Sitagliptin and metformin hydrochloride Pharmathen

Package leaflet: Information for the patient

Sitagliptin/Metformin hydrochloride Pharmathen 50 mg/850 mg film-coated tablets, mg/1,000 mg film-coated tablets

sitagliptin/metformin hydrochloride
Read this entire 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Sitagliptin/Metformin Hydrochloride Pharmathen is and what it is used for

Sitagliptin/Metformin Hydrochloride Pharmathen contains two different medicines called sitagliptin and
metformin.
Sitagliptin belongs to a class of medicines known as DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors).
Metformin belongs to a class of medicines known as biguanides.
Together, they work to control blood sugar levels in adult patients with a form of diabetes called "type 2 diabetes mellitus". This medicine helps increase insulin levels produced after meals and reduces the amount of sugar produced by the body.
Along with diet and exercise, this medicine helps lower blood sugar levels. This medicine may be used alone or in combination with other diabetes 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 and the insulin the body produces does not work properly as it should. Your body may also produce too much sugar.
When this occurs, sugar (glucose) accumulates in the blood. This can lead to serious medical problems such as heart disease, kidney disease, blindness and amputation.

2. What you should know before taking Sitagliptin/Metformin Hydrochloride Pharmathen

Do not take Sitagliptin/Metformin Hydrochloride Pharmathen

• if you are allergic to sitagliptin, metformin, or any of the excipients of this medicine (listed in section 6)
• if you have severely reduced kidney function
• if you have uncontrolled diabetes associated, for example, with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid 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 stomach pain, rapid and deep breathing, drowsiness, or breath with an unusually fruity odour.
• if you have a severe infection or are dehydrated
• if you are about to undergo an X-ray procedure involving a contrast agent. You will need to stop taking Sitagliptin/Metformin Hydrochloride Pharmathen at the time of the X-ray and for 2 or more days afterwards as directed by your doctor, depending on how well your kidneys are functioning
• if you have recently had a heart attack or have serious circulatory problems, such as "shock" or difficulty breathing
• if you have liver problems
• if you drink excessive amounts of alcohol (either daily or occasionally)
• if you are breastfeeding

Do not take Sitagliptin/Metformin Hydrochloride Pharmathen if you have any of the above conditions, and speak with your doctor about alternative methods of managing diabetes. If you are unsure, speak with your doctor, pharmacist, or nurse before taking Sitagliptin/Metformin Hydrochloride Pharmathen.

Warnings and precautions

Cases of inflammation of the pancreas (pancreatitis) have been reported in patients treated with sitagliptin/metformin hydrochloride (see section 4).

If you develop a skin rash with blisters, this may be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop taking Sitagliptin/Metformin Hydrochloride Pharmathen.

Risk of lactic acidosis

Sitagliptin/Metformin Hydrochloride Pharmathen may cause a very rare but serious side effect called lactic acidosis, particularly if the kidneys are not functioning properly. The risk of developing lactic acidosis is higher in the presence of uncontrolled diabetes, severe infections, prolonged fasting, alcohol consumption, dehydration (see below for further information), liver problems, or any other medical condition characterized by reduced oxygen supply to part of the body (such as in the case of severe acute heart disease).

If you have any of the medical conditions described above, consult your doctor for further instructions.

Temporarily stop taking Sitagliptin/Metformin Hydrochloride Pharmathen if you develop a medical condition that may be associated with dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, heat exposure, or if you are drinking less fluid than usual. Consult your doctor for further instructions.

If you experience any of the symptoms of lactic acidosis, stop taking Sitagliptin/Metformin Hydrochloride Pharmathen and contact your doctor or go to the nearest hospital immediately, as this condition may lead to coma. Symptoms of lactic acidosis include:

• vomiting
• stomach ache (abdominal pain)
• muscle cramps
• a general feeling of malaise associated with severe fatigue
• difficulty breathing
• reduced body temperature and slower heart rate

Lactic acidosis is a medical emergency and must be treated in hospital.

Contact your doctor immediately for further instructions if:

• you know you have a hereditary genetic mitochondrial disease (the components that produce energy within cells), such as MELAS (Mitochondrial Encephalopathy, myopathy, Lactic Acidosis and Stroke-like episodes) or Maternal Inherited Diabetes and Deafness (MIDD);
• you experience any of the following symptoms after starting metformin: seizures, reduced cognitive abilities, difficulty with body movements, symptoms indicating nerve damage (e.g. pain or numbness), headache, or hearing loss.

Talk to your doctor or pharmacist before taking Sitagliptin/Metformin Hydrochloride Pharmathen:

• if you have or have had a pancreatic disease (such as pancreatitis)
• if you have or have had gallstones, alcohol dependence, or very high levels of triglycerides (a type of fat) in the blood. These medical conditions may increase your risk of developing pancreatitis (see section 4)
• if you have type 1 diabetes. This is sometimes called insulin-dependent diabetes
• if you have or have had an allergic reaction to sitagliptin, metformin, or sitagliptin/metformin hydrochloride (see section 4)
• if you are taking a sulfonylurea or insulin, diabetes medicines, together with Sitagliptin/Metformin Hydrochloride Pharmathen, as this may cause excessively low blood sugar levels (hypoglycaemia). Your doctor may reduce the dose of the sulfonylurea or insulin.

If you are undergoing major surgery, you must stop taking Sitagliptin/Metformin Hydrochloride Pharmathen during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Sitagliptin/Metformin Hydrochloride Pharmathen.

If you are unsure whether any of the above conditions apply to you, consult your doctor or pharmacist before taking Sitagliptin/Metformin Hydrochloride Pharmathen.

During treatment with Sitagliptin/Metformin Hydrochloride Pharmathen, your doctor will check your kidney function at least once a year, or more frequently if you are elderly and/or if kidney function worsens.

Children and adolescents

Children and adolescents under 18 years of age must not use this medicine. It is not effective in children and adolescents aged between 10 and 17 years. It is not known whether this medicine is safe and effective when used in children under 10 years of age.

Other medicines and Sitagliptin/Metformin Hydrochloride Pharmathen

If you are due to receive an injection of an iodine-containing contrast agent into the bloodstream, for example for an X-ray procedure, you must stop taking Sitagliptin/Metformin Hydrochloride Pharmathen before or during the injection. Your doctor will decide when to stop and when to restart treatment with Sitagliptin/Metformin Hydrochloride Pharmathen.

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. You may need to monitor your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of Sitagliptin/Metformin Hydrochloride Pharmathen. It is particularly important to mention the following:

• medicines (taken orally, inhaled, or injected) used to treat inflammatory diseases such as asthma and 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 for treating high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)
• specific medicines for treating bronchial asthma (β-sympathomimetics)
• iodinated contrast agents or medicines containing alcohol
• certain medicines used to treat stomach problems 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 (for treating irregular heartbeat and other heart-related problems). It may be necessary to monitor digoxin blood levels if taken together with Sitagliptin/Metformin Hydrochloride Pharmathen.

Sitagliptin/Metformin Hydrochloride Pharmathen and alcohol

Avoid excessive alcohol consumption while taking Sitagliptin/Metformin Hydrochloride Pharmathen, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

You must not take this medicine during pregnancy or while breastfeeding. See section 2, Do not take Sitagliptin/Metformin Hydrochloride Pharmathen.

Driving and using machines

This medicine has no effect or negligible effect on the ability to drive and use machines. However, dizziness and drowsiness have been reported with sitagliptin, which may affect your ability to drive or use machinery.

Taking this medicine together with other medicines called sulfonylureas or with insulin may cause hypoglycaemia, which may affect your ability to drive, use machinery, or work without protective barriers.

Sitagliptin/Metformin Hydrochloride Pharmathen contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take Sitagliptin/Metformin hydrochloride Pharmathen

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Take one tablet:

• twice daily by mouth
• with meals to reduce the likelihood of stomach problems.

Your doctor may need to increase your dose to control the sugar level in your blood.
If you have reduced kidney function, your doctor may prescribe you a lower dose.
You must continue the diet recommended by your doctor during treatment with this medicine and ensure that carbohydrate intake is evenly distributed throughout the day.
It is unlikely that this medicine alone will cause abnormally low blood sugar levels (hypoglycaemia). However, when this medicine is used together with a sulphonylurea or insulin, low blood sugar may occur and your doctor may reduce the dose of the sulphonylurea or insulin.

If you take more Sitagliptin/Metformin hydrochloride Pharmathen than you should
If you take more of this medicine than prescribed, contact your doctor immediately. Go to hospital if you experience symptoms of lactic acidosis 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").

If you forget to take Sitagliptin/Metformin hydrochloride Pharmathen
If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and take your next dose at the usual time. Do not take a double dose of this medicine.

If you stop taking Sitagliptin/Metformin hydrochloride Pharmathen
Continue taking this medicine for as long as your doctor prescribes it, so that you can keep controlling your blood sugar level. Do not stop taking this medicine without first talking to your doctor. If you stop treatment with Sitagliptin/Metformin hydrochloride Pharmathen, your blood sugar level may rise again.

If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Sitagliptin/Metformin Hydrochloride Pharmathen and contact a doctor immediately if you experience any of the following serious side effects:
Severe and persistent pain in the abdomen (stomach area), possibly spreading to the back, with or without nausea and vomiting, as these may be signs of inflammation of the pancreas (pancreatitis).
Sitagliptin/Metformin Hydrochloride Pharmathen may cause a very rare (may affect up to 1 in 10,000 people) but very serious side effect called lactic acidosis (see section "Warnings and precautions"). If this occurs, you must stop taking Sitagliptin/Metformin Hydrochloride Pharmathen and seek immediate medical attention at the nearest doctor or hospital, as lactic acidosis can lead to coma.
If you experience a severe allergic reaction (frequency not known), including rash, hives, skin blistering or peeling, or swelling of the face, lips, tongue, or throat, which may cause difficulty breathing or swallowing, stop taking this medicine and contact your doctor immediately. Your doctor may prescribe a medicine to treat your allergic reaction and a different medicine for your diabetes.

Some patients experienced the following side effects after starting sitagliptin while taking metformin:
Common (may affect up to 1 in 10 people): low blood sugar level, nausea, flatulence, vomiting.
Uncommon (may affect up to 1 in 100 people): stomach ache, diarrhoea, constipation, drowsiness.
Some patients experienced diarrhoea, nausea, flatulence, constipation, stomach ache, or vomiting when starting combination treatment with sitagliptin and metformin (frequency is common).

Some patients experienced the following side effects while taking this medicine with a sulfonylurea such as glimepiride:
Very common (may affect more than 1 in 10 people): low blood sugar level.
Common: constipation.

Some patients experienced the following side effects while taking this medicine in combination with pioglitazone:
Common: swelling of the hands or legs.

Some patients experienced the following side effects while taking this medicine with insulin:
Very common: low blood sugar level.
Uncommon: dry mouth, headache.

During clinical studies, some patients experienced the following side effects while taking sitagliptin alone (one of the medicines contained in Sitagliptin/Metformin Hydrochloride Pharmathen) or during post-marketing use of sitagliptin/metformin hydrochloride or sitagliptin alone or in combination with other diabetes medicines:
Common: low blood sugar level, headache, upper respiratory tract infection, stuffy or runny nose and sore throat, osteoarthritis, pain in arms or legs.
Uncommon: dizziness, constipation, itching sensation.
Rare: reduced platelet count.
Frequency not known: kidney problems (sometimes requiring dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of skin blistering).

Some patients taking metformin alone experienced the following side effects:
Very common: nausea, vomiting, diarrhoea, stomach ache, and loss of appetite. These symptoms may occur when you first start taking metformin and usually go away.
Common: metallic taste, reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), sore and red tongue (glossitis), pins and needles (paraesthesia), or pale or yellowish skin). Your doctor may carry out some tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health problems.
Very rare: hepatitis (a liver problem), hives, redness of the skin (rash), or itching sensation.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Sitagliptin/Metformin Hydrochloride Pharmathen

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and on the carton after
"Exp.". The expiry date refers to the last day of that month.
PVC/PE/PVDC-Aluminium foil blisters: Store below 30°C.
PVC/PCTFE-Aluminium foil blisters: This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sitagliptin/Metformin hydrochloride Pharmathen contains
The active substances are sitagliptin and metformin.

• Each film-coated tablet of Sitagliptin/Metformin hydrochloride Pharmathen 50 mg/850 mg (tablet) contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
• Each film-coated tablet of Sitagliptin/Metformin hydrochloride Pharmathen 50 mg/1 000 mg (tablet) contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1 000 mg of metformin hydrochloride.

The other ingredients are:

• Tablet core: microcrystalline cellulose, povidone, croscarmellose sodium, and sodium stearil fumarate.
• Tablet coating: partially hydrolysed polyvinyl alcohol, macrogol, talc, titanium dioxide (E171), red iron oxide (E172), and black iron oxide (E172).

Description of the appearance of Sitagliptin/Metformin hydrochloride Pharmathen and contents of the pack
The film-coated tablets of Sitagliptin/Metformin hydrochloride Pharmathen 50 mg/850 mg are pink, capsule-shaped, film-coated tablets, engraved with "50" on one side and "850" on the other, with approximate dimensions of 20.3 mm in length, 9.9 mm in width, and 6.8 mm in thickness.

The film-coated tablets of Sitagliptin/Metformin hydrochloride Pharmathen 50 mg/1 000 mg are red, capsule-shaped, film-coated tablets, engraved with "50" on one side and "1000" on the other, with approximate dimensions of 21.5 mm in length, 10.5 mm in width, and 7.1 mm in thickness.

Pack containing the appropriate number of white PVC/PE/PVDC-Aluminium foil blisters and transparent PVC/PCTFE-Aluminium foil blisters. Packs containing 56, 60, or 196 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Pharmathen S.A.
Dervenakion 6
15351 Pallini, Attiki
Greece

Manufacturer
Pharmathen International S.A.,
Industrial Park Sapes,
Rodopi Prefecture, Block No 5,
69300 Rodopi,
Greece
and/or
Pharmathen S.A.
Dervenakion 6
15351 Pallini Attiki,
Greece

This medicinal product is authorised in the European Economic Area Member States under the following names: