JARDIANCE: Hypersensitivity to empagliflozin or any of the excipients in
reactions such as angioedema have occurred; patients on dialysis.
TRADJENTA: Hypersensitivity to linagliptin, or any of the excipients in
reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or
bronchial hyperreactivity have occurred.
TRIJARDY XR: Severe renal impairment (eGFR
<30 mL/min/1.73 m2), end-stage renal disease,
or dialysis; acute or chronic metabolic acidosis, including diabetic ketoacidosis;
hypersensitivity to empagliflozin,
linagliptin, metformin, or any of the excipients in TRIJARDY XR, reactions
such as anaphylaxis,
angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have
WARNINGS AND PRECAUTIONS
Lactic Acidosis: TRIJARDY XR
There have been cases of metformin-associated lactic acidosis, including fatal cases. These
cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise,
myalgias, abdominal pain, respiratory distress, or increased somnolence; however,
hypothermia, hypotension, and resistant bradyarrhythmias have occurred with severe acidosis.
Additional findings included elevated blood lactate concentrations (>5 mmol/L),
anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate:
pyruvate ratio, metformin plasma levels generally >5 mcg/mL.
If lactic acidosis is suspected, immediately discontinue TRIJARDY XR and
institute general supportive measures promptly in a hospital setting. Prompt hemodialysis is
recommended to correct the acidosis.
Educate patients and their families about the symptoms of lactic acidosis and, if these
instruct them to discontinue TRIJARDY XR and promptly notify their
Recommendations to reduce the risk include:
- Renal Impairment: Obtain eGFR prior to initiating and annually or more
frequently in patients at increased risk of developing renal impairment.
- Drug Interactions: More frequent monitoring is recommended when administered
with drugs that impair
renal function, result in hemodynamic change, interfere with acid-base balance, or
- Age 65 or Greater: Assess renal function more frequently.
- Radiological Studies with Contrast: Stop TRIJARDY XR at the
time of, or prior to,
an iodinated contrast imaging procedure in patients with an eGFR of
<60 mL/min/1.73m2; patients
with a history of hepatic impairment, alcoholism or heart failure; or patients who will
intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure and
TRIJARDY XR if renal function is stable.
- Surgery and Other Procedures: Discontinue while patients have restricted food
and fluid intake.
- Hypoxic States: Discontinue in conditions associated with hypoxemia.
- Excessive Alcohol Intake: Warn patients against excessive alcohol intake.
- Hepatic Impairment: Avoid use in patients with hepatic disease.
Pancreatitis: TRADJENTA, TRIJARDY XR
Acute pancreatitis, including fatal pancreatitis, has been reported in patients taking
component of TRADJENTA or TRIJARDY XR. Take careful notice of potential
signs and symptoms
of pancreatitis and, if suspected, promptly discontinue and initiate appropriate management.
It is unknown
whether patients with a history of pancreatitis are at increased risk for the development of
while using TRADJENTA or TRIJARDY XR.
Ketoacidosis: JARDIANCE, TRIJARDY XR
Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has
in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose
inhibitors, including empagliflozin. Fatal cases of ketoacidosis have been reported in
empagliflozin. Patients who present with signs and symptoms of metabolic acidosis should be
ketoacidosis, even if blood glucose levels are less than 250 mg/dL. If suspected,
and treat promptly. Before initiating, consider risk factors for ketoacidosis. Patients may
monitoring and temporary discontinuation in situations known to predispose to ketoacidosis.
who undergo scheduled surgery, consider temporarily discontinuing for at least 3 days prior
Volume Depletion: JARDIANCE, TRIJARDY XR
Empagliflozin can cause intravascular volume depletion which may manifest as symptomatic
hypotension or acute
transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis
has been reported
in patients with type 2 diabetes receiving SGLT2 inhibitors, including empagliflozin. Before
volume status and renal function in patients with impaired renal function
(eGFR<60 mL/min/1.73 m2), elderly
patients or patients on loop diuretics. After initiating, monitor for signs and symptoms of
and renal function.
Urosepsis and Pyelonephritis: JARDIANCE, TRIJARDY XR
Serious urinary tract infections including urosepsis and pyelonephritis requiring
been identified in patients receiving SGLT2 inhibitors, including empagliflozin. Treatment
inhibitors increases the risk for urinary tract infections. Evaluate for signs and symptoms
tract infections and treat promptly.
Hypoglycemia: JARDIANCE, TRADJENTA, TRIJARDY XR
The use in combination with insulin or insulin secretagogues can increase
the risk of
hypoglycemia. A lower dose of insulin or the insulin secretagogue may be required.
Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): JARDIANCE, TRIJARDY XR
Serious, life-threatening cases requiring urgent surgical intervention have occurred in both
males. Serious outcomes have included hospitalization, multiple surgeries and death. Assess
presenting with pain or tenderness, erythema, or swelling in the genital or perineal area,
fever or malaise. If suspected, institute prompt treatment and discontinue JARDIANCE
or TRIJARDY XR.
Genital Mycotic Infections: JARDIANCE, TRIJARDY XR
Empagliflozin increases the risk for genital mycotic infections, especially in patients with
infections. Monitor and treat as appropriate.
JARDIANCE: Serious hypersensitivity reactions have occurred with
If hypersensitivity reactions occur, discontinue JARDIANCE, treat promptly,
and monitor until signs and symptoms resolve.
TRADJENTA, TRIJARDY XR: Serious hypersensitivity reactions have occurred
(anaphylaxis, angioedema and exfoliative skin conditions) and empagliflozin (angioedema). If
reactions occur, discontinue TRADJENTA or TRIJARDY XR, treat promptly,
and monitor until signs and symptoms resolve. 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
with TRADJENTA or TRIJARDY XR.
Vitamin B12 Deficiency: TRIJARDY XR
Metformin may lower vitamin B12 levels. Monitor hematologic parameters annually
vitamin B12 at 2- to 3-year intervals.
Severe and Disabling Arthralgia: TRADJENTA, TRIJARDY XR
Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors.
Consider linagliptin as a possible cause for severe joint pain and discontinue, if
Bullous Pemphigoid: TRADJENTA, TRIJARDY XR
There have been reports of bullous pemphigoid requiring hospitalization. Tell patients to
development of blisters or erosions. If bullous pemphigoid is suspected, discontinue.
Heart Failure: TRADJENTA, TRIJARDY XR
Heart failure has been observed with two other members of the dipeptidyl peptidase-4 (DPP-4)
class. Consider risks and benefits of TRADJENTA or TRIJARDY XR in patients
at risk for
heart failure, such as those with a prior history of heart failure and a history of renal
Monitor patients for signs and symptoms. Advise patients of the symptoms of heart failure
and to immediately
report such symptoms. If heart failure develops, consider discontinuation of
TRADJENTA or TRIJARDY XR.
MOST COMMON ADVERSE REACTIONS (≥5%)
JARDIANCE: urinary tract infections and female genital mycotic infections.
TRADJENTA: nasopharyngitis, hypoglycemia (when used in combination with
TRIJARDY XR: upper respiratory tract infections, urinary tract infection,
nasopharyngitis, diarrhea, constipation, headache, gastroenteritis.
JARDIANCE, TRIJARDY XR:
Coadministration of empagliflozin with diuretics may enhance the potential for volume
depletion. Monitor for signs and symptoms.
Carbonic Anhydrase Inhibitors: The concomitant use of carbonic
(e.g., topiramate) and metformin may increase the risk of lactic acidosis. Consider more
Drugs that reduce metformin clearance such as ranolazine,
or cimetidine may increase the accumulation of metformin and increase the risk of lactic
Consider the benefits and risks of concomitant use.
Alcohol: Alcohol is known to potentiate the effect of
metformin on lactate metabolism.
Warn patients against excessive alcohol intake while taking TRIJARDY
TRADJENTA and TRIJARDY XR:
Inducers of P-glycoprotein or CYP3A4 Enzymes: The efficacy of
linagliptin may be
reduced when administered in combination with a strong P-gp or CYP3A4 inducer.
treatments should be used.
USE IN SPECIAL POPULATIONS
Pregnancy: JARDIANCE and TRIJARDY XR are not recommended during the second and third
trimesters. With TRIJARDY XR, discuss the potential for unintended pregnancy with
premenopausal women as therapy with metformin may result in ovulation in some
Lactation: JARDIANCE or TRIJARDY XR are not recommended while
Geriatric Use: Empagliflozin is expected to have diminished glycemic
efficacy in elderly patients with renal impairment. For TRIJARDY XR, assess
renal function more frequently in elderly patients, and dose selection should be cautious,
starting at the lowest dose. The incidence of volume depletion-related adverse reactions and
urinary tract infections increased in T2D patients ≥75 years treated with
Please see TRIJARDY XR
Information, including Boxed Warning and
Please see JARDIANCE
Please see TRADJENTA
*3-in-1 pill is a fixed-dose combination treatment
XR Savings Card Terms & Conditions apply. Medicare/Medicaid/cash-paying
excluded from Savings Card enrollment.