Cladribine: an investigational immunomodulatory agent for multiple sclerosis.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of cladribine, a purine analog undergoing Phase III trials for approval of its use in the treatment of multiple sclerosis (MS). DATA SOURCES: A MEDLINE search (1966-September 2006) was conducted using the key words cladribine and multiple sclerosis. No limits were placed on the search. STUDY SELECTION AND DATA EXTRACTION: Studies and review articles related to cladribine and MS were reviewed. The trials examining the role of cladribine in MS were analyzed. DATA SYNTHESIS: Cladribine is a purine analog that demonstrates lymphocytotoxic activity. Recent data suggest that cladribine may have a role in the treatment of relapsing-remitting and the progressive forms of MS. In these studies, cladribine has shown mixed results in decreasing neurologic disability, as measured by various rating scales, but has consistently shown positive results in reducing the number of enhancing lesions, which reflects a measure of disease activity. To date, there is one ongoing study examining the role of oral cladribine in the treatment of relapsing-remitting MS. The incidence of adverse effects with cladribine has been significantly greater than with placebo, with the most common being myelosuppression. CONCLUSIONS: While data do not support its use as a first-line MS treatment, cladribine may be a promising agent for refractory patients with secondary progressive MS. Further studies are warranted.

Olmesartan medoxomil: an angiotensin II-receptor blocker.

BACKGROUND: Regulation of the activity of the renin-angiotensin-aldosterone system has become important in the management of cardiovascular disease. Olmesartan medoxomil (CS-866) is the newest selective angiotensin II-receptor blocker (ARB) to be approved for the treatment of hypertension. OBJECTIVE: This review describes the mechanism of action, pharmacokinetics, adverse-effect profile, drug-interaction potential, and dosing of olmesartan medoxomil. The results of relevant clinical efficacy and safety trials are also discussed. METHODS: This review is based on data from published clinical efficacy and safety trials and abstracts of conference presentations. To identify appropriate English-language publications for review, MEDLINE (1966-October 2002) and EMBASE (1990-2002) were searched using the terms olmesartan medoxomil, CS-866, angiotensin II-receptor blocker, and hypertension. RESULTS: Olmesartan medoxomil has been reported to be an effective agent for the treatment of hypertension. Its blood pressure-lowering effects were comparable to those of other antihypertensive agents and other ARBs. Effects were seen as early as 2 weeks and persisted when olmesartan medoxomil was administered long term (for 1 year). The maximum recommended daily dose is 40 mg, except in the presence of severe renal insufficiency (creatinine clearance <20 mL/min) or moderate hepatic insufficiency (Child-Pugh score 7-9), when the daily dose should not exceed 20 mg. Olmesartan medoxomil was well tolerated. The most commonly reported adverse effect occurring significantly more often with olmesartan medoxomil than with placebo was dizziness (seen in approximately 3% of patients). The occurrence of clinically significant drug interactions was minimal. CONCLUSIONS: Based on the available literature, olmesartan medoxomil is an effective ARB for the treatment of hypertension, with a favorable adverse-effect and drug-interaction profile.