Drugs
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Intravenous micafungin (Mycamine; Fungard), an echinocandin, inhibits the synthesis of 1,3-beta-D-glucan, an essential cell wall component in many fungi. It is approved in adults (focus of this review) and in neonates and paediatric patients (Pediatric Drugs [in press]) in the EU and elsewhere for the treatment of invasive candidiasis and oesophageal candidiasis, and as prophylactic treatment to prevent Candida infections in haematopoietic stem cell transplant (HSCT) recipients. Intravenous micafungin shows very good activity against clinically relevant isolates of Candida spp. ⋯ Furthermore, it was as well tolerated as caspofungin and fluconazole, and better tolerated than liposomal amphotericin B. The position of micafungin relative to newer antifungal therapies, such as anidulafungin, voriconazole and posaconazole, remains to be fully determined. Thus, micafungin is an emerging option for the treatment of adult patients with invasive or oesophageal candidiasis, and as prophylaxis against Candida infections in HSCT recipients.
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*A new formulation of the nonselective NSAID diclofenac sodium suitable for intravenous bolus injection has been developed using hydroxypropyl beta-cyclodextrin as a solubility enhancer (HPbetaCD diclofenac). * HPbetaCD diclofenac intravenous bolus injection was shown to be bioequivalent to the existing parenteral formulation of diclofenac containing propylene glycol and benzyl alcohol as solubilizers (PG-BA diclofenac), which is relatively insoluble and requires slow intravenous infusion over 30 minutes. * Single-dose HPbetaCD diclofenac 3.75, 9.4, 18.75, 25, 37.5, 50 and 75 mg administered by intravenous bolus injection produced significantly greater responses than placebo for total pain relief (TOTPAR) over 6 hours or pain intensity at 4 hours in the treatment of moderate or severe postoperative dental pain in randomized, double-blind trials. HPbetaCD diclofenac 37.5 and 75 mg were similar in efficacy to intravenous bolus ketorolac 30 mg. * In a well controlled trial, single-dose HPbetaCD diclofenac 75 mg intravenous bolus injection was shown to be superior to PG-BA diclofenac 75 mg intravenous infusion with respect to TOTPAR over 4 hours, indicating faster onset of analgesia in the treatment of moderate or severe postoperative dental pain. Both HPbetaCD diclofenac and PG-BA diclofenac were superior to placebo. * HPbetaCD diclofenac was generally well tolerated during single-dose treatment of postoperative pain. The tolerability profile was similar to that of PG-BA diclofenac, but with a lower incidence of thrombophlebitis.
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The past decade has witnessed significant progress in the management of invasive aspergillosis. Potent, relatively non-toxic antifungal drugs, data on early chest CT scanning and the availability of a non-invasive diagnostic test (serum galactomannan) are the key advances; among these, the contribution of the recently available drugs is the most significant. Safer and earlier intervention resulting in reduced mortality and improved outcome is being demonstrated. ⋯ Reports of emergence of less-susceptible Aspergillus spp. during azole therapy are of concern and close monitoring is needed. Remarkably, the era of polyenes appears to be nearing the end in the therapy of invasive aspergillosis. The promise of newer classes of drugs, immune-modulating therapies and vaccines are exciting future additions to the arsenal against invasive aspergillosis.
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The fentanyl transdermal matrix patch is approved in Japan for the management of moderate to severe cancer-related pain in adults. Bioequivalence, in terms of exposure and the maximum and minimum serum concentrations, has been established between the fentanyl transdermal matrix patch 16.8 mg (100microg/h) and the fentanyl transdermal reservoir patch 10 mg (100microg/h) after single and multiple applications. The fentanyl transdermal matrix patch 2.1-8.4 mg (12.5-50microg/h) effectively managed chronic cancer-related pain in adults in a noncomparative, multicentre, phase II study; 89.4% of recipients rated their global assessment of pain as 'very satisfied', 'satisfied' or 'neither satisfied nor dissatisfied'. ⋯ Given the nature of the therapy, the tolerability profile of the fentanyl transdermal matrix patch was generally acceptable. Topical adverse events included erythema, application-site irritation and pruritus. In general, patients and physicians preferred the fentanyl transdermal matrix patch over the fentanyl transdermal reservoir patch in the pilot study.