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Losartan

Losartan is a drug used to treat high blood pressure (hypertension) and has been examined for congestive heart failure and diabetic nephropathy. It is marketed as Cozaar® by Merck Sharp and Dohme and as Hyzaar® in combination with the thiazide diuretic hydrochlorothiazide (HCT). more...

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Losartan was the first member of the recently introduced class of angiotensin II receptor antagonists. It blocks the action of the peptide hormone angiotensin on its receptors, decreasing arterial vascular tone and production of aldosterone.

Indications:

  • Essential hypertension
  • Hypertension with left ventricular hypertrophy for lowering the risk of cardiovascular morbidity and mortality
  • Diabetes mellitus type 2 with proteinuria for slowing down the progression of kidney disease

Because of proven effectivity and lower costs, the first choice of drug for essential hypertension is a thiazide or beta blocker. The primary use of losartan is for proven stroke prevention. A clinical trial called LIFE demonstrated that losartan works significantly better than atenolol in preventing stroke (PMID 11937178).

Adverse effects

Adverse effects of Losartan include:

  • Dizziness
  • Hyperkalemia

Overdose

An overdose of losartan will result in hypotension and tachycardia.

Availability

In most countries, this medication is available only by prescription.

Read more at Wikipedia.org


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Olmesartan for hypertension
From American Family Physician, 8/15/05 by Kristina E. Ward

Synopsis

Olmesartan (Benicar) is an angiotensin-II receptor blocker (ARB) labeled for the treatment of hypertension as monotherapy or in combination with other antihypertensive agents. Olmesartan blocks the binding of angiotensin II, a potent vasoconstrictor, to angiotensin type 1 ([AT.sub.1]) receptors located in vascular smooth muscle. (1)

Safety

No serious safety issues were reported with olmesartan in clinical trials. The safety record of olmesartan was similar to placebo in seven randomized, double-blind, placebo-controlled phase II and III trials that included 2,540 patients with hypertension. (2) Adverse effects were reported in 42.2 percent and 42.7 percent of olmesartan-treated patients and placebo-treated patients, respectively. Olmesartan may cause hypotension and acute renal failure in patients who are sodium- or volume-depleted or whose renal perfusion is dependent on the renin-angiotensin system. Like all ARBs, olmesartan may precipitate acute renal failure in patients with renal artery stenosis. Significant hyperkalemia has not been reported with olmesartan, although it is possible, especially in patients with other risk factors for hyperkalemia. Of 3,825 patients treated with olmesartan during clinical trials, five reported angioedema. (1) It is not known whether patients who have developed angioedema with angiotensin-converting enzyme (ACE) inhibitors or other ARBs have an increased risk of developing this side effect with olmesartan. No dosage adjustments are needed in older patients or in patients with moderate to marked hepatic or renal impairment. As with other ARBs, olmesartan is U.S. Food and Drug Administration category C during the first trimester of pregnancy and category D during the second and third trimesters. (1) In rare instances, angioedema and rhabdomyolysis from olmesartan have been reported in postmarketing surveillance. (1)

Tolerability

Olmesartan generally is well tolerated. In clinical trials, dizziness occurred in 2.8 percent of olmesartan-treated patients and in 0.9 percent of placebo-treated patients. (2) In a study (3) comparing olmesartan to other ARBs, the incidence of dizziness was similar in olmesartan (1.4 percent), losartan (Cozaar; 0.7 percent), valsartan (Diovan; 1.4 percent), and irbesartan (Avapro; 3.4 percent). Headache was reported by 1.3 percent of patients receiving olmesartan and 2.5 percent receiving candesartan (Atacand). (4) As with other ARBs, the incidence of cough with olmesartan is comparable to that with placebo (0.9 and 0.7 percent, respectively). (1)

Effectiveness

Short-term studies have shown that blood pressure control with olmesartan is similar to that achieved with other ARBs or amlodipine (Norvasc). Olmesartan in a dosage of 20 mg produces an average drop in diastolic blood pressure of 10 mm Hg and a comparable reduction in systolic blood pressure; this is in line with the reductions effected by equivalent dosages of other ARBs, (3,4) or a 5-mg dosage of amlodipine. (5) Olmesartan has been studied in combination with hydrochlorothiazide (Esidrix) and has been found to produce an average additional diastolic blood pressure lowering of 7 to 10 mm Hg (with 20 mg or 40 mg olmesartan, respectively) compared with hydrochlorothiazide alone. (6)

Olmesartan has not been evaluated for the treatment of patients with heart failure or diabetic nephropathy. Although ARBs have been shown to decrease recurrent stroke in hypertensive patients, (7) and mortality and morbidity in patients with hypertension accompanied by left ventricular hypertrophy, (8) no studies have been performed to determine the effect of olmesartan on morbidity and mortality in patients with uncomplicated hypertension.

Price

A one-month supply of Benicar in 20-mg tablets costs approximately $54, which is comparable to the price of other ARBs. Unlike other ARBs, however, the 5-mg, 20-mg, and 40-mg tablets of Benicar are similarly priced, which may be advantageous for self-paying patients.

Simplicity

The recommended starting dosage of olmesartan is 20 mg daily, taken with or without food. If blood pressure control is inadequate after two weeks, the dosage may be increased to a maximum of 40 mg daily. Dosages above 40 mg daily do not provide additional benefit. For patients who may be at risk for volume- or salt-depletion, such as those who have renal impairment and receive diuretics, a lower starting dosage is suggested. Olmesartan is available in 5-mg tablets if needed for dose reductions.

Bottom Line

Olmesartan is a safe and effective antihypertensive agent. There is no evidence that olmesartan is more effective than other ARBs or ACE inhibitors. The longest peer-reviewed studies of olmesartan are of two months' duration; thus, there is no evidence showing olmesartan's long-term benefit for cardiovascular or all-cause mortality. Because of its greater expense and lack of proven benefit over ACE inhibitors, olmesartan should be considered a second-line agent for hypertension except in patients who cannot tolerate ACE inhibitors.

REFERENCES

(1.) Benicar tablets (olmesartan medoxomil). Package insert. Sankyo, March 2003. Accessed online July 25, 2005, at: http://www.benicar.com/pdf/fullPI.pdf.

(2.) Neutel JM. Clinical studies of CS-866, the newest angiotensin II receptor antagonist. Am J Cardiol 2001;87(suppl):37C-43C.

(3.) Oparil S, Williams D, Chrysant SG, Marbury TC, Neutel J. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension [published correction appears in J Clin Hypertens 2001;3:395]. J Clin Hypertens 2001;3:283-91,318.

(4.) Brunner HR, Stumpe KO, Januszewicz A. Antihypertensive efficacy of olmesartan medoxomil and candesartan cilexetil assessed by 24-hour ambulatory blood pressure monitoring in patients with essential hypertension. Clin Drug Invest 2003;23:419-30.

(5.) Chrysant SG, Marbury TC, Robinson TD. Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension. J Hum Hypertens 2003;17:425-32.

(6.) Chrysant SG, Weber MA, Wang AC, Hinman DJ. Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide. Am J Hypertens 2004;17:252-9.

(7.) Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, et al. The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke 2003;34:1699-703.

(8.) Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003.

KRISTINA E. WARD, PHARM.D., and ANNE L. HUME, PHARM.D., B.C.P.S. University of Rhode Island College of Pharmacy, Kingston, Rhode Island

KRISTINA E. WARD, PHARM.D., is a clinical assistant professor and Director of Drug Information Services at the University of Rhode Island College of Pharmacy, Kingston, R.I.

ANNE L. HUME, PHARM.D., B.C.P.S., is a professor at the University of Rhode Island College of Pharmacy, and adjunct professor of family medicine at the Memorial Hospital of Rhode Island, Brown University School of Medicine, Providence, R.I.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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