Expert opinion on drug safety
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Expert Opin Drug Saf · Nov 2004
ReviewSafety of drotrecogin alfa (activated) in the treatment of patients with severe sepsis.
While severe sepsis continues to plague hospitals worldwide, new treatment modalities, including activated recombinant protein C (drotrecogin alfa, Xigris, Lilly), have become a standard treatment alternative in many institutional algorithms. Drotrecogin alfa was shown to have a beneficial effect on mortality versus placebo in the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial (p = 0.005), but its use is not completely without risk. ⋯ After almost three years on the US market, the reported incidence of severe bleeding episodes has risen only slightly from the pre-marketing era, at that time notable for restrictive treatment protocols, devoid of at-risk patients. Drotrecogin alfa, while a promising agent for severe sepsis, requires prudent patient evaluation for bleeding risks.
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Benzodiazepines are the most frequently prescribed antianxiety drugs in the elderly. Despite their usefulness and safety in the younger population, there is concern about the rationale for their use in the elderly. Studies of the therapeutic use of benzodiazepines in the elderly are rare. ⋯ Significant adverse effects that may be associated with benzodiazepine use in the elderly include falls, cognitive impairment, sedation, and impairment of driving skills, all of which are particularly related to the long half-life of benzodiazepines. Long-term use of benzodiazepines should be discouraged because of the risk of dependence, which is a serious problem in the elderly. Unrecognised and untreated benzodiazepine dependence can lead to serious medical complications.
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Urticaria is characterised by transient swellings of the skin, which fluctuate over hours. Deeper swellings of the subcutaneous and submucosal tissue are known as angio-oedema. Drug-induced urticaria has been reported with a wide range of drugs and vaccines. ⋯ Spontaneous reports of drug-induced urticaria to the Committee on Safety of Medicines, UK, over a 40-year period also implicate bupropion, selective serotonin re-uptake inhibitor antidepressants, angiotensin-converting enzyme inhibitors (ACEI), H2 and H1 antihistamines, and systemic antifungals. New evidence suggests that selective COX-2 inhibitors may be tolerated in patients with aspirin-sensitive urticaria. The safety of angiotensin II receptor antagonists in patients with angio-oedema induced by ACEI has not yet been established.
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By the year 2000, droperidol had become a standard drug for the treatment of behavioural emergencies in both psychiatric and medical settings. In 2001, the US FDA issued a 'black box' warning, citing cases of QT prolongation and/or torsades de pointes. As a result, the use of droperidol has been sharply circumscribed. ⋯ The authors conclude that, while in theory droperidol may prolong the QT interval to an extent similar to thioridazine, its long history of clinical use has shown no pattern of sudden deaths analogous to those that provoked the FDA warning. Although the numbers presented by the FDA initially appear alarming, after further evaluation it is clear that more definitive studies should have been carried out. Droperidol is safe, extremely effective, and now underused as a treatment for severely agitated or violent patients.
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The human epidermal growth factor receptor (HER) 2 is overexpressed in approximately 20-25% of human breast cancers and is an independent adverse prognostic factor. Targeted therapy directed against this receptor has been developed in the form of a humanised monoclonal antibody, trastuzumab. This antibody has shown activity as a single agent in metastatic breast cancer both prior to chemotherapy and in heavily pretreated patients. ⋯ Some patients may experience fever, chills, dyspnoea and pain, particularly with the first administration. Unexpectedly, cardiac toxicity has developed in some patients treated with trastuzumab, and this has a higher incidence in those treated in combination with an anthracycline. 'Cross-talk' between the oestrogen receptor and HER2 pathway has stimulated interest in using trastuzumab in combination with endocrine therapy. Current clinical trials are investigating the role of this agent in the adjuvant setting.