Pharmacy & Therapeutics - February 2008 - (Page 94)

DRUG FORECAST uated in almost 6,500 patients; 1,740 of these patients took aliskiren for longer than six months, and 1,250 were treated for longer than one year.10 Table 2 Pharmacokinetics of Aliskiren Parameter Absorption Distribution Metabolism Elimination Time to peak concentration Elimination half-life (P = 0.05). Aliskiren 600 mg was no more effective in further reducing BP than the 300-mg dose. Measure Poor (3%) 49.5% protein binding Cytochrome P450 (CYP 3A4) Urine, feces 1–3 hours 24 hours or irbesartan 150 mg once daily. Aliskiren 75 mg was then given for an additional three-week period. Finally, the aliskiren dose was increased to 150 mg daily for three weeks. The addition of aliskiren 75 mg to ramipril 5 mg yielded a decrease in systolic BP from 143.4 ± 11.1 mm Hg to 139.4 ± 12.7 mm Hg (P = 0.03). The dose increase of aliskiren to 150 mg resulted in a further reduction to 136.4 ± 10.9 mm Hg (P = 0.0006). In the irbesartan trial, the addition of aliskiren 75 mg did not yield a significant decrease in BP. Pool et al.16 Another eight-week multicenter, randomized, double-blinded, placebocontrolled trial investigated aliskiren monotherapy as well as combination therapy with valsartan (Diovan, Novartis) in 1,123 patients with mild-to-moderate hypertension. After a tapering off of current antihypertensive treatment and a three- to four-week placebo run-in period, patients received either oncedaily placebo, aliskiren monotherapy 75, 150, or 300 mg; valsartan monotherapy 80, 160, or 320 mg; a combination of aliskiren/valsartan 75/80 mg; 50/160 mg, or 300/320 mg; or a combination of valsartan/HCTZ 160/12.5 mg. Compared with placebo, aliskiren 300 mg monotherapy significantly reduced mean systolic BP (P < 0.0001) and diastolic BP (P = 0.0001). The aliskiren/valsartan combination significantly decreased mean diastolic BP and systolic BP relative to placebo at all dose combinations: aliskiren 75 mg/ valsartan 80 mg lowered diastolic BP by 3.25 ± 1.21 mm Hg (placebo-corrected mean, P < 0.01) and systolic BP by 4.49 ± 1.87 mm Hg (placebo-corrected mean, P 0.05). Gradman et al.13 The irbesartan study was an eightweek randomized, multicenter, doubleblind, placebo-controlled, active-comparator trial of 652 patients. Patients with severe hypertension (BP > 180/110 mm Hg), type-1 diabetes, poor glucose control, or a history of cardiovascular disease were excluded. After a two-week washout period, patients were randomly assigned to receive aliskiren 150, 300, or 600 mg; irbesartan 150 mg; or placebo. Once-daily aliskiren was as effective as irbesartan at 150 mg. At doses of 300 mg and 600 mg, aliskiren lowered diastolic BP but not systolic BP more than irbesartan 150 mg (12.5/8.9 mm Hg ± 1.2 ± 0.7 mm Hg) Combination Therapies Villamil et al.14 Aliskiren in combination with hydrochlorothiazide (HCTZ) produced greater BP reductions than aliskiren alone in an eight-week, international, double-blind, randomized, placebo-controlled, doseranging multifactorial trial of 2,752 patients. The patients were randomly assigned to receive aliskiren 75, 150, or 300 mg; HCTZ monotherapy 6.25, 12.5, or 25 mg; or aliskiren/HCTZ combinations (except 300/6.25 mg) in a factorial manner. Aliskiren/HCTZ was more effective than placebo (P < 0.0001) or any monotherapy regimen (P < 0.05) in reducing BP, excluding the combinations of aliskiren/ HCTZ 150/6.25 mg and 75/12.5 mg. Treatment was well tolerated. The most frequently reported side effects were head ache (7.2%) and nasopharyngitis (3.8%). O’Brien et al.15 Three individual open-label, non randomized studies examined aliskiren in combination with HCTZ, ramipril (Altace, King), and irbesartan. In the aliskiren/diuretic study, 23 patients received once-daily oral aliskiren 150 mg for three weeks. HCTZ 25 mg once daily was added to the aliskiren in patients (17 out of 23) whose daytime ambulatory BP remained greater than or equal to 130/85 mm Hg. This addition resulted in an overall reduction in systolic BP from a baseline value of 150.6 ± 8.9 mm Hg to 133.8 ± 7 mm Hg (P = 0.0007). In the ACE inhibitor/aliskiren (n = 21) and ARB/aliskiren (n = 23) combination studies, patients received a three-week treatment of oral ramipril 5 mg once daily 94 P&T® • February 2008 • Vol. 33 No. 2

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - February 2008

Pharmacy & Therapeutics - February 2008 Contents Editorial Medication Errors Prescription: Washington The Language of (Forgive Us) Change, As P&T Enters the Digital Age New Drugs/Drug News/New Medical Devices Drug Forecast Use and Outcomes of Antifibrinolytic Therapy in Patients Undergoing Cardiothoracic Surgery at 20 Academic Medical Centers in the United States Evaluation of the Management of Acute Venous Thromboembolism and Its Outcomes: One Institution's Experience American Society of Hematology, 49th Annual Meeting Pharmaceutical Approval Update

Pharmacy & Therapeutics - February 2008

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.