First in a class of drugs called direct renin inhibitors.
Indicated for essential (primary) hypertension.
Has a low bioavailability of approximately 2.5%.
Metabolism by the liver, with renal excretion.
CYP3A4-mediated metabolism, with a half-life 24 hours.
Associated with an increased incidence of non-fatal stroke, renal complications, hyperkalemia and hypotension in patients with diabetes and renal impairment.
Use contraindicated against the use with ARBs or ACEIs in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalemia.
Use associated with ARBs or ACEIs in patients with moderate to severe renal impairment.
Renin is the first enzyme in the renin-angiotensin-aldosterone system.
Aliskiren binds to the S3bp binding site of renin, essential for its activity, and prevents the conversion of angiotensinogen to angiotensin I.
Available as combination therapy with hydrochlorothiazide.
Chronic use of anti hypertensive agents that interfere with angiotensin or aldosterone increases renin production, which drives blood pressure up again.
May have renoprotective effects that are independent of its blood pressure−lowering effect in patients with hypertension, type 2 diabetes, and nephropathy.
According to the AVOID study, treatment with 300 mg of aliskiren daily reduces the mean urinary albumin-to-creatinine ratio by 20%, reduces albuminuria in patients with hypertension, type 2 diabetes, and reduces proteinuria in patients receiving maximal renoprotective treatment with losartan and optimal antihypertensive therapy.
Side effects include:Angioedema, diarrhea, cough, dizziness, hyperkalemia, rash, headache, hypotension, hyperuricemia, gout, and renal stones.
A minor substrate of CYP3A4 and P-glycoprotein.
Reduces furosemide blood levels, while atorvastatin may increase concentrations.
Use with of cyclosporine is contraindicated.
May increase toxicity when administered with ketoconazole or other moderate P-gp inhibitors such as itraconazole, clarithromycin, telithromycin, erythromycin, or amiodarone.
Should not be used in patients with diabetes, or with moderate to severe kidney impairment who are also taking an ACE inhibitor or ARB.
In a multi center, double-blind trial evaluating the effects of this drug on changes in coronary atherosclerosis measured by intravascular ultrasound imaging in patients with blood pressure in the pre-hypertension range: no significant differences were noted between the aliskiren group in the placebo group for primary and secondary endpoints.
This agent should be reserved for use in patients with coronary disease and hypertension who cannot tolerate ACE inhibitors and angiotensin receptor blockers.