Pronunciation:

lin-a-GLIP-tin, met-FOR-min hye-droe-KLOR-ide

Brand Names:

• Jentadueto
• Jentadueto XR

Dosage Forms:

• Tablet
• Tablet, Extended Release

Warnings:

Lactic acidosis can occur due to metformin accumulation during treatment with linagliptin/metformin hydrochloride, and case reports of death, hypothermia, hypotension, and resistant bradyarrhythmias have been reported. The risk of lactic acidosis is increased with renal impairment, concomitant cationic drugs (eg, topiramate), age 65 years or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Onset is often subtle with symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities include elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally greater than 5 mcg/mL. If lactic acidosis is suspected, immediately discontinue therapy, hospitalize patient, and promptly start hemodialysis .

Classifications:

Therapeutic—

Hypoglycemic

Pharmacologic—

Dipeptidyl Peptidase IV Inhibitor

Chemical—

Metformin

Uses of This Medicine:

Linagliptin and metformin combination is used 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. Metformin reduces the absorption of sugar from the stomach, reduces the release of stored sugar from the liver, and helps your body use sugar better. This medicine does not help patients who have insulin-dependent or type 1 diabetes.

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

Before Using This Medicine:

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.

Children—

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

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of linagliptin and metformin combination in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

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.

Other 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 not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Acetrizoic Acid
• Diatrizoate
• Ethiodized Oil
• Iobenzamic Acid
• Iobitridol
• Iocarmic Acid
• Iocetamic Acid
• Iodamide
• Iodipamide
• Iodixanol
• Iodohippuric Acid
• Iodopyracet
• Iodoxamic Acid
• Ioglicic Acid
• Ioglycamic Acid
• Iohexol
• Iomeprol
• Iopamidol
• Iopanoic Acid
• Iopentol
• Iophendylate
• Iopronic Acid
• Ioseric Acid
• Iosimide
• Iotasul
• Iothalamate
• Iotrolan
• Iotroxic Acid
• Ioxaglate
• Ioxitalamic Acid
• Ipodate
• Metrizamide
• Metrizoic Acid
• Tyropanoate Sodium

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.

• Abiraterone Acetate
• Acetazolamide
• Alogliptin
• Apalutamide
• Aspirin
• Bexagliflozin
• Bictegravir
• Brinzolamide
• Bupropion
• Capmatinib
• Carbamazepine
• Chloroquine
• Chlorothiazide
• Chlorpropamide
• Chlorthalidone
• Cimetidine
• Ciprofloxacin
• Dasabuvir
• Delafloxacin
• Dichlorphenamide
• Dofetilide
• Dolutegravir
• Dorzolamide
• Efavirenz
• Enoxacin
• Enzalutamide
• Fedratinib
• Fexinidazole
• Fosphenytoin
• Furosemide
• Gatifloxacin
• Gemifloxacin
• Glimepiride
• Glipizide
• Glyburide
• Grepafloxacin
• Hydrochlorothiazide
• Hydroflumethiazide
• Hydroxychloroquine
• Indapamide
• Iopromide
• Ioversol
• Isavuconazole
• Lanreotide
• Levofloxacin
• Levoketoconazole
• Liraglutide
• Lomefloxacin
• Lumacaftor
• Methazolamide
• Metolazone
• Mitotane
• Moxifloxacin
• Nateglinide
• Norfloxacin
• Octreotide
• Ofloxacin
• Ombitasvir
• Oxcarbazepine
• Paritaprevir
• Pasireotide
• Phenytoin
• Pioglitazone
• Polythiazide
• Primidone
• Ranolazine
• Repaglinide
• Rifabutin
• Rifampin
• Rifapentine
• Semaglutide
• Sitagliptin
• Somatrogon-ghla
• Sotagliflozin
• Sparfloxacin
• St John's Wort
• Tafenoquine
• Thioctic Acid
• Tipranavir
• Tolazamide
• Tolbutamide
• Topiramate
• Triamterene
• Trovafloxacin
• Vandetanib
• Zonisamide

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
• Bitter Melon
• Carteolol
• Carvedilol
• Celiprolol
• Colesevelam
• Esmolol
• Fenugreek
• Glucomannan
• Guar Gum
• Isocarboxazid
• Labetalol
• Levobunolol
• Linezolid
• Methylene Blue
• Metipranolol
• Metoprolol
• Nadolol
• Nebivolol
• Oxprenolol
• Ozanimod
• Patiromer
• Penbutolol
• Phenelzine
• Pindolol
• Practolol
• Procarbazine
• Propranolol
• Psyllium
• Rasagiline
• Rifampin
• Safinamide
• Selegiline
• Sotalol
• Timolol
• Tranylcypromine
• Verapamil

Other interactions—

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

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:

• Adrenal glands (underactive) or
• Alcohol, excessive use or
• Cardiovascular collapse (shock) or
• Congestive heart failure, acute or unstable or
• Dehydration or
• Heart attack, acute or
• Hypoxemia (decreased oxygen in the blood) or
• Liver disease or
• Pituitary gland (underactive) or
• Poorly nourished condition or
• Sepsis (severe infection) or
• Weakened physical condition—Use with caution. May cause side effects to become worse.

• Anemia (low blood cells) or
• Vitamin B12 deficiency—Use with caution. May make these conditions worse.

• Angioedema (swelling of the face, lips, tongue, throat, arms, or legs), history with this medication or other dipeptidyl peptidase-4 (DPP-4) inhibitors—Use with caution. May increase the risk of this condition occurring again.

• Diabetic ketoacidosis or metabolic acidosis (high ketones or acid in the blood or urine) or
• Kidney disease, severe or
• Type I diabetes—Should not be used in patients with these conditions.

• Fever or
• Infection or
• Surgery or
• Trauma—Use with caution. These conditions may cause problems with blood sugar control.

• Heart failure, history of or
• Kidney damage, history of—May increase risk for heart failure.

• 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).

Proper Use of This Medicine:

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.

Take this medicine with meals.

Swallow the extended-release tablet whole. Do not crush, break, or chew it.

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 (extended-release tablets):
  • For type 2 diabetes:
    • Adults:
      • Patients taking metformin alone—The metformin dose is the same as the dose you are already taking plus 5 milligrams (mg) of linagliptin. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 5 mg of linagliptin and 2000 mg of metformin once a day.
      • Patients taking linagliptin alone—At first, one tablet containing 5 mg of linagliptin and 1000 mg of metformin once a day. Your doctor may gradually increase your dose until your blood sugar is controlled. However, the dose is usually not more than 5 mg of linagliptin and 2000 mg of metformin once a day.
      • Patients taking linagliptin and metformin as separate components or Jentadueto® tablets—The metformin dose is the same as the dose you are already taking plus 5 mg of linagliptin. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 5 mg of linagliptin and 2000 mg of metformin once a day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (tablets):
  • For type 2 diabetes:
    • Adults:
      • Patients taking metformin alone—The metformin dose is the same as the dose you are already taking. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 2.5 milligrams (mg) of linagliptin and 1000 mg of metformin 2 times a day.
      • Patients taking linagliptin alone—At first, 1 tablet containing 2.5 mg of linagliptin and 500 mg of metformin 2 times a day. Your doctor may gradually increase your dose until your blood sugar is controlled. However, the dose is usually not more than 2.5 mg of linagliptin and 1000 mg of metformin 2 times a day.
      • Patients taking linagliptin and metformin as separate components—The linagliptin and metformin dose are the same as the dose you are already taking. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 2.5 mg of linagliptin and 1000 mg of metformin 2 times 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—

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.

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

Keep the tablets dry.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects.

Under certain conditions, too much metformin can cause lactic acidosis. It usually occurs when other serious health problems are present, such as a heart attack or kidney failure. Symptoms of lactic acidosis include: stomach discomfort, decreased appetite, diarrhea, fast or shallow breathing, a general feeling of discomfort, muscle pain or cramping, and unusual sleepiness, tiredness, or weakness. If you have more than one of these symptoms together, you should get immediate emergency medical help.

Do not let yourself get dehydrated. Be sure to drink extra fluids when you exercise or increase your activity, or if you have vomiting or diarrhea.

Pancreatitis may occur while you are using this medicine. Check with your doctor right away if you have a sudden and severe stomach pain, chills, constipation, nausea, vomiting, loss of appetite, fever, or lightheadedness.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine before having a major surgery or diagnostic tests, especially tests that use a contrast dye.

It is very important to carefully follow any instructions from your health care team about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team.
• Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines, such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.
• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about the changes in the dosing of their diabetes medicine that might occur with lifestyle changes, such as changes in exercise or diet. Furthermore, counseling on contraception and pregnancy may be needed, because of the problems that can occur in patients with diabetes during pregnancy.
• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.
• In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says you have diabetes and that lists all of your medicines.

This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with certain medicines. Low blood sugar must be treated before it causes you to pass out (unconsciousness).. People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Some symptoms of low blood sugar include: behavior changes that are similar to being drunk, blurred vision, cold sweats, confusion, cool, pale skin, difficulty with thinking, drowsiness, excessive hunger, a fast heartbeat, headaches that continue, nausea, shakiness, slurred speech, or unusual tiredness or weakness. Talk to your doctor about how to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your medicine, overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual. High blood sugar can be very serious and must be treated right away. It is important that you learn which symptoms you have in order to treat it quickly. Talk to your doctor about the best way to treat high blood sugar.

This medicine may cause severe and disabling joint pain. Call your doctor right away if you have severe joint pain while using this medicine.

This medicine may cause bullous pemphigoid. Tell your doctor right away if you have large, hard skin blisters while you are using this medicine.

Check with your doctor right away if you have chest pain or tightness, decreased urine output, dilated neck veins, extreme fatigue, irregular breathing, irregular heartbeat, swelling of the face, fingers, feet, or lower legs, trouble breathing, or weight gain. These may be signs of heart failure.

Limit the amount of alcohol you drink while you are using this medicine. Heavy alcohol use can increase your chances of serious side effects.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

Anxiety

blurred vision

chills

cold sweats

confusion

cool, pale skin

depression

dizziness

fast heartbeat

headache

increased hunger

loss of consciousness

nausea

nightmares

seizures

shakiness

slurred speech

unusual tiredness or weakness

Incidence not known

Bloating

constipation

darkened urine

fainting spells

fever

indigestion

irregular heartbeat

large, hard skin blisters

large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

loss of appetite

pains in the stomach, side, or abdomen, possibly radiating to the back

severe joint pain

vomiting

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Diarrhea

excess air or gas in the stomach or intestines

feeling of fullness

heartburn

lack or loss of strength

muscle aches

passing gas

sore throat

stuffy or runny nose

Incidence not known

Cough

decreased appetite

difficulty with moving

flaking and falling off of the skin

hives or welts, itching, or skin rash

muscle aching or cramping

muscle pains or stiffness

redness of the skin

swollen joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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