Escitalopram : a review of its use in the management of major depressive and anxiety disorders

Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Asberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1-2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8-12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use.CONCLUSIONS: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selective inhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders.     

Escitalopram: a review of its use in the management of major depressive disorder

Escitalopram (Cipralex, Lexapro), the active S-enantiomer of the racemic selective serotonin reuptake inhibitor (SSRI) citalopram (RS-citalopram), is a highly selective inhibitor of the serotonin transporter protein. It possesses a rapid onset of antidepressant activity, and is an effective and generally well tolerated treatment for moderate-to-severe major depressive disorder (MDD). Pooled analyses from an extensive clinical trial database suggest that escitalopram is consistently more effective than citalopram in moderate-to-severe MDD. Preliminary studies suggest that escitalopram is as effective as other SSRIs and the extended-release (XR) formulation of the serotonin/noradrenaline (norepinephrine) reuptake inhibitor venlafaxine, and may have cost-effectiveness and cost-utility advantages. However, additional longer-term, comparative studies evaluating specific efficacy, tolerability, health-related quality of life and economic indices would be helpful in definitively positioning escitalopram relative to these other agents in the treatment of MDD. Nevertheless, available clinical and pharmacoeconomic data indicate that escitalopram is an effective first-line option in the management of patients with MDD.     

Escitalopram: a pharmacoeconomic review of its use in depression

Escitalopram (Cipralex), a new highly selective serotonin reuptake inhibitor (SSRI), is the active S-enantiomer of RS-citalopram. It is effective in the treatment of patients with major depressive disorder (MDD) and may have a faster onset of therapeutic effect than citalopram. It has also been shown to lead to improvements in measures of QOL. Escitalopram is generally well tolerated, with nausea being the most common adverse event associated with its use. Modelled pharmacoeconomic analyses found escitalopram to have a cost-effectiveness and cost-utility advantage over other SSRIs, including generic citalopram and fluoxetine and branded sertraline, and also over the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine extended-release (XR). These studies used a decision-analytic approach with a 6-month time horizon and were performed in Western Europe (year of costing 2000 or 2001). Cost-effectiveness ratios for escitalopram, in terms of cost per successfully treated patient over 6 months, ranged from Euro 871 to Euro 2598 in different countries, based on direct costs and remission rates, and were consistently lower (i.e. more favourable) than the ratios for comparators (Euro 970 to Euro 3472). Outcomes similarly favoured escitalopram when indirect costs (represented by those associated with sick leave and loss of productivity) were included. The results of comparisons with citalopram, fluoxetine and sertraline were not markedly affected by changes to assumptions in sensitivity analyses, although comparisons with venlafaxine XR were sensitive to changes in the remission rate. The mean number of QALYs gained during the 6-month period was similar for all drugs evaluated, but direct costs were lower with escitalopram, leading to lower cost-utility ratios than for comparators. Incremental analyses performed in two of the studies confirmed the cost-effectiveness and cost-utility advantage of escitalopram. A prospective, 8-week comparative pharmacoeconomic analysis found that escitalopram achieved similar efficacy to venlafaxine XR, but was associated with 40% lower direct costs (Euro 85 vs Euro 142 per patient over 8 weeks; 2001 costs), although this difference did not reach statistical significance. In both the modelled and prospective analyses, the differences in overall direct costs were mainly due to lower secondary care costs (in particular those related to hospitalisation) with escitalopram. In the prospective analysis, escitalopram had lower estimated drug acquisition costs than venlafaxine XR. CONCLUSION: Escitalopram, the S-enantiomer of RS-citalopram and a highly selective SSRI, is an effective antidepressant in patients with MDD, has a favourable tolerability profile, and, on the basis of available data, appears to have a rapid onset of therapeutic effect. Modelled pharmacoeconomic analyses from Western Europe suggest that it may be a cost-effective alternative to generic citalopram, generic fluoxetine and sertraline. Although the available data are less conclusive in comparison with venlafaxine XR, escitalopram is at least as cost effective as the SNRI based on a prospective study, and potentially more cost effective based on modelled analyses. Overall, clinical and pharmacoeconomic data support the use of escitalopram as first-line therapy in patients with MDD.     

Dutasteride: a review of its use in the management of prostate disorders

Dutasteride (Avodart), an oral synthetic 4-azasteroid, is a potent, selective, irreversible inhibitor of type 1 and type 2 5alpha-reductase (5AR), the enzyme that converts testosterone to dihydrotestosterone (DHT) intracellularly. Although type 2 5AR predominates, both isoenzymes are overexpressed in prostate tissue in benign prostatic hyperplasia (BPH) and at all stages in some prostate cancers. Oral dutasteride 0.5 mg once daily is approved for the treatment of moderate to severe symptomatic BPH in men with an enlarged prostate to improve symptoms, and to reduce the risk of acute urinary retention (AUR) and the need for BPH-related surgery.In pivotal 2-year phase III trials, oral dutasteride 0.5 mg once daily improved urinary symptoms, decreased total prostate volume (TPV), and reduced the risk of AUR and BPH-related surgery in men with moderate to severe symptoms of BPH and prostate enlargement. The good efficacy and tolerability of dutasteride was maintained for up to 4 years in open-label extension studies. Results of the pre-planned, 2-year interim analysis of the CombAT trial showed that the combination of dutasteride and tamsulosin was superior to either drug as monotherapy in improving BPH-related symptoms, peak urinary flow and BPH-related health status. The overall adverse event profile for combination therapy was consistent with those reported for both monotherapies. Although drug-related adverse events were more frequent with combination therapy versus both monotherapies, most did not result in treatment cessation. Dutasteride is being investigated for its efficacy in reducing the risk of prostate cancer in at-risk men in the 4-year REDUCE study and as treatment to extend the time to progression in men with low-risk localized prostate cancer who would otherwise undergo watchful waiting in the 3-year REDEEM study. Thus, dutasteride is an effective treatment option in patients with moderate to severe symptomatic BPH and demonstrable prostatic enlargement, and may have potential to reduce the risk of developing biopsy-detectable prostate cancer in at-risk individuals or extending the time to progression in low-risk localized prostate cancer.     

Desirudin: a review of its use in the management of thrombotic disorders

Desirudin, a recombinant hirudin used in the prevention and management of thromboembolic disease, is a thrombin inhibitor which binds directly and with high affinity to clot-bound and fluid phase thrombin. As a prophylaxis in patients undergoing hip replacement surgery, desirudin was significantly more effective in reducing the incidence of deep vein thrombosis (DVT) than either unfractionated or low molecular weight heparin. However, results in patients with acute coronary syndromes are less conclusive. A significant reduction with desirudin compared with heparin in the incidence of death or non-fatal (re)infarction at 24 hours in patients with acute myocardial infarction (MI) was reported in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial but not in the TIMI (Thrombolysis and Thrombin Inhibition in Myocardial Infarction) 9B trial. Despite the early reduction shown in GUSTO IIb, desirudin was not associated with an improved long term clinical benefit at 30 days compared with heparin. Similar results were seen in patients with unstable angina/non-Q-wave MI enrolled in the GUSTO IIb trial. In addition, desirudin and heparin showed similar efficacy in preventing restenosis 30 weeks after coronary angioplasty for unstable angina, despite desirudin being associated with a significant reduction in the rate of cardiac events within the first 96 hours. Desirudin is as well tolerated as heparin with a similar incidence of moderate and severe bleeding, intracranial haemorrhage or stroke reported when trialled in the prevention of DVT associated with hip replacement surgery or the treatment of acute coronary syndromes. However, in the GUSTO IIb trial a significantly higher incidence of transfusions was observed in patients with unstable angina/non-Q-wave MI. Conclusions: Desirudin is clearly more effective than heparin in the prevention of DVT in patients undergoing elective hip replacement, although cost factors may influence its ultimate place in therapy. In the treatment of acute coronary syndromes the role of desirudin is less certain; however, it may be useful for patients in whom heparin therapy is not a viable option.     

Rupatadine: a review of its use in the management of allergic disorders

Rupatadine (Rupafin, Rinialer, Rupax, Alergoliber) is a selective oral histamine H(1)-receptor antagonist that has also been shown to have platelet-activating factor (PAF) antagonist activity in vitro. It is indicated for use in seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and chronic idiopathic urticaria (CIU) in patients aged >/=12 years.Clinical trials show that rupatadine is an effective and generally well tolerated treatment for allergic rhinitis and CIU. It has a rapid onset of action and a prolonged duration of activity. Importantly, it has no significant effect on cognition, psychomotor function or the cardiovascular system. Once-daily rupatadine significantly improves allergic rhinitis symptoms in patients with SAR, PAR or persistent allergic rhinitis (PER) compared with placebo, and provides similar symptom control to that of loratadine, desloratadine, cetirizine or ebastine. In patients with CIU, longer-term use of rupatadine improves CIU symptoms to a greater extent than placebo. It is as well tolerated as other commonly used second-generation H(1)-receptor antagonists. Thus, the introduction of rupatadine extends the range of oral agents available for the treatment of allergic disorders, including allergic rhinitis and CIU.     

Esomeprazole: a review of its use in the management of acid-related disorders

Esomeprazole (S-isomer of omeprazole), the first single optical isomer proton pump inhibitor, generally provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In a large well designed 8-week trial in patients (n >5000) with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving lansoprazole. Respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Overall, esomeprazole was also better than omeprazole, although these differences were not always statistically significance. Ninety-two to 94% of esomeprazole recipients (40mg once daily) achieved healed oesophagitis versus 84 to 90% of omeprazole recipients (20mg once daily). Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. Resolution of heartburn was also significantly better with esomeprazole 40mg than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healing in these patients. Once-daily esomeprazole 20 or 40mg for 4 weeks resolved symptoms in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Symptoms were effectively managed in the long-term with symptom-driven on-demand esomeprazole (20 or 40mg once daily). Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Seven days' treatment (twice-daily esomeprazole 20mg plus amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in >/=86% of patients (intention-to-treat), a rate that was similar to equivalent omeprazole-based regimens. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents, with a tolerability profile similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients), with very few (<1%) drug-related serious adverse events reported. CONCLUSIONS: Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.     

Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders

Fluvoxamine is a potent and selective serotonin reuptake inhibitor (SSRI) that has little or no effect on other monoamine reuptake mechanisms. Relative to other SSRIs, fluvoxamine is a weak inhibitor of cytochrome P450 (CYP) 2D6, a moderate inhibitor of CYP2C19 and CYP3A4 and a potent inhibitor of CYP1A2. In randomised, double-blind trials. fluvoxamine 100 to 300 mg/day for 6 to 10 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) compared with placebo. Response rates of 38 to 52% have been reported with fluvoxamine, compared with response rates of 0 to 18% with placebo. In patients with OCD, fluvoxamine had similar efficacy to that of clomipramine and, in smaller trials, the SSRIs paroxetine and citalopram and was significantly more effective than desipramine. Maintenance therapy with fluvoxamine may reduce the likelihood of relapses in up to 67% of patients with OCD. Fluvoxamine < or = 300 mg/day for 6 to 8 weeks was as effective as imipramine in patients with panic disorder, and significantly more effective than placebo. In addition, treatment with fluvoxamine < or = 300 mg/day for > or = 8 weeks improved symptoms of social phobia (social anxiety disorder), post-traumatic stress disorder (PTSD), pathological gambling, compulsive buying, trichotillomania, kleptomania, body dysmorphic disorder, eating disorders and autistic disorder. Large trials comparing the efficacy of fluvoxamine and other SSRIs in patients with anxiety disorders are warranted. Fluvoxamine is generally well tolerated; in postmarketing studies, nausea was the only adverse event occurring in >10% of patients with less commonly reported events including somnolence, asthenia, headache, dry mouth and insomnia. Fluvoxamine is associated with a low risk of suicidal behaviour, sexual dysfunction and withdrawal syndrome. Fewer anticholinergic or cardiovascular events are associated with fluvoxamine than tricyclic antidepressants. Although comparative data are lacking, the tolerability profile of fluvoxamine appears to be broadly similar to those of other SSRIs. CONCLUSION: Fluvoxamine has demonstrated short term efficacy in the treatment of OCD, panic disorder, social phobia, PTSD and in a range of obsessive-compulsive spectrum disorders. The drug is as effective as clomipramine in patients with OCD but appears to have a better tolerability profile. On the basis of current treatment guidelines, fluvoxamine, like other SSRIs, is recommended as first-line treatment for a number of anxiety disorders. It appears to offer some pharmacokinetic advantages and a different drug interaction profile to the other SSRIs with a broadly similar spectrum of adverse events. However, direct comparisons are required to assess the relative efficacy and tolerability of the different agents of this drug class.     

The pharmacological management of childhood anxiety disorders: a review

Rationale Pediatric anxiety is a prevalent psychiatric disorder that may have important implications for school, social, and academic function. Psychopharmacological approaches to the treatment of pediatric anxiety have expanded over the past 20 years and increasing empirical evidence helps guide current clinical practice. Objective To review studies which examine the pharmacological treatment of pediatric anxiety disorders, including obsessive–compulsive disorder and to summarize treatment implications. Methods All relevant studies were searched using MEDLINE and PsycINFO search engines, supplemented by a manual bibliographical search; studies published between 1985 and 2006 that met inclusion criteria were examined. Results This article provides a systematic review of the psychopharmacological treatment of pediatric anxiety disorders based on available empirical evidence, with a focus on randomized controlled trials. General treatment principles and pharmacological management of specific pediatric anxiety disorders are also reviewed. Conclusion There is good evidence to support the efficacy of several pharmacological agents including the selective serotonin reuptake inhibitors to treat pediatric anxiety and obsessive–compulsive disorder, although there are still many unanswered questions.     

Esomeprazole: a review of its use in the management of acid-related disorders in the US

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as a single optical isomer. It provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In large well designed 8-week trials in patients with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as the baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole 40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole recipients (20mg once daily). In a study in >5000 patients, respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Resolution of heartburn was also significantly better with esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Ten days' triple therapy (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents. The tolerability profile is similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients) and very few (<1%) drug-related serious adverse events were reported. CONCLUSIONS: Esomeprazole is an effective and well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind trials, esomeprazole provided significantly better efficacy than omeprazole or lansoprazole in terms of both healing rates and resolution of symptoms. Long-term therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole was also effective in patients with symptomatic GORD. Thus, esomeprazole has emerged as an effective option for first-line therapy in the management of acid-related disorders.     

Cetirizine: a review of its use in allergic disorders

Cetirizine is a selective, second-generation histamine H1 receptor antagonist, with a rapid onset, a long duration of activity and low potential for interaction with drugs metabolised by the hepatic cytochrome P450 system. Cetirizine was generally more effective than other H1 receptor antagonists at inhibiting histamine-induced wheal and flare responses. Cetirizine is an effective and well tolerated agent for the treatment of symptoms of seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and chronic idiopathic urticaria (CIU) in adult, adolescent and paediatric patients. In adults with these allergic disorders, cetirizine was as effective as conventional dosages of ebastine (SAR, PAR, CIU), fexofenadine (SAR), loratadine (SAR, CIU) or mizolastine (SAR). This agent was significantly more effective, and with a more rapid onset of action, than loratadine in 2-day studies in environmental exposure units (SAR). In paediatric patients, cetirizine was as at least as effective as chlorphenamine (chlorpheniramine) [SAR], loratadine (SAR, PAR) and oxatomide (CIU) in the short term, and more effective than oxatomide and ketotifen (PAR) in the long term. Cetirizine was effective in reducing symptoms of allergic asthma in adults and reduced the relative risk of developing asthma in infants with atopic dermatitis sensitised to grass pollen or house dust mite allergens. It had a corticosteroid-sparing effect in infants with severe atopic dermatitis and was effective in ameliorating reactions to mosquito bites in adults. Cetirizine was well tolerated in adults, adolescents and paediatric patients with allergic disorders. In adult, adolescent and paediatric patients aged 2-11 years, the incidence of somnolence with cetirizine was dose related and was generally similar to that with other second-generation H1 receptor antagonists. Although, its sedative effect was greater than that of fexofenadine in some clinical trials and that of loratadine or fexofenadine in a postmarketing surveillance study. In infants aged 6-24 months, the tolerability profile of cetirizine was similar to that of placebo. Cetirizine did not have any adverse effects on cognitive function in adults, or cognitive function, behaviour or achievement of psychomotor milestones in paediatric patients. Cetirizine was not associated with cardiotoxicity. CONCLUSION: Cetirizine is well established in the treatment of symptoms of SAR, PAR or CIU. It demonstrated a corticosteroid-sparing effect and reduced the relative risk of developing asthma in sensitised infants with atopic dermatitis. Cetirizine was effective in the treatment of allergic cough and mosquito bites; however, its precise role in these indications has yet to be clearly established. On the basis of its favourable efficacy and tolerability profile and rapid onset of action, cetirizine provides an important option for the treatment of a wide range of allergic disorders.     

Fluvastatin: a review of its use in lipid disorders

Fluvastatin is an HMG-CoA reductase inhibitor used to treat patients with hypercholesterolaemia. Since fluvastatin was last reviewed in Drugs, trials have shown its efficacy in the secondary prevention of coronary heart disease (CHD) events and death and have expanded knowledge of its effects in primary CHD prevention and its mechanisms of activity. In addition to reducing total (TC) and low density lipoprotein (LDL-C) cholesterol, fluvastatin has antiatherogenic, antithrombotic and antioxidant effects, can improve vascular function, and may have immunomodulatory effects. Although fluvastatin interacts with bile acid sequestrants (requiring separation of doses), its pharmacokinetics permit oral administration to most patient groups. Fluvastatin is well tolerated, with adverse effects usually mild and transient. Use of fluvastatin to reduce lipids in patients with primary hypercholesterolaemia is well established. Its effects are similar in most patient groups, with 20 to 80 mg/day reducing LDL-C by 22 to 36%, triglycerides (TG) by 12 to 18% and apolipoprotein B by 19 to 28% and increasing high density lipoprotein cholesterol by 3.3 to 5.6%. Attempts to find fluvastatin dosages with efficacy equivalent to that of other HMG-CoA reductase inhibitors produce variable results, but larger per-milligram fluvastatin dosages are needed when patients switch from other HMG-CoA reductase inhibitors. Combinations of fluvastatin with fibric acid derivatives and bile acid sequestrants produce additive effects. Small noncomparative studies suggest fluvastatin reduces LDL-C in patients with hypercholesterolaemia secondary to kidney disorders by < or = 40.5% and with type 2 diabetes mellitus by < or = 32%. Three large randomised, double-blind trials show fluvastatin can help prevent CHD events or death and slow disease progression in patients with CHD with or without hypercholesterolaemia. In the Fluvastatin Angiographic Restenosis trial in patients undergoing balloon angioplasty, fluvastatin 80 mg/day for 40 weeks reduced the postangioplasty rate of deaths plus myocardial infarctions (1.5% vs 4% with placebo, p < 0.025) without altering vessel luminal diameters. In the Lipoprotein and Coronary Atherosclerosis Study in patients with coronary artery stenosis, luminal diameter reduced to a significantly lesser extent after fluvastatin 20 mg twice daily than placebo after 2.5 years (-0.028 vs -0.01 mm, p < 0.005). The Lescol in Symptomatic Angina study found reductions in all cardiac events or cardiac death in patients after 1 year of fluvastatin 40 mg/day (1.6% vs 5.6% for placebo, p < 0.05). CONCLUSIONS: An evolving pattern of data suggests that, in addition to its well established efficacy and cost effectiveness in reducing hypercholesterolaemia, fluvastatin may now also be considered for use in the secondary prevention of CHD.     

Eprosartan: a review of its use in the management of hypertension

The angiotensin II receptor antagonist eprosartan is approved for the treatment of essential hypertension and may be administered using a convenient once-daily regimen. The drug is a well tolerated and effective antihypertensive agent with benefit in the secondary prevention of cerebrovascular events, independent of blood pressure (BP)-lowering effects. Eprosartan has a low potential for serious adverse events and has not been associated with clinically significant drug interactions, establishing it as a promising agent for combination antihypertensive strategies. Unlike ACE inhibitors such as enalapril, eprosartan does not have a tendency to cause persistent nonproductive cough. Accordingly, eprosartan represents a useful therapeutic option in the management of patients with hypertension, including those who have had a stroke and those with co-morbid type 2 diabetes mellitus.     

Eprosartan: a review of its use in the management of hypertension

Eprosartan is a potent and selective angiotensin II subtype 1 receptor antagonist. Results of large (n > 100) randomised double-blind studies in patients with mild, moderate or severe hypertension demonstrated that the antihypertensive efficacy of eprosartan (usually 400 to 800 mg/day as a single daily dose or in 2 divided doses) is significantly greater than that of placebo and at least as good as that of enalapril. In placebo-controlled trials, eprosartan achieved mean reductions from baseline in trough sitting systolic blood pressure of 6.3 to 15 mm Hg and in diastolic blood pressure of 4.1 to 9.7 mm Hg. Response rates associated with once daily administration of eprosartan 400 to 800 mg were approximately double those with placebo. Overall, eprosartan was well tolerated with a similar tolerability profile to that of placebo. In comparative trials, in which the incidence of persistent dry cough was evaluated as the primary end-point, enalapril was several-fold more likely to induce this adverse event than eprosartan (the difference being statistically significant regardless of study population and definition of cough). In conclusion, the angiotensin II receptor antagonist eprosartan is a well tolerated and effective antihypertensive agent that is administered once or twice daily without regard to meals. Eprosartan has a low potential for serious adverse events, and the drug has not been associated with clinically significant drug interactions. Unlike ACE inhibitors such as enalapril, eprosartan does not have a high propensity to cause persistent nonproductive cough. Thus, eprosartan represents a useful therapeutic option in the management of patients with hypertension.     

Telmisartan: a review of its use in the management of hypertension

Telmisartan (Micardis, Pritor), a highly selective angiotensin II (AII) type 1 (AT1) receptor antagonist, is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. The long elimination half-life of telmisartan ensures the drug provides effective reductions in blood pressure (BP) across the entire 24-hour dosage interval. Extensive evidence from well designed clinical trials and the clinical practice setting indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with coexisting type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 6 hours of this period. Independent of its effect on BP, telmisartan displays favourable effects on insulin resistance, lipid levels, left ventricular hypertrophy (LVH) and renal function. The consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-lowering effect in the long term, combined with its favourable tolerability profile, mean that telmisartan is a valuable first-line treatment option for the management of essential hypertension.     

Ciclesonide: a review of its use in the management of asthma

Ciclesonide (Alvesco) is an inhaled corticosteroid used in the preventative treatment of persistent bronchial asthma in adults, adolescents and, in some countries, children. The drug is delivered by a non-chlorofluorocarbon hydrofluoroalkane (HFA) metered-dose inhaler (MDI). In the lungs, ciclesonide is converted to an active metabolite, which is responsible for the beneficial effects of the drug in patients with asthma. Ciclesonide and its active metabolite have low systemic bioavailability and therefore have a low potential to produce systemic adverse events. Inhaled ciclesonide delivered by HFA-MDI is effective in the prophylactic treatment of persistent asthma in adults, adolescents and children, and is generally well tolerated. In general, ciclesonide improves lung function and reduces asthma symptoms and rescue medication use in adults and adolescents with asthma of varying severity. The drug is generally no less effective than other inhaled corticosteroids with regard to maintaining or improving lung function and may have a more favourable tolerability profile than some other agents in this class. Ciclesonide has also shown efficacy in paediatric patients with asthma. Data on its long-term effects on other clinical outcomes, such as asthma exacerbations, would be of interest. Further comparative and long-term studies would also be beneficial in order to definitively position ciclesonide with respect to other inhaled corticosteroids. In the meantime, ciclesonide offers an effective and well tolerated first-line preventative treatment option for persistent asthma.     

Pranlukast: a review of its use in the management of asthma

Pranlukast (Onon, Azlaire), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C(4), LTD(4) and LTE(4). It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients. The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225 mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma. In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely. CONCLUSIONS: Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting beta(2)-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma.     

Lacidipine: a review of its use in the management of hypertension

Lacidipine (Caldine, Lacimen, Lacipil, Midotens, Motens) is a once-daily, orally-administered, lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity, resulting in a lack of reflex tachycardia. It has a long duration of action and a high degree of vascular selectivity. In addition to calcium channel-modulated vasodilation, lacidipine displays antioxidant activity greater than that of other dihydropyridine calcium antagonists. In randomised, well-controlled trials, lacidipine 2-6 mg orally once daily had antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor). Lacidipine was effective in elderly patients (including those with isolated systolic hypertension), African Nigerian patients and patients with concurrent type 2 diabetes mellitus. During long-term treatment for 4 or 5 years in patients with isolated systolic hypertension or essential hypertension, the incidence of cardiovascular events and mortality with lacidipine was similar to that with chlorthalidone or atenolol. The European Lacidipine Study on Atherosclerosis (ELSA), in which 2334 patients with hypertension were randomised to 4 years of therapy with lacidipine 4-6 mg/day or the beta-blocker atenolol 50-100 mg/day, demonstrated significantly lower atherosclerotic progression and plaque formation with lacidipine compared with atenolol in patients completing the full 4 years of the study. Between-group differences in favour of lacidipine for the primary efficacy variable (mean change in carotid artery intima-media thickness) did not reach statistical significance in the intent-to-treat population. The tolerability profile of lacidipine (headache, flushing, pedal oedema, dizziness and palpitations) is similar to that of other dihydropyridine calcium antagonists, but with a lower incidence of peripheral oedema. Data from the ELSA study suggest that the incidence of serious adverse events during long-term lacidipine therapy is similar to that with atenolol. CONCLUSION: Lacidipine is an effective, well tolerated, once-daily, oral antihypertensive agent that can be used in a wide variety of patients. As with other members of its class, lacidipine has shown potentially beneficial antiatherosclerotic effects, although definitive data with respect to possible superiority over other drug classes are still required. Therefore, lacidipine is an attractive therapy for the long-term management of essential hypertension.     

Glucosamine: a review of its use in the management of osteoarthritis

Glucosamine occurs naturally in all human tissues. It stimulates the synthesis of glycosaminoglycan, proteoglycan and hyaluronic acid, although the precise mechanism of action remains to be established. Formulated as glucosamine sulphate (Dona) and various others), glucosamine has been evaluated for its efficacy in relieving the symptoms of osteoarthritis and its disease-modifying potential.In two large randomised, double-blind, multicentre studies in patients with osteoarthritis, oral or intramuscular glucosamine for 4-6 weeks was associated with a greater decrease in symptom severity (as assessed by the Lequesne index) than placebo. In addition, there was a greater proportion of responders (defined as patients with a >or=3-point reduction in the Lequesne index, along with a positive overall assessment by the investigator) at the end of the treatment period with glucosamine than with placebo. In two large 4-week trials, oral glucosamine produced similar improvements to ibuprofen in the Lequesne index in one study and in articular pain scores in the other study. In a smaller 8-week comparative trial, oral glucosamine therapy achieved a significantly greater improvement in articular pain score than ibuprofen, and the investigators rated treatment efficacy as 'good' in a significantly greater proportion of glucosamine than ibuprofen recipients. In comparison with piroxicam, glucosamine significantly improved arthritic symptoms after 12 weeks of therapy and remained effective 8 weeks after treatment was discontinued. Beneficial effects of long-term oral glucosamine therapy in preventing joint space narrowing and improving symptoms were shown in two 3-year placebo-controlled trials in a total of 414 patients with osteoarthritis. Statistically significant differences favouring glucosamine were noted in the per-protocol and intention-to-treat analyses for the primary endpoints for both joint structural changes and symptom modification. Glucosamine has a tolerability profile similar to that of placebo and is better tolerated than ibuprofen or piroxicam. In particular, glucosamine recipients had a markedly lower incidence of gastrointestinal disturbances than those receiving ibuprofen. Other adverse events reported in both glucosamine and ibuprofen recipients were pruritus or skin reactions, flushing and fatigue. In general, a lower incidence of withdrawal from clinical trials was reported for glucosamine recipients than either ibuprofen or piroxicam recipients.CONCLUSION: In short-term clinical trials, glucosamine provided effective symptomatic relief for patients with osteoarthritis of the knee. In addition, glucosamine has shown promising results in modifying the progression of arthritis over a 3-year period. Glucosamine may therefore prove to be a useful treatment option for osteoarthritis.