• Type 2 diabetes (as adjunct to diet and exercise).
• To reduce risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease (empagliflozin).

Contraindicated in:

• Hypersensitivity
• Severe renal impairment (eGFR <30 mL/min/1.73 m²/end-stage renal disease/dialysis)
• Type 1 diabetes
• Diabetic ketoacidosis
• OB: Avoid use during 2nd and 3rd trimesters (may lead to renal impairment in fetus)
• Lactation: Lactation.

Use Cautiously in:

• eGFR <60 mL/min/1.73 m² or concurrent use of loop diuretics (↑ risk of volume depletion or hypotension)
• History of pancreatitis, pancreatic surgery, reduced caloric intake due to illness or surgery, or alcohol abuse (↑ risk of ketoacidosis)
• History of HF or renal impairment (↑ risk of HF)
• Pedi: Safety and effectiveness not established in children
• Geri: Empagliflozin appears on Beers list. Older adults may have ↑ risk of urogenital infections (especially women in the 1st mo of treatment) and euglycemic diabetic ketoacidosis. Use with caution in older adults.

Empagliflozin

CV: hypotension, volume depletion.

Endo: hypoglycemia (↑with other medications).

F and E: hyperphosphatemia, KETOACIDOSIS.

GU: acute kidney injury, genital mycotic infections, ↑ urination, NECROTIZING FASCIITIS OF PERINEUM (FOURNIER'S GANGRENE), renal impairment, urinary tract infections (including pyelonephritis), UROSEPSIS.

Metab: hyperlipidemia.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA).

Linagliptin

CV: HF.

Derm: bullous pemphigoid, localized exfoliation, urticaria.

GI: PANCREATITIS.

Metab: hypoglycemia, hypertriglyceridemia.

MS: RHABDOMYOLYSIS.

Resp: bronchial hyperreactivity.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA).

Drug-Drug:

• ↑risk of hypotension when empagliflozin is used with antihypertensives or diuretics.
• ↑risk of hypoglycemia with sulfonylureas or insulin; dose ↓ of sulfonylurea or insulin may be necessary.
• ↑risk of acute kidney injury when empagliflozin is used with diuretics, ACE inhibitors, angiotensin receptor blockers, or NSAIDs.
• Concurrent use of P-glycoprotein inducers or CYP3A4 inducers, including rifampin may ↓ linagliptin levels and effectiveness; avoid concurrent use.
• Empagliflozin may ↓ lithium levels and effectiveness.

(Generic available)

• Tablets: empagliflozin 10 mg/linagliptin 5 mg; empagliflozin 25 mg/linagliptin 5 mg;

• PO (Adults): Empagliflozin 10 mg/linagliptin 5 mg once daily; may ↑ to empagliflozin 25 mg/linagliptin 5 mg once daily.

Glyxambi

• Empagliflozin — Inhibits proximal renal tubular sodium-glucose co-transporter 2 (SGLT2) which determines reabsorption of glucose from the tubular lumen. Inhibits reabsorption of glucose, lowers renal threshold for glucose and increases excretion of glucose in urine.
• Linagliptin — Inhibits the enzyme dipeptidyl peptidase-4 (DPP-4), which slows the inactivation of incretin hormones, resulting in increased levels of active incretin hormones. These hormones are released by the intestine throughout the day, and are involved in regulation of glucose. Increased/prolonged incretin levels increase insulin release and decrease glucagon levels.

• Improved glycemic control
• Reduced death due to cardiovascular causes

Therapeutic Classification: antidiabetics

Pharmacologic Classification: sodium-glucose co-transporter 2 (SGLT2) inhibitors

Empagliflozin

Absorption: Well absorbed following oral administration.

Distribution: Enters red blood cells, remainder of distribution unknown.

Metabolism/Excretion: Minimally metabolized; excreted in feces (41.2% mostly as unchanged drug) and urine (54.4% half as unchanged drug, half as metabolites).

Half-life: 12.4 hr.

Linagliptin

Absorption: 30% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Approximately 90% excreted unchanged in urine; minimally metabolized.

Half-life: >100 hr (due to saturable binding to DPP-4).

(↓ in A1c)

†Plasma concentrations.

• Instruct patient to take empagliflozin/linagliptin as directed. Take missed doses as soon as remembered, unless it is almost time for next dose; do not double doses. Advise patient to read the Medication Guide before starting and with each Rx refill; in case of changes.
• Explain to patient that empagliflozin/linagliptin helps control hyperglycemia but does not cure diabetes. Therapy is usually long term.
• Instruct patient not to share this medication with others, even if they have the same symptoms; it may harm them.
• Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hyperglycemic or hypoglycemic episodes.
• Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water, and notify health care professional.
• Instruct patient in proper testing of blood glucose and urine ketones. Inform patient that empagliflozin/linagliptin will cause a positive test result when testing for urine glucose. These tests should be monitored closely during periods of stress or illness and health care professional notified if significant changes occur.
• Advise patient to notify health care professional if new pain or tenderness, sores or ulcers, or infections involving the leg or foot occur and to immediately seek care if pain or tenderness, redness, or swelling of the genitals or area from the genitals back to the rectum, along with a fever above 100.4°F or malaise occur.
• Advise patient to notify health care professional promptly if signs and symptoms of pancreatitis, HF (shortness of breath, rapid increase in weight, swelling of feet), or if rash; hives; or swelling of face, lips, or throat occur.
• Advise patient to notify health care professional if signs and symptoms of hypotension occur and to maintain adequate hydration as dehydration may increase risk of hypotension.
• Inform patient that empagliflozin/linagliptin may cause mycotic (yeast) infections. Women may have signs and symptoms of a vaginal yeast infection (vaginal odor, white or yellow vaginal discharge [may be lumpy or look like cottage cheese], vaginal itching). Men may have signs and symptoms of a yeast infection of the penis (redness, itching or swelling of penis; rash on penis; foul smelling discharge from penis; pain in skin around penis). Advise patient to notify health care professional if yeast infection occurs.
• Advise patient to notify health care professional if signs and symptoms of urinary tract infection (burning feeling when passing urine, cloudy urine, pain in pelvis or back) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially other oral hypoglycemic medications.
• Rep: Insulin is the recommended method of controlling blood sugar during pregnancy. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.
• Encourage patient to follow up with routine lab tests for blood glucose and renal function.

em-pa-gli-FLOE-zin/lin-a-GLIP-tin

NDC Code^*

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0164- Glyxambi
    • 0597-0164-07- 1 BOTTLE in 1 CARTON (0597-0164-07) > 7 TABLET, FILM COATED in 1 BOTTLE

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0164- Glyxambi
    • 0597-0164-30- 30 TABLET, FILM COATED in 1 BOTTLE (0597-0164-30)

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0164- Glyxambi
    • 0597-0164-39- 30 BLISTER PACK in 1 CARTON (0597-0164-39) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0164- Glyxambi
    • 0597-0164-90- 90 TABLET, FILM COATED in 1 BOTTLE (0597-0164-90)

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0182- Glyxambi
    • 0597-0182-07- 1 BOTTLE in 1 CARTON (0597-0182-07) > 7 TABLET, FILM COATED in 1 BOTTLE

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0182- Glyxambi
    • 0597-0182-30- 30 TABLET, FILM COATED in 1 BOTTLE (0597-0182-30)

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0182- Glyxambi
    • 0597-0182-39- 30 BLISTER PACK in 1 CARTON (0597-0182-39) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 0597- Boehringer Ingelheim Pharmaceuticals, Inc.
  • 0597-0182- Glyxambi
    • 0597-0182-90- 90 TABLET, FILM COATED in 1 BOTTLE (0597-0182-90)

• 70518- REMEDYREPACK INC.
  • 70518-2046- Glyxambi
    • 70518-2046-0- 90 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (70518-2046-0)