Pronunciation:

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

Brand Names:

• Zituvimet

Warnings:

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old 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. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information. If metformin-associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride/sitagliptin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended .

Classifications:

Pharmacologic—

Dipeptidyl Peptidase IV Inhibitor

Chemical—

Metformin

Uses of This Medicine:

Sitagliptin and metformin combination is used together with proper diet and exercise to treat high blood sugar levels caused by type 2 diabetes. Sitagliptin 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 intestines, reduces the release of stored sugar from the liver, and helps your body use sugar better.

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 sitagliptin 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 sitagliptin and metformin combination in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart 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 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
• Acarbose
• Acetazolamide
• Alogliptin
• Aspirin
• Bexagliflozin
• Bictegravir
• Brinzolamide
• Bupropion
• Capmatinib
• Chloroquine
• Chlorothiazide
• Chlorpropamide
• Chlorthalidone
• Cimetidine
• Ciprofloxacin
• Dasabuvir
• Delafloxacin
• Diatrizoate
• Dichlorphenamide
• Dofetilide
• Dolutegravir
• Dorzolamide
• Enoxacin
• Ethiodized Oil
• Fedratinib
• Fexinidazole
• 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
• Metformin
• Methazolamide
• Metolazone
• Metrizamide
• Moxifloxacin
• Nateglinide
• Norfloxacin
• Octreotide Acetate
• Ofloxacin
• Ombitasvir
• Paritaprevir
• Pasireotide Diaspartate
• Pioglitazone
• Polythiazide
• Pramlintide
• 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
• Atenolol
• Betaxolol
• Bisoprolol
• Bitter Melon
• Carteolol
• Carvedilol
• Celiprolol
• Colesevelam
• Esmolol
• Fenugreek
• Glecaprevir
• Glucomannan
• Goldenseal
• Guar Gum
• Hydrastis
• 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
• 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
• Cardiovascular collapse (shock) or
• Dehydration or
• Heart attack, acute or
• Heart failure, history of or
• Hypoxemia (decreased oxygen in the blood) or
• Liver disease or
• Sepsis (severe infection)—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 1 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.

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 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 food.

Swallow the tablet whole. Do not break or cut 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 (tablets):
  • For type 2 diabetes:
    • Adults:
      • Patients not currently treated with metformin—At first, 50 milligrams (mg) of sitagliptin and 500 mg of metformin 2 times a day. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 100 mg of sitagliptin and 2000 mg of metformin per day.
      • Patients already treated with metformin—At first, give 50 milligrams (mg) of sitagliptin 2 times a day and the same metformin dose you are already taking. For patients already taking 850 mg of metformin 2 times a day, take 50 mg of sitagliptin and 1000 mg of metformin 2 times a day. Your doctor may adjust your dose until your blood sugar is controlled. However, the dose is usually not more than 100 mg of sitagliptin and 2000 mg of metformin per 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.

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, including 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 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 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 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.

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.

This medicine cause kidney problems, including acute kidney failure. Check with your doctor right away if you have agitation, coma, confusion, decreased urine output, depression, dizziness, headache, hostility, irritability, lethargy, muscle twitching, nausea, rapid weight gain, seizures, stupor, swelling of the face, ankles, or hands, or unusual tiredness or weakness.

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, headache, nausea, shakiness, slurred speech, or unusual tiredness or weakness. Talk to your doctor about how to treat low blood sugar.

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.

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:

Incidence not known

Agitation

anxiety

blistering, peeling, or loosening of the skin

bloating

bloody or cloudy urine

blurred vision

chest pain or tightness

chills

clay-colored stools

cold sweats

coma

confusion

constipation

cough

dark urine

decreased appetite

decrease urine output

depression

diarrhea

difficulty in moving

difficulty swallowing

dilated neck veins

dizziness

fast heartbeat

fever

general feeling of discomfort

headache

hives, itching, skin rash

hostility

increased hunger

indigestion

irregular heartbeat

irritability

joint or muscle pain

large, hard skin blisters

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

lethargy

loss of appetite

muscle cramps, pain, spasms, stiffness, or twitching

nausea

nervousness

nightmares

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

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

rapid weight gain

red irritated eyes

red skin lesions, often with a purple center

shakiness

seizures

sleepiness

slurred speech

sore throat

sores, ulcers, or white spots in the mouth or on the lips

stomach pain or discomfort

stupor

swelling of the face, ankles, or hands

trouble breathing

unpleasant breath odor

unusual tiredness or weakness

vomiting

vomiting of blood

weight gain

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

Body aches or pain

ear congestion

loss of voice

sneezing

stuffy or runny nose

Incidence not known

Arm or leg pain

back pain

inflammation, irritation, soreness, or swelling of the mouth

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.