Dosing Information

TRADJENTA Family
TRADJENTA Family

Multiple dosing options with flexibility

TO INITIATE JENTADUETO, DETERMINE THE APPROPRIATE AMOUNT OF
METFORMIN IN COMBINATION WITH TRADJENTA*
TRADJENTA
TRADJENTA
One 5-mg tablet, once daily
METFORMIN
+1000 mg metformin/day
+1700 mg metformin/day
+2000 mg metformin/day

CHOOSE THE APPROPRIATE REGIMEN†
JENTADUETO
twice-daily dosing
JENTADUETO
2.5 mg/500 mg
JENTADUETO
2.5 mg/850 mg
JENTADUETO
2.5 mg/1000 mg
JENTADUETO XR
once-daily dosing
JENTADUETO XR
5 mg/1000 mg
JENTADUETO XR
2.5mg/1000 mg
2 tablets once daily

*Individualize the starting dose of JENTADUETO or JENTADUETO XR based on the effectiveness and tolerability. Do not exceed total daily dose of linagliptin 5 mg and metformin 2000 mg.

† In patients already treated with linagliptin and metformin or JENTADUETO, switch to JENTADUETO XR containing 5 mg of linagliptin total daily dose and a similar total daily dose of metformin once daily with a meal.
FDC=fixed-dose combination.

Multiple dosing options with flexibility

To initiate Jentadueto, determine the appropriate amount of
metformin in combination with Tradjenta*
Tradjenta
One 5-mg tablet, once daily
Metformin
+1000 mg metformin/day
Choose the appropriate FDC regimen✝
Jentadueto (twice-daily dosing)
2.5 mg/500 mg
Jentadueto XR (once-daily dosing)
5 mg/1000 mg
To initiate Jentadueto, determine the appropriate amount of
metformin in combination with Tradjenta*
Tradjenta
One 5-mg tablet, once daily
Metformin
+1700 mg metformin/day
Choose the appropriate FDC regimen✝
Jentadueto (twice-daily dosing)
2.5 mg/850 mg
Jentadueto XR (once-daily dosing)
5 mg/1000 mg
Jentadueto XR (once-daily dosing)
2.5 mg/1000 mg
2 tablets once daily
To initiate Jentadueto, determine the appropriate amount of
metformin in combination with Tradjenta*
Tradjenta
One 5-mg tablet, once daily
Metformin
+2000 mg metformin/day
Choose the appropriate FDC regimen✝
Jentadueto (twice-daily dosing)
2.5 mg/1000 mg
Jentadueto XR (once-daily dosing)
2.5 mg/1000 mg
2 tablets once daily

⁎ Individualize the starting dose of JENTADUETO or JENTADUETO XR based on the effectiveness and tolerability. Do not exceed total daily dose of linagliptin 5 mg and metformin 2000 mg.
‡ In patients already treated with linagliptin and metformin or JENTADUETO, switch to JENTADUETO XR containing 5 mg of linagliptin total daily dose and a similar total daily dose of metformin once daily with a meal.
FDC=fixed-dose combination.

 

Dosing for Jentadueto

The dosage of JENTADUETO should be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended dose of 2.5 mg linagliptin/1000 mg metformin hydrochloride twice daily. JENTADUETO should be given twice daily with meals with gradual dose escalation to reduce the gastrointestinal side effects of metformin.

Recommended Starting Dose

  • In patients not currently treated with metformin, initiate JENTADUETO treatment with 2.5 mg linagliptin/500 mg metformin hydrochloride twice daily
  • In patients already treated with metformin, start with 2.5 mg linagliptin and the current dose of metformin taken at each of the two daily meals (eg, a patient on metformin 1000 mg twice daily would be started on 2.5 mg linagliptin/1000 mg metformin hydrochloride twice daily with meals)
  • Patients already treated with linagliptin and metformin individual components may be switched to JENTADUETO containing the same doses of each component

No studies have been performed specifically examining the safety and efficacy of JENTADUETO in patients previously treated with other oral antihyperglycemic agents and switched to JENTADUETO. Any change in therapy should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

Insulin secretagogues or insulins

Coadministration of JENTADUETO with an insulin secretagogue (eg, sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

Monitoring of renal function

  • Before initiation of therapy with JENTADUETO and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal impairment is anticipated (eg, elderly), renal function should be assessed more frequently and JENTADUETO discontinued if evidence of renal impairment is present
  • Radiological studies and surgical procedures: JENTADUETO should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure necessitating restricted intake of food or fluids, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been confirmed to be normal
 

Dosing for Jentadueto XR

The dosage of JENTADUETO XR should be individualized on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended total daily dose of linagliptin 5 mg and metformin hydrochloride 2000 mg. JENTADUETO XR should be given once daily with a meal.

Recommended Starting Dose

  • In patients currently not treated with metformin, initiate JENTADUETO XR treatment with 5 mg linagliptin/1000 mg metformin hydrochloride extended-release once daily with a meal
  • In patients already treated with metformin, start JENTADUETO XR with 5 mg of linagliptin total daily dose and a similar total daily dose of metformin once daily with a meal
  • In patients already treated with linagliptin and metformin or JENTADUETO, switch to JENTADUETO XR containing 5 mg of linagliptin total daily dose and a similar total daily dose of metformin once daily with a meal

JENTADUETO XR should be swallowed whole. The tablets must not be split, crushed, dissolved, or chewed before swallowing.

No studies have been performed specifically examining the safety and efficacy of JENTADUETO XR in patients previously treated with other oral antihyperglycemic agents and switched to JENTADUETO XR. Any change in therapy should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

Recommended Dosing in renal impairment

Assess renal function prior to initiation of JENTADUETO XR and periodically thereafter.

JENTADUETO XR is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2.

Initiation of JENTADUETO XR in patients with an eGFR between 30-45 mL/min/1.73 m2 is not recommended.

In patients taking JENTADUETO XR whose eGFR later falls below 45 mL/min/1.73 m2, assess benefit risk of continuing therapy.

Discontinue JENTADUETO XR if the patient’s eGFR later falls below 30 mL/min/1.73 m2.

Discontinuation for iodinated contrast imaging procedures

Discontinue JENTADUETO XR before or at the time of an iodinated contrast imaging procedure in patients: with an eGFR between 30 and 60 mL/min/1.73 m2; with a history of liver disease, alcoholism or heart failure; or who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart JENTADUETO XR if renal function is stable.

Insulin secretagogues or insulin

Coadministration of JENTADUETO XR with an insulin secretagogue (eg, sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

A1C Reductions in a Final-Dose Combination

A1C reductions in a
fixed-dose combination

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Important Safety Information

WARNING: LACTIC ACIDOSIS

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.

Risk factors include renal impairment, concomitant use of certain drugs, age ≥ 65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full Prescribing Information.

If lactic acidosis is suspected, discontinue JENTADUETO or JENTADUETO XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

INDICATION AND LIMITATIONS OF USE

JENTADUETO and JENTADUETO XR tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

JENTADUETO and JENTADUETO XR should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

JENTADUETO and JENTADUETO XR have not been studied in patients with a history of pancreatitis, and it is unknown if using JENTADUETO or JENTADUETO XR increases the risk of developing pancreatitis in these patients.

CONTRAINDICATIONS: Severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2); acute or chronic metabolic acidosis, including diabetic ketoacidosis; hypersensitivity to linagliptin, metformin, or any of the excipients in JENTADUETO or JENTADUETO XR, reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have occurred with linagliptin.

WARNINGS AND PRECAUTIONS

Lactic Acidosis: 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 JENTADUETO or JENTADUETO 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 symptoms occur instruct them to discontinue and promptly notify their healthcare provider.

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 increase metformin accumulation.
  • Age 65 or Greater: Assess renal function more frequently.
  • Radiological Studies with Contrast: Stop JENTADUETO or JENTADUETO XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR of 30-60 mL/min/1.73 m2; patients with a history of hepatic impairment, alcoholism, or heart failure; or patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure, and restart JENTADUETO or JENTADUETO 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: Acute pancreatitis, including fatal pancreatitis, has been reported in patients taking linagliptin. 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 pancreatitis while using JENTADUETO or JENTADUETO XR.

Heart Failure: Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider the risks and benefits of JENTADUETO or JENTADUETO XR in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. 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 JENTADUETO or JENTADUETO XR.

Use with Medications Known to Cause Hypoglycemia: The use in combination with insulin or insulin secretagogues increases the risk of hypoglycemia. A lower dose of insulin or insulin secretagogue may be required.

Hypersensitivity Reactions: Discontinue JENTADUETO or JENTADUETO XR, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. 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 angioedema with JENTADUETO or JENTADUETO XR.

Vitamin B12 Levels: Metformin may lower Vitamin B12 levels. Monitor hematologic parameters annually and routine serum Vitamin B12 measurement at 2- to 3- year intervals.

Severe and Disabling Arthralgia: Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider linagliptin as a possible cause for severe joint pain and/or disabling arthralgia and discontinue, if appropriate.

Bullous Pemphigoid: There have been reports of bullous pemphigoid requiring hospitalization. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue JENTADUETO or JENTADUETO XR.

MOST COMMON ADVERSE REACTIONS (≥5%): nasopharyngitis, diarrhea, hypoglycemia (when used in combination with sulfonylurea), nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.

DRUG INTERACTIONS
Metformin:

Carbonic Anhydrase Inhibitors (e.g topiramate): The concomitant use with metformin may increase the risk of lactic acidosis. Consider more frequent monitoring.

Drugs that Reduce Metformin Clearance, such as ranolazine, vandetanib, dolutegravir or cimetidine, may increase the accumulation of metformin and increase the risk of lactic acidosis. 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.

Linagliptin: The efficacy of linagliptin may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. Alternative treatments should be used.

USE IN SPECIFIC POPULATIONS
  • Pregnancy: JENTADUETO or JENTADUETO XR should be used during pregnancy only if clearly needed. Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women.
  • Lactation: Exercise caution when administering JENTADUETO or JENTADUETO XR to a nursing woman.
  • Geriatric Use: JENTADUETO or JENTADUETO XR should be used with caution as age increases, as aging can be associated with reduced renal function.

CL-JDJDX-100007 7.12.19

Please see Prescribing Information for JENTADUETO, including Boxed Warning regarding risk of lactic acidosis and Medication Guide.

Please see Prescribing Information for JENTADUETO XR, including Boxed Warning regarding risk of lactic acidosis and Medication Guide.