Drugs
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Letrozole is a highly selective, nonsteroidal, third-generation aromatase inhibitor approved for first-line and extended adjuvant therapy in postmenopausal women with hormone-responsive, early-stage breast cancer. Binding of letrozole to the haeme component of the cytochrome P450 subunit of aromatase inhibits estrogen biosynthesis throughout the body. As first-line adjuvant therapy in approximate, equals 8000 postmenopausal women with hormone-responsive, early-stage breast cancer, once-daily letrozole 2.5mg significantly prolonged disease-free survival (DFS; primary endpoint) and reduced the risk of relapse at distant sites relative to once-daily tamoxifen 20mg in the ongoing Breast International Group 1-98, double-blind, multinational trial. ⋯ Extended adjuvant therapy with once-daily letrozole 2.5mg significantly prolonged DFS relative to placebo treatment at a median follow-up of 30 months (primary endpoint) in the MA-17 trial in approximate, equals 5000 postmenopausal women who were disease free after 4.5-6 years of tamoxifen therapy for hormone-responsive, early-stage breast cancer. Letrozole treatment for up to 5 years was generally well tolerated in this clinical setting. As first-line treatment, relative to tamoxifen, letrozole was associated with a significantly lower incidence of venous thromboembolitic events, vaginal bleeding, hot flushes and night sweating, whereas the incidence of cardiac failure, bone fractures and arthralgia was higher in letrozole recipients.
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Review
Inhaled mometasone furoate: A review of its use in persistent asthma in adults and adolescents.
Inhaled mometasone furoate (Asmanex) is a synthetic corticosteroid indicated for the first-line maintenance prophylactic therapy of persistent asthma in adults and adolescents. It is formulated for delivery via a breath-actuated dry powder inhaler (DPI) [Twisthaler]. Inhaled mometasone furoate delivered by DPI is effective in treating patients with persistent asthma. ⋯ Once-daily administration of mometasone furoate 200 microg in the evening was more effective than administration of the same dosage in the morning. The drug is well tolerated, with low systemic bioavailability and minimal systemic activity. Therefore, it is an effective and convenient option for controller therapy of persistent asthma in adults and adolescents.
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Biochemical markers of bone turnover are used increasingly during the clinical development of drugs for the treatment of metabolic bone diseases such as Paget's disease, osteoporosis and cancer that has metastasised to the bone. However, assessing the optimal value of these markers is often complicated, and such an assessment is an obvious prerequisite for rational use of the markers and, consequently, potential improvement of clinical drug development. Biochemical markers of bone turnover are substances in the blood or urine that are produced or released during bone remodelling. ⋯ However, their role in the development of new drugs is still limited to dose selection, and potential relationships with clinical outcomes remain to be investigated in instances of new mechanisms of action. Biochemical markers of bone turnover are a valuable asset for drug development, but their rational use is determined by a number of variables. Correctly manipulating these may improve clinical development of drugs for the treatment of patients with metabolic bone diseases such as osteoporosis and cancer metastatic to the bone.
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Lubiprostone (Amitiza) is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of the gastrointestinal epithelium, resulting in increased fluid secretion. In two pivotal, randomised, double-blind, multicentre phase III studies in patients with chronic idiopathic constipation, the frequency of spontaneous bowel movements (SBMs) was significantly greater in patients receiving lubiprostone 24microg twice daily than in those receiving placebo at each weekly timepoint throughout both 4-week studies (p < 0.05). ⋯ Lubiprostone was generally well tolerated in clinical trials with no reports of treatment-related serious adverse events in pivotal trials. Nausea was the most common adverse event, occurring in up to 31% of patients receiving lubiprostone.
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The incidence of multiresistance in Gram-positive cocci causing infections in critically ill patients admitted to the intensive care unit (ICU) has increased notably in recent years. Thus, therapeutic proposals have been modified according to the emergence of multiresistant cocci and adapted to epidemiological markers of individual infectious processes, geographical variations of these markers, the availability of new antibacterials, and advances in the knowledge of pharmacokinetic and pharmacodynamic aspects of their use. ⋯ Therapeutic proposals should be developed within the framework of the antibacterial policy of each hospital. The present review is focused on the description of the therapeutic strategies for the main infectious processes caused by Gram-positive cocci in severely ill patients admitted to the ICU according to a review of the pertinent literature and the clinical experience of the authors.