Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

BACKGROUND: Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. METHODS: In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. RESULTS: The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CONCLUSION: CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment.

Pharmacotherapy for weight loss: the cardiovascular effects of the old and new agents.

WHAT IS KNOWN AND OBJECTIVE: Obesity affects approximately one-third of the American population, and its prevalence continues to increase. It is a significant risk factor for cardiovascular diseases and contributes to increased healthcare costs and mortality. The objective is to review the current literature on the cardiovascular effects of weight loss pharmacotherapy agents. METHODS: Literature was accessed through MEDLINE/PubMed (up to April 2013) using the search terms obesity, weight loss, pharmacotherapy, cardiovascular adverse effects and cardiovascular side effects. References of the articles identified and www.clinicaltrials.gov were also reviewed. Relevant guidelines, review articles, clinical trials, meta-analyses, case series, FDA documentation and prescribing information were included and limited to English language articles. RESULTS AND DISCUSSION: With the newly FDA-approved weight loss pharmacotherapy, treatment options for obesity are more diverse. However, safety concerns, including adverse cardiovascular effects, have played a significant role in the history of weight loss pharmacotherapy and will likely play a role in the future of the new agents, lorcaserin and phentermine/topiramate, as well. WHAT IS NEW AND CONCLUSION: Long-term cardiovascular outcomes studies with and without high-risk cardiovascular patients are still needed for both lorcaserin and phentermine/topiramate before these agents can be recommended in these patient populations. It is yet to be determined whether modest weight loss benefit of these new agents outweighs the cardiovascular risks.