such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity.

Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue the drug  and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using this formulation.
Heart Failure: An association between DPP-4 inhibitor treatment and heart failure has been observed in cardiovascular outcomes trials for two other members of the DPP-4 inhibitor class. These trials evaluated patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Consider the risks and benefits of GLYXAMBI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of GLYXAMBI.
Hypotension: Empagliflozin causes intravascular volume contraction. Symptomatic hypotension may occur after initiating empagliflozin  particularly in patients with renal impairment, the elderly, in patients with low systolic blood pressure, and in patients on diuretics. Before initiating this formulation, assess for volume contraction and correct volume status if indicated. Monitor for signs and symptoms of hypotension after initiating therapy and increase monitoring in clinical situations where volume contraction is expected.
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. GLYXAMBI is not indicated for the treatment of patients with type 1 diabetes mellitus.
Acute Kidney Injury and Impairment in Renal Function: Empagliflozin causes intravascular volume contraction and can cause renal impairment. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors, including empagliflozin; some reports involved patients younger than 65 years of age.
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. 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.
Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia. The use of empagliflozin or linagliptin in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin was associated with a higher rate of hypoglycemia compared with placebo in a clinical trial. Therefore, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with  this drug.
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 mycotic genital mycotic infections. Monitor and treat as appropriate.
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with linagliptin . These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with linagliptin, with some reports occurring after the first dose.
Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema to another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with this product. There have been postmarketing reports of serious hypersensitivity reactions, (e.g., angioedema) in patients treated with empaglifozin (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 linagliptin or empagliflozin.
Increased Low-Density Lipoprotein Cholesterol (LDL-C): Increases in LDL-C can occur with empagliflozin . Monitor and treat as appropriate.
Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider as a possible cause for severe joint pain and discontinue drug if appropriate.
Bullous Pemphigoid: Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving GLYXAMBI. If bullous pemphigoid is suspected, GLYXAMBI should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with this drug or any other antidiabetic drug.
Lower limb amputations: An increase in cases of lower limb amputation (primarily of the toe) has been observed in ongoing 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 preventative footcare.
See prescribing information for full details.

Pancreatitis, Heart Failure, Hypotension, Ketoacidosis, Acute Kidney Injury and Impairment in Renal Function, Urosepsis and Pyelonephritis, Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues, Genital Mycotic Infections, Hypersensitivity Reactions, Increased Low-Density Lipoprotein Cholesterol (LDL-C), Severe and Disabling Arthralgia, Bullous Pemphigoid.       
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 Linagliptin:
Inducers of P-glycoprotein or CYP3A4 Enzymes: Rifampin decreased linagliptin exposure, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Therefore, use of alternative treatments is strongly recommended when linagliptin is to be administered with a strong P-gp or CYP3A4 inducer.

Pregnancy: Based on animal data showing adverse renal effects, from empagliflozin, GLYXAMBI is not recommended during the second and third trimesters of pregnancy.
Lactation: There is no information regarding the combined presence of GLYXAMBI, or its individual components in human milk, the effects on the breastfed infant, or the effects on milk production.
See prescribing information for full details.

In the event of an overdose with this drug, contact the nearest hospital immediately. 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, and removal of linagliptin by hemodialysis or peritoneal dialysis is unlikely.

Storage: Do not store above 25°C.