Sodium oxybate is safe and effective for the treatment of cataplexy. Potential disadvantages include a multiple dosing regimen, abuse potential, cost, and a closed distribution system. Potential advantages demonstrated in clinical trials include significant decreases in the number of weekly cataplexy attacks, improvement in daytime sleepiness, and improvement in the Clinical Global Impression of Change score and nighttime awakenings. Overall, sodium oxybate provides a new option for the treatment of cataplexy.

Brivaracetam is an analogue of levetiracetam that is Food and Drug Administration-approved for adjunctive treatment of partial-onset seizures in patients 16 years and older. In placebo-controlled trials adjunct brivaracetam demonstrated efficacy in reducing the frequency of seizures. The most commonly reported adverse effects are somnolence, dizziness, and fatigue. Clinical trials have evaluated brivaracetam for safety and efficacy in adjunctive treatment of partial-onset seizures in patients 16 years and older for up to 16 weeks. Brivaracetam's mechanism is similar to that of levetiracetam but with greater receptor binding affinity on synaptic vesicle protein 2A and inhibitory effects on sodium channels. Clinically significant differences between these agents are undetermined. Brivaracetam is available as oral tablets, oral solution, and intravenous solution. The Food and Drug Administration-approved dose is 50 mg twice daily, and titration is not required. Brivaracetam does not need dose adjustment for renal impairment and has minimal drug-drug interactions. Current limitations of brivaracetam include lack of head-to-head trials, limited long-term safety and efficacy data, and cost. Overall, brivaracetam is a viable adjunct therapeutic option for refractory partial-onset seizures in those who have failed conventional therapies.

Mixed dyslipidemia, characterized by a lipid triad of elevated triglycerides (TG), elevated low-density lipoprotein-cholesterol (LDL-C) and reduced high-density lipoprotein-cholesterol (HDL-C), is a common and frequently difficult to manage condition. The use of combination medications is often needed to effectively treat the lipid triad. The co-administration of statins and fibrates may provide the desired endpoints but safety issues such as toxicity to the muscles, liver and kidneys are a concern. Given the potency of rosuvastatin to lower LDL-C and fenofibrate’s effectiveness in lowering TG, the use of this specific combination may be desirable in treating mixed dyslipidemia. Pharmacokinetic studies revealed no significant interactions with the concomitant use of rosuvastatin and fenofibrate or its active metabolite fenofibric acid. Clinical studies evaluating the efficacy and safety of this combination therapy demonstrate significant reductions in TG and LDL-C levels, and elevations in HDL-C. Safety data from clinical trials reveal no major adverse reactions. However, case reports of adverse events have been published and monitoring for potential adverse reactions of the individual agents is advised. Overall, current data suggest the combination of rosuvastatin and fenofibrate or fenofibric acid is a safe combination to utilize when managing difficult to treat mixed dyslipidemia patients.

Indiplon is a novel pyrazolopyrimidine, nonbenzodiazepine γ-aminobutyric acid (GABA) agonist studied for the treatment of insomnia. This article reviews the chemistry, pharmacology, clinical pharmacokinetics, drug interactions, clinical trials, safety, tolerability, contraindications, use in special populations, and dosing of indiplon. OVID, International Pharmaceutical Abstracts (IPA), and PubMed databases were searched (1966 to February 2009) for the keywords indiplon, NBI-34060, and insomnia. References of key articles were also reviewed to identify additional publications. Only English language articles were selected for review. Indiplon has been shown to have high affinity and selectivity for the GABAα1 receptor subunit associated with sedation. In clinical studies, indiplon has demonstrated efficacy in improving latency to sleep onset, latency to persistent sleep, total sleep time, wake time after sleep onset, number of awakenings after sleep onset, and overall sleep quality when compared to placebo. Indiplon has a favorable safety profile with limited rebound insomnia and no tolerance. Neurocrine Biosciences, Incorporated received an Approvable Letter from the United States Food and Drug Administration in December 2007 for the indiplon IR 5 mg and 10 mg capsules based on meeting three additional requirements. At the time of this writing, indiplon remains unapproved.

IntroductionWith the proposed expansion of healthcare coverage, evolving models of pharmacy practice, and continual efforts to improve healthcare safety and quality, there is a critical need for leadership in pharmacy to guide the profession through these opportunities for growth and change. It is also critical that schools and colleges of pharmacy continue to develop student pharmacists as leaders in order to meet present and future challenges within the profession.

Clostridium diffi cile infections (CDI) have increased in frequency throughout the world. In addition to an increase in frequency, recent CDI epidemics have been linked to a hypervirulent C. diffi cile strain resulting in greater severity of disease. Although most mild to moderate cases of CDI continue to respond to metronidazole or vancomycin, refractory and recurrent cases of CDI may require alternative therapies. This review provides a brief overview of CDI and summarizes studies involving alternative antibiotics, toxin binders, probiotics, and immunological therapies that can be considered for treatment of acute and recurrent CDI in severe and refractory situations.

Cardiovascular disease remains the leading cause of death in the world. A significant amount of clinical data are available to demonstrate the positive influence that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has on slowing the progression of cardiovascular disease and improving clinical outcomes. Achieving the treatment goals for cholesterol in cardiovascular disease continues to present challenges. Recent clinical trial information is available assessing the use of more aggressive initial doses of statin therapy based on initial low-density lipoprotein cholesterol (LDL-C) measurements in an attempt to reach treatment goals sooner. Six clinical trials assessed low-, moderate- and high-risk individuals as well as those with type 2 diabetes mellitus to determine if this treatment approach is both safe and effective. The studies concluded that initial dosing of statin therapy determined by a baseline LDL-C measurement demonstrates good achievement in reaching treatment goals and does not result in a higher rate of adverse effects.

Francisella tularensis is a Gram-negative coccobacillus that is rarely encountered in clinical practice. Patients can present with cutaneous, pulmonary, cardiac, mucous membrane, or gastrointestinal involvement. A clinician should have a heightened suspicion in endemic areas or when outbreaks appear. Diagnosis is achieved through serological testing or polymerase chain reaction assays. Although historically the treatment of choice was streptomycin, gentamicin is now preferred due to its availability and relatively safer side effect profile with extended-interval dosing. Limited published evidence exists on the effectiveness of extended-interval gentamicin for tularemia. This case series describes four patients with pulmonic tularemia successfully treated with extended-interval dosing of gentamicin without treatment failure or relapse.