Aliskiren

Pharmacon (renin inhibitor) for the treatment of arterial hypertension. The molecular formula is C32H55N3O8. The average half-life is about 20.0 -60.0h. Aliskiren interferes with the body's own renin-angiotensin-aldosterone system by competitively inhibiting the protease renin. This suppresses the formation of angiotensin I from angiotensinogen. The levels of angiotensin II and aldosterone drop. Compensatory, the concentration of renin increases, but the renin activity decreases in contrast to treatment with ACE inhibitors and AT1 receptor blockers.

As its effect is additive to other antihypertensives, it is often used in combination (thiadiazide diuretics, ACE inhibitors or the calcium channel blocker amlodipine).

Aliskiren is orally effective.

The bioavailability of aliskiren is low at 2.6% and is also reduced by high-fat diets. The renin inhibitor should therefore be taken with a light meal and always at the same time of day (150 mg to 300 mg daily as a single dose).

The plasma levels of aliskiren increase considerably when strong inhibitors of cytochrome P450 3A4 such as azole antifungals are taken at the same time, less markedly when comedicated with atorvastatin (SORTIS). About 50% of the absorbed active substance is metabolized. Despite elevated levels in patients with kidney and liver function impairment and in older people, no dose reduction is planned, although daily doses of 75 mg are already considered effective for people over 65 years of age.

Common side effects are gastro-intestinal complaints such as diarrhoea (1-10%) and exanthema (0.1-1.0%), as well as angioedema. Coughing is more common than with placebo (0.9% vs. 0.6%), but apparently less common than with ACE inhibitors.

Serum potassium increases above 5.5 mval/l are occasional with monotherapy (0.9%), but are common in combination with the ACE inhibitor ramipril in a study of diabetics (5.5%). Tonic-clonic seizures are rare.

Aliskiren must not be taken together with grapefruit juice. The active substance is also contained in medicines as aliskiren hemifumarate.

Drugs containing ketoconazole (for fungal infections) as well as amiodarone (for cardiac arrhythmia), clarithromycin, erythromycin or telithromycin (for bacterial infections) and verapamil (for coronary heart disease or high blood pressure) increase the effect of aliskiren.

Hypersensitivity to the active substance or one of the excipients

Hereditary or idiopathic angioedema

Combination of aliskiren with ACE inhibitors or angiotensin II receptor blockers

In patients with diabetes mellitus (type 1 and type 2)

For patients with limited kidney function (GFR <60 mL/min)

Pregnancy and lactation (no studies are available)

Rasilez (D, A, CH), Riprazo (A), Sprimeo (A), Tekturna (A, USA)

Aliskiren was approved in the USA in March 2007, in Switzerland in June 2007 and in the EU in August 2007.

Aliskiren has antiproliferative and anti-inflammatory effects (inhibition of TNF-alpha and interleukin -6: beneficial effect on psoriatic skin changes - Pawloski PL et al. 2018)

1. Békássy ZD et al (2018) Aliskiren inhibits renin-mediated complement activation. Kidney Int 94:689-700.
2. Graefe KH et al. Pharmak with effects on the vascular system. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart p.177

3. Pawloski PL et al (2018) Aliskiren: Preclinical evidence for the treatment of hyperproliferative skindisorders. Biomed Pharmacother 104:151-157.

4. Toh S et al (2012) Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. Arch Internal Med 172:1582-1589.