EFFICIB 50 mg/1000 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Efficib 50mg/850mg film-coated tablets

Efficib 50mg/1000mg film-coated tablets

sitagliptin/metformin hydrochloride

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Efficib and what is it used for
2. What you need to know before you take Efficib
3. How to take Efficib
4. Possible side effects
5. Storage of Efficib
6. Contents of the pack and other information

1. What is Efficib and what is it used for

Efficib contains two different medicines called sitagliptin and metformin.

• Sitagliptin belongs to a class of medicines called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors)
• Metformin belongs to a class of medicines called biguanides.

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

Together with diet and exercise, this medicine helps to lower your blood sugar levels. This medicine can be used alone or with certain other medicines for diabetes (insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?

Type 2 diabetes is a disease in which your body does not produce enough insulin and the insulin your body produces does not work as well as it should. Your body may also produce too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems, such as heart disease, kidney disease, blindness, and amputations.

2. What you need to know before you take Efficib

Do not take Efficib

• if you are allergic to sitagliptin, metformin, or any of the other ingredients of this medicine (listed in section 6)
• if you have severe kidney disease
• if you have uncontrolled diabetes with, for example, severe hyperglycemia, 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” build up in the blood, which can lead to diabetic pre-coma. The symptoms include stomach pain, rapid and deep breathing, drowsiness, or unusual fruity odor to the breath
• if you have a severe infection or are dehydrated
• if you are going to have an X-ray where you will be injected with a contrast agent. You will need to stop taking Efficib at the time of the X-ray and for 2 or more days after, as directed by your doctor, depending on your kidney function
• if you have recently had a heart attack or have severe circulatory problems, such as “shock” or breathing difficulties
• if you have liver problems
• if you drink excessive amounts of alcohol (either every day or only from time to time)
• if you are breast-feeding.

Do not take Efficib if any of the above applies to you and consult your doctor about other ways to control your diabetes. If you are not sure, consult your doctor, pharmacist, or nurse before taking Efficib.

Warnings and precautions

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

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

Risk of lactic acidosis

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

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

Consult your doctor promptly to advise you on how to proceed if:

• You know you have a genetic disease that affects the mitochondria (the energy-producing components within cells), such as MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD).
• You experience any of the following symptoms after starting treatment with metformin: convulsions, cognitive impairment, difficulty with body movements, symptoms indicating nerve damage (e.g., pain or numbness), migraines, and hearing loss.

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

Stop taking Efficib and contact a doctor or the nearest hospital immediately if you experience any symptoms of 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 in body temperature and heart rate

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

Consult your doctor or pharmacist before starting Efficib:

• if you have or have had pancreatitis (inflammation of the pancreas)
• if you have or have had gallstones, alcohol dependence, or very high blood levels of triglycerides (a type of fat). These medical conditions may increase your risk of developing pancreatitis (see section 4)
• if you have type 1 diabetes. This disease is also known as insulin-dependent diabetes
• if you have had an allergic reaction to sitagliptin, metformin, or Efficib (see section 4)
• if you are taking a sulfonylurea or insulin, other diabetes medicines, because you may experience low blood sugar levels (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 Efficib during the procedure and for some time after. Your doctor will decide when you should stop taking Efficib and when you can restart it.

If you are not sure if any of the above applies to you, consult your doctor or pharmacist before taking Efficib.

During treatment with Efficib, 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 worsening.

Children and adolescents

Children and adolescents under 18 years of age should not use this medicine. It is not effective in children and adolescents aged 10 to 17 years. It is not known if this medicine is safe and effective when used in children under 10 years of age.

Other medicines and Efficib

If you need to be given an injection of a contrast agent that contains iodine into your bloodstream, for example, in the context of an X-ray or scan, you should stop taking Efficib before or at the time of the injection. Your doctor will decide when you should stop taking Efficib and when you can restart it.

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

• medicines (taken orally, inhaled, or injected) used to treat diseases that cause inflammation, such as asthma and arthritis (corticosteroids)
• medicines that increase urine production (diuretics)
• medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• certain medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)
• medicines used to treat bronchial asthma (beta-2 adrenergic agonists)
• iodinated contrast agents or medicines that contain alcohol
• certain medicines used to treat stomach problems, such as cimetidine
• ranolazine, a medicine used to treat angina pectoris
• dolutegravir, a medicine used to treat HIV infection
• vandetanib, a medicine used to treat a specific type of thyroid cancer (medullary thyroid cancer)
• digoxin (for irregular heartbeat and other heart problems). Your doctor may need to check your digoxin blood levels if you are taking Efficib.

Taking Efficib with alcohol

Avoid excessive alcohol intake while taking Efficib, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. You should not take this medicine during pregnancy. You should not take this medicine if you are breast-feeding. See section 2, Do not take Efficib.

Driving and using machines

The ability to drive and use machines may be unaffected or minimally affected by this medicine. However, cases of dizziness and drowsiness have been reported during treatment with sitagliptin, which may affect your ability to drive and use machines.

Taking this medicine with sulfonylureas or insulin may cause hypoglycemia, which may affect your ability to drive and use machines or work without a safe support.

Efficib contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially “sodium-free”.

3. How to take Efficib

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

• Take one tablet:
• • twice a day by mouth
  • with food to reduce the chance of stomach upset

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

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

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

It is unlikely that treatment with this medicine alone will cause abnormally low blood sugar levels (hypoglycemia). Hypoglycemia may occur when this medicine is taken with a sulfonylurea or insulin, so your doctor may need to reduce the dose of your sulfonylurea or insulin.

If you take more Efficib than you should

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

If you forget to take Efficib

If you miss a dose, take it as soon as you remember. If you do not remember until the time of your next dose, skip the missed dose and continue with your normal schedule. Do not take a double dose of this medicine.

If you stop taking Efficib

Keep taking this medicine for as long as your doctor tells you to, to help keep your blood sugar levels under control. Do not stop taking this medicine without talking to your doctor first. If you stop taking Efficib, your blood sugar levels may increase again.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

STOP taking Efficib and contact a doctor immediately if you notice any of the following serious side effects:

• Severe and persistent stomach pain (which may radiate to the back) with or without nausea and vomiting, as these may be signs of pancreatitis.

Efficib may cause a very rare but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this happens, stop taking Efficib and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to coma.

If you have a severe allergic reaction (frequency not known), including skin rash, hives, blisters on the skin/peeling of the skin, 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 medicine to treat the allergic reaction and change your diabetes medicine.

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

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

Uncommon (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 (frequency classified as common).

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

Very common (may affect more than 1 in 10 people): low blood sugar levels

Common: constipation

Some patients have experienced the following side effects when taking this medicine with pioglitazone:

Common: swelling of hands or feet

Some patients have experienced the following side effects when taking this medicine with insulin:

Very common: low blood sugar levels

Uncommon: dry mouth, headache

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

Common: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose, and sore throat, arthrosis, pain in the arm or leg

Uncommon: dizziness, constipation, itching

Rare: reduced platelet count

Frequency not known: kidney problems (which may require dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of skin blistering)

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

Very common: nausea, vomiting, diarrhea, stomach pain, and loss of appetite. These symptoms usually occur when you start taking metformin and will normally go away

Common: metallic taste, low vitamin B12 levels in the blood (symptoms may include extreme tiredness, pain, and redness of the tongue, or numbness). Your doctor may ask for tests to find out the cause of your symptoms because some of them may also be caused by diabetes or other health problems not related to this medicine.

Very rare: hepatitis (a liver problem), hives, skin rash, or itching

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Efficib

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

Do not use this medicine after the expiry date which is stated on the blister and on the carton after EXP. The expiry date is the last day of the month stated.

Do not store above 25 °C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help to protect the environment.

6. Package contents and further information

Composition of Efficib

• The active substances are sitagliptin and metformin.

• Each film-coated tablet of Efficib 50 mg/850 mg (tablet) contains sitagliptin phosphate monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
• Each film-coated tablet of Efficib 50 mg/1,000 mg (tablet) contains sitagliptin phosphate monohydrate equivalent to 50 mg of sitagliptin and 1,000 mg of metformin hydrochloride.

• The other ingredients are:

• Tablet core: 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), red iron oxide (E172), and black iron oxide (E172).

Appearance and package contents of the product

• The film-coated tablets of Efficib 50 mg/850 mg are oval, pink, and engraved with "515" on one side.
• The film-coated tablets of Efficib 50 mg/1,000 mg are oval, red, and engraved with "577" on one side.

Opaque blisters (PVC/PE/PVDC and aluminum). Packs of 14, 28, 56, 60, 112, 168, 180, and 196 film-coated tablets, multiple packs containing 196 (2 packs of 98) and 168 (2 packs of 84) film-coated tablets. Pack of 50 x 1 film-coated tablet in a precut unit-dose blister.

Only some pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

You can request more information about this medicine from the local representative of the marketing authorisation holder:

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

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.