Olmesartan Medoxomil Tablets (Benicar—Sankyo Pharma Inc.)—A New ARB
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved another Angiotensin II Receptor Blocker (ARB) for the treatment of hypertension. The newest entry, olmesartan medoxomil, will be marketed by Sankyo Pharma Inc. and promoted by Forest Laboratories under the trade name "Benicar." Olmesartan medoxomil is a prodrug and is rapidly and completely converted to olmesartan during absorption.1
Indications
Olmesartan is indicated for the treatment of hypertension. It may be used as monotherapy or in combination with other antihypertensives.1
Dosage
The recommended starting dose is 20 mg once daily. The dose may be increased to 40 mg if further blood pressure reduction is required after 2 weeks of therapy. Initial dosage adjustment is not required in elderly patients with moderate to marked renal or hepatic dysfunction. A lower dose and/or close monitoring are recommended in patients who are volume contracted.1 It may be taken without regard to meals.
Olmesartan medoxomil is available as 5-mg, 20-mg, and 40-mg tablets.
Potential Advantages
Olmesartan is not metabolized by, or does not affect the cytochrome P450 isoenzymes, thus drug-drug interaction involving olmesartan and drugs affecting this metabolic system is unlikely. The drug has a long elimination half-life (10-15 hours) providing diastolic and systolic trough-to-peak ratios of 0.68 to 0.69, respectively.2 Its starting dose appears to be more efficacious than some other ARBs. In a study comparing olmesartan to losartan, valsartan, and irbesartan, olmesartan was reported to produce greater reduction in diastolic blood pressure.2 The doses used in this randomized, double-blind, parallel-group study were: olmesartan 20 mg/d, losartan 50 mg/d, valsartan 80 mg/d, or irbesartan 150 mg/d for 8 weeks. Each group had 142-146 subjects. Diastolic blood pressure was significantly (P < 0.05) lower with olmesartan (11.5 mm Hg) compared to losartan (8.2 mm Hg), valsartan (7.9 mm Hg), and irbesartan (9.9 mm Hg). No statistically significant difference was detected with systolic blood pressure reduction. Ambulatory mean 24-hour diastolic blood pressure was lower with olmesartan (8.5 mm Hg) compared to losartan (6.2 mm Hg) and valsartan (5.6 mm Hg) but not irbesartan (7.4 mm Hg). A similar trend was seen with mean systolic blood pressure.
Potential Disadvantages
Dizziness is the side effect that occurred at a higher frequency than placebo (3% vs 1%).1
Comments
Olmesartan is the seventh ARB to be introduced into this crowded market. As with other ARBs, it is an inhibitor of angiotensin II AT1 receptors. At the starting dose, olmesartan produces a greater reduction in diastolic blood pressure than losartan or valsartan. This difference may be related to the drugs’ pharmacokinetics as other long-acting ARBs such as irbesartan, telmisartan, and candesartan have also been found to be more efficacious than losartan.3-5 The antihypertensive efficacy of olmesartan has been confirmed in more than 3500 patients. It has a low incidence of side effects with frequencies similar to placebo.6 Sankyo is pricing the drug about 10% less than other ARBs (average wholesale cost is $1.31/d and is the same for all strengths).
Clinical Implications
ARBs’ ability to reduce blood pressure has been well documented. There is also evidence that ARBs may be effective in heart failure and renoprotection in type 2 diabetics.7-9 Currently, ARBs are an alternative to angiotensin II converting enzyme inhibitors (ACEI) in patients who are intolerant of these agents, most commonly secondary to ACEI-induced cough. Olmesartan is an effective long-acting ARB that is not likely to be affected by drug-drug or drug-food interaction. Being the newest ARB, it lacks the clinical track record of older ARBs.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
References
1. Benicar Product Information. Sankyo Pharma Inc. April 2002.
2. Oparil S, et al. J Clin Hypertens. 2001;3:283-291.
3. Burnier M, Brunner HR. Lancet. 2000;355:637-645.
4. Mallion J, et al. J Hum Hypertens. 1999;13(10): 657-664.
5. Kassler-Taub K, et al. Am J Hypertens. 1998;11(Pt 4):445-453.
6. Brunner HR. J Hum Hypertens. 2002;16(Suppl 2): S13-S16.
7. Jong P, et al. J Am Coll Cardiol. 2002;39(3):463-470.
8. Brenner BM, et al. N Engl J Med. 2001;345(12): 861-869.
9. Lewis E, et al. N Engl J Med. 2001;345(12):851-860.
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