Prospect: information for the user

Ristfor 50 mg/850 mg film-coated tablets

Ristfor 50 mg/1,000 mg film-coated tablets

sitagliptin/metformin hydrochloride

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section4.

1.What is Ristfor and for what it is used

2.What you need to knowbefore starting to take Ristfor

3.How to take Ristfor

4.Possible adverse effects

5.Storage of Ristfor

6.Contents of the package andadditional information

Ristforcontains two distinct medications, called sitagliptin and metformin.

• Sitagliptin belongs to a class of medications known as DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors)
• Metformin belongs to a class of medications known as biguanides.

They act together to control blood sugar levels in adult patients with a form of diabetes called “type 2 diabetes mellitus”.This medication helps increase insulin levels produced after a meal and reduces the amount of sugar produced by the body.

Along with a diet and exercise, this medication helps lower blood sugar levels.This medication can be used alone or with certain diabetes medications (insulin, sulfonylureas, or thiazolidinediones).

What is type 2 diabetes?

Type 2 diabetes is a disease in which the body does not produce enough insulin and the insulin produced by the body does not function as well as it should.The body may also produce too much sugar.When this occurs, sugar (glucose) accumulates in the blood.This can lead to serious medical problems, such as heart diseases (cardiovascular), kidney diseases (renal), blindness, and amputations.

Do not take Ristfor

• if you are allergic to sitagliptin, metformin, or any of the other ingredients in this medication (listed in section 6)
• if you have severe kidney function reduction
• if you have uncontrolled diabetes, for example, severe hyperglycemia (high blood sugar), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see "Risk of lactic acidosis" below), or ketoacidosis. Ketoacidosis is a condition in which substances called "ketone bodies" accumulate in the blood, which can lead to diabetic precoma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or if your breath develops an unusual fruity odor
• if you have a severe infection or are dehydrated
• if you are scheduled to undergo a radiographythat requires the injection of a contrast agent.You will need to stop taking Ristfor at the time of the radiography and for 2 or more days after, as instructed by your doctor, depending on the functioning of your kidneys
• if you have recently had a heart attack or havesevere circulatory problems, such as "shock" or difficulty breathing
• if you have liver problems (hepatic)
• if you consume excessive alcohol (whether daily or occasionally)
• if you are breastfeeding.

Do not take Ristfor if any of the above circumstances apply to you and consult your doctor about other ways to control your diabetes. If you are unsure, consult your doctor, pharmacist, or nurse before starting to take Ristfor.

Warnings and precautions

Cases of pancreatitis have been reported in patients treated with Ristfor (see section 4).

If you notice blisters on your skin, it may be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop taking Ristfor.

Risk of lactic acidosis

Ristfor may cause a rare but serious side effect called lactic acidosis, especially if your kidneys do not function properly. The risk of developing lactic acidosis is also increased with uncontrolled diabetes, severe infections, prolonged fasting, or alcohol consumption, dehydration (see more information below), liver problems, and any medical condition in which a part of the body has a reduced oxygen supply (such as acute and severe heart disease).

If any of the above applies to you, consult your doctor for further instructions.

Stop taking Ristfor for a short period if you have a condition that may be associated with dehydration(significant loss of body fluids), such as intense vomiting, diarrhea, fever, exposure to heat, or if you drink less fluid than normal. Consult your doctor for further instructions.

Stop taking Ristfor and contact a doctor or the nearest hospital immediately if you experience any of the symptoms that produce lactic acidosis, as this condition can lead to coma.

The symptoms of lactic acidosis include:

-vomiting

-stomach pain (abdominal pain)

-muscle cramps

-general feeling of discomfort, with intense fatigue

-difficulty breathing

-reduction of body temperature and heart rate

Lactic acidosis is a medical emergency and should be treated in a hospital.

Consult your doctor or pharmacist before starting to take Ristfor:

• if you have or have had pancreatitis
• if you have or have had gallstones, alcohol addiction, or have very high levels of triglycerides (a type of fat) in your blood. These medical conditions may increase your risk of developing pancreatitis (see section 4)
• if you have type 1 diabetes.This disease is also known asinsulin-dependent diabetes
• if you have an allergy to sitagliptin, metformin, or Ristfor(see section 4)
• if you are taking a sulfonylurea or insulin, other diabetes medications, as you may experience low blood sugar (hypoglycemia). Your doctor may need to reduce the dose of the sulfonylurea or insulin you are taking

If you need to undergo major surgery, you should stop taking Ristfor while the procedure is being performed and for a period of time after. Your doctor will decide when to interrupt treatment with Ristfor and when to restart it.

If you are unsure whether you are affected by any of the above circumstances, consult your doctor or pharmacist before starting to take Ristfor.

During treatment with Ristfor, your doctor will check your kidney function at least once a year or more frequently if you are an elderly person and/or if your kidney function is deteriorating.

Children and adolescents

Children and adolescents under 18 years old should not use this medication. It is not effective in children and adolescents aged 10 to 17 years. The safety and efficacy of this medication in children under 10 years old are unknown.

Other medications and Ristfor

If you need to receive an injection of a contrast agent containing iodine, for example, in the context of a radiography or examination, you should stop taking Ristfor before the injection or at the time of the injection. Your doctor will decide when to interrupt treatment with Ristfor and when to restart it.

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust the dose of Ristfor. It is especially important to mention the following:

• medications (taken orally, inhaled, or injected) used to treat inflammatory diseases, such as asthma and arthritis (corticosteroids)
• medications that increase urine production (diuretics)
• medications used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• specific medications used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)
• medications specifically used to treat asthma (β-adrenergic agonists)
• iodinated contrast agents or medications containing alcohol
• specific medications used to treat stomach problems, such as cimetidine
• ranolazine, a medication used to treat angina pectoris
• dolutegravir, a medication used to treat HIV infection
• vandetanib, a medication used to treat a specific type of thyroid cancer (medullary thyroid cancer)
• digoxin (to treat irregular heartbeat and other heart problems). You may need to have your digoxin blood level checked if you are taking Ristfor.

Taking Ristfor with alcohol

Avoid excessive alcohol consumption while taking Ristfor, as this may increase the risk of lactic acidosis (see "Warnings and precautions").

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medication.You should not take this medication during pregnancy. Do not take this medication if you are breastfeeding. See section 2,Do not take Ristfor.

Driving and operating machinery

The influence of this medication on the ability to drive and operate machinery is negligible or insignificant.However, cases of dizziness and somnolence have been reported during treatment with sitagliptin, which may affect your ability to drive and operate machinery.

Taking this medication with sulfonylureas or insulin may cause hypoglycemia, which may affect your ability to drive and operate machinery or work without a secure support.

Ristfor contains sodium

This medication contains less than 23 mg of sodium(1 mmol) per tablet; it is essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

• Take a tablet:
• • twice a day by mouth
  • with food to reduce the likelihood of stomach discomfort

• Your doctor may need to increase the dose to control blood sugar levels.

• If you have reduced renal function, your doctor may prescribe a lower dose.

You must continue with the diet recommended by your doctor during treatment with this medication and be careful to distribute carbohydrate intake evenly throughout the day.

It is unlikely that treatment with this medication alone will cause an abnormal drop in blood sugar (hypoglycemia). A drop in blood sugar may occur when this medication is taken with a medication containing sulfonylurea or insulin, so it is likely that your doctor will consider reducing the dose of your sulfonylurea or insulin.

If you take more Ristfor than you should

If you take more than the prescribed dose of this medication, contact your doctor immediately. Go to the hospital if you experience symptoms of lactic acidosis such as feeling cold or unwell, intense nausea or vomiting, stomach pain, unexplained weight loss, muscle cramps, or agitated breathing (see "Warnings and precautions").

If you forget to take Ristfor

If you forget to take a dose, take it as soon as you remember. If you do not remember until your next scheduled dose, skip the missed dose and continue with your regular treatment. Do not take a double dose of this medication.

If you interrupt treatment with Ristfor

Continue taking this medication as directed by your doctor to help control your blood sugar levels. Do not stop taking this medication without first consulting your doctor. If you stop taking Ristfor, your blood sugar levels may increase again.

If you have any other questions about using this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

STOP taking Ristfor and see your doctor immediately if you notice any of the following serious side effects:

• Intense and persistent abdominal pain (stomach area) that can reach the back with or without nausea and vomiting, as these may be signs of pancreatitis (inflammation of the pancreas).

Ristfor may cause a very rare but serious side effect (may affect up to 1 in 10,000 people), called lactic acidosis (see "Warnings and precautions"). If this happens to you,you muststop taking Ristfor and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to coma.

If you have a severe allergic reaction (unknown frequency), including skin rash, urticaria, blisters on the skin/skin peeling and swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing, stop taking this medicine and consult your doctor immediately. Your doctor will prescribe a medication to treat the allergic reaction and change the medication for diabetes treatment.

Some patients taking metformin have experienced the following side effects after starting treatment with sitagliptin:

Frequent (may affect up to 1 in 10 people):low blood sugar,nausea, gas, vomiting

Infrequent (may affect up to 1 in 100 people):stomach pain, diarrhea, constipation, drowsiness

Some patients have experienced diarrhea, nausea, gas, constipation, stomach pain, or vomiting when starting treatment with the combination of sitagliptin and metformin (classified as frequent).

Some patients have experienced the following side effects when taking this medicine with a sulfonylurea such as glimepiride:

Frequent (may affect more than 1 in 10 people):low blood sugar

Frequent:constipation

Some patients presented the following side effects while taking this medicine in combination with pioglitazone:

Frequent: swelling of hands or feet

Some patients presented the following side effects while taking this medicine in combination with insulin:

Frequent:low blood sugar

Infrequent: dry mouth, headache

Some patients have experienced the following side effects during clinical studies while taking sitagliptin alone (one of the medicines containedRistfor) or during use after approval ofRistforor sitagliptin alone or with other diabetes medications:

Frequent:low blood sugar, headache,upper respiratory tract infection,nasal congestion or mucous, and sore throat, arthritis, arm or leg pain

Infrequent:dizziness, constipation, itching

Rare: reduction in platelet count

Unknown frequency: kidney problems (which may require dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of blister on the skin)

Some patients have experienced the following side effects after taking metformin alone:

Frequent:nausea, vomiting, diarrhea, stomach pain, and loss of appetite. These symptoms may appear when you start taking metformin and usually disappear

Frequent:metallic taste, decrease or low levels of vitamin B12 in the blood (symptoms may include extreme fatigue, pain and redness of the tongue (glossitis), tingling (paresthesia) or pale or yellowish skin). Your doctor may request tests to determine the cause of your symptoms because some of them may be caused by diabetes or other unrelated health problems.

Rare: hepatitis (liver problem), urticaria, skin redness (rash) or itching

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the blister pack and on the container after CAD. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Ristfor

• The active ingredients are sitagliptina and metformina.

• Each film-coated tablet of Ristfor 50 mg/850 mg contains sitagliptina phosphate monohydrate equivalent to 50 mg of sitagliptina and 850 mg of metformin hydrochloride.
• Each film-coated tablet of Ristfor 50 mg/1.000 mg contains sitagliptina phosphate monohydrate equivalent to 50 mg of sitagliptina and 1.000 mg of metformin hydrochloride.

• The other components are:

• Core tablet: microcrystalline cellulose (E460), povidone K 29/32 (E1201), sodium lauryl sulfate and sodium stearyl fumarate.
• Film coating: polyvinyl alcohol, macrogol 3350, talc (E553b), titanium dioxide (E171), iron oxide red (E172) and iron oxide black (E172).

Appearance of the product and contents of the pack

• The film-coated tablets of Ristfor 50 mg/850 mg are oval-shaped, pink in color, and have the inscription “515” on one side.
• The film-coated tablets of Ristfor 50 mg/1.000 mg are oval-shaped, red in color, and have the inscription “577” on one side.

Blister packs (PVC/PE/PVDC and aluminum). Packs of 14, 28, 56, 60, 112, 168, 180, 196 film-coated tablets, multiple packs containing 196 (2 boxes of 98) and 168 (2 boxes of 84) film-coated tablets. Pack of 50 x 1 film-coated tablet in a pre-cut single-dose blister pack.

Only some pack sizes may be marketed.

Marketing authorization holder and responsible person for manufacturing

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of the last revision of this leaflet: {MM/AAAA}.

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.