Linagliptin and metformin hydrochloride

What is Linagliptin and metformin hydrochloride?

• Linagliptin and metformin hydrochloride (JENTADUETO) contains linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin hydrochloride (HCl), a biguanide used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

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Linagliptin

What are the uses of this medicine?

• This medicine can be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

Limitations of Use:

• JENTADUETO is not for people with type 1 diabetes.
• JENTADUETO is not for people with diabetic ketoacidosis (increased ketones in the blood or urine).
• If you have had pancreatitis in the past, it is not known if you have a higher chance of getting pancreatitis while you take JENTADUETO.

How does this medicine work?

• JENTADUETO combines 2 antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin, a member of the biguanide class.

Linagliptin Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation.

Metformin

• Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose.
• Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
• With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• have severe kidney problems.
• have a condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in the blood or urine).
• are allergic to linagliptin (TRADJENTA), metformin, or any of the ingredients in JENTADUETO.

Symptoms of a serious allergic reaction to JENTADUETO may include:

• skin rash, itching, flaking or peeling
• raised red patches on your skin (hives)
• swelling of your face, lips, tongue and throat that may cause difficulty in breathing or swallowing
• difficulty with swallowing or breathing

What drug interactions can this medicine cause?

• Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving JENTADUETO.
• Carbonic anhydrase inhibitors may increase risk of lactic acidosis. Consider more frequent monitoring.
• Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use.
• Rifampin decreased linagliptin exposure, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-gp inducer or CYP 3A4 inducer.
• Coadministration of JENTADUETO 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
• Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.

Is this medicine FDA approved?

• Initial U.S. Approval: 2012

How should this medicine be used?

• Individualize the starting dose of JENTADUETO based on the patient's current regimen.

Recommended dosage:

• The maximum recommended dose is 2.5 mg linagliptin/1000 mg metformin HCl twice daily.

Recommended starting dose:

• In patients currently not treated with metformin, initiate treatment with 2.5 mg linagliptin/500 mg metformin HCl twice daily.
• In patients already treated with metformin, start with 2.5 mg linagliptin and the current dose of metformin HCl taken at each of the two daily meals (e.g., a patient on metformin HCl 1000 mg twice daily would be started on 2.5 mg linagliptin/1000 mg metformin HCl 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.

• Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR)
• Do not use in patients with eGFR below 30 mL/min/1.73 m2
• Initiation is not recommended in patients with eGFR between 30 - 45 mL/min/1.73 m2
• Assess risk/benefit of continuing if eGFR falls below 45 mL/min/1.73 m2
• Discontinue if eGFR falls below 30 mL/min/1.73 m2

• JENTADUETO may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.

Administration:

• Take JENTADUETO exactly as your doctor tells you to take it.
• Take JENTADUETO 2 times each day with meals. Taking JENTADUETO with meals may lower your chance of having an upset stomach.
• If you miss a dose, take it with food as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule. Do not take 2 doses of JENTADUETO at the same time.
• If you take too much JENTADUETO, call your doctor or local poison control center or go to the nearest hospital emergency room right away.
• Your doctor may tell you to take JENTADUETO along with other diabetes medicines. Low blood sugar can happen more often when JENTADUETO is taken with certain other diabetes medicines. See "WHAT ARE THE POSSIBLE SIDE EFFECTS OF JENTADUETO?"
• Check your blood sugar as your doctor tells you to.
• Your doctor will do blood tests to check how well your kidneys are working before and during your treatment with JENTADUETO.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets:
• 2.5 mg linagliptin/500 mg metformin HCl
• 2.5 mg linagliptin/850 mg metformin HCl
• 2.5 mg linagliptin/1000 mg metformin HCl

This medicine is available in fallowing brand namesː

• JENTADUETO

What side effects can this medication cause?

The most common side effects of this medicine include:

• stuffy or runny nose
• sore throat
• diarrhea

JENTADUETO may cause serious side effects, including:

• Lactic acidosis
• Inflammation of the pancreas (pancreatitis)
• Heart failure
• Low blood sugar (hypoglycemia)
• Allergic (hypersensitivity) reactions
• Low vitamin B12 (vitamin B12 deficiency)
• Joint pain
• Skin reaction

What special precautions should I follow?

• Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. If metformin-associated lactic acidosis is suspected, immediately discontinue JENTADUETO and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
• There have been reports of acute pancreatitis, including fatal pancreatitis. If pancreatitis is suspected, promptly discontinue JENTADUETO.
• Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits of JENTADUETO in patients who have known risk factors for heart failure. Monitor for signs and symptoms.
• Insulin secretagogues and insulin are known to cause hypoglycemia. When used with an insulin secretagogue (e.g., sulfonylurea (SU)) or insulin, consider lowering the dose of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.
• Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema, and exfoliative skin conditions) have occurred with JENTADUETO. If hypersensitivity reactions occur discontinue JENTADUETO, treat promptly, and monitor until signs and symptoms resolve.
• Metformin may lower vitamin B12 levels. Monitor hematologic parameters annually.
• Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue drug if appropriate.
• 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.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• Hypoglycemia
• Lactic acidosis

Management of overdosage:

• In the event of an overdose with JENTADUETO, contact the Poison Control Center.
• Removal of linagliptin by hemodialysis or peritoneal dialysis is unlikely.
• Hemodialysis may be useful partly for removal of accumulated metformin from patients in whom JENTADUETO overdosage is suspected.

Can this medicine be used in pregnancy?

• The limited data with JENTADUETO and linagliptin use in pregnant women are not sufficient to inform a JENTADUETO-associated or linagliptin-associated risk for major birth defects and miscarriage.

Can this medicine be used in children?

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

What are the active and inactive ingredients in this medicine?

• Active Ingredients: linagliptin and metformin hydrochloride
• Inactive Ingredients: arginine, corn starch, copovidone, colloidal silicon dioxide, magnesium stearate, titanium dioxide, propylene glycol, hypromellose, talc

2.5 mg/500 mg and 2.5 mg/850 mg tablets also contain yellow ferric oxide. 2.5 mg/850 mg and 2.5 mg/1000 mg tablets also contain red ferric oxide.

Who manufactures and distributes this medicine?

• Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield,USA.
• Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany.

What should I know about storage and disposal of this medication?

• Store JENTADUETO at room temperature between 68°F and 77°F (20°C and 25°C).
• Keep tablets dry.
• Keep JENTADUETO and all medicines out of the reach of children.

• Dailymed label info on Linagliptin and metformin hydrochloride
• FDA Linagliptin and metformin hydrochloride

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