Asigefort

Package leaflet: Information for the patient

Asigefort, 50 mg + 850 mg, film-coated tablets
Asigefort, 50 mg + 1000 mg, film-coated tablets
Sitagliptin + Metformin hydrochloride
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, 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 or pharmacist. See section 4.

Leaflet contents

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

1. What Asigefort is and what it is used for

Asigefort 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 physical exercise, it helps lower blood glucose levels. This medicine may be used as the sole antidiabetic treatment 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. As a result, 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 Asigefort

When not to use Asigefort

• if the patient is allergic to sitagliptin and 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 severe infection or dehydration,
• if the patient is scheduled for a radiological examination with intravascular administration of contrast medium. The use of Asigefort must be discontinued during the radiological examination and for 2 or more days thereafter, as advised by the physician, 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 Asigefort 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 using Asigefort.
Warnings and precautions
Cases of pancreatitis have been reported in patients taking sitagliptin in combination with metformin (see section 4).
If the patient develops skin blisters, this may be a symptom of a disease known as bullous pemphigoid. The doctor may advise the patient to discontinue taking Asigefort.
Risk of lactic acidosis
Asigefort 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 detailed information below), liver dysfunction, 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 a doctor for further instructions.
Temporarily discontinue use of Asigefort if the patient develops any illness 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 use of Asigefort 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 mitochondrial disorder (mitochondria are cellular structures responsible for energy production), 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 experiences any of the following symptoms: seizures, worsening cognitive function, difficulty moving the body, symptoms indicating nerve damage (e.g. pain or numbness), migraine or deafness.

Before starting Asigefort, discuss with your doctor or pharmacist:

• if the patient has or has had a pancreatic disorder (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 currently has or has previously experienced allergic reactions to sitagliptin, metformin or Asigefort (see section 4),
• if the patient is taking a sulfonylurea derivative or insulin, antidiabetic medicines together with Asigefort, as this may lead to excessive lowering of blood glucose (hypoglycaemia). The doctor may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is undergoing major surgery, Asigefort must not be used during the procedure and for some time afterwards. The doctor will decide when the patient should stop and resume treatment with Asigefort.
If in doubt, discuss this with your doctor or pharmacist before using Asigefort.
While taking Asigefort, 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 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 not known whether this medicine is safe and effective when used in children under 10 years of age.
Asigefort 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 Asigefort before or at the latest at the time of administration. The doctor will decide when the patient should stop and resume treatment with Asigefort.
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 dose adjustments of Asigefort 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,
• 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 Asigefort with digoxin.

Asigefort and alcohol
Avoid consuming excessive amounts of alcohol while taking Asigefort, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").
Pregnancy and breastfeeding
If the patient is pregnant, suspects she may be pregnant, plans to become pregnant, or is breastfeeding, she should consult her doctor or pharmacist before using this medicine. Do not use this medicine during pregnancy. This medicine must not be used during breastfeeding. See section 2 "When not to use Asigefort".
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 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.
Asigefort 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 take Asigefort

This medicine should always be taken as directed by your doctor or pharmacist. If you have any doubts,
please consult your doctor or pharmacist.

• Take one tablet:
• twice daily, by mouth;
• 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 ensure
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 if this medicine is taken together with a sulfonylurea
derivative or insulin – in such a case, your doctor may reduce the dose of the sulfonylurea or insulin.

Taking more Asigefort than recommended
If you take more of this medicine than recommended, contact your doctor immediately.
Go to hospital if symptoms of lactic acidosis occur, such as feeling cold or uncomfortable,
severe nausea or vomiting, stomach pain, unexplained weight loss, muscle cramps or rapid
breathing (see section "Warnings and precautions").

Missing a dose of Asigefort
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 of this
medicine.

Stopping Asigefort
To maintain control of your blood sugar levels, take this medicine for as long as your doctor
advises. Do not stop taking this medicine without first consulting your doctor.
Stopping treatment with Asigefort may result in increased 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.

STOP taking Asigefort 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 – these may be symptoms of pancreatitis.

Asigefort very rarely (may occur in no more than 1 in 10,000 patients) may cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If lactic acidosis occurs, STOP taking Asigefort and contact your doctor or the nearest hospital immediately, as lactic acidosis may lead to coma.

In case of a severe allergic reaction (frequency unknown), including rash, hives, skin blisters, skin peeling, or swelling of the face, lips, tongue, or throat, which may cause difficulty breathing or swallowing, treatment with the medicine must be discontinued and medical advice sought immediately. Your doctor may prescribe medication 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:

• Common (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

In some patients, diarrhoea, nausea, bloating, constipation, stomach pain, or vomiting occurred after starting treatment with sitagliptin in combination with metformin (common).

In some patients taking this medicine in combination 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: 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, in some patients taking sitagliptin alone (one of the active substances in Asigefort) or after marketing authorisation during treatment with sitagliptin alone, sitagliptin in combination with metformin, or with other antidiabetic medicines, the following adverse reactions were observed:

• Common: 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: 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 in the mouth, reduced or low levels of vitamin B in the blood (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling or numbness sensations (paraesthesiae), 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), hives, skin redness (rash), or itching.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. 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 authorisation holder.
By reporting adverse reactions, additional information on the safety of this medicine can be collected.

5. How to store Asigefort

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the stated month.
OPA/Aluminum/PVC//Aluminum foil blister:
No special temperature storage requirements for this medicinal product.
Store in the original packaging to protect from moisture.
PVC/PE/PVDC/PE/PVC//Aluminum foil blister:
Do not store above 30°C. Store in the original packaging to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such practices help protect the environment.

6. Contents of the packaging and other information

What Asigefort contains

• The active substances in this medicine are sitagliptin and metformin hydrochloride.
  Asigefort, 50 mg + 850 mg, film-coated tablets: Each film-coated tablet contains 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
  Asigefort, 50 mg + 1000 mg, film-coated tablets: Each film-coated tablet contains 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
• Other components (excipients) are: povidone K30, microcrystalline cellulose, mannitol, sodium lauryl sulfate, magnesium stearate in the tablet core; hypromellose type 2910 (6 mPa·s), titanium dioxide (E 171), talc, propylene glycol (E 1520), iron oxide red (E 172) in the tablet coating. See section 2 "Asigefort contains sodium".

What Asigefort looks like and contents of the pack
Asigefort, 50 mg + 850 mg, film-coated tablets: pink, oval, biconvex film-coated tablets with the imprint C4 on one side (approximately 20 x 11 mm in size).
Asigefort, 50 mg + 1000 mg, film-coated tablets: dark pink, oval, biconvex film-coated tablets with the imprint C3 on one side (approximately 21 x 11 mm in size).
Asigefort is available in packs containing:

• 28, 56 film-coated tablets in blisters,
• 28, 56 film-coated tablets in calendar packs.

Not all pack sizes may be marketed.
Marketing Authorisation Holder
TAD Pharma GmbH
Heinz-Lohmann-Straße 5
27472 Cuxhaven
Germany
Manufacturer/Importer
KRKA, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto
Slovenia
TAD Pharma GmbH
Heinz-Lohmann-Straße 5
27472 Cuxhaven
Germany
For further information about this medicine and its names in other countries of the European Economic Area, please contact the representative of the marketing authorisation holder:
KRKA-POLSKA Sp. z o.o.
Równoległa Street 5
02-235 Warsaw
Phone: 22 57 37 500