Izumis

Patient Information Leaflet

IZUMIS 500 mg, 750 mg and 1000 mg prolonged-release tablets

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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people. It may be harmful even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:
What IZUMIS is and what it is used for

2. What you need to know before taking IZUMIS
3. How to take IZUMIS
4. Possible side effects
5. How to store IZUMIS
6. Contents of the pack and other information

1. What IZUMIS is and what it is used for

IZUMIS contains the active substance metformin hydrochloride and belongs to a group of medicines called biguanides, used in the treatment of diabetes.
IZUMIS is used in adults for the treatment of type 2 diabetes when changes in diet and physical exercise alone do not provide adequate control of blood glucose (sugar in the blood). Insulin is a hormone that allows body tissues to take up glucose from the blood and use it for energy or store it for later use. People with type 2 diabetes either do not produce enough insulin in their pancreas or their body does not respond properly to the insulin it produces. This leads to an accumulation of glucose in the blood, which may cause various serious long-term problems; therefore, it is important that you continue taking the medicine, even if you may not have obvious symptoms.
IZUMIS increases the body's sensitivity to insulin and helps restore the way your body normally uses glucose.
IZUMIS prolonged-release tablets are associated with stable body weight or modest weight loss. IZUMIS prolonged-release tablets are specially designed to release the medicine slowly into your body and are therefore different from many other types of tablets containing metformin.

2. What you need to know before taking IZUMIS

Do not take IZUMIS
if you are allergic to metformin hydrochloride or to any of the other ingredients of this medicine
(listed in section 6);
if you have liver problems;
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 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 pre-coma. Symptoms include stomach pain, rapid deep breathing, drowsiness and fruity-smelling breath;

• if you are dehydrated. Dehydration may lead to kidney problems, which could put you at risk of lactic acidosis (see 'Warnings and precautions');
• if you have a severe infection, such as an infection affecting your lungs or bronchial system or nephritis. Severe infections may lead to kidney problems, which could put you at risk of lactic acidosis (see 'Warnings and precautions');
• if you have been treated for acute heart problems or have recently had a heart attack or have severe circulatory problems or breathing difficulties. This could lead to insufficient oxygen supply to tissues, which may put you at risk of lactic acidosis (see 'Warnings and precautions');
• if you are a heavy drinker of alcohol;
• if you are under 18 years of age;
• if you are about to undergo a radiographic procedure involving intravascular administration of iodinated contrast agents.

Warnings and precautions
Talk to your doctor or pharmacist before taking IZUMIS.
Risk of lactic acidosis
IZUMIS may cause a very rare but very serious side effect called lactic acidosis, particularly if your kidneys are not functioning properly. The risk of developing lactic acidosis is also higher in the presence of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see further information below), 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 IZUMIS 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 fluids than normal. Consult your doctor for further instructions.
Stop taking IZUMIS and contact your doctor or go immediately to the nearest hospital if you experience any of the symptoms of lactic acidosis, as this condition may lead to coma.
Symptoms of lactic acidosis include:

• vomiting
• abdominal pain
• muscle cramps
• a general feeling of malaise associated with severe fatigue
• difficulty breathing
• decreased body temperature and slower heart rate
  Lactic acidosis is a medical emergency and must be treated in hospital.

If you are undergoing major surgery, you must stop taking IZUMIS during the procedure and for a certain period afterwards. Your doctor will decide when you should stop and when you should resume treatment with IZUMIS.
During treatment with this medicine, 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.
During treatment with this medicine, you may find parts of the tablet in your faeces. If this happens, do not be concerned – this is normal with this type of medicine.
Continue to follow the dietary advice provided by your doctor and ensure you consume carbohydrates regularly throughout the day.
Metformin may cause reduced absorption of vitamin B12. Monitoring of blood levels of vitamin B12 is recommended in patients at risk of developing vitamin B12 deficiency.
Do not stop taking this medicine without consulting your doctor.
Other medicines and IZUMIS
If you are due to receive an injection of an iodinated contrast agent into the bloodstream, for example for an X-ray examination, you must stop taking IZUMIS before or at the time of injection. Your doctor will decide when you should stop and when you should resume treatment with IZUMIS.
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
You may need to have more frequent blood glucose and kidney function tests, or your doctor may decide to adjust your dose of IZUMIS. It is particularly important to mention the following:

• Steroids such as prednisolone, mometasone, beclometasone.
• Medicines that increase urine production (diuretics such as furosemide).
• Medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib).
• Some medicines for the treatment of high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).
• Sympathomimetic drugs including adrenaline and dopamine used to treat heart attacks and low blood pressure. Adrenaline is also present in some dental anaesthetics.
• Medicines that may alter the amount of IZUMIS in your blood, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).

IZUMIS and alcohol
Avoid excessive alcohol consumption during treatment with IZUMIS, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, suspect you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
IZUMIS taken alone does not cause hypoglycaemia (low blood sugar levels) and therefore should not affect your ability to drive or use machines.
However, it is important to know that IZUMIS taken with other antidiabetic medicines may cause hypoglycaemia, so in this case you must be especially careful when driving or using machines.
IZUMIS contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dosage unit, which means it is essentially "sodium-free".

3. How to take IZUMIS

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Your doctor may prescribe IZUMIS to be taken alone or in combination with other oral antidiabetic medicines or insulin.
Swallow the tablets whole with a glass of water; do not chew them.
Normally, you should take the tablets once daily during the evening meal.
In some cases, your doctor may advise you to take the tablets twice daily. Always take them with food.

Recommended dose
Generally, treatment will start with 500 mg of IZUMIS daily. Approximately 2 weeks after starting treatment, your doctor may check your blood sugar levels and adjust the dose accordingly. The maximum daily dose is 2000 mg of IZUMIS.
If you have reduced kidney function, your doctor may prescribe a lower dose.

If you take more IZUMIS than you should
If you accidentally take extra tablets, there is usually no cause for concern. However, if you experience unusual symptoms, contact your doctor. In the case of a significant overdose, lactic acidosis is more likely to occur. Symptoms of lactic acidosis are non-specific and may include vomiting, abdominal pain with muscle cramps, a general feeling of being unwell with severe fatigue and difficulty breathing. Other symptoms may include lowered body temperature and slowed heart rate. If you experience any of these symptoms, seek immediate medical attention, as lactic acidosis can lead to coma. Immediately stop taking IZUMIS and contact a doctor or the nearest emergency department right away.
If you have taken an excessive dose of the medicine, or if a child has accidentally ingested this medicine, contact a doctor, hospital, or Poison Control Centre immediately to assess risks and receive further instructions.

If you forget to take IZUMIS
Take it as soon as you remember, with food. Do not take a double dose to make up for the missed dose.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:
IZUMIS may cause a very rare but serious side effect called lactic acidosis (see section "Warnings and precautions").
If this occurs, you must stop taking IZUMIS and contact a doctor or go immediately to the nearest emergency room,
because lactic acidosis can lead to coma.
IZUMIS may cause abnormalities in liver function tests and hepatitis (inflammation of the liver), which may lead to jaundice.
If you develop yellowing of the eyes and/or skin, contact your doctor immediately.
Other possible side effects are listed below according to their frequency:

Very common (may affect more than 1 in 10 people)
diarrhoea, nausea, vomiting, stomach pain or loss of appetite. If these symptoms occur, do not stop taking the tablets,
as they usually disappear within about 2 weeks. Taking the tablets with a meal or immediately after a meal may help.

Common (may affect more than 1 in 100 people)

• altered taste
• reduced vitamin B12 levels

Very rare (may affect up to 1 in 10,000 people)

• Skin rashes including redness, itching and urticaria

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://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 IZUMIS

Keep this medicine out of the sight and reach of children.
No special storage conditions are required for this medicine.
Do not use this medicine after the expiry date stated on the blister and packaging following "Exp.".
The expiry date refers to the last day of that month.
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. Contents of the pack and other information

What IZUMIS contains
What IZUMIS 500 mg prolonged-release tablets contain

• The active substance is metformin hydrochloride. Each prolonged-release tablet contains 500 mg of metformin hydrochloride (equivalent to 390 mg of metformin base).
• The other components are: sodium carmellose, hypromellose 100,000 cP, hypromellose 5 cP, microcrystalline cellulose, magnesium stearate.

What IZUMIS 750 mg prolonged-release tablets contain

• The active substance is metformin hydrochloride. Each prolonged-release tablet contains 750 mg of metformin hydrochloride (equivalent to 585 mg of metformin base).
• The other components are: sodium carmellose, hypromellose 100,000 cP, magnesium stearate.

What IZUMIS 1000 mg prolonged-release tablets contain

• The active substance is metformin hydrochloride. Each prolonged-release tablet contains 1000 mg of metformin hydrochloride (equivalent to 780 mg of metformin base).
• The other components are: sodium carmellose, hypromellose 100,000 cP, magnesium stearate.

Description of the appearance of IZUMIS and contents of the pack
The 500 mg prolonged-release tablets are white to off-white tablets, approximately 19 x 9.2 mm, capsule-shaped, uncoated, with the number '500' engraved on one side and smooth on the other side.
The 750 mg prolonged-release tablets are white to off-white tablets, approximately 19 x 9.2 mm, capsule-shaped, uncoated, with the number '750' engraved on one side and smooth on the other side.
The 1000 mg prolonged-release tablets are white to off-white tablets, approximately 22 x 10.5 mm, capsule-shaped, uncoated, with the number '1000' engraved on one side and smooth on the other side.

Marketing Authorisation Holder
Farmaceutici Caber S.r.l. - Via del Mare, 36 – Pomezia (RM) – Italy
Manufacturer
Savio Industrial S.r.l., Via Emilia, 21 – Pavia
This medicinal product is authorised in the European Economic Area Member States under the following names:
Estonia: PREMET
Poland: IRUKA
Italy: IZUMIS