Dafiro

amlodipine / valsartan

This is a summary of the European Public Assessment Report (EPAR). It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the studies performed, to reach their recommendations on how to use the medicine.
If you need more information about your medical condition or your treatment, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information on the basis of the CHMP recommendations, read the Scientific Discussion (also part of the EPAR).

What is Dafiro?

Dafiro is a medicine that contains two active substances, amlodipine and valsartan. It is available as tablets (dark yellow and round: 5 mg amlodipine and 80 mg valsartan; dark yellow and oval: 5 mg amlodipine and 160 mg valsartan; light yellow and oval: 10 mg amlodipine and 160 mg valsartan).

What is Dafiro used for?

Dafiro is used in patients who have essential hypertension (high blood pressure) that is not adequately controlled on either amlodipine or valsartan taken alone. ‘Essential’ means that the hypertension has no obvious cause. Dafiro is not recommended for use in patients below 18 years of age, because of a lack of information on safety and effectiveness in this age group.

The medicine can only be obtained with a prescription.

How is Dafiro used?

Dafiro is taken by mouth as one tablet once a day with some water, with or without food. The dose of Dafiro to be used depends on the doses of amlodipine or valsartan that the patient was taking before. The patient may need to take separate tablets or capsules before switching to the combination tablet. Dafiro should be used with caution in patients who have problems with their liver or biliary obstructive disorders (problems with the elimination of bile).

How does Dafiro work?

Dafiro contains two active substances, amlodipine and valsartan. Both are anti-hypertensives that have been available separately in the European Union (EU) since the mid-1990s. They work in similar ways to reduce blood pressure by allowing the blood vessels to relax. By lowering the blood pressure, the risks associated with high blood pressure, such as having a stroke, are reduced.

Amlodipine is a calcium channel blocker. It blocks special channels on the surface of cells called calcium channels, through which calcium ions normally enter the cells. When calcium ions enter the cells in the muscles of blood vessel walls, this causes contraction. By reducing the flow of calcium into the cells, amlodipine prevents the cells from contracting and this helps the blood vessels to relax.
Valsartan is an ‘angiotensin II receptor antagonist’, which means that it blocks the action of a hormone in the body called angiotensin II. Angiotensin II is a powerful vasoconstrictor (a substance that narrows blood vessels). By blocking the receptors to which angiotensin II normally attaches, valsartan stops the hormone having an effect, allowing the blood vessels to widen.

How has Dafiro been studied?

Because amlodipine and valsartan have been used for many years, the company presented information on the two substances from earlier studies and the scientific literature, as well as new studies that used a combination of the two active substances.

Five main studies involving nearly 5,200 patients, mostly with mild to moderate hypertension, were carried out. Two studies (involving almost 3,200 patients) compared the effectiveness of amlodipine, valsartan or a combination of both substances with the effectiveness of placebo (a dummy treatment). Two studies (involving 1,891 patients) compared the effects of the combination in patients whose hypertension was not adequately controlled with either 10 mg amlodipine or 160 mg valsartan. The fifth, smaller study compared the effectiveness of the combination with that of lisinopril and hydrochlorothiazide (another combination used to treat hypertension) in 130 patients with severe hypertension. In all studies, the main measure of effectiveness was the reduction in diastolic blood pressure (the blood pressure measured between two heartbeats). The blood pressure was measured in ‘millimetres of mercury’ (mmHg).

The company also presented evidence that the levels of amlodipine and valsartan in the blood were the same in people taking Dafiro and people taking the separate medicines.

What benefit has Dafiro shown during the studies?

The combination of amlodipine and valsartan was more effective at reducing blood pressure than placebo or either valsartan or amlodipine taken alone. In the studies comparing the effectiveness of the combination in patients who were already taking either amlodipine or valsartan, the blood pressure in patients taking valsartan alone had fallen by 6.6 mmHg after eight weeks, compared with 9.6 and 11.4 mmHg in the patients adding 5 or 10 mg amlodipine, respectively. Patients taking amlodipine alone had a fall of 10.0 mmHg, compared with 11.8 mmHg in the patients adding 160 mg valsartan.

What is the risk associated with Dafiro?

The most common side effects with Dafiro (seen in between 1 and 10 patients in 100) are headache, nasopharyngitis (inflammation of the nose and throat), influenza (flu), various types of oedema (swelling), fatigue (tiredness), flushing (reddening), asthenia (weakness) and hot flushes. For the full list of all side effects reported with Dafiro, see the Package Leaflet.

Dafiro should not be used in patients who may be hypersensitive (allergic) to amlodipine or other medicines in the ‘dihydropyridine derivatives’ class, to valsartan, or to any of the other ingredients. It must not be used in women who are more than three months pregnant. Its use during the first three months of pregnancy is not recommended. Dafiro must also not be used in patients who have severe liver, kidney or bile problems, or in patients undergoing dialysis (a blood clearance technique).

Why has Dafiro been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Dafiro’s benefits are greater than its risks for the treatment of essential hypertension in patients whose blood pressure is not adequately controlled on amlodipine or valsartan monotherapy. The Committee recommended that Dafiro be given marketing authorisation.

Other information about Dafiro

The European Commission granted a marketing authorisation valid throughout the EU for Dafiro to Novartis Europharm Limited on 16 January 2007.

This EPAR was last updated on 07/09/2011 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

27/07/2011  Dafiro -EMEA/H/C/000776 -WS/100/G

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Agents acting on the renin-angiotensin system

Therapeutic indication

Treatment of essential hypertension.
Dafiro is indicated in patients whose blood pressure is not adequately controlled on amlodipine or valsartan monotherapy.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents