Rasitrio - Aliskiren / amlodipine / hydrochlorothiazide

PLEASE NOTE: MEDICINAL PRODUCT IS NO LONGER AUTHORIZED

What is Rasitrio - Aliskiren / amlodipine / hydrochlorothiazide?

Rasitrio is a medicine that contains the active substances aliskiren, amlodipine and hydrochlorothiazide. It is available as tablets with the following concentrations: 150/5 / 12.5 mg; 300/5 / 12.5 mg; 300/5/25 mg; 300/10 / 12.5 mg; and 300/10/25 mg.

What is Rasitrio used for?

Rasitrio is used to treat essential hypertension (high blood pressure) in adult patients whose blood pressure is already adequately controlled with the combination of aliskiren, amlodipine and hydrochlorothiazide administered concomitantly with the same dosage. The term 'essential' indicates that hypertension has no obvious cause.

The medicine can only be obtained with a prescription.

How is Rasitrio used - Aliskiren / amlodipine / hydrochlorothiazide?

The patient should take one tablet once a day with a light meal, preferably at the same time each day. The tablet should be swallowed whole with water and should not be taken along with grapefruit juice.

The concentration of the Rasitrio tablet taken by the patient depends on the doses of aliskiren, amlodipine and hydrochlorothiazide previously administered. Patients should switch to the Rasitrio tablet of the fixed combination containing the same doses as the components previously used individually.

How does Rasitrio - Aliskiren / amlodipine / hydrochlorothiazide work?

Rasitrio contains three active substances: aliskiren, amlodipine and hydrochlorothiazide.

Aliskiren is a renin inhibitor that blocks the activity of an enzyme called renin, involved in the production of a substance called angiotensin I in the body. Angiotensin I is converted to the hormone angiotensin II, which is a powerful vasoconstrictor (a substance that causes narrowing of blood vessels). By blocking renin activity, angiotensin I and angiotensin II levels are reduced. This involves vasodilation (dilation of the blood vessels) with consequent reduction in blood pressure.

Amlodipine is a calcium channel blocker that blocks particular channels on the surface of cells called calcium channels, through which calcium ions normally pass. By entering the muscle cells of the blood vessel walls, calcium ions determine a contraction. By reducing the flow of calcium into the cells, amlodipine prevents the contraction of blood vessel walls, thereby reducing blood pressure.

Hydrochlorothiazide is a diuretic that increases urine production by reducing the volume of fluid in the blood and lowering blood pressure.

The combination of these three active ingredients reduces blood pressure more than one of the individually administered medicines.

How has Rasitrio been studied?

In a main study of 1 191 patients with moderate or severe hypertension, Rasitrio associations containing the three active substances and combinations containing only two active ingredients were compared: aliskiren and amlodipine, amlodipine and hydrochlorothiazide, aliskiren and hydrochlorothiazide. Patients were treated for eight weeks. The main measure of effectiveness was the average reduction in systolic blood pressure (arterial pressure during heart contraction) with patients in a sitting position.

The company has also presented studies showing that the tablet containing all three substances is absorbed by the body in the same way as the separate tablets.

What benefit has Rasitrio shown during the studies?

The association of Rasitrio has been shown to be more effective than the double associations for the reduction of systolic pressure. After eight weeks, a mean reduction in systolic pressure in a sitting position of 37.4 mmHg was found in patients treated with Rasitrio. Reductions of 28.2 mmHg, 30.6 mmHg and 30.8 mmHg were respectively observed for aliskiren and hydrochlorothiazide, aliskiren and amlodipine, and amlodipine and hydrochlorothiazide.

What is the risk associated with Rasitrio?

The most frequent adverse reactions for Rasitrio are hypotension, peripheral edema and dizziness. For the full list of all side effects reported with Rasitrio, see the package leaflet.

Rasitrio should not be used in people who are hypersensitive (allergic) to aliskiren, amlodipine or hydrochlorothiazide, to any of the excipients of the medicine or to other substances derived from dihydropyridine (a group that includes amlodipine) or sulfonamide (which includes hydrochlorothiazide). It must not be used in patients who have experienced angioedema (subcutaneous swelling), who suffer from severe liver or kidney problems, or who have too low levels of potassium in the blood or too high levels of calcium in the blood. It should not be taken in conjunction with ciclosporin or itraconazole (a medicine that reduces the activity of the immune system) or with medicines that can slow the breakdown of aliskiren in the body such as quinidine (used to correct an irregular heart rhythm). It must not be given to people with very low blood pressure, who suffer from shock, who have a narrowing of the aortic valve or who suffer from heart failure following an acute heart attack. It must not be given to women who have been pregnant for more than 3 months or during breastfeeding. Use of the medicine in the first three months of pregnancy is not recommended. For the full list of limitations, see the package leaflet.

Why has Rasitrio - Aliskiren / amlodipine / hydrochlorothiazide been approved?

The main study showed a greater reduction in blood pressure with Rasitrio compared to the combination of two active ingredients. Studies have also shown that the active ingredients contained in Rasitrio are absorbed by the body in the same way as the active ingredients administered in separate tablets. The CHMP noted that taking the three active substances in a single tablet, unlike taking them as separate tablets, may lead to greater compliance with the treatment.

The CHMP therefore decided that Rasitrio's benefits are greater than its risks and recommended that it be given marketing authorization.