Metformax sr combi

Package leaflet: information for the patient

Metformax SR Combi, 50 mg + 500 mg, modified-release tablets
Metformax SR Combi, 50 mg + 1000 mg, modified-release tablets
Metformax SR Combi, 100 mg + 1000 mg, modified-release tablets
Sitagliptinum + Metformini hydrochloridum
Please read this leaflet carefully before 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 further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not share it with others. This medicine may harm other people, 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.

Table of contents

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

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

Metformax SR 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 called 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 insulin release after meals
and reduces the amount of glucose produced by the body.
Used together with diet and exercise, this medicine helps lower blood glucose levels. It may be used
either as the only antidiabetic treatment or in combination with certain other antidiabetic medicines
(insulin, sulfonylureas, 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 happens, 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 SR Combi

When not to take Metformax SR 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 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 to undergo a radiological examination with intravascular administration of contrast agents. The use of Metformax SR Combi must be discontinued during the radiological examination and for a period of 2 or more days, as recommended by the physician, 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.

Do not take Metformax SR 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 SR Combi.
Warnings and precautions
Cases of pancreatitis have been reported in patients taking Metformax SR Combi (see section 4).
If the patient develops skin blisters, this may be a sign of a disease known as bullous pemphigoid. The doctor may advise the patient to discontinue taking Metformax SR Combi.
Risk of lactic acidosis
Metformax SR 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 is also increased in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more detailed information below), liver dysfunction, 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 the use of Metformax SR Combi if the patient develops a medical condition that may be associated with 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.
Discontinue the use of Metformax SR 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 associated with 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 disease affecting mitochondria (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 treatment, the patient experiences 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 Metformax SR Combi, discuss the following with your doctor or pharmacist:

• if the patient has or has had pancreatic disease (such as 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 been diagnosed with type 1 diabetes. This is sometimes referred to as insulin-dependent diabetes.
• if the patient currently has or has previously experienced allergic reactions to sitagliptin, metformin, or the medicine Metformax SR Combi (see section 4).
• if the patient is taking a sulfonylurea derivative or insulin, along with Metformax SR Combi, as this may lead to excessively low blood sugar levels (hypoglycaemia). The doctor may reduce the dose of the sulfonylurea derivative or insulin. If the patient is undergoing major surgery, Metformax SR Combi must not be taken during and for some time after the procedure. The doctor will decide when the patient should stop and resume treatment with Metformax SR Combi.

If in doubt whether any of the above statements apply, discuss this with your doctor or pharmacist before taking Metformax SR Combi.
While being treated with Metformax SR 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
This medicine 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 not known whether this medicine is safe and effective for use in children under 10 years of age.
Metformax SR Combi and other medicines
If the patient is to receive an intravenous iodine-containing contrast agent, for example for an X-ray or CT scan, the patient must stop taking Metformax SR Combi before or at the latest at the time of such injection. The doctor will decide when the patient should stop and resume treatment with Metformax SR Combi.
Inform your doctor or pharmacist about all medicines currently used or 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 assessments, or dose adjustments of Metformax SR Combi by the doctor. It is especially 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 Metformax SR Combi is taken with digoxin.

Metformax SR Combi and alcohol
Avoid consuming excessive amounts of alcohol while taking Metformax SR Combi, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").
Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine. Do not use this medicine during pregnancy or while breastfeeding. See section 2, When not to take Metformax SR Combi.
Driving and operating machinery
This medicine has no effect or has a negligible effect on the ability to drive and operate machinery. 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 sulfonylurea derivatives or with insulin may lead to hypoglycaemia, which in turn may affect the ability to drive and operate machinery or work without secure foot support.
Metformax SR Combi contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Metformax SR Combi

This medicine should always be taken as directed by the doctor. If in doubt, consult
the doctor or pharmacist.
The doctor will inform the patient how many tablets of Metformax SR Combi should be taken and when
they should be taken.
The maximum daily dose is 100 milligrams of sitagliptin and 2000 milligrams of metformin.
Usually, the tablets should be taken once daily with the evening meal.
In some cases, the doctor may recommend taking the tablets twice daily.
The tablets should always be taken with food to reduce the risk of stomach upset.
Swallow the tablets whole with a glass of water; do not chew.
To control blood sugar levels, the doctor may increase the dose of the medicine.
If the patient has reduced kidney function, the doctor may prescribe a lower dose.
While taking this medicine, continue to follow the diet recommended by the doctor and pay attention to
even carbohydrate intake throughout the day.
It is unlikely that taking this medicine alone would lead to abnormally low blood sugar levels (hypoglycaemia). Low blood sugar may occur when this medicine is used 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 Metformax SR Combi than prescribed
If more of this medicine is taken than prescribed, contact the doctor immediately. Go to 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 SR Combi
If a dose is missed, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and continue with the regular dosing schedule. Do not take a double dose to make up for a missed dose.
Stopping Metformax SR Combi
To maintain control of blood sugar levels, the medicine should be taken for as long as the doctor recommends. Do not stop taking this medicine without first consulting the doctor. Discontinuing treatment with Metformax SR Combi may cause blood sugar levels to rise again.
If there are any further doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should DISCONTINUE taking Metformax SR Combi and immediately contact your
doctor 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, as these may be symptoms of pancreatitis. Metformax SR Combi may very rarely cause (in no more than 1 in 10,000 people) a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If lactic acidosis occurs in a patient, treatment with Metformax SR Combi must be discontinued and immediate contact made with a doctor or the nearest hospital, as lactic acidosis may lead to coma.

In case of a severe allergic reaction (frequency unknown, cannot be estimated from available data), including rash, urticaria, skin blisters and/or skin peeling, and swelling of the face, lips, tongue, and throat, which may cause difficulty in breathing or swallowing, the medicine should be discontinued and immediate medical advice sought. The doctor may prescribe medication to treat the allergic reaction and another medicine for the treatment of diabetes.
In some patients receiving metformin, the following adverse reactions occurred after starting sitagliptin:

Common (may occur in no more than 1 in 10 people): low blood sugar levels, nausea, bloating, vomiting
Uncommon (may occur in no more than 1 in 100 people): stomach pain, diarrhoea, constipation, drowsiness

Some patients experienced diarrhoea, nausea, bloating, constipation, stomach pain, or vomiting 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 occur in more than 1 in 10 people): low blood sugar levels
Common: constipation

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

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

In clinical trials and post-marketing experience, some patients taking sitagliptin alone (one of the active substances in Metformax SR Combi), or Metformax SR Combi, or sitagliptin alone or in combination with other antidiabetic medicines, experienced the following adverse reactions:
Common: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose and sore throat, osteoarthritis, 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 after starting metformin and usually resolve over time.
Common: metallic taste, reduced or low levels of vitamin B(_{12}) in the blood (symptoms may include extreme tiredness, pain and redness of the tongue (glossitis), tingling sensation (paraesthesiae), or pale or yellowish skin colouration). The doctor may order certain tests to identify the cause of symptoms, as some of them may also be caused by diabetes or other health problems unrelated to treatment.
Very rare: 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 Drug Reactions of 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.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Metformax SR 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 cardboard container
after "EXP". The expiry date refers to the last day of the indicated month.
Do not store above 25°C.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the packaging and other information

What Metformax SR Combi contains
The active substances in this medicine are sitagliptin and metformin.
Metformax SR Combi, 50 mg + 500 mg: Each tablet contains sitagliptin hydrochloride monohydrate, corresponding to 50 mg of sitagliptin, and 500 mg of metformin hydrochloride.
Metformax SR Combi, 50 mg + 1000 mg: Each tablet contains sitagliptin hydrochloride monohydrate, corresponding to 50 mg of sitagliptin, and 1000 mg of metformin hydrochloride.
Metformax SR Combi 100 mg + 1000 mg: Each tablet contains sitagliptin hydrochloride monohydrate, corresponding to 100 mg of sitagliptin, and 1000 mg of metformin hydrochloride.

The other ingredients are:

• Extended-release layer containing metformin: hypromellose K100M CR, hypromellose E50, magnesium stearate
• Immediate-release layer containing sitagliptin: calcium hydrogen phosphate, microcrystalline cellulose, sodium stearyl fumarate, sodium croscarmellose (see section 2 “Metformax SR Combi contains sodium”).

Additionally, the tablet coating contains:

• For Metformax SR Combi, 100 mg + 1000 mg and 50 mg + 500 mg (Opadry II orange): polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc, yellow iron oxide (E172), red iron oxide (E172)
• For Metformax SR Combi, 50 mg + 1000 mg (Opadry II white): polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc.

What Metformax SR Combi looks like and contents of the pack
Metformax SR Combi, 50 mg + 500 mg: Orange, elongated, biconvex, film-coated tablets, 17.2 mm x 8.4 mm in size.
Metformax SR Combi, 50 mg + 1000 mg: White, elongated, biconvex, film-coated tablets, with the imprint “50” on one side and “1000” on the other, 22.2 mm x 10.8 mm in size.
Metformax SR Combi, 100 mg + 1000 mg: Orange, elongated, biconvex, film-coated tablets, with the imprint “100” on one side and “1000” on the other, 22.2 mm x 10.8 mm in size.

Blister packs made of PVC/PVDC/Aluminum in cardboard cartons. Pack sizes of 14, 28, 30, 56, 60, 98, 112, 180, or 200 modified-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o.
ul. Emilii Plater 53
00-113 Warsaw
tel.: (22) 345 93 00

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Merckle GmbH
Graf-Arco-Str. 3
89079 Ulm
Germany
Merckle GmbH
Ludwig-Merckle-Strasse 3
89143 Blaubeuren
Germany

This medicinal product is authorised for sale in the European Economic Area under the following names:
Bulgaria: Метформакс XR Комби
Croatia: Gluformin Combi
Czech Republic: Sitagliptin/Metformin Teva CR
Spain: Estequen
Germany: Sitagliptin/Metformin-ratiopharm
Poland: Metformax SR Combi
Portugal: Simedur
Slovakia: Sitagliptin/Metformin XR Teva