Sitagliptin + metformin hydrochloride tzf

Package leaflet: Information for the user

Sitagliptin + Metformin hydrochloride TZF, 50 mg + 850 mg, film-coated tablets
Sitagliptin + Metformin hydrochloride TZF, 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, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not give it 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, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Sitagliptin + Metformin hydrochloride TZF is and what it is used for

Sitagliptin + Metformin hydrochloride TZF 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 as
monotherapy 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 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 Sitagliptin + Metformin hydrochloride TZF

When not to take Sitagliptin + Metformin hydrochloride TZF:

• 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 severe infection or dehydration,
• if the patient is scheduled for a radiological examination with intravascular administration of contrast agents. The use of Sitagliptin + Metformin hydrochloride TZF 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 myocardial infarction 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 Sitagliptin + Metformin hydrochloride TZF if any of the above contraindications apply. Consult a physician to determine alternative methods of diabetes control. If in doubt, discuss with a doctor, pharmacist, or nurse before taking Sitagliptin + Metformin hydrochloride TZF.

Warnings and precautions

Pancreatitis has been reported in patients taking Sitagliptin + Metformin hydrochloride TZF (see section 4).

If the patient develops skin blisters, this may be a sign of a disease known as bullous pemphigoid. The physician may advise the patient to discontinue taking Sitagliptin + Metformin hydrochloride TZF.

Risk of lactic acidosis

Sitagliptin + Metformin hydrochloride TZF 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 in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more details 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 physician for further instructions.

Contact a physician immediately for further guidance 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.

Temporarily discontinue use of Sitagliptin + Metformin hydrochloride TZF if the patient has 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 physician for further instructions.

Discontinue use of Sitagliptin + Metformin hydrochloride TZF 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,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

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

Before starting Sitagliptin + Metformin hydrochloride TZF, discuss 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, sometimes referred to as insulin-dependent diabetes.
• if the patient has current or past allergic reactions to sitagliptin, metformin, or Sitagliptin + Metformin hydrochloride TZF (see section 4).
• if the patient is taking a sulfonylurea derivative or insulin together with Sitagliptin + Metformin hydrochloride TZF, as this may lead to excessively low blood sugar levels (hypoglycaemia). The physician may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is undergoing major surgery, Sitagliptin + Metformin hydrochloride TZF must not be taken during the procedure and for some time afterwards. The physician will decide when the patient should stop and restart treatment with Sitagliptin + Metformin hydrochloride TZF.

If in doubt whether any of the above statements apply, discuss with a physician or pharmacist before taking Sitagliptin + Metformin hydrochloride TZF.

During treatment with Sitagliptin + Metformin hydrochloride TZF, 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

This medicine should not be used in children and adolescents under 18 years of age. The 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.

Sitagliptin + Metformin hydrochloride TZF and other medicines

If the patient is to receive an iodine-containing contrast agent injected into the bloodstream, for example for an X-ray or CT scan, the patient must stop taking Sitagliptin + Metformin hydrochloride TZF before or at the latest at the time of injection. The physician will decide when the patient should stop and restart treatment with Sitagliptin + Metformin hydrochloride TZF.

Inform the physician or pharmacist about all medicines currently 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 Sitagliptin + Metformin hydrochloride TZF by the physician.

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),
• diuretics (medicines that increase urine production),
• 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 asthma (β-sympathomimetics),
• iodine-containing contrast agents or medicines containing alcohol,
• certain 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 Sitagliptin + Metformin hydrochloride TZF with digoxin.

Sitagliptin + Metformin hydrochloride TZF and alcohol

Avoid consuming excessive amounts of alcohol while taking Sitagliptin + Metformin hydrochloride TZF, 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 a physician or pharmacist before taking this medicine.

This medicine should not be used during pregnancy or while breastfeeding. See section 2. When not to take Sitagliptin + Metformin hydrochloride TZF.

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 with sitagliptin, 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.

Sitagliptin + Metformin hydrochloride TZF contains sodium

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

3. How to take Sitagliptin + Metformin hydrochloride TZF

This medicine should always be taken as directed by the doctor. If in doubt, consult the doctor or pharmacist.

• Take one tablet:
• twice daily, orally;
• with meals to reduce the likelihood of gastrointestinal upset.
  • To control blood sugar levels, the doctor may increase the dose of the medicine.
  • If the patient has impaired 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 a regular intake 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 Sitagliptin + Metformin hydrochloride TZF than prescribed
If more than the prescribed dose of this medicine is taken, contact the doctor immediately.
Go to 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 Sitagliptin + Metformin hydrochloride TZF
If a dose is missed, take it as soon as possible. If the next dose is approaching, skip the missed dose and continue with the regular dosing schedule. Do not take a double dose of this medicine.
Stopping Sitagliptin + Metformin hydrochloride TZF
To maintain control of blood sugar levels, the medicine should be taken for as long as directed by the doctor. Do not stop taking this medicine without first consulting the doctor.
Discontinuing treatment with Sitagliptin + Metformin hydrochloride TZF may lead to increased blood sugar levels.
If there are any further questions 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 will experience them.
You should STOP taking Sitagliptin + Metformin hydrochloride TZF 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 – these may be symptoms of pancreatitis.

Sitagliptin + Metformin hydrochloride TZF may very rarely (may occur in up to 1 in 10,000 patients) cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If lactic acidosis occurs, you must stop taking Sitagliptin + Metformin hydrochloride TZF and immediately contact your doctor or nearest hospital, as lactic acidosis may lead to coma.
In case of a severe allergic reaction (frequency not known), including rash, hives, skin blisters or skin peeling, and swelling of the face, lips, tongue or throat, which may cause difficulty in breathing or swallowing, you should stop taking the medicine and immediately contact your doctor. Your doctor may prescribe medication to treat the allergic reaction and another medicine (switch to a different medicine) for the treatment of diabetes.

In some patients taking metformin, the following adverse reactions occurred after starting sitagliptin:

Common (may occur in up to 1 in 10 patients): low blood sugar levels, nausea, bloating, vomiting
Uncommon (may occur in 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 occur in 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, in some patients taking sitagliptin alone (one of the active substances in Sitagliptin + Metformin hydrochloride TZF) or after market authorization, when taking Sitagliptin + Metformin hydrochloride TZF or sitagliptin alone or in combination with other antidiabetic medicines, the following adverse reactions occurred:

Common: low blood sugar levels, headache, upper respiratory tract infection, stuffy 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 after starting metformin and usually resolve over time.
Common: metallic taste, reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling or numbness sensations (paraesthesiae), or pallor or yellowing of the skin). Your doctor may order certain tests to determine 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, you should inform your doctor or pharmacist.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C; 02-222 Warsaw
Phone: +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 responsible entity.
By reporting adverse reactions, additional information on the safety of this medicine can be collected.

5. How to store Sitagliptin + Metformin hydrochloride TZF

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 the outer
carton after "EXP". The expiry date refers to the last day of the specified month.
Store below 30°C.
Medicines must not be disposed of via the sewage system 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 Sitagliptin + Metformin hydrochloride TZF contains
The active substances in this medicine are sitagliptin and metformin.
Sitagliptin + Metformin hydrochloride TZF, 50 mg + 850 mg, film-coated tablets
Each film-coated tablet contains 50 mg of sitagliptin as sitagliptin hydrochloride monohydrate and 850 mg of metformin hydrochloride.
Sitagliptin + Metformin hydrochloride TZF, 50 mg + 1000 mg, film-coated tablets
Each tablet contains 50 mg of sitagliptin as sitagliptin hydrochloride monohydrate and 1000 mg of metformin hydrochloride.
The other ingredients are:
Tablet core: povidone K29/32, microcrystalline cellulose type 102, crospovidone, sodium stearyl fumarate
Tablet coating: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, iron oxide red (E 172), iron oxide black (E 172), iron oxide yellow (E 172) – applies only to the strength (50 mg + 850 mg)

What Sitagliptin + Metformin hydrochloride TZF looks like and contents of the pack
Sitagliptin + Metformin hydrochloride TZF, 50 mg + 850 mg
Pink, elongated oval film-coated tablet, with a breakline engraved on one side and 'SA' on the other. The breakline on the tablet is intended only to facilitate breaking for easier swallowing and does not ensure equal dosing.
Tablet dimensions: 19.5 ± 0.5 mm.

Sitagliptin + Metformin hydrochloride TZF, 50 mg + 1000 mg
Reddish-brown, elongated oval film-coated tablet, with a breakline between 'S' and 'B' engraved on one side and a breakline on the other side. The breakline on the tablet is intended only to facilitate breaking for easier swallowing and does not ensure equal dosing.
Tablet dimensions: 21.3 ± 0.5 mm.

Packaging
PVC/PVDC/Aluminium blister.
56 film-coated tablets packed with the leaflet in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Tarchomińskie Zakłady Farmaceutyczne „Polfa” Spółka Akcyjna
ul. A. Fleminga 2
03-176 Warszawa
Telephone number: 22 811-18-14
For further information about this medicine, please contact the Marketing Authorisation Holder.

Manufacturer
Galenicum Health S.L.
Calle De San Gabriel 50
08950 Esplugues de Llobregat
Spain
SAG Manufacturing S.L.
Carretera Nacional 1 Km 36
28750 San Augustin del Guadalix
Spain
Tarchomińskie Zakłady Farmaceutyczne „Polfa” Spółka Akcyjna
ul. A. Fleminga 2
03-176 Warszawa