For doctors

What is it?

Rasilez HCT is a medicine that contains the active substances aliskiren and hydrochlorothiazide. It is available as oval tablets (white: 150 mg aliskiren and 12.5 mg hydrochlorothiazide; pale yellow: 150 mg aliskiren and 25 mg hydrochlorothiazide; pale violet: 300 mg aliskiren and 12.5 mg hydrochlorothiazide; light yellow: 300 mg aliskiren and 25 mg hydrochlorothiazide).

What is it used for?

Rasilez HCT is used to treat essential hypertension (high blood pressure) in adults. ‘Essential’ means that no specific cause for the hypertension can be found.
Rasilez HCT is used in patients whose blood pressure is not adequately controlled by aliskiren or hydrochlorothiazide taken alone. It can also be used in patients whose blood pressure is adequately controlled with aliskiren and hydrochlorothiazide taken as separate tablets, to replace the same doses of the two active substances.
The medicine can only be obtained with a prescription.

How is it used?

The recommended dose of Rasilez HCT is one tablet per day. It should be taken with a light meal preferably at the same time each day, but grapefruit juice should not be taken together with Rasilez HCT. The dose depends on the doses of aliskiren and/or hydrochlorothiazide that the patient was taking before.
Patients previously taking only aliskiren or hydrochlorothiazide may need to take the two substances as separate tablets and adjust the doses before switching to Rasilez HCT. After two to four weeks of taking Rasilez HCT, the dose can be increased in patients whose blood pressure remains uncontrolled. In patients already adequately controlled with the two active substances, the dose of Rasilez HCT must contain the same doses of aliskiren and hydrochlorothiazide that the patient was taking before. Rasilez HCT should be used with caution in patients who have problems with their liver and it must not be used in patients with severe liver or kidney problems.

How does it work?

Rasilez HCT contains two active substances, aliskiren and hydrochlorothiazide.
Aliskiren is a renin inhibitor. It blocks the activity of a human enzyme called renin, which is involved in the production of a substance called angiotensin I in the body. Angiotensin I is converted into the hormone angiotensin II, which is a powerful vasoconstrictor (a substance that narrows blood vessels). By blocking the production of angiotensin I, levels of both angiotensin I and angiotensin II fall. This causes vasodilation (widening of the blood vessels), so that the blood pressure drops. Hydrochlorothiazide is a diuretic, which is another type of treatment for hypertension. It works by increasing urine output, reducing the amount of fluid in the blood and reducing blood pressure. The combination of the two active substances has an additive effect, reducing the blood pressure more than either medicine alone. By lowering blood pressure, the risk caused by high blood pressure, such as having a stroke, is reduced.

How has it been studied?

Aliskiren on its own has been authorised in the European Union (EU) since August 2007 as Rasilez, Enviage, Sprimeo, Tekturna and Riprazo. The company presented information used in the assessment of aliskiren and from the published literature to support its application for Rasilez HCT, as well as information from additional studies.
Overall, the company presented the results of nine main studies involving a total of almost 9,000 patients with essential hypertension. Most studies involved patients with mild to moderate hypertension and one involved patients with severe hypertension. The studies compared the combination of aliskiren and hydrochlorothiazide with placebo (a dummy treatment), with aliskiren or hydrochlorothiazide taken alone, or with other medicines for hypertension (valsartan, irbesartan, lisinopril or amlodipine). The studies lasted for between eight weeks and a year, and the main measure of effectiveness was the change in blood pressure either during the resting phase of the heartbeat (diastolic) or when the chambers of the heart were contracting (systolic).
Three additional studies were carried out to show that the active substances were absorbed in the body in the same way when they taken as separate tablets and as Rasilez HCT.

What benefits has it shown during the studies?

Rasilez HCT was more effective than placebo in reducing blood pressure. In patients whose blood pressure was not adequately controlled on either aliskiren or hydrochlorothiazide alone, switching to the combination resulted in greater falls in blood pressure than remaining on one active substance alone.

What is the risk associated?

The most common side effect with Rasilez HCT (seen in between 1 and 10 patients in 100) is diarrhoea. For the full list of all side effects reported with Rasilez HCT, see the Package Leaflet. Rasilez HCT should not be used in people who may be hypersensitive (allergic) to aliskiren, hydrochlorothiazide, any of the other ingredients or sulfonamides. It must not be used in patients who have had angioedema (swelling under the skin) with aliskiren, who have severe kidney or liver problems, or whose blood potassium levels are too low or blood calcium levels are too high. It must not be taken with ciclosporin (a medicine that reduces the activity of the immune system) or other medicines that may slow down the breakdown of aliskiren in the body, such as quinidine (used to correct irregular heartbeat) or verapamil (used to treat heart problems). It must not be used in women who are more than three months pregnant or breast-feeding. Its use during the first three months of pregnancy is not recommended.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Rasilez HCT’s benefits are greater than its risks for the treatment of essential hypertension in adults whose blood pressure is not adequately controlled on aliskiren or hydrochlorothiazide used alone, or adequately controlled with aliskiren and hydrochlorothiazide, given concurrently, at the same dose level as in the combination. The Committee recommended that Rasilez HCT be given marketing authorisation.

Further information

The European Commission granted a marketing authorisation valid throughout the EU for Rasilez HCT to Novartis Europharm Limited on 16 January 2009.

Name

Rasilez HCT 300 mg/12.5 mg film-coated tablets

Composition

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide.

Excipients: Each tablet contains 25 mg lactose monohydrate and 24.5 mg wheat starch.

For a full list of excipients, see section 6.1.

Pharmaceutical Form

Film-coated tablet

Violet white, biconvex, ovaloid film-coated tablet imprinted with “CVI” on one side and “NVR” on the other.