Pronunciation:

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

Brand Names:

• Kombiglyze XR

Dosage Forms:

• Tablet, Extended Release

Warnings:

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 greater than 5 mcg/mL. Risk factors include renal impairment, concomitant use of certain drugs, age greater than 65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. If lactic acidosis is suspected, discontinue use and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended .

Classifications:

Therapeutic—

Hypoglycemic

Pharmacologic—

Saxagliptin

Chemical—

Metformin

Uses of This Medicine:

Saxagliptin and metformin combination is used with diet and exercise to treat high blood sugar (glucose) levels in patients with type 2 diabetes. Saxagliptin helps to control blood sugar levels by making the pancreas gland release more insulin. It also signals the liver to stop producing sugar 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 saxagliptin 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 saxagliptin and metformin combination in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution for patients receiving this medicine. This medicine is not recommended in patients 80 years of age and older who have kidney problems.

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 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.

• Abametapir
• Abiraterone Acetate
• Acetazolamide
• Alogliptin
• Aspirin
• Bexagliflozin
• Bictegravir
• Brinzolamide
• Bupropion
• Capmatinib
• Carbamazepine
• Ceritinib
• Chloroquine
• Chlorothiazide
• Chlorpropamide
• Chlorthalidone
• Cimetidine
• Ciprofloxacin
• Dasabuvir
• Delafloxacin
• Diatrizoate
• Dichlorphenamide
• Dofetilide
• Dolutegravir
• Dorzolamide
• Enoxacin
• Ethiodized Oil
• Fedratinib
• Fexinidazole
• Fosnetupitant
• Furosemide
• Gatifloxacin
• Gemifloxacin
• Glimepiride
• Glipizide
• Glyburide
• Grepafloxacin
• Hydrochlorothiazide
• Hydroflumethiazide
• Hydroxychloroquine
• Indapamide
• Insulin
• Insulin Aspart, Recombinant
• Insulin Bovine
• Insulin Degludec
• Insulin Detemir
• Insulin Glargine, Recombinant
• Insulin Glulisine
• Insulin Lispro, Recombinant
• Iodipamide
• Iodixanol
• Iohexol
• Iopamidol
• Iopanoic Acid
• Iopromide
• Iothalamate
• Iotrolan
• Ioversol
• Ioxaglate
• Ipodate
• Isavuconazole
• Lanreotide Acetate
• Levofloxacin
• Levoketoconazole
• Liraglutide
• Lomefloxacin
• Mavacamten
• Methazolamide
• Metolazone
• Metrizamide
• Moxifloxacin
• Nateglinide
• Netupitant
• Norfloxacin
• Octreotide Acetate
• Ofloxacin
• Omaveloxolone
• Ombitasvir
• Paritaprevir
• Pasireotide Diaspartate
• Phenobarbital
• Pioglitazone
• Polythiazide
• Pramlintide
• Primidone
• Ranolazine
• Repaglinide
• Semaglutide
• Simeprevir
• Sitagliptin
• Somatrogon-ghla
• Sotagliflozin
• Sparfloxacin
• Tafenoquine
• Thioctic Acid
• 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
• Acetohexamide
• Atenolol
• Betaxolol
• Bisoprolol
• Bitter Melon
• Carteolol
• Carvedilol
• Celiprolol
• Chlorpropamide
• Colesevelam
• Esmolol
• Fenugreek
• Glecaprevir
• Gliclazide
• Glimepiride
• Glipizide
• Gliquidone
• Glucomannan
• Glyburide
• Goldenseal
• Guar Gum
• Hydrastis
• Insulin
• Insulin Aspart, Recombinant
• Insulin Bovine
• Insulin Degludec
• Insulin Detemir
• Insulin Glulisine
• Insulin Lispro, Recombinant
• Isocarboxazid
• Labetalol
• Levobunolol
• Linezolid
• Methylene Blue
• Metipranolol
• Metoprolol
• Nadolol
• Nebivolol
• Oxprenolol
• Ozanimod
• Patiromer
• Penbutolol
• Phenelzine
• Pibrentasvir
• Pindolol
• Practolol
• Procarbazine
• Propranolol
• Psyllium
• Rasagiline
• Rifampin
• Safinamide
• Selegiline
• Sotalol
• Timolol
• Tirzepatide
• Tolazamide
• Tolbutamide
• 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:

• Alcohol, excessive use or
• Congestive heart failure or
• Dehydration or
• Gallstones, history of or
• Hypertriglyceridemia (high triglycerides or fats in the blood) or
• Kidney disease or
• Liver disease or
• Pancreas problems, history of or
• Sepsis (severe infection) or
• Weakened physical condition—Use with caution. May cause side effects to become worse.

• Anemia 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 other dipeptidyl peptidase-4 (DPP-4) inhibitors—Use with caution. May increase the risk of this condition occurring again.

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

• Kidney disease, severe or
• Metabolic acidosis (including diabetic ketoacidosis)—Should not be used in patients with these conditions.

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 unwanted effects.

This medicine usually comes with a Medication Guide. Read the information carefully and make sure you understand it before taking this medicine. If you have any questions, ask your doctor.

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

Take the medicine with the evening meal to help reduce unwanted stomach effects that may occur during the first few weeks of treatment.

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

While taking the extended-release tablet, part of the tablet may pass into your stools. This is normal and is nothing to worry about.

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:
    • For patients taking metformin alone:
      • Adults—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 5 milligrams (mg) of saxagliptin and 2000 mg of metformin once a day.
      • Children—Use and dose must be determined by your doctor.
    • For patients taking saxagliptin alone:
      • Adults—At first, one tablet containing 5 milligrams (mg) of saxagliptin and 500 mg of metformin once a day. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 5 mg of saxagliptin and 2000 mg of metformin once a day.
      • Children—Use and dose must be determined by your doctor.
    • For patients using 2.5 milligrams (mg) of saxagliptin and extended-release metformin together:
      • Adults—One tablet containing 2.5 mg of saxagliptin and 1000 mg of metformin 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.

Precautions While Using This Medicine:

Your doctor will want to 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.

Let your doctor or dentist know you are taking this medicine. Your doctor may advise you to temporarily stop taking this medicine before you have major surgery or diagnostic tests, including procedures that use contrast dye.

Under certain conditions, too much metformin can cause a condition called lactic acidosis. The symptoms of lactic acidosis are severe, appear quickly, and usually occur when other health problems are present, such as a heart attack or kidney failure. Symptoms of lactic acidosis include abdominal or 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 symptoms of lactic acidosis occur, you should get immediate emergency medical help.

Pancreatitis (swelling and inflammation of the pancreas) may occur while you are using this medicine. Check with your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

If you are rapidly gaining weight, having shortness of breath, chest pain, extreme tiredness or weakness, irregular breathing, irregular heartbeat, or excessive swelling of the hands, wrist, ankles, or feet, check with your doctor immediately. These may be symptoms of a heart problem.

This medicine may cause serious types of allergic reactions, including anaphylaxis and angioedema. These conditions may be life-threatening and require immediate medical attention. Check with your doctor right away if you have a rash, itching, a large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs, trouble breathing, or chest tightness.

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. Talk to your doctor about the best way 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 joint pain. Call your doctor right away if you have severe joint pain with this medicine.

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

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:

More common

Anxiety

bladder pain

bloody or cloudy urine

blurred vision

body aches or pain

chills

cold sweats

confusion

cool, pale skin

cough

depression

difficult, burning, or painful urination

difficulty with breathing

dizziness

ear congestion

fast heartbeat

fever

frequent urge to urinate

headache

increased hunger

loss of voice

lower back or side pain

nasal congestion

nausea

nightmares

runny nose

seizures

shakiness

slurred speech

sneezing

sore throat

unusual tiredness or weakness

Rare

Cough or hoarseness

Incidence not known

Black, tarry stools

bleeding gums

blood in the urine or stools

constipation

darkened urine

difficulty with swallowing

hives or skin rash

indigestion

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

pinpoint red spots on the skin

puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

tightness in the chest

unusual bleeding or bruising

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

muscle aches

Less common

Abdominal or stomach pain

itching

pain or tenderness around the eyes and cheekbones

redness of the skin

weakness

welts

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.