Tradjenta

Dosage Forms & Strengths

tablet

• 5mg

Type 2 Diabetes Mellitus

Indicated for adults with type 2 diabetes mellitus along with diet and exercise to lower blood sugar; may be used as monotherapy or in combination with other common antidiabetic medications including metformin, sulfonylurea, pioglitazone, or insulin

5 mg PO qDay

Dosage Modifications

Hepatic or renal impairment: No dosage adjustment required

Dosing Considerations

Not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings

Has not been studied in patients with a history of pancreatitis; unknown whether patients with a history of pancreatitis are at an increased risk of developing pancreatitis when taking linagliptin

Administration

May administer with or without food

When used in combination with other antidiabetic agents, a lower dose of the insulin secretagogue (eg, sulfanylurea) or insulin may be required to reduce the risk of hypoglycemia

Safety and efficacy not established

Dosage Forms And Strengths

TRADJENTA (linagliptin) 5 mg tablets are light red, round, biconvex, bevel-edged, film-coated tablets with “D5” debossed on one side and the Boehringer Ingelheim logo debossed on the other side.

Storage And Handling

TRADJENTA tablets are available as light red, round, biconvex, bevel-edged, film-coated tablets containing 5 mg of linagliptin. TRADJENTA tablets are debossed with “D5” on one side and the Boehringer Ingelheim logo on the other side.

They are supplied as follows:

Bottles of 30 (NDC 0597-0140-30)
Bottles of 90 (NDC 0597-0140-90)

Cartons containing 10 blister cards of 10 tablets each (10 x 10) (NDC 0597-0140-61), institutional pack.

If repackaging is required, dispense in a tight container as defined in USP.

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Store in a safe place out of reach of children.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA. Revised: Aug 2017

TRADJENTA®
(TRAD gen ta)
(linagliptin) Tablets

Read this Medication Guide carefully before you start taking TRADJENTA and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. If you have any questions about TRADJENTA, ask your doctor or pharmacist.

What is the most important information I should know about TRADJENTA?

Serious side effects can happen to people taking TRADJENTA, including:

• Inflammation of the pancreas (pancreatitis) which may be severe and lead to death. Certain medical problems make you more likely to get pancreatitis.

  Before you start taking TRADJENTA, tell your doctor if you have ever had:

  • inflammation of your pancreas (pancreatitis)
  • stones in your gallbladder (gallstones)
  • a history of alcoholism
  • high blood triglyceride levels

Stop taking TRADJENTA and call your doctor right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

• Heart failure. Heart failure means your heart does not pump blood well enough.
  Before you start taking TRADJENTA, tell your doctor if you have ever had heart failure or have problems with your kidneys. Contact your doctor right away if you have any of the following symptoms:
  • increasing shortness of breath or trouble breathing, especially when you lie down
  • swelling or fluid retention, especially in the feet, ankles or legs
  • an unusually fast increase in weight
  • unusual tiredness

  These may be symptoms of heart failure.

What is TRADJENTA?

• TRADJENTA is a prescription medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.
• TRADJENTA is not for people with type 1 diabetes.
• TRADJENTA 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 TRADJENTA.

It is not known if TRADJENTA is safe and effective in children under 18 years of age.

Who should not take TRADJENTA?

Do not take TRADJENTA if you:

• are allergic to linagliptin or any of the ingredients in TRADJENTA. See the end of this Medication Guide for a complete list of ingredients in TRADJENTA.

  Symptoms of a serious allergic reaction to TRADJENTA 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

If you have any of these symptoms, stop taking TRADJENTA and contact your doctor or go to the nearest hospital emergency room right away.

What should I tell my doctor before using TRADJENTA?

Before you take TRADJENTA, tell your doctor if you:

• have or have had inflammation of your pancreas (pancreatitis).
• have any other medical conditions . are pregnant or plan to become pregnant. It is not known if TRADJENTA will harm your unborn baby. If you are pregnant, talk with your doctor about the best way to control your blood sugar while you are pregnant.
• are breastfeeding or plan to breastfeed. It is not known if TRADJENTA passes into your breast milk. Talk with your doctor about the best way to feed your baby if you take TRADJENTA.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

TRADJENTA may affect the way other medicines work, and other medicines may affect how TRADJENTA works.

Especially tell your doctor if you take

• other medicines that can lower your blood sugar
• rifampin (Rifadin®, Rimactane®, Rifater®, Rifamate®)*, an antibiotic that is used to treat tuberculosis Ask your doctor or pharmacist for a list of these medicines if you are not sure if your medicine is one that is listed above.

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.

How should I take TRADJENTA?

• Take 1 tablet 1 time each day with or without food.
• Your doctor will tell you when to take TRADJENTA.
• Talk with your doctor if you do not understand how to take TRADJENTA.
• If you miss a dose, take it 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 two doses of TRADJENTA at the same time.
• Your doctor may tell you to take TRADJENTA along with other diabetes medicines. Low blood sugar can happen more often when TRADJENTA is taken with certain other diabetes medicines. See “What are the possible side effects of TRADJENTA?”
• If you take too much TRADJENTA, call your doctor or Poison Control Center at 1-800-222-1222 or go to the nearest hospital emergency room right away.
• When your body is under some types of stress, such as fever, trauma (such as a car accident), infection, or surgery, the amount of diabetes medicine that you need may change. Tell your doctor right away if you have any of these conditions and follow your doctor’s instructions.
• Check your blood sugar as your doctor tells you to.
• Stay on your prescribed diet and exercise program while taking TRADJENTA. . Your doctor will check your diabetes with regular blood tests, including your blood sugar levels and your hemoglobin A1C.

What are the possible side effects of TRADJENTA?

TRADJENTA may cause serious side effects, including:

• See “What is the most important information I should know about TRADJENTA?”
• low blood sugar (hypoglycemia). If you take TRADJENTA with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while you take TRADJENTA. Signs and symptoms of low blood sugar may include:
  • headache
  • drowsiness
  • weakness
  • dizziness
  • confusion
  • irritability
  • hunger
  • fast heart beat
  • sweating
  • feeling jittery
• Allergic (hypersensitivity) reactions. Serious allergic reactions can happen after your first dose or up to 3 months after starting TRADJENTA. Symptoms may include:
  • swelling of your face, lips, throat, and other areas on your skin
  • difficulty with swallowing or breathing
  • raised, red areas on your skin (hives)
  • skin rash, itching, flaking, or peeling

If you have these symptoms, stop taking TRADJENTA and call your doctor or go to the nearest hospital emergency room right away.

• Joint pain. Some people who take medicines called DPP-4 inhibitors like TRADJENTA, may develop joint pain that can be severe. Call your doctor if you have severe joint pain.
• Skin reaction. Some people who take medicines called DPP-4 inhibitors like TRADJENTA, may develop a skin reaction called bullous pemphigoid that can require treatment in a hospital. Tell your doctor right away if you develop blisters or the breakdown of the outer layer of your skin (erosion). Your doctor may tell you to stop taking TRADJENTA.

The most common side effects of TRADJENTA include stuffy or runny nose and sore throat, cough, and diarrhea These are not all the possible side effects of TRADJENTA. For more information, ask your doctor or pharmacist. Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store TRADJENTA?

• Store TRADJENTA between 68°F and 77°F (20°C and 25°C)

Keep TRADJENTA and all medicines out of the reach of children.

General information about the safe and effective use of TRADJENTA.

Medicines are sometimes prescribed for purposes other than those listed in Medication Guides. Do not use TRADJENTA for a condition for which it was not prescribed. Do not give TRADJENTA to other people, even if they have the same symptoms you have. It may harm them. This Medication Guide summarizes the most important information about TRADJENTA. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about TRADJENTA that is written for health professionals. For more information, go to www.TRADJENTA.com (or scan the code below to go to www.TRADJENTA.com) or call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257, or (TTY) 1-800-459-9906.

What are the ingredients in TRADJENTA?

Active Ingredient: linagliptin

Inactive Ingredients: mannitol, pregelatinized starch, corn starch, copovidone, and magnesium stearate. The film coating contains the following inactive ingredients: hypromellose, titanium dioxide, talc, polyethylene glycol, and red ferric oxide.

What is type 2 diabetes?

Type 2 diabetes is a condition in which your body does not make enough insulin, and/or the insulin that your body produces does not work as well as it should. Your body can also make too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems.

The main goal of treating diabetes is to lower your blood sugar to a normal level. High blood sugar can be lowered by diet and exercise, and by certain medicines when necessary.

Talk to your doctor about how to prevent, recognize, and take care of low blood sugar (hypoglycemia), high blood sugar (hyperglycemia), and other problems you have because of your diabetes.

This Medication Guide has been approved by the U. S. Food and Drug Administration.

Tradjenta is a prescription medication used to treat type 2 diabetes in adults. Tradjenta belongs to a group of drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors, which help lower blood sugar levels by regulating the amount of insulin released.

This medication comes in tablet form and is taken once a day, with or without food.

Common side effects include stuffy nose, sore throat, and low blood sugar levels.

Tradjenta is a prescription medicine used to treat type 2 diabetes in adults. Tradjenta helps to lower blood sugar along with diet and exercise.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tradjenta is part of the drug class:

• Dipeptidyl peptidase 4

Linagliptin is an oral diabetes medicine that helps control blood sugar levels. It works by regulating the levels of insulin your body produces after eating.

Linagliptin is used together with diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus. This medicine is not for treating type 1 diabetes.

Linagliptin may also be used for purposes not listed in this medication guide.

Weak to moderate inhibitor of CYP3A4; does not inhibit or induce CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 4A11 in vitro.1

A P-glycoprotein substrate.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Drug interactions unlikely with substrates of CYP isoenzymes 3A4, 2C9, or 2C8; no adjustment of linagliptin dosage recommended.1

CYP3A4 inducers decrease exposure to linagliptin, resulting in subtherapeutic and likely ineffective concentrations.1 23 Alternative to linagliptin strongly recommended when potent CYP3A4 inducers must be used.1

Drugs Affecting or Affected by P-glycoprotein Transport

Reported to inhibit P-glycoprotein-mediated transport at high concentrations (see Specific Drugs under Interactions).1 However, at therapeutic concentrations, linagliptin considered unlikely to cause interactions with other P-glycoprotein substrates; no adjustment of linagliptin dosage recommended.1

P-glycoprotein inducers decrease exposure to linagliptin, resulting in subtherapeutic and likely ineffective concentrations.1 23 Alternative to linagliptin strongly recommended when potent P-glycoprotein inducers must be used.1

Drugs Affected by Organic Cation Transporter (OCT)

Drug interactions unlikely with substrates of OCT; no adjustment of linagliptin dosage recommended.1

Specific Drugs

Linagliptin is used together with proper diet and exercise to treat high blood sugar levels caused by type 2 diabetes. Linagliptin helps to control blood sugar levels by increasing substances in the body that make the pancreas release more insulin. It also signals the liver to stop producing sugar (glucose) when there is too much sugar in the blood. This medicine does not help patients who have insulin-dependent or type 1 diabetes.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of linagliptin in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of linagliptin in the elderly.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Balofloxacin
• Besifloxacin
• Carbamazepine
• Ciprofloxacin
• Efavirenz
• Enoxacin
• Enzalutamide
• Fleroxacin
• Flumequine
• Fosphenytoin
• Gatifloxacin
• Gemifloxacin
• Lanreotide
• Levofloxacin
• Lomefloxacin
• Mitotane
• Moxifloxacin
• Nadifloxacin
• Norfloxacin
• Octreotide
• Ofloxacin
• Oxcarbazepine
• Pasireotide
• Pazufloxacin
• Pefloxacin
• Phenytoin
• Primidone
• Prulifloxacin
• Rifabutin
• Rifampin
• Rifapentine
• Rufloxacin
• Sparfloxacin
• St John's Wort
• Thioctic Acid
• Tipranavir
• Tosufloxacin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Atenolol
• Betaxolol
• Bisoprolol
• Carteolol
• Carvedilol
• Celiprolol
• Esmolol
• Labetalol
• Levobunolol
• Metipranolol
• Metoprolol
• Nadolol
• Nebivolol
• Oxprenolol
• Penbutolol
• Pindolol
• Practolol
• Propranolol
• Sotalol
• Timolol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetic ketoacidosis (high ketones and acid in the blood) or
• Type 1 diabetes—Should not be used in patients with these conditions.

• Fever or
• Infection of any type or
• Surgery (major) or
• Trauma—These conditions may cause temporary problems with blood sugar control and your doctor may want to treat you with insulin.

• Hypercholesterolemia (high cholesterol in the blood) or
• Hypertriglyceridemia (high triglycerides and fats in the blood) or
• Obesity or
• Pancreas problems, history of—Use with caution. May increase risk for pancreatitis (swelling of the pancreas).

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine usually comes with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Carefully follow the special meal plan your doctor gave you. This is the most important part of controlling your diabetes, and is necessary if the medicine is to work properly. Exercise regularly and test for sugar in your blood or urine as directed.

You may take this medicine with or without food.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For type 2 diabetes:
    • Adults—5 milligrams (mg) once a day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Flaking, peeling, or swelling of the skin.
• Trouble swallowing.
• Low blood sugar can happen. The chance of low blood sugar may be raised when this medicine is used with other drugs for high blood sugar (diabetes). Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call your doctor right away if you have any of these signs. Follow what you have been told to do if you get low blood sugar. This may include taking glucose tablets, liquid glucose, or some fruit juices.
• Very bad and sometimes deadly pancreas problems (pancreatitis) have happened with Tradjenta. This could happen at any time during care. Signs of pancreatitis include very bad stomach pain, very bad back pain, or very upset stomach or throwing up. Call your doctor right away if you have any of these signs.
• Drugs like this one may cause joint pain that can be very bad and disabling. Call your doctor right away if you have very bad joint pain or any joint pain that does not go away.
• A skin reaction called bullous pemphigoid has happened with drugs like this one. Sometimes, people have had to go to the hospital. Call your doctor right away if you have blisters or if your skin starts to break down.
• Heart failure has happened in people taking drugs like this one. Tell your doctor if you have ever had heart failure or kidney problems. Call your doctor right away if you feel very tired or you have shortness of breath, a big weight gain, or swelling in the arms or legs.

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.

The safety evaluation of Tradjenta 5 mg once daily in patients with type 2 diabetes is based on 14 placebo-controlled trials, 1 active-controlled study, and one study in patients with severe renal impairment. In the 14 placebo-controlled studies, a total of 3625 patients were randomized and treated with Tradjenta 5 mg daily and 2176 with placebo. The mean exposure in patients treated with Tradjenta across studies was 29.6 weeks. The maximum follow-up was 78 weeks.

Tradjenta 5 mg once daily was studied as monotherapy in three placebo-controlled trials of 18 and 24 weeks’ duration and in five additional placebo-controlled studies lasting ≤18 weeks. The use of Tradjenta in combination with other antihyperglycemic agents was studied in six placebo-controlled trials: two with metformin (12 and 24 weeks’ treatment duration); one with a sulfonylurea (18 weeks’ treatment duration); one with metformin and sulfonylurea (24 weeks’ treatment duration); one with pioglitazone (24 weeks’ treatment duration); and one with insulin (primary endpoint at 24 weeks).

In a pooled dataset of 14 placebo-controlled clinical trials, adverse reactions that occurred in ≥2% of patients receiving Tradjenta (n = 3625) and more commonly than in patients given placebo (n = 2176), are shown in Table 1. The overall incidence of adverse events with Tradjenta were similar to placebo.

Rates for other adverse reactions for Tradjenta 5 mg vs placebo when Tradjenta was used in combination with specific anti-diabetic agents were: urinary tract infection (3.1% vs 0%) and hypertriglyceridemia (2.4% vs 0%) when Tradjenta was used as add-on to sulfonylurea; hyperlipidemia (2.7% vs 0.8%) and weight increased (2.3% vs 0.8%) when Tradjenta was used as add-on to pioglitazone; and constipation (2.1% vs 1%) when Tradjenta was used as add-on to basal insulin therapy.

Following 104 weeks’ treatment in a controlled study comparing Tradjenta with glimepiride in which all patients were also receiving metformin, adverse reactions reported in ≥5% of patients treated with Tradjenta (n = 776) and more frequently than in patients treated with a sulfonylurea (n = 775) were back pain (9.1% vs 8.4%), arthralgia (8.1% vs 6.1%), upper respiratory tract infection (8.0% vs 7.6%), headache (6.4% vs 5.2%), cough (6.1% vs 4.9%), and pain in extremity (5.3% vs 3.9%).

Other adverse reactions reported in clinical studies with treatment of Tradjenta 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 Tradjenta 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
In the placebo-controlled studies, 199 (6.6%) of the total 2994 patients treated with Tradjenta 5 mg reported hypoglycemia compared to 56 patients (3.6%) of 1546 placebo-treated patients. The incidence of hypoglycemia was similar to placebo when Tradjenta was administered as monotherapy or in combination with metformin, or with pioglitazone. When Tradjenta was administered in combination with metformin and a sulfonylurea, 181 of 792 (22.9%) patients reported hypoglycemia compared with 39 of 263 (14.8%) patients administered placebo in combination with metformin and a sulfonylurea. Adverse reactions of hypoglycemia were based on all reports of hypoglycemia. A concurrent glucose measurement was not required or was normal in some patients. Therefore, it is not possible to conclusively determine that all these reports reflect true hypoglycemia.

In the study of patients receiving Tradjenta as add-on therapy to a stable dose of insulin for up to 52 weeks (n=1261), no significant difference in the incidence of investigator reported hypoglycemia, defined as all symptomatic or asymptomatic episodes with a self-measured blood glucose ≤70 mg/dL, was noted between the Tradjenta- (31.4%) and placebo- (32.9%) treated groups. During the same time period, severe hypoglycemic events, defined as requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions, were reported in 11 (1.7%) of Tradjenta treated patients and 7 (1.1%) of placebo treated patients. Events that were considered life-threatening or required hospitalization were reported in 3 (0.5%) patients on Tradjenta and 1 (0.2%) on placebo.

Use in Renal Impairment
Tradjenta was compared to placebo as add-on to pre-existing antidiabetic therapy over 52 weeks in 133 patients with severe renal impairment (estimated GFR <30 mL/min). For the initial 12 weeks of the study, background antidiabetic therapy was kept stable and included insulin, sulfonylurea, glinides, and pioglitazone. For the remainder of the trial, dose adjustments in antidiabetic background therapy were allowed.

In general, the incidence of adverse events including severe hypoglycemia was similar to those reported in other Tradjenta trials. The observed incidence of hypoglycemia was higher (Tradjenta, 63% compared to placebo, 49%) due to an increase in asymptomatic hypoglycemic events especially during the first 12 weeks when background glycemic therapies were kept stable. Ten Tradjenta-treated patients (15%) and 11 placebo-treated patients (17%) reported at least one episode of confirmed symptomatic hypoglycemia (accompanying finger stick glucose ≤54 mg/dL). During the same time period, severe hypoglycemic events, defined as an event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions, were reported in 3 (4.4%) Tradjenta-treated patients and 3 (4.6%) placebo-treated patients. Events that were considered life-threatening or required hospitalization were reported in 2 (2.9%) patients on Tradjenta and 1 (1.5%) patient on placebo.

Renal function as measured by mean eGFR and creatinine clearance did not change over 52 weeks’ treatment compared to placebo.

Laboratory Tests

Changes in laboratory findings were similar in patients treated with Tradjenta 5 mg compared to patients treated with placebo.

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

Increase in Lipase: In a placebo-controlled clinical trial with Tradjenta 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 Tradjenta 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 Tradjenta and placebo arms, respectively.

Vital Signs
No clinically meaningful changes in vital signs were observed in patients treated with Tradjenta.

Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of Tradjenta. 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 (1.2) and Warnings and Precautions (5.1)]
• Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions [see Warnings and Precautions (5.4)]
• Severe and disabling arthralgia [see Warnings and Precautions (5.5)]
• Bullous pemphigoid [see Warnings and Precautions (5.6)]
• Rash
• Mouth ulceration, stomatitis

Take Tradjenta exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take this medicine with or without food. Follow your doctor's instructions.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.

Tradjenta is only part of a treatment program that may also include diet, exercise, weight control, blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Other drugs may increase or decrease the effects of Tradjenta on lowering your blood sugar. Tell your doctor about all your current medicines and any you start or stop using, especially:

• rifampin (to treat tuberculosis); or

• insulin or other oral diabetes medications.

This list is not complete. Other drugs may interact with linagliptin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.