How has it 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 Exforge and people taking the separate medicines.

What benefits has it 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?

The most common side effects with Exforge (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 Exforge, see the Package Leaflet.
Exforge 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. Exforge 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 it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Exforge’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 Exforge be given marketing authorisation.

Further information

The Europea