Sytena plus

Package leaflet: Information for the patient

Sytena Plus, 50 mg + 850 mg, film-coated tablets
Sytena Plus, 50 mg + 1000 mg, film-coated tablets
Sitagliptin + Metformin hydrochloride
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 consult your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others.
It may harm other people, even if their symptoms are the same as yours.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse.
See section 4.
Contents of the leaflet:

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

1. What Sytena Plus is and what it is used for

Sytena Plus contains two different active substances: sitagliptin and metformin.
Sitagliptin belongs to a group of medicines known as 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 as the only antidiabetic medicine 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, and the insulin that is produced does not work properly. The body may also produce too much glucose. When this occurs, 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 using Sytena Plus

When not to use Sytena Plus
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, 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 severe infection or dehydration,
if the patient is scheduled to undergo a radiological procedure with intravascular
administration of contrast agents. The use of Sytena Plus must be discontinued during the radiological procedure and for a period of 2 or more days, as directed 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 intermittently),
if the patient is breastfeeding.
Do not take Sytena Plus if any of the above contraindications apply, and consult your doctor to determine alternative methods of diabetes management. If in doubt, discuss with your doctor, pharmacist, or nurse before using Sytena Plus.

Warnings and precautions
Cases of pancreatitis have been reported in patients taking Sytena Plus (see section 4).
If the patient develops skin blisters, this may be a symptom of a disease known as bullous pemphigoid. Your doctor may advise you to stop taking Sytena Plus.

Risk of lactic acidosis
Sytena Plus 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 infections, prolonged fasting or alcohol consumption, dehydration (see further 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 your doctor for further instructions.

Temporarily discontinue Sytena Plus if the patient has a medical condition that may involve 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 your doctor for further instructions.

Stop taking Sytena Plus and contact your doctor or 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 combined with severe fatigue,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring hospital treatment.
Contact your 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, 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 Sytena Plus, discuss the following with your doctor 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 increase (see section 4).
• if the patient has type 1 diabetes. This is sometimes referred to as insulin-dependent diabetes.
• if the patient has currently or previously experienced allergic reactions to sitagliptin, metformin, or Sytena Plus (see section 4).
• if the patient is taking a sulfonylurea derivative or insulin, antidiabetic medicines together with Sytena Plus, as this may lead to excessively low blood sugar levels (hypoglycaemia). Your doctor may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is undergoing major surgery, Sytena Plus must not be taken during the procedure and for some time afterwards. Your doctor will decide when to stop and resume treatment with Sytena Plus.
If in doubt whether any of the above situations apply to the patient, discuss with your doctor or pharmacist before using Sytena Plus.
While being treated with Sytena Plus, your doctor will monitor 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 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 unknown whether this medicine is safe and effective when used in children under 10 years of age.

Sytena Plus 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 use of Sytena Plus must be stopped before or at the latest at the time of injection. Your doctor will decide when to stop and resume treatment with Sytena Plus.
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 assessments, or dose adjustments of Sytena Plus 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 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 taking Sytena Plus with digoxin.

Sytena Plus and alcohol
Avoid consuming excessive amounts of alcohol while taking Sytena Plus, 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 plans to become pregnant, she should consult her doctor or pharmacist before using this medicine. This medicine should not be used during pregnancy or while breastfeeding. See section 2, When not to use Sytena Plus.

Driving and operating machinery
This medicine has no effect or negligible effect on the ability to drive and operate machinery. However, dizziness and drowsiness have been reported during treatment with sitagliptin, which may affect the ability to drive or 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.

Sytena Plus contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, meaning it is considered “sodium-free”.

3. How to use Sytena Plus

This medicine should always be taken as prescribed by your doctor. If in 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 you have impaired kidney function, your doctor may prescribe a lower dose.
While taking this medicine, continue to follow 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 used together with a sulphonylurea derivative or insulin – in such a case, your doctor may reduce the dose of the sulphonylurea derivative or insulin.
The division line on the tablet is not intended for breaking the tablet.

Taking more Sytena Plus than prescribed
If you take more than the prescribed dose of this medicine, contact your 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").

Missed dose of Sytena Plus
If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed dose.

Stopping Sytena Plus
To maintain control of blood sugar levels, continue taking this medicine for as long as your doctor recommends. Do not stop taking this medicine without consulting your doctor first.
Discontinuing treatment with Sytena Plus may result in a recurrence of elevated 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 will experience them.
You should STOP taking Sytena Plus 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, as these may be symptoms of pancreatitis.
Sytena Plus may very rarely (may occur in fewer than 1 in 10,000 people) cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If this occurs in a patient, treatment with Sytena Plus must be STOPPED and immediate contact made with a doctor or the nearest hospital because lactic acidosis can lead to coma.
In case of a severe allergic reaction (frequency unknown), including rash, hives, skin blisters and/or skin peeling, and 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 for diabetes treatment.

In some patients taking metformin, the following adverse reactions occurred after starting sitagliptin:
Common (may affect fewer than 1 in 10 people): low blood sugar levels, nausea, bloating, vomiting
Uncommon (may affect fewer than 1 in 100 people): stomach pain, diarrhoea, constipation, drowsiness

Diarrhoea, nausea, bloating, constipation, stomach pain, or vomiting occurred 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 people): low blood sugar levels
Common (may affect fewer than 1 in 10 people): constipation

In some patients taking this medicine in combination with pioglitazone, the following adverse reactions occurred:
Common (may affect fewer than 1 in 10 people): 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, the following adverse reactions occurred in some patients during treatment with sitagliptin alone (one of the active substances in Sytena Plus), or after marketing authorization during treatment with Sytena Plus or sitagliptin alone or in combination with other antidiabetic medicines:
Common: low blood sugar levels, headache, upper respiratory tract infection, stuffy nose or runny nose, and 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 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 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 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.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Sytena Plus

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 the cardboard
pack, 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. Proper disposal helps protect
the environment.

6. Contents of the pack and other information

What Sytena Plus contains
The active substances are sitagliptin and metformin hydrochloride.
Sytena Plus, 50 mg + 850 mg, film-coated tablets
Each film-coated tablet (tablet) contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
Sytena Plus, 50 mg + 1000 mg, film-coated tablets
Each film-coated tablet (tablet) contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.

The other ingredients are:
Tablet core: povidone K29/32, microcrystalline cellulose PH 102, crospovidone type A, and sodium stearyl fumarate.
Coating: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172), and black iron oxide (E172).
Additionally, Sytena Plus, 50 mg + 850 mg, film-coated tablets contain: yellow iron oxide (E172).

What Sytena Plus looks like and contents of the pack
Sytena Plus, 50 mg + 850 mg, film-coated tablets
Pink, elongated, oval film-coated tablets with a division line on one side and the letters "SA" on the other side. Tablet diameter: 19.5 ± 0.5 mm.

Sytena Plus, 50 mg + 1000 mg, film-coated tablets
Red to brown, elongated, oval film-coated tablets with a division line between the letters "S" and "B" on one side and a division line on the other side. Tablet diameter: 21.3 ± 0.5 mm.

The medicine is available in PVC/PVDC/aluminum blister packs in a cardboard box. The pack contains 56 film-coated tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Farmak International Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw
tel. +48 22 822 93 06
e-mail: [email protected]

Manufacturer
SAG Manufacturing S.L.U.
Ctra. N-I, Km 36,
San Agustin de Guadalix,
28750 Madrid,
Spain

Galenicum Health, S.L.
Avda. Cornellá 144, 7º-1ª, Edificio Lekla,
Esplugues de Llobregat,
08950 Barcelona,
Spain

This medicine is authorised for marketing in the Member States of the European Economic Area under the following names:
Malta Sytena Plus 50 mg/850 mg & 50 mg/1000 mg film-coated tablets
Poland Sytena Plus