Metformax combi

Package leaflet: Information for the patient

Metformax Combi, 50 mg + 850 mg, film-coated tablets
Metformax Combi, 50 mg + 1000 mg, film-coated tablets
Sitagliptin + Metformini hydrochloridum
Please read this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Metformax Combi is and what it is used for

Metformax Combi 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 known as biguanides.

The combined action of these two medicines helps regulate blood glucose levels in adult patients with diabetes known as "type 2 diabetes." This medicine helps increase the amount of insulin released after meals and reduces the amount of glucose produced by the body. When used together with diet and physical exercise, it helps lower blood glucose levels.
This medicine may be used as the only antidiabetic treatment or in combination with certain other antidiabetic medicines (insulin, sulfonylurea derivatives, or glitazones).

What is type 2 diabetes?
In type 2 diabetes, the body does not produce enough insulin, and the insulin that is produced does not work properly. The body may also produce 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 Metformax Combi

When not to take Metformax Combi:

• if the patient is allergic to sitagliptin or metformin, or to 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, for example 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 may lead to diabetic pre-coma. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness or unusual fruity odour of the breath.
• if the patient has a severe infection or dehydration,
• if the patient is scheduled for a radiological procedure with intravascular administration of contrast agents. The patient must stop taking Metformax Combi before or at the time of the radiological procedure and for 2 or more days afterwards, as directed by the physician, depending on the patient's kidney function.
• if the patient has recently had 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.

Do not take Metformax Combi if any of the above contraindications apply. Consult your doctor to determine alternative methods of diabetes control. If in doubt, discuss this with your doctor, pharmacist or nurse before taking Metformax Combi.

Warnings and precautions

Cases of pancreatitis have been reported in patients taking Metformax Combi (see section 4).

If the patient develops skin blisters, this may be a symptom of a disease called bullous pemphigoid. The doctor may advise the patient to stop taking Metformax Combi.

Risk of lactic acidosis

Metformax Combi may cause a very rare but serious adverse effect called lactic acidosis, especially if the patient has impaired kidney function. The risk of lactic acidosis increases with uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more detailed information below), impaired liver function, and any medical conditions in which a 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, consult a doctor for further instructions.

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

Stop taking Metformax Combi and contact a doctor 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 profound fatigue,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring immediate hospital treatment.

Contact a doctor immediately for further instructions if:

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

Before starting Metformax Combi, discuss with your doctor or pharmacist if:

• the patient has or has had pancreatic disease (e.g. pancreatitis).
• 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).
• the patient has type 1 diabetes, sometimes referred to as insulin-dependent diabetes.
• the patient currently has or has had allergic reactions to sitagliptin, metformin or Metformax Combi (see section 4).
• the patient is taking a sulphonylurea derivative or insulin, antidiabetic medicines together with Metformax Combi, as this may lead to excessively low blood sugar levels (hypoglycaemia). The doctor may reduce the dose of the sulphonylurea derivative or insulin.

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

If in doubt whether any of the above statements apply to the patient, discuss this with your doctor or pharmacist before taking Metformax Combi.

While being treated with Metformax Combi, the doctor 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

Metformax Combi should 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 not known whether this medicine is safe and effective when used in children under 10 years of age.

Metformax Combi and other medicines

If the patient is to receive an intravenous iodine-containing contrast agent, for example during an X-ray or CT scan, the patient must stop taking Metformax Combi before or at the latest at the time of administration. The doctor will decide when the patient should stop and restart treatment with Metformax Combi.

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. The patient may require more frequent monitoring of blood glucose levels and kidney function, or dose adjustments of Metformax Combi by the doctor. It is especially important to inform about the following medicines:

• medicines (taken orally, by inhalation or 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,
• 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 Metformax Combi is taken concomitantly with digoxin.

Metformax Combi and alcohol

Avoid consuming excessive amounts of alcohol while taking Metformax Combi, 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 baby, she should consult her doctor or pharmacist before taking this medicine. This medicine should not be used during pregnancy or while breastfeeding. See section 2, When not to take Metformax Combi.

Driving and using machines

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

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

Metformax Combi contains sodium

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

3. How to take Metformax Combi

This medicine should always be taken exactly 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 gastrointestinal 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
the even distribution of carbohydrates 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
sulfonylurea derivative or insulin – in such a case, the doctor may reduce the dose of the
sulfonylurea derivative or insulin.
Taking more Metformax Combi 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 discomfort, severe nausea or
vomiting, stomach pain, unexplained weight loss, muscle cramps, or rapid breathing (see section
"Warnings and precautions").
Missing a dose of Metformax Combi
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 Metformax Combi
To maintain control of blood sugar levels, take this medicine for as long as directed by your
doctor. Do not stop taking this medicine without consulting your doctor first.
Discontinuing treatment with Metformax Combi may result in increased blood sugar levels.
If you have any further questions about the use of this medicine, consult your doctor or
pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should STOP taking Metformax Combi 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.

Metformax Combi may very rarely (occurring in no more than 1 in 10,000 patients) cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If this occurs, stop taking Metformax Combi immediately and contact your doctor or the nearest hospital, as lactic acidosis may lead to coma.
In case of a severe allergic reaction (frequency unknown), including rash, urticaria, skin blisters or skin peeling, and swelling of the face, lips, tongue or throat, which may cause difficulty in breathing or swallowing, discontinue the medicine and seek immediate medical attention. Your doctor may prescribe treatment for the allergic reaction and may switch you to another medicine (change of medication) for the treatment of diabetes.
In some patients receiving metformin, the following adverse reactions occurred after starting treatment with sitagliptin:
Common (may affect up to 1 in 10 patients): low blood sugar levels, nausea, bloating, vomiting
Uncommon (may affect up to 1 in 100 patients): stomach pain, diarrhoea, constipation, drowsiness

Diarrhoea, nausea, bloating, constipation, stomach pain, or vomiting may occur in some patients after starting treatment with sitagliptin in combination with metformin (common).

In some patients taking this medicine together with a sulfonylurea derivative such as glimepiride, the following adverse reactions occurred:
Very common (may affect more than 1 in 10 patients): low blood sugar levels
Common: constipation

In some patients taking this medicine together with pioglitazone, the following adverse reactions occurred:
Common: swelling of hands or feet

In some patients taking this medicine together with insulin, the following adverse reactions occurred:
Very common: low blood sugar levels
Uncommon: dry mouth, headache

In clinical trials, the following adverse reactions occurred in some patients treated with sitagliptin alone (one of the active substances in Metformax Combi), or after marketing of fixed-dose combination products containing sitagliptin and metformin in tablet form, or sitagliptin alone, or sitagliptin in combination with other antidiabetic medicines:
Common: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose and sore throat, bone and joint inflammation, 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 blistering skin condition)

In some patients taking metformin alone, the following adverse reactions occurred:
Very common: nausea, vomiting, diarrhoea, stomach pain, and loss of appetite. These symptoms may occur when starting metformin treatment and usually resolve over time.
Common: metallic taste
Very rare: decreased vitamin B12 levels, hepatitis (liver disease), urticaria, skin redness (rash), or itching

Reporting of adverse reactions
If any adverse reactions occur, including any 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, 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.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Metformax Combi

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

6. Contents of the pack and other information

What Metformax Combi contains

• The active substances in this medicinal product are sitagliptin and metformin hydrochloride.
• Each Metformax Combi 50 mg + 850 mg film-coated tablet contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
• Each Metformax Combi 50 mg + 1000 mg film-coated tablet contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
• Other ingredients are:
  Tablet core: microcrystalline cellulose (type 102), povidone (K29/32), sodium lauryl sulfate, magnesium stearate (Ph.Eur) [of plant origin] (E470b) (see section 2, "Metformax Combi contains sodium").

Coating:
Opadry QX Pink (321A640002) for Metformax Combi 50 mg + 850 mg film-coated tablets contains:
grafted copolymer of polyethylene glycol and poly(vinyl alcohol) (E 1209), talc (E 553b), titanium dioxide (E 171), glycerol monocaprylocaprate (E 471), polyvinyl alcohol (E 1203), iron oxide red (E 172).

Opadry QX Brown (321A265038) for Metformax Combi 50 mg + 1000 mg film-coated tablets contains:
grafted copolymer of polyethylene glycol and poly(vinyl alcohol) (E 1209), talc (E 553b), titanium dioxide (E 171), iron oxide red (E 172), glycerol monocaprylocaprate (E 471), polyvinyl alcohol (E 1203), iron oxide black (E 172).

What Metformax Combi looks like and contents of the pack
Metformax Combi 50 mg + 850 mg are oval, biconvex, film-coated tablets approximately 20.5 mm x 9.5 mm in size, pink in colour, with the imprint “S476” on one side.
Metformax Combi 50 mg + 1000 mg are oval, biconvex, film-coated tablets approximately 21.5 mm x 10.0 mm in size, brown in colour, with the imprint “S477” on one side.
Packs of PVC/PVDC/Aluminium blisters in a cardboard box:
Pack sizes: 30, 60, 98 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o., ul. Emilii Plater 53, 00-113 Warszawa, Poland
tel. +48 22 345 93 00, (logo of the marketing authorisation holder)

Manufacturer
Laboratorios Liconsa S.A., Avda. Miralcampo, Nº 7, Polígono Industrial Miralcampo
19200 Azuqueca de Henares, Guadalajara, Spain