Sitagliptin and metformin hydrochloride Sun: detailed information

Patient Information Leaflet

Sitagliptin/Metformin Hydrochloride SUN 50 mg/850 mg film-coated tablets, mg/1,000 mg film-coated tablets

sitagliptin/metformin hydrochloride
Please read all of 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 questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Sitagliptin/Metformin Hydrochloride SUN is and what it is used for
What you need to know before taking Sitagliptin/Metformin Hydrochloride SUN
How to take Sitagliptin/Metformin Hydrochloride SUN
Possible side effects
How to store Sitagliptin/Metformin Hydrochloride SUN
Contents of the pack and other information

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

Sitagliptin/Metformin Hydrochloride SUN contains two different medicines called sitagliptin and
metformin.

sitagliptin belongs to a class of medicines called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors)
metformin belongs to a class of medicines called 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 the levels of insulin released after meals and reduces the amount of sugar produced by the body.
Together with diet and physical exercise, this medicine helps lower blood sugar levels. This medicine can be used alone or in combination with certain 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 produced by the body does not work as effectively as it should. Your body may also produce too much sugar. When this happens, sugar (glucose) builds up 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 SUN

Do not take Sitagliptin/Metformin Hydrochloride SUN

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 hyperglycemia (high blood glucose levels), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see below “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called “ketone bodies” accumulate in the blood and may lead to diabetic precoma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, and breath with an unusual fruity odor.
if you have a severe infection or are dehydrated
if you are about to undergo an X-ray procedure involving the use of a contrast agent. You will need to stop taking Sitagliptin/Metformin Hydrochloride SUN 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 circulation problems, such as “shock” or difficulty breathing
if you have liver problems
if you drink excessive amounts of alcohol (either regularly or occasionally)
if you are breastfeeding

Do not take Sitagliptin/Metformin Hydrochloride SUN if you have any of the conditions listed above and
speak with your doctor about other methods of managing diabetes. If you are unsure, consult your
doctor, pharmacist, or nurse before taking Sitagliptin/Metformin Hydrochloride SUN.
Warnings and precautions
Cases of pancreatitis (inflammation of the pancreas) have been reported in patients treated with Sitagliptin/Metformin Hydrochloride SUN (see section 4).
If you develop blisters on your skin, this may be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop treatment with Sitagliptin/Metformin Hydrochloride SUN.
Risk of lactic acidosis
Sitagliptin/Metformin Hydrochloride SUN 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 or 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 severe heart disease).
If you have any of the medical conditions described above, consult your doctor for further instructions.
Temporarily stop taking Sitagliptin/Metformin Hydrochloride SUN if you develop a medical condition that may be associated with dehydration (significant loss of body fluids), such as severe vomiting, diarrhea, 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 SUN and contact your doctor or go to the nearest hospital immediately,
as lactic acidosis may lead to coma.
Symptoms of lactic acidosis include:

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

Lactic acidosis is a medical emergency and must be treated in a hospital.
Consult your doctor or pharmacist before taking Sitagliptin/Metformin Hydrochloride SUN:

if you have or have had a disease of the pancreas (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 SUN (see section 4)
if you are taking a sulfonylurea or insulin, diabetes medicines, together with Sitagliptin/Metformin Hydrochloride SUN, as excessively low blood sugar levels (hypoglycemia) may occur. Your doctor may reduce the dose of sulfonylurea or insulin.

If you are undergoing major surgery, you must stop taking Sitagliptin/Metformin Hydrochloride SUN 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 SUN.
If you are unsure whether any of the conditions listed above apply to you, consult your doctor or pharmacist before taking Sitagliptin/Metformin Hydrochloride SUN.
During treatment with Sitagliptin/Metformin Hydrochloride SUN, your doctor will monitor 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 SUN
If you are to receive an injection of iodinated contrast medium into the bloodstream, for example for an X-ray procedure, you must stop taking Sitagliptin/Metformin Hydrochloride SUN before or during the injection. Your doctor will decide when to stop and when to restart treatment with Sitagliptin/Metformin Hydrochloride SUN.
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 SUN. It is particularly important to mention the following:

medicines (taken orally, inhaled, or injected) used to treat inflammatory conditions, 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 used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)
specific medicines for the treatment of 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 (used to treat irregular heartbeat and other heart problems). Blood levels of digoxin may need to be monitored if taken together with Sitagliptin/Metformin Hydrochloride SUN.

Sitagliptin/Metformin Hydrochloride SUN and alcohol
Avoid excessive alcohol consumption while taking Sitagliptin/Metformin Hydrochloride SUN, 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, are planning to become pregnant, or are 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 SUN”.
Driving and using machines
This medicine has no 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 and use machines.
Taking this medicine together with other medicines called sulfonylureas or with insulin may cause hypoglycemia, which may affect your ability to drive, use machines, or work without protective barriers.
Sitagliptin/Metformin Hydrochloride SUN contains hydrogenated castor oil
This may cause stomach discomfort or diarrhea.

3. How to take Sitagliptin/Metformin hydrochloride SUN

Take this medicine exactly as your doctor has told you. If you are not sure, 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 help 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 your dose of sulphonylurea or insulin.
If you take more Sitagliptin/Metformin hydrochloride SUN 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 SUN
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 regular time. Do not take a double dose of this medicine.
If you stop taking Sitagliptin/Metformin hydrochloride SUN
Continue taking this medicine for as long as your doctor prescribes it, so that you can keep your blood sugar level under control. Do not stop taking this medicine without first talking to your doctor. If you stop taking Sitagliptin/Metformin hydrochloride SUN, your blood sugar level may rise again.
If you have any questions 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 everyone gets them.

STOP taking Sitagliptin/Metformin hydrochloride SUN and contact your doctor immediately if you notice any of the following serious side effects:

Severe and persistent pain in the abdomen (stomach area), which may extend to the back, with or without nausea and vomiting, as these may be signs of inflammation of the pancreas (pancreatitis).

Sitagliptin/Metformin hydrochloride SUN 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 SUN and seek immediate medical attention at the nearest doctor or hospital, because lactic acidosis can lead to coma.

If you experience a severe allergic reaction (frequency not known), including rash, hives, skin blisters/skin peeling, and swelling of the face, lips, tongue, or throat, which may cause difficulty breathing or swallowing, stop treatment with 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 taking metformin have experienced the following side effects after starting therapy with sitagliptin:

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 have experienced diarrhoea, nausea, flatulence, constipation, stomach ache, or vomiting when starting combination therapy with sitagliptin and metformin (frequency is common).

Some patients have 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 have experienced the following side effects while taking this medicine in combination with pioglitazone:

Common: swelling of the hands or legs

Some patients have experienced the following side effects while taking this medicine in combination with insulin:

Very common: low blood sugar level
Uncommon: dry mouth, headache

During clinical studies, some patients experienced the following side effects when taking sitagliptin alone (one of the medicines contained in Sitagliptin/Metformin hydrochloride SUN) or during post-marketing use of Sitagliptin/Metformin hydrochloride SUN 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, feeling of itching
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 blister)

Some patients taking metformin alone have 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 resolve over time.
Common: metallic taste
Very rare: decreased vitamin B12 levels, hepatitis (a liver problem), hives, skin redness (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:
www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sitagliptin/Metformin hydrochloride SUN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and the carton after "EXP". The expiry date refers to the last day of that month.
Do not store above 25 °C.
Do not dispose of any medicine 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 SUN contains

The active substances are sitagliptin and metformin.
- Each film-coated tablet of Sitagliptin/Metformin hydrochloride SUN 50 mg/850 mg contains sitagliptin fumarate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
- Each film-coated tablet of Sitagliptin/Metformin hydrochloride SUN 50 mg/1\ 000 mg (tablet) contains sitagliptin fumarate equivalent to 50 mg of sitagliptin and 1\ 000 mg of metformin hydrochloride.
The other ingredients are:
- Tablet core: hydroxypropyl cellulose (E463), calcium hydrogen phosphate (E341), crospovidone (E1202), hydrogenated castor oil (see section 2), glyceryl dibehenate, magnesium stearate (E470b).
- Film coating: hypromellose, hydroxypropyl cellulose (E463), titanium dioxide (E171), talc (E553b), stearic acid, red iron oxide (E172), yellow iron oxide (E172).

Description of the appearance of Sitagliptin/Metformin hydrochloride SUN and contents of the pack
Sitagliptin/Metformin hydrochloride SUN 50 mg/850 mg film-coated tablets:
Film-coated pink oval tablets, approximately 20 mm x 10 mm x 6 mm in size, with the imprint "SC1" in relief on one side.
Sitagliptin/Metformin hydrochloride SUN 50 mg/1\ 000 mg film-coated tablets:
Film-coated brown to reddish-brown oval tablets, approximately 22 mm x 11 mm x 7 mm in size, with the imprint "SC7" in relief on one side.
HDPE bottle with silica/carbon desiccant.
Pack sizes of 28 and 56 film-coated tablets in a bottle with child-resistant closure or 200 film-coated tablets in a bottle with screw cap.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132JH Hoofddorp
The Netherlands

Manufacturer
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132JH Hoofddorp
The Netherlands
Terapia S.A.
Str. Fabricii nr. 124
Cluj-Napoca, 400632
Romania

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien/България/Česká republika/
Denmark/Eesti/Ελλάδα/Hrvatska/Ireland/Ísland/
Κύπρος/Latvija/Lietuva/Luxembourg/Luxemburg/Hungary/
Malta/Netherlands/Norway/Austria/Portugal/
Slovenia/Slovakia/Finland/Finland/Sweden
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands/Niederlande/Нидерландия/Nizozemsko/
Nederlandene/Netherlands/Ολλανδία/Nizozemska/Olanda/Olanda/
Ολλανδία/Nīderlande/Nyderlandai/Italy/Niederlande/Olanda/
L-Olanda/Nederlandia/Niederlande/Olanda/
Nizozemska/Holandsko/Alankomaat/Nederländerna/Nederländerna
Tel./тел./tlf./τηλ./Sími/τηλ./Tlf./Puh./
+31 (0)23 568 5501

Germany
Sun Pharmaceuticals Germany GmbH
Hemmelrather Weg 201
51377 Leverkusen
Germany
Tel. +49 (0) 214 40399 0

Spain
Sun Pharma Laboratorios, S.L.
Rambla de Catalunya 53-55
08007 Barcelona
Spain
Tel. +34 93 342 78 90

France
Sun Pharma France
11-15, Quai de Dion Bouton
92800 Puteaux
France
Tel. +33 1 41 44 44 50

Italy
Sun Pharma Italia Srl
Viale Giulio Richard, 3
20143 Milan
Italy
Tel. +39 02 33 49 07 93

Poland
Ranbaxy (Poland) Sp. Z o.o.
ul. Kubickiego 11
02-954 Warsaw
Poland
Tel. +48 22 642 07 75

Romania
Terapia S.A.
Str. Fabricii nr 124
Cluj-Napoca, Cluj county
Romania
Tel. +40 (264) 501 500

United Kingdom (Northern Ireland)
Sun Pharma UK Limited
6-9 La Piazza
Stockley Park
Uxbridge
UB11 1FW
United Kingdom

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu