Synjardy - Empagliflozin/metformin hydrochloride uses, dose and side effects

Synjardy contains two active substances, empagliflozin, and metformin. Both belong to a group of medicines called “oral diabetes medicines”. These are medicines taken by mouth to treat type 2 diabetes.

What is type 2 diabetes?

Type 2‑ diabetes is a disease caused by both genes and lifestyle. If you have type 2 diabetes, your pancreas does not produce enough insulin to control blood glucose levels, and the body is unable to use its insulin effectively. This produces high levels of glucose in the blood that can lead to medical problems such as heart disease, kidney disease, blindness, and poor circulation in the arms and legs.

How Synjardy works

Empagliflozin belongs to a group of medicines called sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors). It works by blocking the protein SGLT2 in the kidneys. This causes blood sugar ( glucose ) to be removed via the urine. Metformin works in a different way to lower blood sugar levels, mainly by blocking the formation of glucose in the liver.

In this way, Synjardy reduces the amount of sugar in the blood. This drug may also help prevent heart disease.

What Synjardy is used for

Synjardy is used as an adjunct to diet and exercise to treat type 2 diabetes in adult patients (18 years or older) if diabetes cannot be controlled by adding metformin alone or metformin together with other diabetes medicines.
Synjardy can also be combined with other medicines for the treatment of diabetes. It can be medicines that are taken orally or that are given as an injection, such as insulin.
In addition, Synjardy can be used as an alternative to taking both empagliflozin and metformin as separate tablets. To avoid overdose, you mustn’t continue to take separate tablets of empagliflozin and metformin while taking this medicine.

You must continue with the diet and exercise programs recommended by your doctor, pharmacist, or nurse.

What you need to know before you take Synjardy

Do not use Synjardy:

if you are allergic to empagliflozin, metformin, or any of the other ingredients of this medicine (listed in section 6).
if you have uncontrolled diabetes with, for example, severe hyperglycemia (high blood sugar), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see “Risk of lactic acidosis” below), or ketoacidosis. Ketoacidosis is a condition where substances called ketone bodies to accumulate in the blood, which can lead to diabetic precoma. Symptoms include stomach ache, fast and deep breathing, sleepiness, or your breath having a different, fruity smell.
if you have ever had a diabetic coma ( ketoacidosis ).
if you have severe kidney problems. Your doctor may limit your daily dose or ask you to take another medicine (see also section 3, “How to take Synjardy”).
if you have a severe infection such as an infection in the lung or bronchi or kidney. Severe infections can cause kidney problems, which can put you at risk of lactic acidosis (see “Warnings and precautions”).
if you have lost a lot of water (dehydration), e.g. due to prolonged or severe diarrhea, or if you have vomited several times in a row. Dehydration can cause kidney problems, which can put you at risk of lactic acidosis (see “Warnings and precautions”).
if you are being treated for acute heart failure or have recently had a heart attack, have serious problems with blood circulation, (such as shock ), or have difficulty breathing. This can lead to a lack of oxygen supply to the tissues, and it can increase the risk of lactic acidosis (see section “Warnings and precautions”).
if you have liver problems.
if you drink large amounts of alcohol, either every day or only periodically (see the section “Synjardy with alcohol”).

Warnings and precautions

Risk of lactic acidosis

Synjardy can cause the very rare, but very serious side effect of lactic acidosis, especially if your kidneys are not working properly. The risk of developing lactic acidosis is also increased in uncontrolled diabetes, severe infection, prolonged fasting or alcohol intake, dehydration (see more information below), liver problems, and conditions were a part of the body has reduced oxygen supply (including acute severe heart disease).

If any of the above apply to you, talk to your doctor for more detailed instructions.

Stop taking Synjardy for a short time if you have a condition that may be associated with dehydration (extensive loss of body fluids) such as severe vomiting, diarrhea, fever, exposure to heat, or if you drink less fluid than normal. Talk to your doctor for more detailed instructions.

Stop taking Synjardy and contact your doctor or nearest hospital immediately if you experience any of the symptoms of lactic acidosis as the condition can lead to coma.

The symptoms of lactic acidosis include:

vomiting
abdominal pain (stomach)
muscle cramps
a general feeling of not feeling well and pronounced fatigue
hard to breathe
lowered body temperature and pulse.

Lactatacy dose is an emergency medical condition that must be treated in a hospital.

Talk to your doctor, pharmacist, or nurse before taking this medicine and during treatment:

if you experience rapid weight loss, nausea or vomiting, stomach pain, severe thirst, rapid and deep breathing, confusion, unusual sleepiness or tiredness, a sweet breath, sweet or metallic taste in the mouth, or a different smell of urine or sweat, contact your doctor or nearest hospital immediately. These symptoms may be a sign of “diabetic ketoacidosis” – a rare but serious, sometimes life-threatening, problem you can get with diabetes, due to elevated levels of “ketone bodies” in the urine or blood. This shows in tests. The risk of developing diabetic ketoacidosis may increase with prolonged fasting, high alcohol consumption, dehydration, a sudden reduction in the insulin dose, or a greater need for insulin due to major surgery or a serious illness.
if you have type 1 diabetes – this type usually starts in youth and causes the body not to produce any insulin. Synjardy should not be used for the treatment of patients with type 1 diabetes.
if you may be at risk of dehydration, for example:
- if you are vomiting, have diarrhea or fever, or if you cannot eat or drink
- if you take medicines that increase urine production [diuretics] or lower blood pressure, etc
- if you are over 75 years old. Possible signs are listed in section 4 under “dehydration”. Your doctor may instruct you to stop taking Synjardy until you have recovered to prevent you from losing too much body fluid. Ask what you can do to avoid dehydration.
if you are 85 years of age or older, you should not start taking Synjardy due to limited experience with treatment.
if you have a serious infection of the kidneys or urinary tract along with a fever. Your doctor may ask you to stop taking Synjardy until you have recovered.
If you have to undergo an examination with an iodinated contrast medium (eg X-ray examination or diagnostic imaging). More information can be found below under “Other medicines and Synjardy”.

Talk to your doctor straight away if you experience a combination of symptoms such as pain, tenderness, redness, or swelling of the genitals or the area between the genitals and the rectum along with a fever or feeling generally unwell. These symptoms may be a sign of a rare but serious or even life-threatening infection called necrotizing fasciitis of the perineum or Fournier’s gangrene which destroys the tissue under the skin. Fournier’s gangrene must be treated immediately.

Surgery

If you are going to have a major operation, you must stop taking Synjardy during the operation and for a certain time after it. Your doctor will decide when you must stop taking Synjardy and when you should start taking it again.

Kidney function

During treatment with Synjardy, your doctor will check your kidney function at least once a year, or more often if you are older and/or if your kidney function is deteriorating.

Chiropody

For all patients with diabetes, it is important to check their feet regularly and follow any other foot care advice given by healthcare professionals.

Urine glucose

Urine tests will test positive for sugar while you are taking this medicine, because of how this medicine works.

Children and young people

The drug is not recommended for use in children and adolescents under 18 years of age, as it has not been studied in these patients.

Other medicines and Synjardy

If you need to receive an injection into the blood with a contrast agent containing iodine, for example in connection with an X-ray or CT scan, you must stop taking Synjardy before or at the time of the injection. Your doctor will decide when you must stop taking Synjardy and when you should start taking it again.

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

You may need to have more blood sugar and kidney function tests, or your doctor may need to adjust the dose of Synjardy. You must mention the following:

medicines that increase urine production ( diuretics ), such as Synjardy can increase the risk of losing too much fluid. Your doctor may ask you to stop taking Synjardy. Possible signs of losing too much fluid are listed in section 4.
other medicines that lower the amount of sugar in the blood, for example, insulin or a ‘sulphonylurea’ medicine. Your doctor may want to lower the dose of one of these other medicines, to prevent your blood sugar levels from getting too low (hypoglycemia).
medicines that can change the amount of metformin in the blood, especially if you have impaired kidney function (eg verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).
bronchodilators (beta-2 agonists ) are used in the treatment of asthma.
corticosteroids are used to treat inflammation in diseases such as asthma and arthritis. They can be taken by mouth, as an injection, or with an inhaler.
medicines used to treat pain and inflammation ( NSAIDs and COX 2 inhibitors, such as ibuprofen and celecoxib)
certain medicines for the treatment of high blood pressure ( ACE inhibitors and angiotensin II receptor antagonists)
medicines that contain alcohol (see the section “Synjardy with alcohol”).
iodinated contrast agents (medicines used in X-ray examinations; see section “Warnings and precautions”).
if you are taking lithium because Synjardy can reduce the amount of lithium in your blood.

Synjardy with alcohol

Avoid heavy alcohol intake while taking Synjardy as alcohol may increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Do not use Synjardy if you are pregnant. It is unknown whether the drug is harmful to the unborn child.

Metformin is excreted in breast milk in small amounts. It is unknown whether empagliflozin is excreted in human milk. Do not use Synjardy if you are breastfeeding.

Driving ability and use of machinery

Synjardy has little effect on the ability to drive and use machines.

Taking this medicine in combination with medicines called sulphonylureas or together with insulin can cause too much drop in blood sugar (hypoglycemia), it can cause symptoms such as tremors, sweating, and vision changes, and can affect your ability to drive and use machines. Do not drive vehicles or use tools or machines if you feel dizzy while taking Synjardy.

How to take Synjardy

Always take this medicine as directed by your doctor. Ask your doctor or pharmacist if you are unsure.

How much to take

The dose of Synjardy varies depending on your health and the dose of the diabetes medicines you are currently taking. Your doctor adjusts the dose if necessary and tells you exactly what strength of the medicine you should take.

The recommended dose is one tablet twice a day. Your doctor will usually start Synjardy treatment by prescribing the tablet strength that gives you the same dose of metformin you are already taking (850 mg or 1000 mg twice daily), and the lowest dose of empagliflozin (5 mg twice daily ). If you are already taking both medicines separately, your doctor will start you on a course of Synjardy tablets that will give you the same amount of both medicines.

If you have impaired kidney function, the doctor may prescribe a lower dose or decide to use another medicine.

Ingestion of this medicine

Swallow the tablet whole with water.
Take the tablets with a meal to reduce the risk of stomach upset.
Take one tablet twice daily by mouth.

Your doctor may prescribe Synjardy together with another diabetes medicine. Remember to take all medications as directed by your doctor to achieve the best possible results for your health. Your doctor may need to adjust the doses to get your blood sugar under control.

Appropriate diet and exercise help your body make better use of blood sugar. It is important to continue with the diet and exercise program recommended by the doctor during the time you are taking Synjardy.

If you have taken too much Synjardy

If you have taken too many tablets of Synjardy, you may get lactic acidosis. The symptoms of lactic acidosis are non-specific such as severe nausea, vomiting, stomach pain with muscle cramps, general malaise with severe fatigue, and breathing difficulties. Additional symptoms are lowered body temperature and heart rate.

If you get such symptoms, you may need immediate hospital care, as lactic acidosis can lead to coma. Stop taking Synjardy immediately and contact a doctor immediately or go to the nearest hospital (see section 2). Take the medicine package with you.

If you forget to take Synjardy

If you forget to take a dose, take it as soon as you remember. If you do not remember until it is time for the next dose, skip the missed dose and continue according to your regular schedule. Do not take a double dose of this medicine.

If you stop taking Synjardy

Do not stop taking Synjardy without discussing this with your doctor. Your blood sugar levels may rise when you stop using Synjardy.

If you have any further questions about this medicine, ask your doctor, pharmacist, or nurse.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact a doctor or the nearest hospital immediately if you experience any of the following side effects:

Serious allergic reactions have been reported uncommonly (may affect up to 1 in 100 users)

Possible signs of a serious allergic reaction may include:

swelling of the face, lips, mouth, tongue, or throat and may lead to difficulty breathing or swallowing.

Lactic acidosis is very rare (may affect up to 1 user in 10,000). Synjardy can cause the very rare, but very serious side effect of lactic acidosis (see section 2). If this happens to you, you must stop taking Synjardy and immediately contact a doctor or the nearest hospital, as lactic acidosis can lead to coma.

Diabetic ketoacidosis is rare (may affect up to 1 in 1,000 people)

These are the signs of diabetic ketoacidosis (see section 2):

increased levels of “ketone bodies” in urine or blood
rapid weight loss
nausea or vomiting
stomach pain
severe thirst
rapid and deep breathing
confusion
unusual sleepiness or tiredness
a sweet smell on the breath, a sweet or metallic taste in the mouth, or a different smell of urine or sweat

This can occur regardless of blood sugar levels. Your doctor may decide to temporarily or permanently stop treatment with Synjardy.

Contact your doctor as soon as possible if you notice any of the following side effects:

Low blood sugar (hypoglycemia), is very common (may affect more than 1 in 10 people)

If you take Synjardy together with another medicine that can cause low blood sugar, such as sulphonylurea or insulin, the risk of getting low blood sugar is higher. Signs of low blood sugar may include:

shaking, sweating, feeling very anxious or confused, fast heartbeat
excessive hunger, headache

Your doctor will tell you how to treat low blood sugar levels and what to do if you get any of the signs above. If you have symptoms of low blood sugar, eat dextrose tablets, a sugary snack, or drink fruit juice. If possible, measure your blood sugar and rest.

Urinary tract infections are common (may affect up to 1 in 10 people)

Signs of a urinary tract infection are:

a burning sensation when urinating
cloudy urine
pain in the pelvis, or middle of the back (when the kidneys are infected)

Urinary urgency or the need to urinate more often may be due to the way Synjardy works, but may also be a sign of a urinary tract infection. If you notice an increase in these symptoms, contact your doctor.

Dehydration is uncommon (may affect up to 1 in 100 people)

Signs of dehydration are not specific, but may include:

unusual thirst
dizziness or lightheadedness when standing up
fainting or fainting

Other side effects when taking Synjardy:

Very common

nausea, vomiting
diarrhea or stomach pain
loss of appetite

Usual

fungal infection around the genitals
a larger amount of urine than usual or having to urinate more often
itching
skin rash or redness – these may itch and include raised bumps, blisters, or be oozing
changes in the sense of taste
thirst
blood tests may show an increase in blood fat values ( cholesterol )
constipation

Less common

hives
straining or pain when emptying the bladder
blood tests may show a deterioration of kidney function ( creatinine or urea )
blood tests may show increases in the number of red blood cells in the blood ( hematocrit )

Rare

necrotizing fasciitis of the perineum or Fournier’s gangrene, a serious soft tissue infection of the genitals or the area between the genitals and the rectum

Very rare

reduced level of vitamin B12 in the blood
abnormal liver function tests, inflammation of the liver ( hepatitis )
skin redness ( erythema )
inflammation of the kidneys (tubulointerstitial nephritis)

How to store Synjardy

Keep this medicine out of the sight and reach of children.

Use before the expiry date which is stated on the carton and blister card after EXP. The expiration date is the last day of the specified month.

No special storage instructions.

Do not use this medicine if the package is damaged or shows signs of having been previously opened.

Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.

Contents of the packaging and other information

Contents declaration

The active substances are empagliflozin and metformin.

Each Synjardy 5 mg/850 mg film-coated tablet (tablet) contains 5 mg empagliflozin and 850 mg metformin hydrochloride.

Each Synjardy 5 mg/1000 mg film-coated tablet (tablet) contains 5 mg of empagliflozin and 1000 mg of metformin hydrochloride.

Each Synjardy 12.5 mg/850 mg film-coated tablet (tablet) contains 12.5 mg empagliflozin and 850 mg metformin hydrochloride.

Each Synjardy 12.5 mg/1000 mg film-coated tablet (tablet) contains 12.5 mg empagliflozin and 1000 mg metformin hydrochloride.

Other ingredients are:

Tablet core: corn starch, copovidone, colloidal anhydrous silica, magnesium stearate.
Film coating : hypromellose, macrogol 400, titanium dioxide (E171), talc.Synjardy 5 mg/850 mg and Synjardy 5 mg/1000 mg tablets also contain yellow iron oxide (E172). Synjardy 12.5 mg/850 mg and Synjardy 12.5 mg/1000 mg tablets also contain black iron oxide (E172) and red iron oxide (E172).

Appearance and package sizes of the medicine

Synjardy 5 mg/850 mg film-coated tablets are yellow-white, oval, and biconvex. They have “S5” and the Boehringer Ingelheim logo on one side and “850” on the other side. The tablet is 19.2 mm long and has a width of 9.4 mm.

Synjardy 5 mg/1000 mg film-coated tablets are brown-yellow, oval, and biconvex. They have “S5” and the Boehringer Ingelheim logo on one side and “1000” on the other side. The tablet is 21.1 mm long and has a width of 9.7 mm.

Synjardy 12.5 mg/850 mg film-coated tablets are pinkish white, oval, and biconvex. They have “S12” and the Boehringer Ingelheim logo on one side and “850” on the other side. The tablet is 19.2 mm long and has a width of 9.4 mm.

Synjardy 12.5 mg/1000 mg film-coated tablets are dark brown-purple, oval, and biconvex. They have “S12” and the Boehringer Ingelheim logo on one side and “1000” on the other side. The tablet is 21.1 mm long and has a width of 9.7 mm.

The tablets are available in PVC/aluminum perforated single-dose blisters. Pack sizes are 10 x 1, 14 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1 and 100 x 1 film-coated tablets and multipacks of 120 (2 packs of 60 x 1), 180 (2 packs of 90 x 1) and 200 (2 packs of 100 x 1) film-coated tablets.

Not all pack sizes may be marketed in your country.

Marketing Authorisation Holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Boehringer Ingelheim Hellas Single Member SA

5th km Paiania – Markopoulo

Koropi Attiki, 19441

Greece

Patheon France

40 boulevard de Champaret

Bourgoin Jallieu, 38300

France

Boehringer Ingelheim France

100-104 Avenue de France

75013 Paris