Raltegravir: a review of its use in the management of HIV infection in treatment-experienced patients.

Raltegravir (Isentress), an integrase inhibitor, inhibits the insertion of HIV-1 complementary DNA into the host genome. It is indicated in combination with other antiretroviral therapy (ART) agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple ART agents. It is the first of a new class of ART agents to be approved that, as a result of a different mechanism of action to other ART agents, has good activity against multidrug-resistant HIV-1 strains. In clinical trials in treatment-experienced patients with HIV-1 infection and evidence of viral replication, the addition of oral raltegravir to an optimized background therapy (OBT) regimen improved virological and immunological responses at 16 and 48 weeks to a greater extent than placebo plus OBT. Raltegravir therapy was generally well tolerated, with a similar incidence of mild to moderate adverse events in the treatment and placebo arms. The introduction of integrase inhibitors extends the options available for managing treatment-experienced patients with multiple-drug-resistant HIV-1 infection. Results to date suggest that the combination of raltegravir and OBT will be a valuable treatment option for this difficult-to-treat patient group.

Bicalutamide 150mg: a review of its use in the treatment of locally advanced prostate cancer.

Bicalutamide (Casodex) is a competitive androgen receptor antagonist that inactivates androgen-regulated prostate cell growth and function, leading to cell apoptosis and inhibition of prostate cancer growth. It is administered orally as a once-daily dose. In the EU and a number of other countries, bicalutamide 150 mg/day is approved in men with locally advanced nonmetastatic prostate cancer as immediate therapy either as an adjuvant to active treatment or as monotherapy as an alternative to surgical or medical castration. Combined analysis of the three trials that comprise the bicalutamide Early Prostate Cancer (EPC) programme showed that bicalutamide administered in conjunction with standard care in men with locally advanced prostate cancer offers disease-free survival benefits over standard care alone and is generally well tolerated. Overall survival was improved to a greater extent in the subgroup of patients who received bicalutamide plus radiation therapy compared with radiation therapy alone. Men with localised prostate cancer do not benefit from the addition of bicalutamide to standard care. Combined analysis of two other studies in men with locally advanced prostate cancer show that bicalutamide monotherapy offers better tolerability and higher health-related quality-of-life (HR-QOL) scores for sexual interest and physical capacity compared with surgical or medical castration, while achieving disease-free and overall survival durations that were not significantly different. Thus, when treatment options are being evaluated, bicalutamide as adjuvant therapy or monotherapy should be considered as an alternative to other available hormonal therapies in men with locally advanced prostate cancer, especially in those who wish to maintain an active lifestyle.

Letrozole: a pharmacoeconomic review of its use in postmenopausal women with breast cancer.

Letrozole (Femara), an aromatase inhibitor that blocks estrogen synthesis by inhibiting the final step of the estrogen biosynthetic pathway, is approved for use in a wide range of breast cancer settings. Randomised clinical trials in postmenopausal women with hormone-responsive early-stage breast cancer have demonstrated that, as adjuvant therapy, letrozole has greater efficacy than tamoxifen. It is also more effective than placebo as extended adjuvant therapy after completion of tamoxifen therapy in these patients. In women with hormone-responsive advanced breast cancer, letrozole is superior to tamoxifen in prolonging the time to disease progression and time to treatment failure in a first-line setting, and is at least as effective as anastrozole and more effective than megestrol for some endpoints (in one of two trials) in a second-line setting. Letrozole is generally well tolerated, and in a health-related quality-of-life analysis from a large clinical trial, patient well-being with letrozole as extended adjuvant therapy did not differ from that with placebo. Modelled analyses from the UK and the US suggest that, in postmenopausal women with hormone-receptor-positive early-stage breast cancer, letrozole is likely to be a cost-effective alternative to tamoxifen as adjuvant therapy; moreover, using letrozole as extended adjuvant therapy after tamoxifen, rather than no further treatment, is also a cost-effective treatment strategy. Sensitivity analyses have shown these results to be robust. In terms of direct healthcare costs, pharmacoeconomic models suggest that letrozole is a cost-effective alternative to tamoxifen as first-line therapy in postmenopausal women with hormone-responsive advanced breast cancer from the perspectives of the UK NHS, the Canadian and Italian public healthcare systems and the Japanese national health insurance system. Incremental costs per QALY or progression-free year gained over tamoxifen were well within the recommended limits for acceptability of new agents that are more effective and more expensive than existing therapies in the UK, Japan and Canada. Modelled analyses from the UK and Canada have also suggested that letrozole is cost effective as second-line therapy for advanced breast cancer in postmenopausal women who have disease progression following anti-estrogen therapy. In conclusion, letrozole is an effective and well tolerated treatment for postmenopausal women with early-stage or advanced hormone-responsive breast cancer. Pharmacoeconomic analyses from UK and North American perspectives support the use of letrozole in hormone-responsive early-stage breast cancer in both the adjuvant and extended adjuvant settings. In addition, other modelled analyses conducted in a variety of healthcare systems across different countries consistently suggest that letrozole is cost effective in advanced treatment settings.

Prulifloxacin.

Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum oral fluoroquinolone antibacterial agent. After absorption, prulifloxacin is metabolised by esterases to ulifloxacin. The drug has a long elimination half-life, allowing once-daily administration. Ulifloxacin is generally more active in vitro than other fluoroquinolones against a variety of clinical isolates of Gram-negative bacteria, including community and nosocomial isolates of Escherichia coli, Klebsiella spp., Proteus, Providencia and Morganella spp., Moraxella catarrhalis and Haemophilus spp. The activity of ulifloxacin against Pseudomonas aeruginosa varies between countries. Gram-positive organisms, including meticillin- or oxacillin-susceptible Staphylococcus aureus, Enterococcus spp. and Italian community isolates of Streptococcus pneumoniae are susceptible to ulifloxacin. Activity against Spanish strains of S. pneumoniae is moderate. In well designed clinical trials, good clinical and bacteriological efficacy (similar to that of ciprofloxacin, amoxicillin/clavulanic acid or pefloxacin) was seen with prulifloxacin 600 mg once daily for 10 days in patients with acute exacerbations of chronic bronchitis or complicated lower urinary tract infections (UTIs), and with single-dose prulifloxacin 600 mg in acute, uncomplicated lower UTIs. Prulifloxacin was generally well tolerated in clinical trials, with a similar tolerability profile to that of ciprofloxacin.

Desloratadine: an update of its efficacy in the management of allergic disorders.

UNLABELLED: Desloratadine (Clarinex, Neoclarityn, Aerius, Azomyr, Opulis, Allex), the principal metabolite of loratadine, is itself an orally active, nonsedating, peripheral histamine H(1)-receptor antagonist. It is indicated in the US and Europe for the treatment of seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR) and chronic idiopathic urticaria (CIU). It has a rapid onset of effect, efficacy throughout a 24-hour dosage interval, and sustained efficacy in these allergic conditions, as demonstrated in placebo-controlled trials of up to 6 weeks' duration in adult and adolescent patients. At present, there are no published direct comparisons of desloratadine and other H(1)-antihistamines; however, the principal, potential clinical advantages of desloratadine over late-generation H(1)-antihistamines are the drug's decongestant activity, which has been corroborated in several studies of patients with allergic rhinitis, and its anti-inflammatory effects. Indeed, the decongestant activity of desloratadine did not differ from that of pseudoephedrine in a trial in patients with SAR, and in patients with SAR and coexisting asthma, desloratadine reduced asthma symptoms and beta(2)-agonist use, and improved forced expiratory flow in 1 second. However, these issues warrant further study. Desloratadine is generally well tolerated. The overall incidence of adverse events in adults, adolescents and children was not significantly different to that with placebo, and similar proportions of desloratadine or placebo recipients reported events such as pharyngitis, dry mouth, myalgia, somnolence, dysmenorrhoea or fatigue. Desloratadine does not cause sedation or prolong the corrected QT (QTc) interval, can be administered without regard to concurrent intake of food and grapefruit juice, and appears to have negligible potential for drug interactions mediated by several metabolic systems. CONCLUSION: Although comparative studies with second-generation and other recently developed H(1)-antihistamines are needed to define the drug's clinical profile more clearly, desloratadine can be expected to claim a prominent place in the management of allergic disorders in general, and in the amelioration of specific symptoms of allergy (e.g. nasal congestion) in patients with such disorders.