Symetlip

Package leaflet: Information for the patient

Symetlip, 50 mg + 850 mg, film-coated tablets
Symetlip, 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 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 someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

1. What Symetlip is and what it is used for

Symetlip 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. When used together with diet and 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, sulfonylureas, 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 happens, sugar (glucose) accumulates in the blood. This can lead to serious health problems such as heart disease, kidney disease, vision loss, and limb amputations.

2. Important information before taking Symetlip

When not to take Symetlip

• if the patient is allergic to sitagliptin, 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 a severe infection or dehydration;

• if the patient is scheduled to undergo a radiological examination with intravascular administration of a contrast agent. The intake of Symetlip must be discontinued during the radiological examination and for 2 or more days after the examination, according to the physician's instructions, depending on the patient's kidney function;

• if the patient has recently suffered a heart attack or has experienced 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 Symetlip if any of the above contraindications apply.
Consult a physician to determine alternative methods of diabetes control. In case of doubt, discuss this with your doctor, pharmacist, or nurse before taking Symetlip.
Warnings and precautions
Cases of pancreatitis have been reported in patients taking Symetlip (see section 4).
If the patient develops skin blisters, this may be a symptom of a disease called bullous pemphigoid. The physician may advise the patient to discontinue taking Symetlip.
Risk of lactic acidosis
Symetlip 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 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 a physician for further instructions.
Temporarily discontinue taking Symetlip if the patient has 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 physician for further instructions.
Discontinue taking Symetlip 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 associated with severe fatigue,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring immediate hospital treatment.
Seek immediate medical advice 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).
• the patient develops any of the following symptoms after starting metformin: seizures, worsening of cognitive function, difficulty moving the body, symptoms indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

Before starting Symetlip, 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 be increased (see section 4),
• if the patient has been diagnosed with type 1 diabetes, sometimes referred to as insulin-dependent diabetes,
• if the patient currently has or has previously experienced allergic reactions to sitagliptin, metformin, or Symetlip (see section 4),
• if the patient is taking a sulphonylurea derivative or insulin, antidiabetic medicines, together with Symetlip, as this may lead to excessively low blood sugar levels (hypoglycaemia). The physician may reduce the dose of the sulphonylurea derivative or insulin.

If the patient is scheduled for major surgery, Symetlip 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 Symetlip.
If the patient is unsure whether any of the above statements apply, they should discuss this with their doctor or pharmacist before taking Symetlip.
While taking Symetlip, the physician will monitor kidney function at least once a year, or more frequently if the patient is elderly and/or has deteriorating 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 not known whether this medicine is safe and effective in children under 10 years of age.
Symetlip and other medicines
If the patient is to receive an intravenous iodine-containing contrast agent, for example for an X-ray or CT scan, they must stop taking Symetlip before or at the latest at the time of injection. The physician will decide when the patient should stop and resume treatment with Symetlip.
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or the physician may need to adjust the dose of Symetlip.
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). When taking Symetlip with digoxin, blood digoxin levels should be monitored.

Symetlip and alcohol
Avoid consuming excessive amounts of alcohol while taking Symetlip, 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 a doctor or pharmacist before taking this medicine.
Do not use this medicine during pregnancy or while breastfeeding. See section 2. "When not to take Symetlip".
Driving and operating machinery
This medicine has no effect or a negligible effect on the ability to drive and operate machinery. However, when driving or 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 the ability to work without safe foot support.
Symetlip contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Symetlip

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 to follow the diet recommended by your doctor and pay attention to
an even 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 Symetlip 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").
Missing a dose of Symetlip
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 to make up for a missed dose.
Stopping treatment with Symetlip
To maintain blood sugar control, take this medicine for as long as your doctor recommends. Do not stop taking
this medicine without first consulting your doctor.
Discontinuing treatment with Symetlip may cause blood sugar levels to rise again.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
You should DISCONTINUE treatment with Symetlip and immediately contact your doctor if any of the following serious adverse effects 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.

Very rarely (may occur in no more than 1 in 10,000 patients), Symetlip may cause a very serious adverse effect called lactic acidosis (see section "Warnings and precautions"). If lactic acidosis occurs, you must stop taking Symetlip 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, hives, skin blisters or peeling skin, and swelling of the face, lips, tongue or throat, which may cause difficulty breathing or swallowing, treatment with the medicine must be stopped and immediate medical attention sought. Your doctor may prescribe medication to treat the allergic reaction and another medicine to treat diabetes.

The following adverse effects have been reported in some patients taking metformin after starting sitagliptin:

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 sitagliptin in combination with metformin (frequent).

The following adverse effects have been reported in some patients taking this medicine in combination with a sulfonylurea derivative such as glimepiride:

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

The following adverse effects have been reported in some patients taking this medicine in combination with pioglitazone:

Frequent: swelling of hands or feet.

The following adverse effects have been reported in some patients taking this medicine in combination with insulin:

Very frequent: low blood sugar levels
Uncommon: dry mouth, headache.

In clinical trials, the following adverse effects have been reported in some patients taking sitagliptin alone (one of the active substances in Symetlip) or after marketing authorization of Symetlip, or sitagliptin alone or in combination with other antidiabetic medicines:

Frequent: 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).

The following adverse effects have been reported in some patients taking metformin alone:

Very frequent: nausea, vomiting, diarrhoea, stomach pain and loss of appetite. These symptoms may occur when 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 (paraesthesia), or pale or yellowish skin). Your doctor may order certain tests to determine the cause of your 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 effects

If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring of 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 effects can also be reported directly to the marketing authorization holder.

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

5. How to store Symetlip

Keep this medicine out of 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.
No special storage instructions apply.
Medicines must 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 packaging and other information

What Symetlip contains

• The active substances in this medicine are sitagliptin and metformin.
  • Each coated tablet of Symetlip, 50 mg + 850 mg contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
  • Each coated tablet of Symetlip, 50 mg + 1000 mg contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
• Other ingredients are:
  • Tablet core: microcrystalline cellulose PH 101, microcrystalline cellulose PH 102, povidone K-90, sodium stearyl fumarate, sodium lauryl sulfate.
  • Tablet coating: Opadry II White 85F18422 (50 mg + 850 mg) contains: polyvinyl alcohol, titanium dioxide (E171), polyethylene glycol 3350, 4000, talc. Opadry II Yellow 85F520153 (50 mg + 1000 mg) contains: polyvinyl alcohol, titanium dioxide (E171), polyethylene glycol 3350, 4000, talc and yellow iron oxide (E172).

What Symetlip looks like and contents of the pack
Symetlip, 50 mg + 850 mg, coated tablets
White to off-white, capsule-shaped coated tablets, approximately 20.2 mm by 9.8 mm in size and 6.6 mm ± 0.4 mm thick, with an embossing of “S18” and a division line on one side and “H” on the other side.
Symetlip, 50 mg + 1000 mg, coated tablets
Yellow, capsule-shaped coated tablets, approximately 21.4 mm by 10.4 mm in size and 7.0 mm ± 0.4 mm thick, with an embossing of “S19” and a division line on one side and “H” on the other side.
The division line on the tablet is intended only to facilitate breaking the tablet for easier swallowing and does not indicate division into equal doses.
Blisters made of PVC/Aluminium/OPA/Aluminium, packed in a cardboard box. Packs containing 14, 28, 50, 56, 60, 112, 168, 180 or 196 coated tablets.
Not all pack sizes may be marketed.

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/Importer
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park, Paola PLA3000,
Malta
Farmak International Sp. z o.o.
ul. Chełmżyńska 249
04-458 Warsaw