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Tekturna Monograph

Drug Monograph Evaluation

GENERIC NAME1: Aliskiren
PROPRIETARY NAME1: Tekturna
THERAPEUTIC CLASS2: Antihypertensive
APPROVAL RATING3: S-surrogate
APPROVAL DATE3: 03/05/2007
MANUFACTURER3: Novartis
PRODUCT AVAILABILITY2: 150mg, 300mg oral tablets

INDICATION2,4: It is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents in adults.

MECHANISM OF ACTION/ CLINICAL PHARMACOLOGY1,2,4: Aliskiren is a drug of the class of non-peptide and is orally active. It is a direct renin inhibitor, decreasing plasma renin activity and inhibiting the conversion of angiotensinogen to angiotensin I. ACE-inhibitors can only block the ACE pathway resulting in angiotensin II production via the non-ACE pathway. ARBs also increase the level of angiotensin II through negative feedback mechanism. Aliskiren reduces angiotensin I, angiotensin II, a powerful vasoconstrictor, and aldosterone secretion and sodium reabsorption. It is unknown whether Aliskiren affects ACE or non-ACE pathways. The full antihypertensive effect can be reached by 2 weeks with once-daily dosing in mild-to-moderate hypertension. Unlike ACE-Is, aliskiren has no affinity for ACE and does not increase bradykinin and substance P levels.

PHARMACOKENETICS/PHARMACODYNAMICS1,2,4:
Aliskiren
Absorption - Oral: poorly absorbed (F: 2.5%).
- Peak plasma concentration: 1-3 hours
- High fat meal ↓AUC by 71% & Cmax by 85%.
Distribution Vd= 135L
Protein binding 49.5%
Metabolism CYP3A4
Elimination Unclear, possibly hepatobiliary clearance
Elimination t1/2 20-45 hours

COMPARATIVE EFFICACY:
Aliskiren as monotherapy1:
Six randomized, double-blind, placebo-controlled 8-week clinical trials in patients with mild to moderate hypertension included 2,730 patients given doses of 75-600mg of Aliskiren and 1,231 patients given placebo. 85-90% of the study population responded to Aliskiren within 2 weeks of treatment. Blood...