Velmetia 50 mg/1,000 mg film-coated tablets

 

What is it and how is it used?

The name of your tablet is Velmetia. It 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.

They work together to control blood sugar levels in patients with a form of diabetes called ‘type 2 diabetes mellitus’. Velmetia helps to improve the levels of insulin after a meal and lowers the amount of sugar made by your body.

Along with diet and exercise, this medicine helps lower your blood sugar. Velmetia can be used alone or with certain other medicines for diabetes (insulin, sulphonylureas, or glitazones).

What is type 2 diabetes?

Type 2 diabetes is also called non-insulin-dependent diabetes mellitus, or NIDDM. Type 2 diabetes is a condition in which your body does not make enough insulin, and the insulin that your body produces does not work as well as it should. Your body can also make too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems like heart disease, kidney disease, blindness, and amputation.

What do you have to consider before using it?

Do not take Velmetia:

  • if you are allergic (hypersensitive) to sitagliptin or metformin or any of the other ingredients of Velmetia (listed in section 6)
  • if you have diabetic ketoacidosis (a complication of diabetes with rapid weight loss, nausea or vomiting) or have had a diabetic coma
  • if you have problems with your kidneys
  • if you have a severe infection or are dehydrated
  • if you are going to have an X-ray where you will be injected with a dye. You will need to stop taking Velmetia at the time of the X-ray and for a few days after
  • if you have recently had a heart attack or have severe circulatory problems, such as ‘shock’ or breathing difficulties
  • if you have liver problems
  • if you drink alcohol to excess (either every day or only from time to time)
  • if you are breast-feeding

Do not take Velmetia if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Velmetia.

Take special care with Velmetia
Cases of inflammation of the pancreas (pancreatitis) have been reported in patients receiving Velmetia. Pancreatitis can be a serious, potentially life-threatening medical condition. Stop taking Velmetia and call your doctor if you experience severe and persistent stomach pain, with or without vomiting, because you could have pancreatitis.

Check with your doctor or pharmacist before taking your medicine:

  • if you have or had pancreatitis, gallstones, alcoholism or very high triglycerides. These medical conditions can increase your chance of getting pancreatitis, or getting it again.
  • if you have type 1 diabetes. This is sometimes called insulin-dependent diabetes
  • if you experience some of the following symptoms: feeling cold or uncomfortable, severe nausea or vomiting, abdominal pain, unexplained weight loss, muscular cramps, or rapid breathing. Metformin hydrochloride, one of theingredients in Velmetia, can cause a rare but serious side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital. If you experience some of the symptoms of lactic acidosis stop taking Velmetia and consult a doctor immediately
  • During treatment with Velmetia, your doctor will check your kidney function at least once a year and more frequently if you are elderly or if your kidney function is borderline or at risk of worsening
  • if you have or have had an allergic reaction to sitagliptin, metformin, or Velmetia
  • if you are taking a sulphonylurea or insulin, diabetes medicines, together with Velmetia, as you may experience low blood sugar levels (hypoglycaemia). Your doctor may reduce the dose of your sulphonylurea or insulin
  • if you are going to have an operation undergeneral, spinal or epidural anaesthetic. You may need to stop taking Velmetia for a couple of days before and after the procedure
  • if you are under 18 years of age

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Velmetia.

Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, including herbal medicines.

The following medicines are particularly important:

  • medicines used to treat diseases that involve inflammation, like asthma and arthritis (corticosteroids)
  • specific medicines for the treatment of high blood pressure (ACE inhibitors)
  • medicines which increase urine production (diuretics)
  • specific medicines for the treatment of bronchial asthma (β-sympathomimetics)
  • iodinated contrast agents or alcohol-containing medicines.

Taking Velmetia with food and drink
Take Velmetia with meals to lower your chance of an upset stomach.

Pregnancy and breast-feeding
Women who are pregnant or plan to become pregnant should talk to their doctor before taking Velmetia. You should not use Velmetia during pregnancy.

Metformin passes into human milk in small amounts. It is not known whether sitagliptin passes into human milk. It is not known if Velmetia passes into human breast milk. You must not use Velmetia if you are breast-feeding or plan to breast-feed.

Driving and using machines
Velmetia has no known influence on the ability to drive and use machines. However, when driving or operating machinery, it should be taken into account that dizziness and drowsiness have been reported with sitagliptin.

Taking Velmetia in combination with medicines called sulphonylureas or with insulin can cause hypoglycaemia, which may affect your ability to drive and use machines or work without safe foothold.

How is it used?

Always take Velmetia exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

  • Velmetia should be taken:
  • twice daily by mouth
  • with meals to lower your chance of an upset stomach.
  • Your doctor may need to increase your dose to control your blood sugar.
  • Continue to take Velmetia as long as your doctor prescribes it so you can continue to help control your blood sugar.

You should continue your diet during treatment with Velmetia and take care that your carbohydrate intake is equally distributed over the day. If you are overweight continue your energy-restricted diet as instructed.

Velmetia alone is unlikely to cause abnormally low blood sugar (hypoglycaemia). When Velmetia is used with a sulphonylurea medicine or with insulin, low blood sugar can occur and your doctor may reduce the dose of your sulphonylurea or insulin.

Sometimes you may need to stop taking your medicine for a short time. Talk to your doctor for instructions if you:

  • have a condition that may be associated with dehydration (large loss of body fluids) such as being sick with severe vomiting, diarrhoea or fever, or if you drink fluids a lot less than normal
  • plan to have surgery
  • are due to get an injection of dye or contrast agent as part of an X-ray

If you take more Velmetia than you should
If you take more than the prescribed dosage of Velmetia, contact your doctor immediately.

If you forget to take Velmetia
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 go back to your regular schedule. Do not take a double dose of Velmetia.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

What are possible side effects?

Like all medicines, Velmetia may cause side effects, although not everybody gets them.

Very rarely patients taking metformin (one of the active substances of Velmetia) have experienced a serious condition called lactic acidosis (too much lactic acid in your blood). This is more common in people whose kidneys are not working properly. Stop taking Velmetia and see a doctor straight away if you notice any of the following symptoms:

  • feeling sick (nausea) or being sick (vomiting), abdominal pain, muscular cramps, unexplained weight loss, rapid breathing, and feeling cold or uncomfortable.

Very common side effects (likely to occur in more than 1 per 10 patients).
Common side effects (likely to occur in less than 1 per 10 but more than 1 per 100 patients). Uncommon side effects (likely to occur in less than 1 per 100 but more than 1 per 1,000 patients). Rare side effects (likely to occur in less than 1 per 1,000 but more than 1 per 10,000). Very rare side effects (likely to occur in less than 1 per 10,000).

Some patients taking metformin have experienced the following side effects after starting sitagliptin: Common: nausea
Uncommon: weight loss, loss of appetite, abdominal pain, diarrhoea, low blood sugar, drowsiness

Some patients have experienced stomach discomfort when starting the combination of sitagliptin and metformin together.

Some patients have experienced the following side effects while taking Velmetia with a sulphonylurea:
Very common: low blood sugar
Common: constipation

Some patients have experienced the following side effects while taking Velmetia in combination with rosiglitazone:
Common: headache, cough, diarrhoea, vomiting, low blood sugar, fungal skin infection, upper respiratory infection, swelling of the hands or legs.

Some patients have experienced the following side effects while taking Velmetia in combination with insulin:
Very common: low blood sugar
Uncommon: dry mouth, headache

Some patients have experienced the following side effects while taking sitagliptin alone: Common: low blood sugar, headache
Uncommon: dizziness, constipation

In addition, some patients have reported the following side effects while taking sitagliptin: Common: upper respiratory infection, stuffy or runny nose and sore throat, osteoarthritis, arm or leg pain.

During post-approval use with Velmetia or sitagliptin, one of the medicines in Velmetia, additional side effects have also been reported (frequency not known). These side effects have been reported when Velmetia or sitagliptin have been used alone and/or as part of combination therapy: allergic reactions, which may be serious, including rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing. If you have an allergic reaction, stop taking Velmetia and call your doctor right away. Your doctor may prescribe a medicine to treat your allergic reaction and a different medicine for your diabetes. Other side effects that have been reported include: inflammation of the pancreas; kidney problems (sometimes requiring dialysis); vomiting.

Some patients have experienced the following side effects while taking metformin alone: Very common: nausea, vomiting, diarrhoea, abdominal pain and loss of appetite
Common: a metallic taste
Very rare: decreased vitamin B12 levels, hepatitis (a problem with your liver), redness of the skin (rash) or itching, lactic acidosis (excess of lactic acid in your blood) particularly in patients whose kidneys are not working properly. The symptoms include feeling cold or uncomfortable, severe nausea or vomiting, abdominal pain, unexplained weight loss, or rapid breathing

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How should it be stored?

Keep out of the reach and sight of children.

Do not use Velmetia after the expiry date which is stated on the blister and the carton. The expiry date refers to the last day of the month.

Do not store above 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What is it?

Velmetia is a medicine that contains two active substances, sitagliptin and metformin hydrochloride. It is available as capsule-shaped tablets (pink: 50 mg sitagliptin and 850 mg metformin hydrochloride; red: 50 mg sitagliptin and 1,000 mg metformin hydrochloride).

What is it used for?

Velmetia is used in patients with type 2 diabetes to improve the control of blood glucose (sugar) levels. It is used in addition to diet and exercise in the following ways:

  • in patients who are not satisfactorily controlled on metformin (an antidiabetes medicine) used on its own;
  • in patients who are already taking a combination of sitagliptin and metformin as separate tablets;
  • in combination with a sulphonylurea, a PPAR-gamma agonist such as a thiazolidinedione, or insulin (other types of antidiabetes medicine) in patients who are not satisfactorily controlled on this medicine and metformin. The medicine can only be obtained with a prescription.

How is it used?

Velmetia is taken twice a day. The strength of tablet to use depends on the dose of the other antidiabetes medicines that the patient was taking before. If Velmetia is taken with a sulphonylurea or insulin, the dose of the sulphonylurea or insulin may need to be lowered, to avoid hypoglycaemia (low blood sugar levels).
The maximum dose of sitagliptin is 100 mg a day. Velmetia should be taken with food to avoid any stomach problems caused by metformin.

How does it work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. The active substances in Velmetia, sitagliptin and metformin hydrochloride, each have a different mode of action. Sitagliptin is a dipeptidyl-peptidase-4 (DPP-4) inhibitor. It works by blocking the breakdown of ‘incretin’ hormones in the body. These hormones are released after a meal and stimulate the pancreas to produce insulin. By increasing the levels of incretin hormones in the blood, sitagliptin stimulates the pancreas to produce more insulin when blood glucose levels are high. Sitagliptin does not work when the blood glucose is low. Sitagliptin also reduces the amount of glucose made by the liver, by increasing insulin levels and decreasing the levels of the hormone glucagon. Sitagliptin has been authorised in the European Union (EU) as Januvia and Xelevia since 2007, and as Tesavel since 2008. Metformin works mainly by inhibiting glucose production and reducing its absorption in the gut. Metformin has been available in the EU since the 1950s.
As a result of the action of both active substances, blood glucose levels are reduced and this helps to control type 2 diabetes.

How has it been studied?

Sitagliptin on its own as Januvia/Xelevia/Tesavel can be used with metformin, and with both metformin and a sulphonylurea, in type 2 diabetes patients. The company presented the results of three studies of Januvia/Xelevia to support the use of Velmetia in patients who were not satisfactorily controlled on their existing metformin treatment.
Two of the studies looked at sitagliptin as an add-on to metformin: the first compared it with placebo (a dummy treatment) in 701 patients, and the second compared it with glipizide (a sulphonylurea) in 1,172 patients. The third study compared sitagliptin with placebo, when used as an add-on to glimepiride (another sulphonylurea), with or without metformin, in 441 patients.
The results of three further studies were used to support the use of Velmetia. The first included 1,091 patients who were not satisfactorily controlled on diet and exercise alone and compared the effect of Velmetia with that of metformin or sitagliptin alone. The second included 278 patients who were not satisfactorily controlled on the combination of metformin and rosiglitazone (a PPAR-gamma agonist) and compared the effects of adding sitagliptin or placebo. The third included 641 patients who were not satisfactorily controlled on a stable dose of insulin, three-quarters of whom were also taking metformin. This study also compared the effects of adding sitagliptin or placebo.
In all of the studies, the main measure of effectiveness was the change in the levels of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.
The company carried out additional studies to show that the active substances in Velmetia are absorbed by the body in the same way as the two medicines given separately.

What benefits has it shown during the studies?

Velmetia was more effective than metformin alone. Adding 100 mg sitagliptin to metformin reduced HbA1c levels by 0.67% (from around 8.0%) after 24 weeks, compared with a fall of 0.02% in the patients adding placebo. The effectiveness of adding sitagliptin to metformin was similar to that of adding glipizide. In the study in which sitagliptin was added to glimepiride and metformin, the levels of HbA1c were reduced by 0.59% after 24 weeks, compared with an increase of 0.30% in the patients adding placebo.
In the first of the three further studies, Velmetia was more effective than metformin or sitagliptin alone. In the second, HbA1c levels were reduced by 1.03% after 18 weeks in patients adding sitagliptin to metformin and rosiglitazone, compared with a fall of 0.31% in those adding placebo. Finally, they were reduced by 0.59% after 24 weeks in patients adding sitagliptin to insulin, compared with a fall of 0.03% in those adding placebo. There was no difference in this effect between the patients also taking metformin and those not taking it.

What is the risk associated?

The most common side effect with Velmetia (seen in between 1 and 10 patients in 100) is nausea (feeling sick). For the full list of all side effects reported with Velmetia, see the Package Leaflet. Velmetia should not be used in people who may be hypersensitive (allergic) to sitagliptin, metformin or any of the other ingredients. It must not be used in patients who have diabetic ketoacidosis or pre-coma (dangerous conditions that can occur in diabetes), problems with the kidneys or liver, conditions that may affect the kidneys, or a disease that causes a reduced supply of oxygen to the tissues such as failure of the heart or lungs or a recent heart attack. It must also not be used in patients who consume excessive amounts of alcohol or who are alcoholic, or in women who are breast-feeding. For the full list of restrictions, see the Package Leaflet.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Velmetia’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Further information

The European Commission granted a marketing authorisation valid throughout the EU for Velmetiato Merck Sharp & Dohme Ltd on 16 July 2008 . The marketing authorisation is valid for five years, after which it can be renewed.