Asitalip combo

Package leaflet: Information for the patient

Asitalip Combo, 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. 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 only. 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 side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

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

1. What Asitalip Combo is and what it is used for

Asitalip Combo 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". Asitalip Combo helps increase insulin secretion after meals and reduces the amount of glucose produced by the body. When used together with diet and exercise, this medicine helps lower blood glucose levels. Asitalip Combo 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?
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 using Asitalip Combo

When not to use Asitalip Combo:

• 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, e.g. 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. Treatment with Asitalip Combo must be discontinued during the radiological examination and for two or more days afterwards, according to the physician's instructions, depending on the patient's kidney function;
• if the patient has recently suffered 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 Asitalip Combo 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 or pharmacist before taking Asitalip Combo.

Warnings and precautions

Cases of pancreatitis have been reported in patients taking Asitalip Combo (see section 4).
If the patient develops blisters on the skin, this may be a symptom of a disease known as bullous pemphigoid. The doctor may advise the patient to discontinue treatment with Asitalip Combo.

Risk of lactic acidosis

Asitalip Combo may cause a very rare but serious adverse effect called lactic acidosis, particularly 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 further information below), impaired liver function, and any medical conditions in which 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 the doctor for further instructions.

Temporarily discontinue taking Asitalip Combo if the patient develops 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 the doctor for further instructions.

Discontinue taking Asitalip Combo 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.

Before starting treatment with Asitalip Combo, 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 levels of triglycerides (a type of fat) in the blood. In such cases, the risk of pancreatitis may be increased (see section 4);
• if the patient has type 1 diabetes (insulin-dependent diabetes);
• if the patient has currently or previously experienced allergic reactions to sitagliptin, metformin, or Asitalip Combo (section 4);
• if the patient is taking a sulfonylurea derivative or insulin, antidiabetic medicines together with Asitalip Combo, as this may lead to excessively low blood glucose levels (hypoglycaemia). The doctor may reduce the dose of the sulfonylurea derivative or insulin.

If a major surgical procedure is required, treatment with Asitalip Combo should be discontinued during the procedure and for some time afterwards. The doctor will decide when the patient should stop and resume treatment with Asitalip Combo.

If in doubt, consult your doctor or pharmacist before taking Asitalip Combo.

During treatment with Asitalip Combo, the 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. 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.

Asitalip Combo and other medicines

If the patient is to receive an intravascular iodinated contrast agent, for example for an X-ray or CT scan, treatment with Asitalip Combo must be stopped before or at the latest at the time of administration. The doctor will decide when the patient should stop and resume treatment with Asitalip Combo.

Inform your doctor or pharmacist about any 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, or dose adjustments of Asitalip Combo 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 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 Asitalip Combo with digoxin, digoxin blood levels should be monitored.

Asitalip Combo and alcohol

Avoid consuming excessive amounts of alcohol while taking Asitalip Combo, 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 have a child, she should consult her doctor or pharmacist before using this medicine.

Do not take this medicine during pregnancy or while breastfeeding. See section 2. When not to use Asitalip Combo.

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 with sitagliptin, which may affect the ability to drive and operate machinery.

Taking Asitalip Combo 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.

Asitalip Combo 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 Asitalip Combo

This medicine should always be taken as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.
Take one tablet of Asitalip Combo:

• 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.
The tablet's break line is intended only to facilitate breaking the tablet for easier swallowing and does not indicate division into equal doses.
If the patient has impaired kidney function, the doctor may prescribe a lower dose.
While taking Asitalip Combo, continue the diet recommended by your doctor and pay attention to evenly distributing carbohydrate intake throughout the day.
It is unlikely that taking Asitalip Combo alone would lead to abnormally low blood sugar levels (hypoglycaemia). Low blood sugar may occur when Asitalip Combo 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 Asitalip Combo than prescribed
If you take more Asitalip Combo than prescribed, contact your doctor immediately. 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, go to hospital (see section "Warnings and precautions").
Missing a dose of Asitalip Combo
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 Asitalip Combo
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 first consulting your doctor.
Discontinuing Asitalip Combo may cause an increase in 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 everybody gets them.
You should STOP taking Asitalip Combo and contact your doctor immediately
if any of the following serious adverse reactions occur:

• Severe and persistent pain in the stomach area which may spread to the back, with or without nausea and vomiting – these may be symptoms of pancreatitis.

Asitalip Combo may very rarely (occurring in up to 1 in 10,000 people) cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). In such a case, you must stop taking Asitalip Combo and contact your doctor or nearest hospital immediately, as lactic acidosis may lead to coma.
If a severe allergic reaction occurs (frequency unknown), including rash, hives, skin blisters or peeling of the skin, and swelling of the face, lips, tongue or throat, which may cause difficulty in breathing or swallowing, you should stop taking this medicine and contact your doctor immediately. Your doctor may prescribe a medicine to treat the allergic reaction and another medicine (a different medicine) for the treatment of diabetes.
In some patients taking metformin, the following adverse reactions occurred after starting treatment with 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.
Diarrhoea, nausea, bloating, constipation, stomach pain or vomiting may occur in some patients after starting treatment with sitagliptin in combination with metformin (frequent).

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

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

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

In clinical trials, the following adverse reactions occurred in some patients taking sitagliptin alone (one of the active substances in Asitalip Combo) or after marketing of Asitalip Combo or sitagliptin alone or in combination with other antidiabetic medicines:
Frequent: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose and sore throat, bone and joint pain, pain in arms or legs.
Uncommon: dizziness, constipation, itching.
Rare (may affect up to 1 in 1,000 people): 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 frequent: nausea, vomiting, diarrhoea, stomach pain and loss of appetite. These symptoms may occur after starting metformin and usually resolve over time.
Frequent: metallic taste, reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness, pain and redness of the tongue (glossitis), tingling or numbness sensations (paresthesia), or paleness 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 not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions 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 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 Asitalip Combo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack after "EXP". The expiry date refers to the last day of the stated month.
Store below 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 help protect the environment.

6. Contents of the pack and other information

What Asitalip Combo contains
The active substances are sitagliptin and metformin.
Each film-coated tablet contains sitagliptin hydrochloride monohydrate, equivalent to 50 mg
of sitagliptin and 1000 mg of metformin hydrochloride.
The other ingredients are:
Tablet core: povidone (K 29/32), microcrystalline cellulose, 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).

What Asitalip Combo looks like and contents of the pack
Film-coated tablets in red to brown colour, oval-shaped, with a breakline between the embossed letters “S” and “B” 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 allow division into equal doses.
PVC/PVDC/Aluminium blister in a cardboard box with a patient leaflet.
Pack contains 28 or 56 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Polfarmex S.A.
ul. Józefów 9
99-300 Kutno
Poland
Tel.: +48 24 357 44 44
Fax: +48 24 357 45 45
e-mail: [email protected]

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

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