Products
Aliskiren is commercially available in the form of film-coated tablets (Rasilez, Rasilez HCT + hydrochlorothiazide). It was approved in many countries, in the EU and in the United States in 2007 (Other brand name: Tekturna). Note: Other combination preparations, e.g., with amlodpine (Rasilamlo), are no longer available.
Structure and properties
Aliskiren (C30H53N3O6, Mr = 551.8 g/mol) is present in drugs as aliskiren hemifumarate, a white to yellowish crystalline powder that is readily soluble in water. The active ingredient resembles a peptide but has a nonpeptidic structure.
Effects
Aliskiren (ATC C09XA02) has antihypertensive properties. It selectively inhibits the formation of angiotensin I from angiotensinogen by direct and competitive inhibition of the aspartyl protease renin. This is the first step in the activation of the renin-angiotensin-aldosterone system. Aliskiren binds to the active site of the enzyme and thus prevents the formation of the highly vasoconstrictive and blood pressure-increasing angiotensin II as well as the release of aldosterone (see also under renin-angiotensin system). The drug has a long half-life of 40 hours.
Indications
For the treatment of essential hypertension (high blood pressure).
Dosage
According to the professional information. The tablets are taken once a day. Taking the drug together with fruit juice (grapefruit juice, apple juice, orange juice) leads to a significant decrease in AUC and maximum plasma concentration. Aliskiren should therefore not be taken with fruit juices.
Contraindications
- Hypersensitivity
- Angioedema with a history of aliskiren, hereditary or idiopathic angioedema
- Combination of aliskiren with ACE inhibitors or sartans in patients with diabetes mellitus and patients with impaired renal function.
- Pregnancy and lactation
- Children under 2 years
Full precautions can be found in the drug label.
Interactions
Aliskiren interacts poorly with CYP450, having a low bioavailability of only 2.6% and being a substrate of P-glycoprotein. With concomitant administration of P-gp inhibitors such as ketoconazole and ciclosporin, plasma concentrations may increase to a relevant extent. Other interactions are possible with: ACE inhibitors, sartans, furosemide, NSAIDs, potassium, potassium-sparing diuretics. Dual inhibition of the RAAS is not recommended.
Adverse effects
The most common potential adverse effects include diarrhea, dizziness, lightheadedness, and hyperkalemia.
