Efficib 50 mg/1000 mg film-coated tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

Efficib 50mg/850mg film-coated tablets

Efficib 50mg/1000mg film-coated tablets

sitagliptin/metformin hydrochloride

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Efficib is and what it is used for

Efficib contains two different medicines called sitagliptin and metformin.

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

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

Along with diet and exercise, this medicine helps lower your blood sugar level. This medicine may be used alone or in combination with certain other diabetes medicines (insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?

Type 2 diabetes is a condition in which your body does not produce enough insulin, and the insulin your body does produce 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 (cardiovascular) disease, kidney (renal) disease, blindness, and amputations.

2. What you need to know before taking 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 severely reduced kidney function
• 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, potentially leading to diabetic pre-coma. Symptoms include stomach pain, rapid deep breathing, drowsiness, or fruity-smelling breath
• if you have a serious infection or are dehydrated
• if you are undergoing an X-ray procedure requiring injection of a contrast agent. You will need to stop taking Efficib at the time of the procedure and for 2 or more days afterwards, as directed by your doctor, depending on how well your kidneys are functioning
• if you have recently had a heart attack or have serious circulatory problems, such as “shock” or difficulty breathing
• if you have liver problems (hepatic)
• if you drink alcohol excessively (either daily or occasionally)
• if you are breastfeeding.

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

Warnings and precautions

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

If you develop blisters on the skin, this may be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop taking Efficib.

Risk of lactic acidosis

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

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

Contact your doctor immediately for guidance if:

• You are known to have a genetic mitochondrial disorder (components that produce energy inside cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, 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: seizures, cognitive decline, difficulty with body movements, signs of nerve damage (e.g., pain or numbness), migraine, or hearing loss.

Stop taking Efficib temporarily if you develop a condition that may lead to dehydration (significant loss of body fluids), such as severe vomiting, diarrhea, fever, heat exposure, or if you are drinking less fluid than usual. Consult your doctor for further advice.

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

Symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of discomfort with profound fatigue
• difficulty breathing
• decreased body temperature and slowed heart rate

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

Talk to your doctor or pharmacist before starting Efficib:

• if you have or have had a pancreatic disease (such as pancreatitis)
• if you have or have had gallstones, alcohol addiction, 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 condition may also be called insulin-dependent diabetes
• if you have had or currently have an allergic reaction to sitagliptin, metformin, or Efficib (see section 4)
• if you are taking a sulfonylurea or insulin, or other diabetes medications along with Efficib, as you may experience low blood sugar levels (hypoglycemia). Your doctor may need to reduce the dose of your sulfonylurea or insulin

If you require major surgery, you should stop taking Efficib during the procedure and for some time afterwards. Your doctor will decide when to interrupt and restart treatment with Efficib.

If you are unsure whether any of the above conditions apply to you, consult your doctor or pharmacist before starting Efficib.

During treatment with Efficib, your doctor will monitor your kidney function at least once a year, or more frequently if you are elderly and/or if your kidney function is worsening.

Children and adolescents

Children and adolescents under 18 years of age must not use this medicine. It is not effective in children and adolescents aged between 10 and 17 years. It is unknown whether this medicine is safe and effective when used in children under 10 years of age.

Other medicines and Efficib

If you need to receive an intravenous injection of an iodine-containing contrast agent, for example during an X-ray or scan, you must stop taking Efficib before or at the time of the injection. Your doctor will decide when to interrupt and restart treatment with Efficib.

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. You may require 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, by inhalation, or by injection) used to treat inflammatory conditions 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)
• specific medicines for bronchial asthma (β-sympathomimetics)
• iodinated contrast agents or medicines containing 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 (to treat irregular heartbeat and other heart problems). Blood levels of digoxin may need to be monitored if you are taking Efficib.

Taking Efficib with alcohol

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. You must not take this medicine during pregnancy. Do not take this medicine if you are breastfeeding. See section 2, Do not take Efficib.

Driving and using machines

The effect of this medicine on the ability to drive and use machines is negligible or minor. However, dizziness and drowsiness have been reported during treatment with sitagliptin, which may affect your ability to drive and use machines.

Taking this medicine together with medicines called sulfonylureas or with insulin may cause hypoglycemia, which may impair your ability to drive and use machines or work without secure 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

Follow exactly the instructions for administration of this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

• Take one tablet:

• twice daily, orally

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

You must continue with the diet recommended by your doctor during treatment with this medicine and ensure that carbohydrate intake is evenly distributed throughout the day.

It is unlikely that treatment with this medicine alone will cause abnormally low blood sugar (hypoglycaemia). Low blood sugar may occur when this medicine is taken together with a medicine containing a sulphonylurea or with insulin, so your doctor may consider it necessary to reduce the dose of your sulphonylurea 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 hospital if you experience symptoms of lactic acidosis such as feeling cold or unwell, severe 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 forget to take a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose of this medicine.

If you stop taking Efficib

Continue taking this medicine for as long as your doctor has instructed, to help you control your blood sugar levels. You should not stop taking this medicine without first consulting your doctor. If you stop treatment with Efficib, your blood sugar levels may rise again.

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

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

• Severe and persistent pain in the abdomen (stomach area), which may extend to the back, with or without nausea and vomiting, as these may be signs of inflammation of the pancreas (pancreatitis).

Efficib may cause a very rare (may affect up to 1 in 10,000 people) but very serious adverse effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must 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, blistering or peeling of the skin, and swelling of the face, lips, tongue, or throat, which may cause difficulty breathing or swallowing, stop taking this medicine and consult your doctor immediately. Your doctor will prescribe treatment for the allergic reaction and switch your diabetes medication.

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

Frequent (may affect up to 1 in 10 people): low blood sugar levels, nausea, flatulence, vomiting
Uncommon (may affect up to 1 in 100 people): stomach pain, diarrhoea, constipation, drowsiness

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

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

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

Some patients experienced the following adverse effects while taking this medicine in combination with pioglitazone:

Frequent: swelling of hands or legs

Some patients experienced the following adverse effects while taking this medicine in combination with insulin:

Very frequent: low blood sugar levels
Uncommon: dry mouth, headache

Some patients experienced the following adverse effects during clinical studies while taking sitagliptin alone (one of the medicines contained in Efficib), or during post-approval use of Efficib or sitagliptin alone or in combination with other diabetes medicines:

Frequent: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose, sore throat, osteoarthritis, pain in the arm or leg
Uncommon: dizziness, constipation, itching
Rare: reduction in the number of platelets
Frequency not known: kidney problems (which sometimes require dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of blistering skin rash)

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

Very frequent: nausea, vomiting, diarrhoea, stomach pain, and loss of appetite. These symptoms may occur when you first start taking metformin and usually resolve over time
Frequent: metallic taste, decreased or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling (paraesthesia), or pale or yellowish skin). Your doctor may order tests to determine the cause of your symptoms, as some of these may also be caused by diabetes or other unrelated health conditions.
Very rare: hepatitis (a liver problem), hives, skin redness (rash), or itching

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 stated on the blister and outer packaging following EXP. The expiry date refers to the last day of the month indicated.

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 and packaging you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of Efficib

• The active substances are sitagliptin and metformin.

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

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

• The other components 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), iron oxide red (E172), and iron oxide black (E172).

Appearance of the product and contents of the pack

• Efficib 50 mg/850 mg film-coated tablets are oval-shaped, pink in colour, and marked with "515" on one side.
• Efficib 50 mg/1,000 mg film-coated tablets are oval-shaped, red in colour, and marked with "577" on one side.

Opaque blisters (PVC/PE/PVDC and aluminium). Packs containing 14, 28, 56, 60, 112, 168, 180, 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 tablet in pre-cut single-dose blisters.

Only some pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer Responsible

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

The Netherlands

Further information on this medicinal product is available upon request to the Marketing Authorisation Holder's local representative:

Date of the most recent review of this leaflet: {MM/YYYY}.

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