diabetes

Vokanamet - canagliflozin and metformin

What is Vokanamet - canagliflozin and metformin used for?

Vokanamet is a medicine that contains the active substances canagliflozin and metformin . It is indicated, in addition to diet and exercise, to control blood glucose (sugar) levels in adult patients with type 2 diabetes mellitus inadequately controlled with metformin taken alone; it is also indicated in combination with other antidiabetic medicines, including insulin, when these medicines, in combination with metformin, do not provide adequate diabetes control. Vokanamet can also be used as a replacement for canagliflozin and metformin taken separately.

How is Vokanamet used - canagliflozin and metformin?

Vokanamet is available as tablets containing canagliflozin and metformin in various strengths (50/850 mg, 150/850 mg, 50/1000 mg and 150/1000 mg) and can only be obtained with a prescription. The recommended dose is one tablet twice a day. The dosage of the tablet depends on the therapy followed by the patient before starting treatment with Vokanamet. The starting dose of Vokanamet should provide canagliflozin at a dose of 50 mg and the dose of metformin already taken (or closer to that therapeutically appropriate). The canagliflozin dose can subsequently be increased as needed.

When Vokanamet is used as an add-on to insulin or to medicines that promote insulin production (for example, sulfonylureas), it may be necessary to reduce the dose of these medicines to decrease the risk of the patient's blood sugar lowering too much. For more information, see the package leaflet.

How does Vokanamet - canagliflozin and metformin work?

Type 2 diabetes is a disease in which the pancreas does not produce enough insulin to control the level of glucose in the blood or where the body is unable to use insulin effectively, which leads to increased levels of glucose in the blood. Vokanamet contains two different active ingredients, each with a different mechanism of action:

  • canagliflozin works by blocking a protein in the kidneys, called sodium-glucose cotransport type 2 (SGLT2). SGLT2 is a protein responsible for the reabsorption of glucose into the bloodstream (bloodstream), when the blood is filtered through the kidneys. By blocking the action of SGLT2, canagliflozin induces the elimination of more glucose through the urine and, consequently, the reduction of the concentration of glucose in the blood. Canagliflozin in the form of separate tablets is authorized in the EU under the trade name Invokana from 15 November 2013.
  • Metformin acts mainly by inhibiting the production of glucose and reducing its absorption in the intestine. It has been available in the EU since the 1950s.

Thanks to the combined action of the two active ingredients, the rate of glucose in the blood is reduced and this serves to control type 2 diabetes.

What benefit has Vokanamet - canagliflozin and metformin shown during the studies?

The benefits of canagliflozin used in combination with metformin have emerged from several major studies, which were evaluated at the time of Invokana's authorization. The studies, which were attended by over 5, 000 adults with type 2 diabetes, analyzed the effects of canagliflozin taken at daily doses of 100 and 300 mg, examining in particular the mechanism of reduction of the blood level of a substance called glycosylated hemoglobin (HbA1c ), which gives an indication of the effectiveness of glucose control. Within two studies evaluating the efficacy of canagliflozin as an adjunctive therapy to metformin, the reduction in HbA1c levels after 26 weeks was greater than 0.91-1.16% compared to placebo (a dummy treatment) when canagliflozin was added to metformin; canagliflozin also induced reductions similar to those of two other antidiabetic medicines, glimepiride and sitagliptin, after 52 weeks of treatment. Three further studies examined canagliflozin used as an adjunctive therapy to a combination treatment with metformin and a sulphonylurea or pioglitazone. Added to metformin and a sulphonylurea, canagliflozin induced reductions in HbA1c levels higher than 0.71-0.92% compared to the reductions observed with placebo after 26 weeks of treatment and reductions similar to those seen with sitagliptin (another diabetic medicine) after 52 weeks. Added to metformin and pioglitazone, canagliflozin was superior to placebo, as it led to reductions in HbA1c levels higher than 0.62-0.76% compared to what was observed with the addition of placebo. Canagliflozin has also been studied as an adjunctive therapy in patients taking only insulin, or insulin in combination with other antidiabetic medicines, including metformin, and in patients taking a sulphonylurea. The addition of canagliflozin to therapy was effective compared to placebo in reducing HbA1c levels by 0.65-0.73% after 18 weeks of therapy in insulin-treated patients and 0.74-0.83% of patients treated with a sulphonylurea.

What is the risk associated with Vokanamet - canagliflozin and metformin?

The most common side effects with Vokanamet (which may affect more than 1 in 10 people) are hypoglycaemia (low blood glucose concentration), if the medicine is used in combination with insulin or a sulphonylurea, and vulvovaginal candidiasis (a fungal infection female genital area caused by Candida). Vokanamet should not be administered to:

  • patients with diabetic ketoacidosis or diabetic precoma (serious complications of diabetes);
  • patients with moderate or severe renal impairment or with acute conditions with potential renal impairment such as dehydration or severe infection;
  • patients with a condition that could deprive tissues of oxygen (for example, heart or respiratory failure);
  • patients suffering from hepatic impairment or suffering from alcoholism or alcohol intoxication.

For the full list of limitations, see the package leaflet.

Why has Vokanamet - canagliflozin and metformin been approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Vokanamet's benefits are greater than its risks and recommended that it be approved for use in the EU. The benefits of metformin are sufficiently demonstrated and studies have shown the added benefit of adding canagliflozin to metformin for blood glucose control. Metformin also induces weight loss, which is considered an advantage in diabetic patients. The CHMP also noted that administering the combination of canagliflozin and metformin in a single tablet could be an additional therapeutic option for subjects with type 2 diabetes and improve adherence to therapy.

Regarding safety, the CHMP is of the opinion that the side effects observed with Vokanamet are acceptable and manageable in clinical practice.

What measures are being taken to ensure the safe and effective use of Vokanamet - canagliflozin and metformin?

A risk management plan has been developed to ensure that Vokanamet is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Vokanamet, including the appropriate precautions to be followed by healthcare professionals and patients.

Further information is available in the summary of the risk management plan.

Other information on Vokanamet - canagliflozin and metformin

On 23 April 2014, the European Commission issued a marketing authorization for Vokanamet, valid throughout the European Union. For more information about treatment with Vokanamet, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist. Last update of this summary: 05-2014