Pronunciation:

sit-a-GLIP-tin FOS-fate, sim-va-STAT-in

Brand Names:

• Juvisync

Classifications:

Pharmacologic—

Sitagliptin

Uses of This Medicine:

Sitagliptin and simvastatin combination is used together with a proper diet and exercise to treat type 2 diabetes. It is also used together with a proper diet to treat high cholesterol and triglyceride (fats) levels in the blood. This medicine may help prevent medical problems caused by clogged blood vessels such as heart attacks and strokes.

Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. It 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.

Simvastatin belongs to the group of medicines called statins. It works to reduce the amount of cholesterol in the blood by blocking the production of cholesterol.

This medicine was available only with your doctor's prescription. The Juvisync™ product will no longer be marketed in the United States as of September 26, 2013, but may be available in other countries.

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 simvastatin 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 simvastatin combination in the elderly. However, elderly patients are more likely to have age-related kidney or muscle problems, which may require caution and an adjustment in the dose for patients receiving sitagliptin and simvastatin combination.

Breast-feeding—

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

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.

• Amprenavir
• Atazanavir
• Boceprevir
• Ceritinib
• Clarithromycin
• Cobicistat
• Cyclosporine
• Danazol
• Darunavir
• Erythromycin
• Fosamprenavir
• Gemfibrozil
• Idelalisib
• Indinavir
• Itraconazole
• Ketoconazole
• Letermovir
• Levoketoconazole
• Lopinavir
• Mibefradil
• Mifepristone
• Nefazodone
• Nelfinavir
• Nirmatrelvir
• Paritaprevir
• Posaconazole
• Ribociclib
• Ritonavir
• Saquinavir
• Telaprevir
• Telithromycin
• Tipranavir
• Voriconazole

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
• Acenocoumarol
• Adagrasib
• Amiodarone
• Amlodipine
• Asciminib
• Azithromycin
• Bempedoic Acid
• Bezafibrate
• Carbamazepine
• Chloroquine
• Chlorothiazide
• Chlorpropamide
• Chlorthalidone
• Ciprofibrate
• Ciprofloxacin
• Clofibrate
• Colchicine
• Conivaptan
• Dabigatran Etexilate
• Dabrafenib
• Dalfopristin
• Daptomycin
• Darolutamide
• Delafloxacin
• Delavirdine
• Digoxin
• Diltiazem
• Dronedarone
• Duvelisib
• Elexacaftor
• Eltrombopag
• Encorafenib
• Enoxacin
• Eslicarbazepine Acetate
• Fedratinib
• Fenofibrate
• Fenofibric Acid
• Fexinidazole
• Fluconazole
• Fosnetupitant
• Furosemide
• Fusidic Acid
• Gatifloxacin
• Gemifloxacin
• Glecaprevir
• 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
• Ivosidenib
• Lanreotide Acetate
• Larotrectinib
• Lefamulin
• Leflunomide
• Lenacapavir
• Leniolisib
• Levamlodipine
• Levofloxacin
• Lomefloxacin
• Lomitapide
• Lorlatinib
• Lumacaftor
• Mavacamten
• Metformin
• Metolazone
• Midostaurin
• Momelotinib
• Moxifloxacin
• Nateglinide
• Netupitant
• Niacin
• Norfloxacin
• Octreotide Acetate
• Ofloxacin
• Olutasidenib
• Omaveloxolone
• Pacritinib
• Pasireotide Diaspartate
• Pazopanib
• Phenobarbital
• Phenprocoumon
• Pibrentasvir
• Pirtobrutinib
• Polythiazide
• Pramlintide
• Primidone
• Quinupristin
• Ranolazine
• Repaglinide
• Risperidone
• Ritlecitinib
• Simeprevir
• Somatrogon-ghla
• Sparfloxacin
• Tadalafil
• Teriflunomide
• Thioctic Acid
• Tolazamide
• Tolbutamide
• Triamterene
• Trofinetide
• Trovafloxacin
• Verapamil
• Warfarin

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
• Albiglutide
• Alitretinoin
• Atenolol
• Betaxolol
• Bisoprolol
• Bosentan
• Carteolol
• Carvedilol
• Celiprolol
• Cilostazol
• Clopidogrel
• Efavirenz
• Esmolol
• Fosphenytoin
• Fostemsavir
• Glecaprevir
• Interferon Beta
• Labetalol
• Levobunolol
• Levothyroxine
• Metipranolol
• Metoprolol
• Nadolol
• Nebivolol
• Oat Bran
• Oxcarbazepine
• Oxprenolol
• Pectin
• Penbutolol
• Phenytoin
• Pibrentasvir
• Pindolol
• Practolol
• Propranolol
• Rifampin
• Sotalol
• St John's Wort
• Ticagrelor
• Timolol

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.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Cranberry Juice
• Grapefruit Juice

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 use, excessive or history of or
• Chinese ancestry or
• Gallbladder stones or
• Hypothyroidism (an underactive thyroid), uncontrolled or
• Kidney disease or
• Liver disease, history of or
• Pancreas problems, history of—Use with caution. May cause side effects to become worse.

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

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

• Electrolyte disorders, severe or
• Endocrine disorders, severe or
• Epilepsy (seizures), not well-controlled or
• Hypotension (low blood pressure) or
• Major surgery or trauma, recent or
• Metabolic disorders, severe or
• Sepsis (severe infection in the blood)—Patients with these conditions may be at risk for muscle or kidney problems.

• Muscle pain, tenderness, or weakness, history of—Use with caution. May make these conditions worse.

Proper Use of This Medicine:

Take this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Your doctor will give you instructions about diet, exercise, testing your blood sugar, and adjusting your dose when you are sick. Carefully follow your doctor's instructions.

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

If you are taking diltiazem (Cardizem®), dronedarone (Multaq®), or verapamil (Calan®, Isoptin®, Verelan®) together with this medicine, your dose of Juvisync™ should not be higher than 100 milligrams (mg) of sitagliptin and 10 mg of simvastatin per day, unless otherwise directed by your doctor. Do not use more than 100 mg of sitagliptin and 20 mg of simvastatin per day together with amiodarone (Cordarone®), amlodipine (Norvasc®), lomitapide (Juxtapid™), or ranolazine (Ranexa®). When used together with higher doses of Juvisync™, these medicines may increase your risk of muscle injury and could result in kidney problems.

Avoid drinking grapefruit juice while you are taking this medicine. Grapefruit juice may increase your risk of muscle injury and could result in kidney problems.

Do not drink large amounts of alcohol with this medicine. This could cause unwanted effects on the liver.

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 and high cholesterol:
    • For patients who are not taking sitagliptin or simvastatin:
      • Adults—At first, 100 milligrams (mg) of sitagliptin and 40 mg of simvastatin combination once a day in the evening. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For patients who are already taking simvastatin:
      • Adults—At first, 100 milligrams (mg) of sitagliptin and the dose of simvastatin you are already taking. It is taken once a day in the evening. Your doctor may adjust your dose as needed.
      • 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:

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Do not use this medicine if you are also taking any of the following medicines: boceprevir (Victrelis®), cobicistat-containing products (Stribild®), cyclosporine (Gengraf®, Neoral®, Sandimmune®), danazol (Danocrine®), gemfibrozil (Lopid®), nefazodone (Serzone®), telaprevir (Incivek®), certain antibiotics (such as clarithromycin, erythromycin, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole, Nizoral®), or medicines to treat HIV/AIDS (such as atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, Crixivan®, Kaletra®, Lexiva®, Norvir®, Prezista®, Reyataz®). Using these medicines together with sitagliptin and simvastatin combination may increase your risk of muscle injury and could result in kidney problems.

Chinese patients who are taking large amounts of niacin (greater than or equal to 1 gram or 1000 milligrams per day) together with this medicine may have an increased risk for muscle injury. Talk to your doctor if you are Chinese or have Chinese ancestry and take large amounts of niacin (Niacor®, Niaspan®). You may need a different dose of this medicine.

Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness, especially if you also have unusual tiredness or a fever. These could be symptoms of serious muscle problems, such as myopathy or immune-mediated necrotizing myopathy (IMNM). Myopathy is more common when high doses of simvastatin (eg, 80 milligrams) are used, but some people get myopathy with lower doses.

Call your doctor right away if you have dark-colored urine, diarrhea, a fever, muscle cramps or spasms, muscle pain or stiffness, or unusual tiredness or weakness. These could be symptoms of a serious muscle problem called rhabdomyolysis, which can cause kidney problems.

Call your doctor right away if you have dark-colored urine, a general feeling of tiredness or weakness, a headache, light-colored stools, loss of appetite, stomach pain, upper right stomach pain, vomiting, weight loss, or yellow eyes or skin. These could be symptoms of liver damage.

Tell your doctor right away if you have sudden and severe stomach pain, nausea, vomiting, fever, or lightheadedness. These may be symptoms of pancreatitis (swelling and inflammation of the pancreas).

This medicine may cause serious allergic reactions, including anaphylaxis, angioedema, or certain skin conditions (Stevens-Johnson syndrome). These reactions can be life-threatening and require immediate medical attention. Call your doctor right away if you have a rash, itching, blistering, peeling, or loosening of the skin, fever or chills, trouble breathing or swallowing, or any swelling of your hands, face, mouth, or throat while you are using this medicine.

This medicine may cause hypoglycemia (low blood sugar). Low blood sugar can also occur if you delay or miss a meal or snack, exercise more than usual, drink alcohol, cannot eat because of nausea or vomiting, take certain medicines, or take sitagliptin with another type of diabetes medicine (eg, insulin, glimepiride, metformin, or pioglitazone). Symptoms of low blood sugar must be treated before they cause you to pass out (unconsciousness). People feel different symptoms with low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly.

Symptoms of low blood sugar include anxiety, behavior changes 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, nervousness, nightmares, restless sleep, shakiness, slurred speech, or unusual tiredness or weakness.

If symptoms of low blood sugar occur, check your blood sugar level. If you have low blood sugar, eat glucose tablets or gel, corn syrup, honey, or sugar cubes, or drink fruit juice, non-diet soft drinks, or sugar dissolved in water. Glucagon is a medicine that is used in emergency situations when severe symptoms, such as seizures (convulsions) or unconsciousness occur. Have a glucagon kit available, along with a syringe and needle, and know how to use it. The members of your family should also know how to use glucagon.

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 with a list of all your medicines.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine if you have major surgery, a major injury, or you develop other serious health problems.

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

blurred vision

chills

cold sweats

confusion

cool, pale skin

depression

dizziness

fainting

fast or irregular heartbeat

headache

increased hunger

nausea

nightmares

seizures

shakiness

slurred speech

unusual tiredness or weakness

Less common

Bladder pain

bloody or cloudy urine

difficult, burning, or painful urination

dry mouth

flushed, dry skin

frequent urge to urinate

fruit-like breath odor

increased thirst

increased urination

loss of consciousness

lower back or side pain

stomachache

sweating

swelling

troubled breathing

unexplained weight loss

vomiting

Rare

Bloating

constipation

dark-colored urine

fever

indigestion

loss of appetite

muscle cramps or spasms

muscle pain, tenderness, wasting, or weakness

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

yellow eyes or skin

Incidence not known

Agitation

black, tarry stools

bleeding gums

blistering, peeling, or loosening of the skin

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

chest pain

decreased urine output

diarrhea

difficulty with moving

difficulty with swallowing

feeling of warmth

hives

increased sensitivity of the skin to sunlight

irritability

joint or muscle pain

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

lethargy

pinpoint red spots on the skin

rapid weight gain

red, irritated eyes

red, sore, or itching skin

red skin lesions, often with a purple center

redness of the face, neck, arms, and occasionally, upper chest

seizures

severe sunburn

skin rash

sore throat

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

sores, welts, or blisters on the skin

swollen glands

swollen joints

tightness in the chest

unsteadiness or awkwardness

unusual bleeding or bruising

weakness in the arms, hands, legs, or feet

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

cough that produces mucus

ear congestion

loss of voice

runny or stuffy nose

sneezing

Less common

Burning feeling in the chest or stomach

dizziness or lightheadedness

feeling of constant movement of self or surroundings

pain or tenderness around the eyes and cheekbones

sensation of spinning

skin rash that is encrusted, scaly, and oozing

tenderness in the stomach area

trouble with sleeping

Incidence not known

Acid or sour stomach

being forgetful

belching

decreased interest in sexual intercourse

excess air or gas in the stomach or intestines

full feeling

hair loss

heartburn

inability to have or keep an erection

loss in sexual ability, desire, drive, or performance

passing gas

problems with memory

stomach discomfort, upset, or pain

thinning of the hair

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.