Pharmacokinetic and clinical implications of dabigatran use in severe renal impairment for stroke prevention in nonvalvular atrial fibrillation.

OBJECTIVE: To review the literature regarding the pharmacokinetic (PK) and clinical implications of the use of dabigatran in severe renal impairment for stroke prevention in nonvalvular atrial fibrillation (AF). DATA SOURCES: Searches of MEDLINE (2000-April 2012) and the Cochrane Database (2000-April 2012) were conducted. Key search terms included dabigatran, renal impairment, renal failure, and renal dysfunction. Additional limits included articles written in English and those involving human subjects. Bibliographic reviews were conducted to identify other pertinent data. STUDY SELECTION AND DATA EXTRACTION: Primary data were considered eligible for inclusion if they were from studies that evaluated the PKs of dabigatran in renal impairment or the effect of renal impairment on the risk for major bleeding with dabigatran. DATA SYNTHESIS: Dabigatran is an oral direct thrombin inhibitor indicated for the prevention of stroke and systemic thromboembolism in patients with nonvalvular AF, at a dose of 150 mg twice daily. Renal elimination is responsible for approximately 80% of dabigatran's clearance; thus, dose adjustment is required for patients with severe renal impairment. The approved dosing regimen for patients with creatinine clearance 15-30 mL/min (75 mg twice daily) was derived from PK modeling studies, limiting its applicability to the clinical setting. CONCLUSIONS: At this time, there is limited evidence to support safety or efficacy outcomes with the use of dabigatran for stroke prevention in patients with severe renal impairment and nonvalvular AF. Postmarketing data and large clinical trials are needed to determine the role of dabigatran in this population.

Colchicine for the primary prevention of the postpericardiotomy syndrome.

OBJECTIVE: To review literature regarding the safety and efficacy of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS). DATA SOURCES: Searches of MEDLINE (1966-April 2011) and Cochrane Database (1993-April 2011) were conducted. Key search terms included postpericardiotomy syndrome, postcardiac injury syndrome, and colchicine. Limits were set for articles written in English with human subjects. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. All primary data were eligible for inclusion if they evaluated the safety and/or efficacy of colchicine for the primary prevention of PPS. Two prospective trials were identified and included for review. DATA SYNTHESIS: PPS occurs in 10-40% of patients who undergo cardiac surgery and is associated with significant morbidity. Effective medications used for the treatment of PPS include nonsteroidal antiinflammatory drugs or corticosteroids. Unfortunately, effective drug therapy for the primary prevention of PPS does not exist. Colchicine, an antiinflammatory agent with possible immunopathic antifibroblast properties, has shown benefit in the treatment and secondary prevention of pericarditis; thus, its use for primary prevention of PPS has been investigated. Limited data evaluating colchicine for the primary prevention of PPS have been published. However, results of the largest, well-designed trial showed positive efficacy outcomes for colchicine reducing the incidence of PPS with minimal adverse effects. CONCLUSIONS: At this time, there are not sufficient data to recommend colchicine as routine therapy for the primary prevention of PPS in patients undergoing cardiac surgery. Large clinical trials need to be conducted.

Agitated delirium associated with therapeutic doses of sustained-release bupropion.

CASE DESCRIPTION: We report a case of a patient initiated on therapeutic doses of sustained-release bupropion for the management of major depressive disorder who subsequently developed acute agitated delirium that required ICU level care. This patient's history was significant for alcohol and cannabis abuse but he was currently detoxified and beyond the withdrawal period. Throughout the course of treatment, all maintenance medications, including bupropion, were discontinued and the patient required escalating doses of benzodiazepines and typical antipsychotics to resolve symptoms. The patient's delirium subsided after approximately 5 days. CONCLUSION: Dopamine is thought to play a role in the pathophysiology of delirium and given the mechanism of action of this drug and the presence of delirium risk factors in our patient, we are faced with a likely causative factor of this acute delirious episode.