The purpose of VACO PBM-MAP drug monographs is to provide a comprehensive drug review for making formulary decisions. These documents will be updated when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current.
Indications: Aliskiren (Tekturna®), a direct renin inhibitor, was approved by the FDA for the treatment of patients with hypertension (HTN).
Efficacy: Treatment with aliskiren in published placebo and/or active-controlled trials of 4 to 13 weeks duration demonstrated a reduction in the primary endpoint of mean trough sitting diastolic blood pressure (DBP) in patients with mild to moderate essential HTN. Statistically significant reductions in DBP (placebo-subtracted) ranged from 2.0 to 5.4 mm Hg for aliskiren 150 mg and 3.4 to 7.5 mm Hg with aliskiren 300 mg once daily. Reductions in systolic blood pressures (SBP) of 2.1 to 9.2 mm Hg and 5.0 to 11.2 mm Hg were seen in patients receiving aliskiren 150 mg and 300mg, respectively. In the aliskiren treatment groups, approximately 31-36% of patients receiving aliskiren 150 mg and 37 to 42% of patients on 300 mg achieved blood pressure control (defined as BP < 140/90 mm Hg) compared to 16 to 28% of patients in the placebo groups. In addition, it was reported that 38 to 59% and 50 to 68% of patients responded to treatment (i.e., DBP < 90 mm Hg and/or > 10 mm Hg reduction) with aliskiren 150 mg and 300 mg, respectively; these results compared to 21 to 48% of patients receiving placebo. In trials that included an active comparator, there was not a significant difference in DBP reduction with aliskiren 150 mg and irbesartan 150 mg (although the difference between aliskiren 300 mg and irbesartan 150 mg was significant), or with aliskiren 150 mg or 300 mg compared to losartan 100 mg. There was a slightly greater reduction in DBP with valsartan 160 mg and 320 mg compared with aliskiren 150 mg that was statistically significant. The majority of combinations with aliskiren and hydrochlorothiazide were found to provide a significantly greater reduction in DBP compared to the respective monotherapy components. Combination therapy with aliskiren and valsartan was more effective at lowering blood pressure compared to treatment with either agent alone.
Safety: Aliskiren is generally well-tolerated. Discontinuation due to an adverse event was reported in 2.2% of patients receiving aliskiren compared to 3.5% on placebo. Angioedema has rarely been reported in patients receiving treatment with aliskiren. Symptomatic hypotension may occur in patients who may be sodium or volume depleted (e.g., in patients receiving diuretic therapy) upon initial therapy with aliskiren. It is recommended to correct the volume depletion prior to starting aliskiren; otherwise therapy should be initiated under close medical supervision. The most frequently occurring adverse events (reported in > 1% of patients receiving aliskiren with similar or greater incidence in patients on placebo) included headache, nasopharyngitis, dizziness, fatigue, upper respiratory tract infection, back pain, and cough. One clinical trial comparing the tolerability of aliskiren and an angiotensin-converting enzyme inhibitor (ACEI) reported that cough occurred in 0.8% of patients on aliskiren compared to 1.7% of patients receiving lisinopril.As with the ACEIs and angiotensin II receptor antagonists (ARBs), product information for aliskiren contains a boxed warning for use in pregnancy. Administration of medications that act at the renin-angiotensin-aldosterone system (RAAS) during pregnancy has resulted in neonatal morbidity and mortality; therefore, aliskiren should be discontinued as soon as possible after a patient becomes pregnant.
Laboratory Monitoring: Since aliskiren acts at the RAAS, recommendations for monitoring serum potassium and kidney function should be similar as with other agents acting on the RAAS (e.g., ACEIs, ARBs, aldosterone antagonists). The frequency of routine monitoring should take into consideration the patient’s concomitant therapy and comorbid conditions. It is recommended that electrolytes and kidney function be routinely monitored in patients with diabetes mellitus receiving concomitant treatment with an ACEI due to an increase in serum potassium. In clinical trials of patients with essential hypertension, reports of increased potassium, blood urea nitrogen, and serum creatinine were similar to placebo. In addition, published results of comparison trials of aliskiren and an ACEI or ARB reported that blood chemistry levels remained normal in the majority of patients.
Dose: The initial recommended total daily dose of aliskiren is 150 mg administered once daily. The dose may be increased to 300 mg once daily after two weeks if the blood pressure goal is not achieved. Doses greater than 300 mg once daily did not provide additional blood pressure reduction but did increase the frequency of diarrhea. It is recommended that aliskiren be administered at a consistent interval in relation to meals as a high fat meal decreased the absorption of the drug; although, the clinical significance of this is unknown.
Cost: The monthly drug cost for therapy with aliskiren is $18.90 to $20.70, depending on the dose. The prices for other commonly recommended antihypertensive agents are approximately $0.13 to $0.35 per month for a thiazide diuretic; $0.70 to $4.85 per month for an ACEI; and $10.50 per month for a calcium channel blocker.
Place in Therapy: A thiazide-type diuretic is recommended as initial therapy, either as monotherapy or in combination with other antihypertensive agents, in patients with uncomplicated HTN. Therapy with other antihypertensive drug classes should be considered in patients who are inadequately controlled or have a compelling indication for another drug class. As the long-term morbidity and mortality of aliskiren has yet to be established, it is recommended that aliskiren be reserved for patients with HTN who do not tolerate or are not controlled on antihypertensive medications within the drug classes currently recommended as initial or alternative/supplemental therapy per VHA/DoD national clinical practice guidelines for the treatment of HTN, and that are available on the VA National Formulary.
National PBM Drug Monograph
VA Pharmacy Benefits Management Service and the Medical Advisory Panel