Mifomet

Patient Information Leaflet

MIFOMET, 50 mg + 850 mg, film-coated tablets
MIFOMET, 50 mg + 1000 mg, film-coated tablets
Sitagliptinum + Metformini hydrochloridum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Leaflet Contents

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

1. What Mifomet is and what it is used for

Mifomet contains two different active substances: sitagliptin and metformin.

• Sitagliptin belongs to a group of medicines called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors).
• Metformin belongs to a group of medicines called biguanides. The combined action of these two medicines helps regulate blood glucose levels in adult patients with a type of diabetes known as "type 2 diabetes." This medicine helps increase insulin release after meals and reduces the amount of glucose produced by the body. When used together with diet and exercise, it helps lower blood glucose levels. This medicine may be used alone as an antidiabetic treatment or in combination with certain other antidiabetic medicines (insulin, sulfonylurea derivatives, or glitazones).

What is type 2 diabetes?
Type 2 diabetes is a condition in which the body does not produce enough insulin, the insulin produced does not work properly, or the body produces too much glucose. When this occurs, sugar (glucose) accumulates in the blood. This may lead to serious health problems, such as heart disease, kidney disease, vision loss, and limb amputations.

2. Important information before taking Mifomet

When not to take Mifomet:

• if the patient is allergic to sitagliptin or metformin or any of the other ingredients of this medicine (listed in section 6),
• if the patient has significantly reduced kidney function,
• if the patient has uncontrolled diabetes, e.g. severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, sudden 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 and which may lead to diabetic pre-coma. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness or an unusual fruity odour of the breath,
• if the patient has a severe infection or dehydration,
• if the patient is scheduled for a radiological examination with intravascular administration of contrast agents. Treatment with Mifomet must be discontinued during the radiological examination and for 2 or more days afterwards, according to the physician's instructions, depending on the patient's kidney function,
• if the patient has recently experienced a heart attack or has severe circulatory disorders such as shock or breathing difficulties,
• if the patient has liver disease,
• if the patient consumes excessive amounts of alcohol (either daily or occasionally),
• if the patient is breastfeeding. Mifomet should not be taken if any of the above contraindications apply. The patient should consult a physician to determine alternative methods of diabetes control. If in doubt, discuss this with a physician, pharmacist, or nurse before taking Mifomet.

Warnings and precautions

Pancreatitis has been reported in patients taking Mifomet (see section 4). If the patient develops blisters on the skin, this may be a symptom of a condition known as bullous pemphigoid. The physician may advise the patient to discontinue taking Mifomet.

Risk of lactic acidosis

Mifomet may cause a very rare but serious adverse effect called lactic acidosis, particularly if the patient has impaired kidney function. The risk of lactic acidosis is also increased in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see further information below), liver dysfunction, and any medical conditions in which part of the body is inadequately supplied with oxygen (e.g. acute severe heart disease). If any of the above conditions apply to the patient, the patient should consult a physician for further instructions.

Temporarily discontinue use of Mifomet if the patient develops a medical condition that may lead to dehydration (significant loss of body water), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient drinks less fluid than usual. Consult a physician for further instructions.

Discontinue use of Mifomet and contact a physician or the nearest hospital immediately if the patient experiences any symptoms of lactic acidosis, as this condition may lead to coma. Symptoms of lactic acidosis include:

• vomiting,
• abdominal pain,
• muscle cramps,
• general malaise accompanied by severe fatigue,
• breathing difficulties,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring immediate hospital treatment. Contact a physician immediately for further instructions if:

• the patient has a genetically inherited mitochondrial disease (energy-producing structures in cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD),
• after starting metformin, the patient develops any of the following symptoms: seizures, worsening cognitive function, difficulty moving, symptoms indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

Before starting treatment with Mifomet, discuss the following with a physician or pharmacist:

• if the patient has or has had pancreatic disease (e.g. pancreatitis),
• if the patient has or has had gallstones, alcohol dependence, or very high blood triglyceride levels (a type of fat). In such cases, the risk of pancreatitis may be increased (see section 4),
• if the patient has type 1 diabetes. This is sometimes referred to as insulin-dependent diabetes,
• if the patient has experienced allergic reactions to sitagliptin, metformin, or Mifomet (see section 4),
• if the patient is taking a sulfonylurea derivative or insulin, antidiabetic medicines together with Mifomet, as this may lead to excessively low blood glucose levels (hypoglycaemia). The physician may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is undergoing major surgery, Mifomet must not be taken during the procedure and for some time afterwards. The physician will decide when the patient should stop and resume treatment with Mifomet.

If the patient is unsure whether any of the above statements apply, they should discuss this with a physician or pharmacist before taking Mifomet.

During treatment with Mifomet, the physician will monitor the patient's kidney function at least once a year, or more frequently if the patient is elderly and/or has worsening kidney function.

Children and adolescents

Mifomet must not be used in children and adolescents under 18 years of age. This medicine is not effective in children and adolescents aged 10 to 17 years. It is unknown whether this medicine is safe and effective in children under 10 years of age.

Mifomet and other medicines

If the patient is to receive an intravenous iodine-containing contrast agent, for example during an X-ray or CT scan, treatment with Mifomet must be discontinued before or at the latest at the time of administration. The physician will decide when the patient should stop and resume treatment with Mifomet.

Inform the physician or pharmacist about all medicines currently used, recently used, or planned for use. The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or a dose adjustment of Mifomet by the physician. It is particularly important to inform about the following medicines:

• medicines (taken orally, by inhalation, or by injection) used to treat inflammatory conditions such as asthma or 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 used to treat bronchial asthma (β-sympathomimetics),
• iodine-containing contrast agents or medicines containing alcohol,
• some medicines used to treat gastrointestinal disorders, 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 (used to treat heart rhythm disorders and other heart conditions). Blood digoxin levels should be monitored when Mifomet is taken concomitantly with digoxin.

Mifomet and alcohol

Avoid consuming excessive amounts of alcohol while taking Mifomet, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a physician or pharmacist before taking this medicine. This medicine must not be used during pregnancy. This medicine must not be used during breastfeeding. See section 2, When not to take Mifomet.

Driving and operating machinery

This medicine has no or negligible influence on the ability to drive and operate machinery. However, when driving and operating machinery, consider that dizziness and drowsiness have been reported with sitagliptin use, which may affect the ability to drive and operate machinery.

Taking this medicine together with medicines called sulfonylurea derivatives or insulin may lead to hypoglycaemia, which in turn may affect the ability to drive and operate machinery or work without secure foot support.

Mifomet contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet; therefore, this medicine is considered "sodium-free".

3. How to take Mifomet

This medicine should always be taken as directed by the physician. In case of doubt, consult
your doctor or pharmacist.

• Take one tablet:
  • twice daily, orally;
  • with meals to reduce the likelihood of stomach upset.
• To control blood sugar levels, your doctor may increase the dose of this medicine.
• If the patient has impaired kidney function, the doctor may prescribe a lower dose. While taking this medicine, continue the diet recommended by your doctor and pay attention to evenly distributing carbohydrate intake throughout the day. It is unlikely that taking this medicine alone will lead to abnormally low blood sugar levels (hypoglycaemia). Low blood sugar may occur when this medicine is taken together with a sulphonylurea derivative or insulin; in such a case, the doctor may reduce the dose of the sulphonylurea derivative or insulin.

Taking more Mifomet than prescribed

If you take more of this medicine than prescribed, contact your doctor immediately.
Go to the hospital if symptoms of lactic acidosis occur, 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").

Missing a dose of Mifomet

If you miss a dose, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose of this medicine.

Stopping Mifomet

To maintain control of blood sugar levels, take this medicine for as long as your doctor recommends. Do not stop taking this medicine without first consulting your doctor. Discontinuing Mifomet may cause blood sugar levels to rise again.

If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
You should STOP taking Mifomet and contact your doctor immediately if any of the following serious adverse reactions occur:

• Severe and persistent abdominal pain (in the stomach area), possibly radiating to the back, with or without nausea and vomiting – these may be symptoms of pancreatitis. Mifomet very rarely may cause (may occur in no more than 1 in 10,000 patients) a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If lactic acidosis occurs in a patient, the treatment with Mifomet must be discontinued and immediate contact with a doctor or the nearest hospital is required, as lactic acidosis may lead to coma.

In case of a severe allergic reaction (frequency unknown), including rash, hives, skin blisters, skin peeling, or swelling of the face, lips, tongue, or throat, which may cause difficulty in breathing or swallowing, you must stop taking the medicine and contact your doctor immediately. Your doctor may prescribe medication to treat the allergic reaction and another medicine (a different medicine) for the treatment of diabetes.

In some patients taking metformin, the following adverse reactions occurred after starting treatment with alogliptin:

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

Uncommon (may affect up to 1 in 100 people): stomach pain, diarrhoea, constipation, drowsiness.

Some patients experienced diarrhoea, nausea, bloating, constipation, stomach pain, or vomiting after starting treatment with alogliptin in combination with metformin (frequent).

In some patients taking this medicine together with a sulfonylurea derivative such as glimepiride, the following adverse reactions occurred:

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

Frequent: constipation.

In some patients taking this medicine together with pioglitazone, the following adverse reactions occurred:

Frequent: swelling of hands or feet.

In some patients taking this medicine together with insulin, the following adverse reactions occurred:

Very frequent: low blood sugar levels.

Uncommon: dry mouth, headache.

In clinical trials, the following adverse reactions occurred in some patients during treatment with alogliptin alone (one of the active substances in Mifomet) or after marketing authorization during treatment with Mifomet or alogliptin alone or in combination with other antidiabetic medicines:

Frequent: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose, sore throat, bone and joint pain, pain in arms or legs.

Uncommon: dizziness, constipation, itching.

Rare: decreased platelet count.

Frequency not known: kidney disorders (sometimes requiring dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of skin blistering).

In some patients taking metformin alone, the following adverse reactions occurred:

Very frequent: nausea, vomiting, diarrhoea, stomach pain, and loss of appetite. These symptoms may occur after starting metformin and usually resolve over time.

Frequent: metallic taste, reduced or low blood levels of vitamin B12 (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling or numbness sensations (paraesthesiae), or pale or yellowish skin). Your doctor may order certain tests to identify the cause of symptoms, as some of them may also be caused by diabetes or other unrelated health problems.

Very rare: hepatitis (liver disease), urticaria, skin redness (rash), or itching.

Reporting of adverse reactions

If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.

By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Mifomet

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton following "EXP".
The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Mifomet contains
The active substances in this medicine are sitagliptin and metformin.
Each film-coated tablet (tablet) of Mifomet, 50 mg + 850 mg contains sitagliptin hydrochloride in an amount equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
Each film-coated tablet (tablet) of Mifomet, 50 mg + 1000 mg contains sitagliptin hydrochloride in an amount equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.

Other ingredients are:
Tablet core: microcrystalline cellulose type 102, sodium croscarmellose, povidone (K30), sodium lauryl sulfate, and sodium stearyl fumarate.
Coating of Mifomet, 50 mg + 850 mg, film-coated tablets (Opadry Pink): polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172), and black iron oxide (E172).
Coating of Mifomet, 50 mg + 1000 mg, film-coated tablets (Opadry Red): polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172), and black iron oxide (E172).

What Mifomet looks like and contents of the pack
Mifomet, 50 mg + 850 mg, film-coated tablets are pink, capsule-shaped film-coated tablets measuring 20.2 mm × 9.9 mm, with an engraved mark "L50" on one side and smooth on the other side.
Mifomet, 50 mg + 1000 mg, film-coated tablets are red, capsule-shaped film-coated tablets measuring 21.4 mm × 10.5 mm, with an engraved mark "H50" on one side and smooth on the other side.
Blister packs made of PVC/PE/PVDC/Aluminium in a cardboard box.
The pack contains 56 film-coated tablets.

Marketing Authorisation Holder
Bausch Health Poland sp. z o.o.
Przemysłowa Street 2
35-105 Rzeszów
Poland
Tel.: +48 17 865 51 00

Manufacturer
Remedica Ltd.
Aharnon Street
Limassol Industrial Estate
3056 Limassol
Cyprus

Bausch Health Poland sp. z o.o.
Kosztowska Street 21
41-409 Mysłowice
Poland