Empagliflozin-Linagliptin

Empagliflozin/Linagliptin is a combination prescription medication used for treating the symptoms of type 2 diabetes mellitus.

• Empagliflozin/Linagliptin is available under the following different brand names: Glyxambi

Adult dosage

Tablet

• 10mg/5mg
• 25mg/5mg

Type 2 Diabetes Mellitus

Adult and geriatric dosage

• 10 mg/5 mg orally every day in the morning, taken with or without food
• The dose may be increased to 25 mg/5mg once daily if needed and tolerated

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Empagliflozin/Linagliptin include:

• urinary tract infection
• common cold symptoms
• upper respiratory tract infections
• genital yeast infection
• increased urination
• joint pain
• nausea
• runny or stuffy nose
• diarrhea
• cough
• elevated blood cholesterol or fat
• diarrhea.

Serious side effects of Empagliflozin/Linagliptin include:

• severe or ongoing pain in your joints;
• serious skin reaction--itching, blisters, breakdown of the outer layer of skin;
• ketoacidosis (too much acid in the blood)--nausea, vomiting, stomach pain, confusion, unusual drowsiness, or trouble breathing;
• pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;
• dehydration symptoms--dizziness, weakness, feeling light-headed (like you might pass out);
• signs of a bladder infection--pain or burning when you urinate, blood in your urine, pain in the pelvis or back; or
• symptoms of heart failure--shortness of breath (even while lying down), swelling in your legs or feet, rapid weight gain.

Rare side effects of Empagliflozin/Linagliptin include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Empagliflozin/Linagliptin has severe interactions with no other drugs.
• Empagliflozin/Linagliptin has serious interactions with the following drugs:
  • abametapir
  • amobarbital
  • apalutamide
  • benazepril
  • dabrafenib
  • fexinidazole
  • idelalisib
  • ivosidenib
  • lasmiditan
  • lorlatinib
  • secobarbital
  • sotorasib
  • tepotinib
  • tipranavir
  • tucatinib
  • voxelotor
• Empagliflozin/Linagliptin has moderate interactions with at least 104 other drugs.
• Empagliflozin/Linagliptin has minor interactions with the following drug:
  • ribociclib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Severe renal impairment, end-stage renal disease, or dialysis
• Hypersensitivity to empagliflozin, Linagliptin, or excipients (e.g., anaphylaxis, angioedema, exfoliative skin conditions, urticaria, bronchial hyperreactivity)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Empagliflozin/Linagliptin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Empagliflozin/Linagliptin?”

Cautions

• Acute pancreatitis, including fatal pancreatitis, is reported; if pancreatitis is suspected, promptly discontinue and initiate appropriate management; it is unknown whether patients with a history of pancreatitis are at risk for the development of the disease while receiving therapy
• Serious hypersensitivity reactions, (e.g., angioedema) in patients treated with empagliflozin reported postmarketing; onset of these reactions occurred predominantly within the first 3 months after initiation of treatment with this drug, with some reports occurring after the first dose; angioedema reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors; use caution in a patient with a history of angioedema to another DPP-4 inhibitor; unknown whether such patients will be predisposed to angioedema with this drug; discontinue therapy and treat promptly if it occurs per standard of care
• Heart failure has been observed with two other members of the DPP-4 inhibitor class; consider risks and benefits of empagliflozin in patients with risk factors for heart failure; monitor for signs and symptoms; if heart failure develops, advise patients of characteristic symptoms of heart failure and to immediately report such symptoms; manage accordingly to the standard of care and consider interrupting treatment
• Bullous pemphigoid was reported with DPP-4 inhibitor use, which required hospitalization; in reported cases, patients recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP-4 inhibitor; patients should report the development of blisters/erosions; discontinue DPP-4 therapy and consult a dermatologist if bullous pemphigoid suspected
• Hypoglycemia risk increased with insulin and insulin secretagogues (e.g., sulfonylureas); a lower dose of insulin or the insulin secretagogue may be required
• Genital mycotic infections may occur; patients with a history of genital mycotic infections and uncircumcised males are more susceptible; monitor and treat as appropriate
• Empagliflozin increases the risk for urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated
• Necrotizing fasciitis of the perineum (Fournier gangrene) was reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4ºF or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary
• Reports of serious hypersensitivity reactions in patients treated with Linagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions; if signs and symptoms occur, promptly institute appropriate monitoring and treatment and initiate alternative treatment for diabetes
• Dose-related increases in LDL-C reported
• No conclusive evidence of macrovascular risk reduction with empagliflozin or any other antidiabetic agent
• Severe and disabling arthralgia was reported 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 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
• Volume depletion
  • Empagliflozin can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine; acute kidney injury, some requiring hospitalization, and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including empagliflozin reported postmarketing
  • 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
  • Before initiating therapy in patients with one or more of these characteristics, assess volume status and renal function; in patients with volume depletion, correct this condition before initiating treatment; monitor for signs and symptoms of volume depletion, and renal function after initiating therapy
• Ketoacidosis
  • Ketoacidosis was reported in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors
  • Drug combination not indicated for the treatment of type 1 diabetes mellitus
  • Patients receiving therapy who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels; ketoacidosis may be present even if blood glucose levels are less than 250 mg/dL; if ketoacidosis is suspected, discontinue therapy, evaluate patient, and institute treatment promptly; treatment of ketoacidosis may require insulin, fluid and carbohydrate replacement
  • Fatal cases of ketoacidosis reported in patients taking empagliflozin (SGLT2 inhibitors) reported; monitor for signs of ketoacidosis and advise patients to seek immediate medical attention for symptoms (e.g., difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue or sleepiness)
  • In some but not all cases, factors predisposing to ketoacidosis such as insulin dose reduction, acute febrile illness, reduced caloric intake, surgery, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse was identified
  • Before initiating therapy, consider factors in the patient’s history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
  • Consider temporarily discontinuing therapy for at least 3 days for patients who undergo scheduled surgery
  • Restart once the patient’s oral intake is back to baseline and any other risk factors for ketoacidosis (blood acid buildup) are resolved
  • Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved before restarting the therapy
  • Educate patients on signs and symptoms of ketoacidosis and instruct patients to discontinue the drug and seek medical attention immediately if signs and symptoms occur
  • Acute kidney injury and renal impairment
  • Empagliflozin causes intravascular volume contraction and can cause renal impairment; before initiating therapy, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs); consider temporarily discontinuing therapy in the setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure); monitor for signs and symptoms of acute kidney injury
  • If acute kidney injury occurs, discontinue therapy promptly and institute treatment; renal function abnormalities can occur after initiating therapy; evaluate and monitor renal function periodically thereafter; more frequent renal function monitoring is recommended in patients with an eGFR above 60 mL/min/1.73 m2 therapy is not recommended when eGFR is persistently below 45 mL/min/1.73 m2 and is contraindicated in patients with an eGFR below 30 mL/min/1.73 m2

Pregnancy and Lactation

• 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
• Lactation
  • There is no information regarding the presence in human milk, effects on the breastfed infant, or effects on milk production; since the potential for serious adverse reactions, including the 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