Glyxambi Side Effects Center

Last updated on RxList: 4/25/2022
Glyxambi Side Effects Center

What Is Glyxambi?

Glyxambi (empagliflozin and linagliptin) is a combination of an inhibitor of the sodium-glucose co-transporter (SGLT2) and an inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

What Are Side Effects of Glyxambi?

Common side effects of Glyxambi include:

Dosage for Glyxambi

The recommended dose of Glyxambi is 10 mg empagliflozin/5 mg linagliptin once daily in the morning, taken with or without food. In patients tolerating Glyxambi, the dose may be increased to 25 mg empagliflozin/5 mg linagliptin once daily.

What Drugs, Substances, or Supplements Interact with Glyxambi?

Glyxambi may interact with diuretics and strong P-gp or CYP3A4 inducers. Tell your doctor all medications and supplements you use.

Glyxambi During Pregnancy and Breastfeeding

During pregnancy, Glyxambi should be taken only if prescribed. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Glyxambi (empagliflozin and linagliptin) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

______________ is another term for type 2 diabetes. See Answer
Glyxambi Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives, itching, flaking or peeling skin; trouble swallowing, difficult breathing; swelling of your face, lips, tongue, or throat.

Seek medical attention right away if you have signs of a serious genital infection (penis or vagina): burning, itching, odor, discharge, pain, tenderness, redness or swelling of the genital or rectal area, fever, not feeling well. These symptoms may get worse quickly.

Stop taking this medicine and call your doctor at once if you have:

  • a light-headed feeling, like you might pass out;
  • 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;
  • dehydration--dizziness, confusion, feeling very thirsty, less urination;
  • signs of a bladder infection--pain or burning when you urinate, blood in your urine, pain in pelvis or back; or
  • symptoms of heart failure--shortness of breath (even while lying down), swelling in your legs or feet, rapid weight gain.

Common side effects may include:

  • a bladder infection; or
  • cold symptoms such as runny or stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Glyxambi (Empagliflozin and Linagliptin Tablets)

SLIDESHOW

Type 2 Diabetes: Signs, Symptoms, Treatments See Slideshow
Glyxambi Professional Information

SIDE EFFECTS

The following important adverse reactions are described below and elsewhere in the labeling:

  • Pancreatitis [see WARNINGS AND PRECAUTIONS]
  • Ketoacidosis [see WARNINGS AND PRECAUTIONS]
  • Volume Depletion [see WARNINGS AND PRECAUTIONS]
  • Urosepsis and Pyelonephritis [see WARNINGS AND PRECAUTIONS]
  • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see WARNINGS AND PRECAUTIONS]
  • Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) [see WARNINGS AND PRECAUTIONS]
  • Genital Mycotic Infections [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  • Severe and Disabling Arthralgia [see WARNINGS AND PRECAUTIONS]
  • Bullous Pemphigoid [see WARNINGS AND PRECAUTIONS]
  • Heart Failure [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Empagliflozin And Linagliptin

The safety of concomitantly administered empagliflozin (daily dose 10 mg or 25 mg) and linagliptin (daily dose 5 mg) has been evaluated in a total of 1363 patients with type 2 diabetes treated for up to 52 weeks in active-controlled clinical trials. The most common adverse reactions with concomitant administration of empagliflozin and linagliptin based on a pooled analyses of these studies are shown in Table 1.

Table 1 : Adverse Reactions Reported in ≥5% of Patients Treated with Empagliflozin and Linagliptin

Adverse Reactions GLYXAMBI (%) 10 mg/5 mg
n=272
GLYXAMBI (%) 25 mg/5 mg
n=273
Urinary tract infectiona 12.5 11.4
Nasopharyngitis 5.9 6.6
Upper respiratory tract infection 7.0 7.0
aPredefined adverse event grouping, including, but not limited to, urinary tract infection, asymptomatic bacteriuria, cystitis

Empagliflozin

Adverse reactions that occurred in ≥2% of patients receiving empagliflozin and more commonly than in patients given placebo included (10 mg, 25 mg, and placebo): urinary tract infection (9.3%, 7.6%, and 7.6%), female genital mycotic infections (5.4%, 6.4%, and 1.5%), upper respiratory tract infection (3.1%, 4.0%, and 3.8%), increased urination (3.4%, 3.2%, and 1.0%), dyslipidemia (3.9%, 2.9%, and 3.4%), arthralgia (2.4%, 2.3%, and 2.2%), male genital mycotic infections (3.1%, 1.6%, and 0.4%), and nausea (2.3%, 1.1%, and 1.4%).

Thirst (including polydipsia) was reported in 0%, 1.7%, and 1.5% for placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively.

Empagliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion. Events related to volume depletion (hypotension and syncope) were reported in 3 patients (1.1%) treated with GLYXAMBI plus metformin.

Linagliptin

Adverse reactions reported in ≥2% of patients treated with linagliptin 5 mg and more commonly than in patients treated with placebo included: nasopharyngitis (7.0% and 6.1%), diarrhea (3.3% and 3.0%), and cough (2.1% and 1.4%).

Other adverse reactions reported in clinical studies with treatment of linagliptin monotherapy were hypersensitivity (e.g., urticaria, angioedema, localized skin exfoliation, or bronchial hyperreactivity) and myalgia.

In the clinical trial program, pancreatitis was reported in 15.2 cases per 10,000 patient year exposure while being treated with linagliptin compared with 3.7 cases per 10,000 patient year exposure while being treated with comparator (placebo and active comparator, sulfonylurea). Three additional cases of pancreatitis were reported following the last administered dose of linagliptin.

Hypoglycemia

Table 2 summarizes the reports of hypoglycemia with empagliflozin and linagliptin over a treatment period of 52 weeks.

Table 2 Incidence of Overalla and Severeb Hypoglycemic Adverse Reactions

Add-on to Metformin (52 weeks) GLYXAMBI (%) 10 mg/5 mg
(n=136)
GLYXAMBI (%) 25 mg/5 mg
(n=137)
Overall 2.2 3.6
Severe 0 0
aOverall hypoglycemic events: plasma or capillary glucose of less than or equal to 70 mg/dL or requiring assistance
bSevere hypoglycemic events: requiring assistance regardless of blood glucose

Laboratory Tests

Empagliflozin And Linagliptin

Changes in laboratory findings in patients treated with the combination of empagliflozin and linagliptin included increases in cholesterol and hematocrit compared to baseline.

Empagliflozin

Increases In Serum Creatinine And Decreases In Egfr

Initiation of empagliflozin causes an increase in serum creatinine and decrease in eGFR within weeks of starting therapy and then these changes stabilize. In a study of patients with moderate renal impairment, larger mean changes were observed. In a long-term cardiovascular outcomes trial, the increase in serum creatinine and decrease in eGFR generally did not exceed 0.1 mg/dL and -9.0 mL/min/1.73 m², respectively, at Week 4, and reversed after treatment discontinuation, suggesting acute hemodynamic changes may play a role in the renal function changes observed with empagliflozin.

Increase In Low-Density Lipoprotein Cholesterol (LDL-C)

Dose-related increases in low-density lipoprotein cholesterol (LDL-C) were observed in patients treated with empagliflozin. LDL-C increased by 2.3%, 4.6%, and 6.5% in patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. The range of mean baseline LDL-C levels was 90.3 to 90.6 mg/dL across treatment groups.

Increase In Hematocrit

Median hematocrit decreased by 1.3% in placebo and increased by 2.8% in empagliflozin 10 mg and 2.8% in empagliflozin 25 mg treated patients. At the end of treatment, 0.6%, 2.7%, and 3.5% of patients with hematocrits initially within the reference range had values above the upper limit of the reference range with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively.

Linagliptin

Increase In Uric Acid

Changes in laboratory values that occurred more frequently in the linagliptin group and ≥1% more than in the placebo group were increases in uric acid (1.3% in the placebo group, 2.7% in the linagliptin group).

Increase In Lipase

In a placebo-controlled clinical trial with linagliptin in type 2 diabetes mellitus patients with micro-or macroalbuminuria, a mean increase of 30% in lipase concentrations from baseline to 24 weeks was observed in the linagliptin arm compared to a mean decrease of 2% in the placebo arm. Lipase levels above 3 times upper limit of normal were seen in 8.2% compared to 1.7% patients in the linagliptin and placebo arms, respectively.

Increase In Amylase

In a cardiovascular safety study comparing linagliptin versus glimepiride in patients with type 2 diabetes mellitus, amylase levels above 3 times upper limit of normal were seen in 1.0% compared to 0.5% of patients in the linagliptin and glimepiride arms, respectively.

The clinical significance of elevations in lipase and amylase with linagliptin is unknown in the absence of other signs and symptoms of pancreatitis.

Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of linagliptin and empagliflozin. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Acute Pancreatitis, including Fatal Pancreatitis [see INDICATIONS AND USAGE]
  • Ketoacidosis
  • Urosepsis and Pyelonephritis
  • Necrotizing Fasciitis of the Perineum (Fournier's gangrene)
  • Hypersensitivity Reactions including Anaphylaxis, Angioedema, and Exfoliative Skin Conditions
  • Severe and Disabling Arthralgia
  • Bullous Pemphigoid
  • Acute Kidney Injury
  • Skin Reactions (e.g., rash, urticaria)
  • Mouth Ulceration, Stomatitis
  • Rhabdomyolysis

DRUG INTERACTIONS

Table 3 : Clinically Relevant Interactions with GLYXAMBI

Diuretics
Clinical Impact Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.
Intervention Before initiating GLYXAMBI, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating GLYXAMBI. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy.
Insulin or Insulin Secretagogues
Clinical Impact 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.
Intervention Coadministration of GLYXAMBI with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.
Positive Urine Glucose Test
Clinical Impact SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests.
Intervention Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.
Interference with 1,5-anhydroglucitol (1,5-AG) Assay
Clinical Impact Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors.
Intervention Monitoring glycemic control with 1,5-AG assay is not recommended. Use alternative methods to monitor glycemic control.
Inducers of P-glycoprotein or CYP3A4 Enzymes
Clinical Impact 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.
Intervention Use of alternative treatments is strongly recommended when linagliptin is to be administered with a strong P-gp or CYP3A4 inducer.

Read the entire FDA prescribing information for Glyxambi (Empagliflozin and Linagliptin Tablets)

© Glyxambi Patient Information is supplied by Cerner Multum, Inc. and Glyxambi Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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