Linagliptin and metformin

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take linagliptin and metformin twice daily with meals, unless your doctor tells you otherwise.

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.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Your doctor may want you to stop taking this medicine for a short time if you become ill, have a fever or infection, or if you have surgery or a medical 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.

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

Store at room temperature away from moisture and heat.

Avoid drinking alcohol. It lowers blood sugar and may increase your risk of lactic acidosis.

Usual Adult Dose for Diabetes Type 2:

Linagliptin-metformin immediate release tablets:
-Initial dose for patients currently not receiving metformin: linagliptin 2.5 mg/metformin 500 mg orally twice a day
-Initial dose for patients currently receiving metformin: linagliptin 2.5 mg in combination with one-half of current metformin dose orally twice a day
-Initial dose for patients currently receiving linagliptin and metformin as individual components: switch to combination product containing the same doses of each component orally twice a day
Maintenance dose: Individualize dose based on safety and efficacy
Maximum dose: linagliptin 5 mg/day; metformin 2000 mg/day

Linagliptin-metformin extended-release tablets:
-Initial dose for patients currently not receiving metformin: linagliptin 5 mg/metformin extended-release 1000 mg orally once a day
-Initial dose for patients currently receiving metformin: linagliptin 5 mg in combination with a similar total daily dose of metformin orally once a day
-Initial dose for patients currently receiving linagliptin and metformin as individual components: switch to combination product containing similar doses of each component orally once a day
Maintenance dose: Individualize dose based on safety and efficacy
Maximum dose: linagliptin 5 mg/day; metformin 2000 mg/day

Comments:
-Patients taking two linagliptin 2.5 mg/metformin 1000 mg extended-release tablets should take the 2 tablets together once a day.
-When used in combination with insulin or an insulin secretagogue, a lower dose of insulin or the insulin secretagogue may be necessary to reduce the risk of hypoglycemia.

Use: To improve glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise when treatment with both linagliptin and metformin are appropriate.

Other drugs may increase or decrease the effects of linagliptin and metformin 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 medicine.

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

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 linagliptin and metformin, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to linagliptin and metformin 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 and metformin combination 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 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 linagliptin and metformin.

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 linagliptin and metformin, 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 linagliptin and metformin 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
• Iopromide
• Iopronic Acid
• Ioseric Acid
• Iosimide
• Iotasul
• Iothalamate
• Iotrolan
• Iotroxic Acid
• Ioxaglate
• Ioxitalamic Acid
• Ipodate
• Metrizamide
• Metrizoic Acid
• Tyropanoate Sodium

Using linagliptin and metformin 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.

• Aspirin
• Balofloxacin
• Besifloxacin
• Bupropion
• Carbamazepine
• Ciprofloxacin
• Dasabuvir
• Dofetilide
• Dolutegravir
• Efavirenz
• Enoxacin
• Enzalutamide
• Fleroxacin
• Flumequine
• Fosphenytoin
• Gatifloxacin
• Gemifloxacin
• Ioversol
• Lanreotide
• Levofloxacin
• Lomefloxacin
• Mitotane
• Moxifloxacin
• Nadifloxacin
• Norfloxacin
• Octreotide
• Ofloxacin
• Ombitasvir
• Oxcarbazepine
• Paritaprevir
• Pasireotide
• Pazufloxacin
• Pefloxacin
• Phenytoin
• Pioglitazone
• Primidone
• Prulifloxacin
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rufloxacin
• Sparfloxacin
• St John's Wort
• Thioctic Acid
• Tipranavir
• Tosufloxacin
• Vandetanib

Using linagliptin and metformin 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
• Esmolol
• Fenugreek
• Furazolidone
• Glucomannan
• Guar Gum
• Iproniazid
• Isocarboxazid
• Labetalol
• Levobunolol
• Linezolid
• Methylene Blue
• Metipranolol
• Metoprolol
• Moclobemide
• Nadolol
• Nebivolol
• Nialamide
• Oxprenolol
• Patiromer
• Penbutolol
• Phenelzine
• Pindolol
• Practolol
• Procarbazine
• Propranolol
• Psyllium
• Ranolazine
• Rasagiline
• Rifampin
• Safinamide
• Selegiline
• Sotalol
• Timolol
• Tranylcypromine
• Verapamil

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. 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 linagliptin and metformin. Make sure you tell your doctor if you have any other medical problems, especially:

• Adrenal glands (underactive) or
• Alcohol, excessive use 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
• Shock (low blood pressure, blood circulation is poor) 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 and acid in the blood) or
• Kidney disease, severe or
• Type I 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).

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, oral:

Jentadueto 2.5/500: Linagliptin 2.5 mg and metformin hydrochloride 500 mg

Jentadueto 2.5/850: Linagliptin 2.5 mg and metformin hydrochloride 850 mg

Jentadueto 2.5/1000: Linagliptin 2.5 mg and metformin hydrochloride 1000 mg

Tablet Extended Release, oral:

Jentadueto XR 2.5/1000: Linagliptin 2.5 mg and metformin hydrochloride 1000 mg

Jentadueto XR 5/1000: Linagliptin 5 mg and metformin hydrochloride 1000 mg

• Antidiabetic Agent, Biguanide
• Antidiabetic Agent, Dipeptidyl Peptidase 4 (DPP-4) Inhibitor

Applies to linagliptin / metformin: oral tablet, oral tablet extended release

Along with its needed effects, linagliptin / metformin 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 while taking linagliptin / metformin:

• Anxiety
• blurred vision
• chills
• cold sweats
• coma
• confusion
• cool, pale skin
• depression
• dizziness
• fast heartbeat
• headache
• increased hunger
• nausea
• nightmares
• seizures
• shakiness
• slurred speech
• unusual tiredness or weakness

• 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 of linagliptin / metformin 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:

• Diarrhea
• excess air or gas in the stomach or intestines
• full feeling
• heartburn
• lack or loss of strength
• muscle aches
• passing gas
• sore throat
• stuffy or runny nose

• 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

Linagliptin-metformin immediate release tablets:
-Initial dose for patients currently not receiving metformin: linagliptin 2.5 mg/metformin 500 mg orally twice a day
-Initial dose for patients currently receiving metformin: linagliptin 2.5 mg in combination with one-half of current metformin dose orally twice a day
-Initial dose for patients currently receiving linagliptin and metformin as individual components: switch to combination product containing the same doses of each component orally twice a day
Maintenance dose: Individualize dose based on safety and efficacy
Maximum dose: linagliptin 5 mg/day; metformin 2000 mg/day

Linagliptin-metformin extended-release tablets:
-Initial dose for patients currently not receiving metformin: linagliptin 5 mg/metformin extended-release 1000 mg orally once a day
-Initial dose for patients currently receiving metformin: linagliptin 5 mg in combination with a similar total daily dose of metformin orally once a day
-Initial dose for patients currently receiving linagliptin and metformin as individual components: switch to combination product containing similar doses of each component orally once a day
Maintenance dose: Individualize dose based on safety and efficacy
Maximum dose: linagliptin 5 mg/day; metformin 2000 mg/day

Comments:
-Patients taking two linagliptin 2.5 mg/metformin 1000 mg extended-release tablets should take the 2 tablets together once a day.
-When used in combination with insulin or an insulin secretagogue, a lower dose of insulin or the insulin secretagogue may be necessary to reduce the risk of hypoglycemia.

Use: To improve glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise when treatment with both linagliptin and metformin are appropriate.

-Severe renal impairment (eGFR below 30 mL/min/1.73 m2): Use is contraindicated
-Moderate renal impairment (eGFR 30 to 45 mL/min/1.73 m2): Do not initiate therapy
During therapy:
-If eGFR falls below 45 mL/min/1.73 m2: Assess risk vs benefit of continuing therapy.
-If eGFR falls below 30 mL/min/1.73 m2: Discontinue therapy.

IODINATED CONTRAST PROCEDURE:
-Stop this drug at time of, or prior to, an iodinated contrast imaging procedure for patients with an eGFR between 30 and 60 mL/min/1.73 m2.
-Stop this drug in patients who will be administered intra-arterial iodinated contrast.
-Stop this drug in patients with a history of hepatic impairment, alcoholism, or heart failure.
-Reevaluate eGFR 48 hours after the imaging procedure; this drug may be restarted once adequate renal function is confirmed.