Nicorandil: serious gastrointestinal ulceration

(1) Nicorandil is a vasodilator with limited efficacy, marketed for symptomatic relief of angina pectoris. Oral ulcerations, sometimes quite large, are an adverse effect of nicorandil that has been known since the 1990s. Cases of painful anal ulceration were reported later. (2) More recently, it has emerged that nicorandil can also cause very painful chronic ulceration of the colon and small intestine. Painful parastomal ulceration has also been reported in patients with ileostomies or colectomies. (3) Gastrointestinal ulceration has been reported from the mouth to the perineum. It is sometimes associated with skin ulcers. (4) In some cases the lesions are sufficiently extensive and refractory to warrant surgery (colostomy) or immunosuppressant treatment. However, simply withdrawing nicorandil generally leads to recovery with a few weeks. (5) Nicorandil should not be considered a standard treatment for angina pectoris. It is better to choose another drug such as a betablocker. Nicorandil must be withdrawn if cutaneous or gastrointestinal ulceration occurs.     

Lindane: serious neurological effects

(1) Cutaneous application of lindane carries a risk of systemic adverse effects, including serious neurological disorders. Lindane is readily absorbed through the skin, especially damaged skin and in children. (2) In practice, lindane has no place in the treatment of either lice or scabies.     

Voriconazole: serious adverse effects and interactions

Data contained in the French national pharmacovigilance database confirm the hepatic, cardiac, visual and cutaneous adverse effects of voriconazole, and the risk of drug interactions. Neuropsychological disorders (hallucinations, delirium, etc.) have also been reported.     

更昔洛韦致白细胞严重降低1例

［摘要］文中报道了使用更昔洛韦致白细胞严重降低的1例病例。提醒我们必须关注此药的不良反应,严格控制其适应证、用量及疗程。     

Bevacizumab: serious neurological disorders and nasal perforations

The list of bevacizumab's adverse effects continues to grow: the latest additions are reversible posterior leukoencephalopathy and perforation of the nasal septum.     

Multiple sclerosis: interferon beta for some serious forms

(1) Multiple sclerosis is a neurological disorder characterised by disseminated inflammatory lesions of the myelin sheath, the white fatty layer that covers the neurons in the brain and spinal column. The clinical repercussions are highly variable, ranging from minor deficits to severe disability and even death. Some patients have exacerbations separated by remissions of varying length, while others experience fairly steady progression of disability. This review article, based on Prescrire's standard in-house methodology, examines treatments proposed to slow the progression of multiple sclerosis. (2) For exacerbations (4 trials, a total of 140 patients), an improvement was noted in 64% of patients treated with intravenous methylprednisolone for 5 days, versus 40% of patients on placebo. (3) Interferon beta is the best-assessed of the disease-modifying drugs. Various marketed interferon beta products have been compared with one another in trials involving more than 1000 patients in total. There are no major differences in effectiveness or adverse effects. The latter are frequent, especially a flu-like syndrome and depression. (4) After a first episode suggestive of multiple sclerosis (3 trials, a total of 1160 patients), 35% of patients treated with interferon beta subsequently developed the disease, versus 50% of patients in the placebo groups. This advantage seemed to persist for at least 8 years. (5) In relapsing-remitting multiple sclerosis (4 trials, a total of 1426 patients), interferon beta prevented about one exacerbation every 2.5 to 3 years but had no clear preventive impact on progression of disability. (6) In secondary progressive multiple sclerosis (5 trials, a total of 3082 patients), interferon beta's effectiveness, if present, was limited to patients who continued to have exacerbations. (7) Natalizumab does not appear to be more effective than interferon beta. It is associated with serious adverse effects, about which only limited information is available. (8) Glatiramer has not been shown to prevent exacerbations or progression of disability. Intravenous immunoglobulin is still being tested in multiple sclerosis. In initially aggressive forms of multiple sclerosis, mitoxantrone has a negative risk-benefit balance (2 trials, 236 patients); it prevents less than one exacerbation during two years of treatment but causes heart failure in 1% to 2% of patients after 10 months of treatment. (9) Patients' anxiety as their disability worsens must not overshadow the fact that there are no treatments available with strong clinical effectiveness, and that all existing treatments carry a risk of serious adverse effects. Pending the arrival of something better, only interferon beta has a favourable risk-benefit balance, and only in selected patients.     

High pressure injection injuries: a serious occupational hazard

High pressure injection equipment such as airless paint sprayers, high pressure grease guns, and fuel injection apparatus constitute a serious safety hazard resulting in significant morbidity. These devices are capable of delivering contaminants such as paint, solvents, and grease at pressures ranging from 600-12,000 psi. This allows the substance to penetrate through a minute skin wound and to spread widely through fascial planes and tendon sheaths and to produce significant vascular compression and systemic toxicity. High pressure injection injuries frequently result in amputation. Fifty-five suspected high pressure injection injury cases were evaluated. Twenty were determined to be actual injection injuries from equipment producing pressures in the range of 1,500-12,000 psi. The injected contaminants included latex paint, mineral spirits, and concrete sealer. Fourteen injuries involved digits. Digital amputation was necessary in three patients. Hospital admissions averaged 6.5 days. Successful management of these cases involves awareness of the impending problem and rapid referral of the patient to an emergency department and to a competent orthopedic or plastic surgeon.     

Telavancin: a novel lipoglycopeptide for serious Gram-positive infections

Telavancin, a once-daily dosing lipoglycopeptide derived from vancomycin, has a broad-spectrum microbiologic activity against Gram-positive bacteria, including vancomycin-resistant staphylococci. Telavancin displays a dual mode of action and a rapid bactericidal killing. The in vitro activity of telavancin is superior to vancomycin and comparable with, or greater than, linezolid, daptomycin and other novel lipoglycopeptides. Telavancin is effective against Gram-positive pathogens in animal models of soft tissue infections and deep-seated infections including endocarditis, pneumonia and bacteremia. Clinical experience with telavancin in Phase II and III studies for complicated skin and skin structure infections have demonstrated similar efficacy and tolerability compared with standard anti-staphylococcal β-lactams and vancomycin. Telavancin is in Phase III studies for nosocomial pneumonia. Telavancin seems to be promising as a novel agent for empiric therapy or as an alternative agent in serious infections caused by clinically important resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin intermediate-susceptible S. aureus, vancomycin-resistant S. aureus and vancomycin-resistant enterococci.     

Telavancin: a novel lipoglycopeptide for serious gram-positive infections

Telavancin, a once-daily dosing lipoglycopeptide derived from vancomycin, has a broad-spectrum microbiologic activity against gram-positive bacteria, including vancomycin-resistant staphylococci. Telavancin displays a dual mode of action and a rapid bactericidal killing. The in vitro activity of telavancin is superior to vancomycin and comparable with, or greater than, linezolid, daptomycin and other novel lipoglycopeptides. Telavancin is effective against gram-positive pathogens in animal models of soft tissue infections and deep-seated infections including endocarditis, pneumonia and bacteremia. Clinical experience with telavancin in Phase II and III studies for complicated skin and skin structure infections have demonstrated similar efficacy and tolerability compared with standard anti-staphylococcal beta-lactams and vancomycin. Telavancin is in Phase III studies for nosocomial pneumonia. Telavancin seems to be promising as a novel agent for empiric therapy or as an alternative agent in serious infections caused by clinically important resistant gram-positive pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin intermediate-susceptible S. aureus, vancomycin-resistant S. aureus and vancomycin-resistant enterococci.     

Carbapenems in serious infections: a risk-benefit assessment.

The tolerability of the 2 most frequently used carbapenems, imipenem/cilastatin and meropenem, is reviewed. Both of these drugs, but especially imipenem, are potentially neurotoxic and may cause seizures if overdosed relative to renal function and/or bodyweight. The therapeutic margin is considerably narrower with imipenem/cilastatin which cannot be given at doses required for treatment of bacterial meningitis. Meropenem on the other hand, is considerably less prone to cause seizures and its tolerability and efficacy are well documented in 3 relatively large, controlled studies in adults and children with meningitis. They showed that meropenem was as effective and well tolerated as cefotaxime or ceftriaxone. Another potential advantage of meropenem over imipenem/cilastatin is that it can be given intravenously at a high rate without increased risk of nausea or vomiting. An obvious reason for using a carbapenem instead of a cephalosporin for empirical treatment of life-threatening infections is that both imipenem/cilastatin and meropenem have a broader spectrum of activity. They are also more resistant to hydrolysis by the most common beta-lactamases, including the class I cephalosporinase frequently produced by Enterobacter spp. and Pseudomonas spp. and the extended spectrum enzymes, now commonly found in Escherichia coli and Klebsiella spp.