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This paper provides an overview of research, guidelines, and clinical considerations for the use of medications for chronic pain in the management of patients with an alcohol use disorder. A review of the literature identified randomized controlled trials, epidemiological cohort studies, consensus guidelines, and one systematic review and meta-analysis. Where gaps in the literature existed, clinical experience of the authors is included. Use of nonopioid medications should be given priority and may offer a more favorable risk profile as well as benefits beyond pain management, such as improvement in anxiety, depression, or insomnia. Pregabalin and gabapentin have additional benefits to decrease alcohol cravings or time to relapse after a period of abstinence from alcohol. Drug interactions between selected analgesics and alcohol, disulfiram, or naltrexone require careful consideration.
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OBJECTIVE: To systematically evaluate the clinical consequences of mycophenolate dose reduction in renal transplant recipients on tacrolimus-based regimens. DATA SOURCES: PubMed (1949-July 2010), EMBASE (1980-July 2010), Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Web of Science were searched using the terms mycophenolate mofetil, tacrolimus, dose reduction, and kidney and/or renal transplant. References from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies reporting on rejection rate, allograft survival, or renal function were included and ranked according to the US Preventive Services Task Force classification; excluded were studies that were dose-finding or used cyclosporine only, involved patients on enteric-coated mycophenolate sodium or those with multiorgan transplant, or provided no information on concomitant immunosuppressants. Data extracted were study design, sample size, immunosuppression regimen, type of transplant, and allograft outcomes. DATA SYNTHESIS: Of 13 studies included, 1 was level I evidence, 3 were level II-2, 6 were level II-3, and 3 were level III evidence. Three focused on tacrolimus-based regimens, whereas 7 included either cyclosporine or tacrolimus. The only prospective, randomized, multicenter trial demonstrated that early taper of mycophenolate dosage to 1 g/day can be utilized without increased risk of rejection, compared with late tapering, but the rejection rate was high (30-40%). Overall, we found conflicting evidence regarding the impact of mycophenolate dose reduction on rejection rate and allograft loss and that discontinuing mycophenolate led to an increased risk of graft loss as high as 8 fold. Allograft survival was lowest in patients with gastrointestinal complications and those in whom mycophenolate was discontinued, compared with patients with neither gastrointestinal complications nor mycophenolate discontinuation. CONCLUSIONS: Weak evidence suggests that mycophenolate dose modifications, either reduction or discontinuation, may increase rejection rate and graft loss; however, this is more apparent in cyclosporine-based regimens. Prospective, well-designed trials are necessary to definitively determine the impact of dose reduction in renal transplant recipients on tacrolimus-based regimens.
