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Trijardy XR

Last reviewed on RxList: 10/13/2020
Trijardy XR Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Trijardy XR?

Trijardy XR (empagliflozin, linagliptin, and metformin hydrochloride extended-release tablets) is a combination of a sodium-glucose co-transporter 2 (SGLT2) inhibitor, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Empagliflozin is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease.

What Are Side Effects of Trijardy XR?

Side effects of Trijardy XR include:

Dosage for Trijardy XR

The starting dose of Trijardy XR is individualized based on the patient's current regimen. The maximum recommended dose of Trijardy XR is 25 mg empagliflozin, 5 mg linagliptin and 2000 mg metformin HCl.

Trijardy XR In Children

Safety and effectiveness of Trijardy XR in pediatric patients under 18 years of age have not been established.

What Drugs, Substances, or Supplements Interact with Trijardy XR?

Trijardy XR may interact with other medicines such as:

  • topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide),
  • drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine),
  • alcohol,
  • diuretics,
  • insulin or insulin secretagogues,
  • corticosteroids,
  • phenothiazines,
  • thyroid products,
  • estrogens,
  • oral contraceptives,
  • phenytoin,
  • nicotinic acid,
  • sympathomimetics,
  • calcium channel blockers,
  • isoniazid, and
  • rifampin

Tell your doctor all medications and supplements you use.

Trijardy XR During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Trijardy XR; it is not recommended during the second and third trimesters of pregnancy because it may harm a fetus. It is unknown if Trijardy XR passes into breast milk. Because of the potential for serious adverse reactions in breastfed infants, including the potential for empagliflozin to affect postnatal renal development, Trijardy XR is not recommended while breastfeeding.

Additional Information

Our Trijardy XR (empagliflozin, linagliptin, and metformin hydrochloride extended-release tablets), for Oral Use 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.

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.

SLIDESHOW

Type 2 Diabetes: Signs, Symptoms, Treatments See Slideshow
Trijardy XR 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 rare but 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:

  • severe or ongoing pain in your joints;
  • lactic acidosis--unusual muscle pain, trouble breathing, stomach pain, vomiting, slow or irregular heart rate, dizziness, feeling cold, or feeling very weak or tired;
  • 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 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:

  • stomach pain, diarrhea, constipation;
  • a bladder infection;
  • headache; or
  • cold symptoms such as 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 Trijardy XR (Empagliflozin, Linagliptin, and Metformin Hydrochloride Extended-release Tablets)

QUESTION

______________ is another term for type 2 diabetes. See Answer
Trijardy XR Professional Information

SIDE EFFECTS

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

  • Lactic Acidosis [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
  • Pancreatitis [see WARNINGS AND PRECAUTIONS]
  • Heart Failure [see WARNINGS AND PRECAUTIONS]
  • Hypotension [see WARNINGS AND PRECAUTIONS]
  • Ketoacidosis [see WARNINGS AND PRECAUTIONS]
  • Acute Kidney Injury [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]
  • Vitamin B12 Deficiency [see WARNINGS AND PRECAUTIONS]
  • Severe and Disabling Arthralgia [see WARNINGS AND PRECAUTIONS]
  • Bullous Pemphigoid [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, Linagliptin And Metformin

The safety of concomitantly administered empagliflozin (daily dose 10 mg or 25 mg), linagliptin (daily dose 5 mg) and metformin has been evaluated in a total of 686 patients with type 2 diabetes treated for up to 52 weeks in an active-controlled clinical trial. The most common adverse reactions are shown in Table 1.

Table 1 : Adverse Reactions Reported in ≥5% of Patients Treated with Empagliflozin, Linagliptin, and Metformin in an Active-Controlled Clinical Trial of 52 Weeks

Empagliflozin 10 mg + Linagliptin 5 mg + Metformin
n=136
Empagliflozin 25 mg + Linagliptin 5 mg + Metformin
n=137
Upper respiratory tract infection10.3%8.0%
Urinary tract infectiona9.6%10.2%
Nasopharyngitis8.1%5.8%
Diarrhea6.6%2.2%
Constipation5.1%5.8%
Headache5.1%5.1%
Gastroenteritis2.9%5.8%
aPredefined grouping, including, but not limited to, urinary tract infection, asymptomatic bacteriuria, cystitis

Hypoglycemia

The incidence of hypoglycemia (defined as plasma or capillary glucose of less than 54 mg/dL) was 0.7% in patients receiving empagliflozin 10 mg/linagliptin 5 mg/metformin and 0.7% in patients receiving empagliflozin 25 mg/linagliptin 5 mg/metformin. Events of severe hypoglycemia (requiring assistance regardless of blood glucose) did not occur in this trial.

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 empagliflozin, linagliptin and metformin combination therapy.

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.

Metformin

The most common (>5%) established adverse reactions due to initiation of metformin therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.

In a 24-week clinical trial in which extended-release metformin or placebo was added to glyburide therapy, the most common (>5% and greater than placebo) adverse reactions in the combined treatment group were hypoglycemia (13.7% vs 4.9%), diarrhea (12.5% vs 5.6%), and nausea (6.7% vs 4.2%).

Laboratory Tests

Empagliflozin

Increases in Serum Creatinine and Decreases in eGFR: Initiation of empagliflozin causes an increase in serum creatinine and decrease in eGFR. Patients with hypovolemia may be more susceptible to these changes.

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.

Metformin

Decrease in Vitamin B12: In metformin clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels was observed in approximately 7% of patients.

Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of linagliptin, empagliflozin, or metformin. 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
  • Skin Reactions (e.g., rash, urticaria)
  • Mouth Ulceration, Stomatitis
  • Cholestatic, hepatocellular, and mixed hepatocellular liver injury
  • Rhabdomyolysis

Read the entire FDA prescribing information for Trijardy XR (Empagliflozin, Linagliptin, and Metformin Hydrochloride Extended-release Tablets)

Related Resources for Trijardy XR

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

SLIDESHOW

Type 2 Diabetes: Signs, Symptoms, Treatments See Slideshow

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