PBM P&T Practices: The HEAT Initiative Is Gaining Momentum.

The pharmacy benefit management (PBM) industry has recently fallen into the crosshairs of government investigations about the high cost of pharmaceuticals. The authors focus on the PBM-based P&T and formulary practices under scrutiny.

Biosimilars in the United States: Emerging Issues in Litigation.

Many first-generation biologics will lose their patent protection by 2020. The biosimilars market is not only attractive but also competitive and tough. The United States (US) is the world's largest pharmaceutical market and is critical to the success of most drugs. However, unclear regulatory requirements and confusing patent resolution procedures create hurdles to market entry of biosimilars. Trade secret exposure and scant exclusivity and adoption also limit the market access of biosimilars. Both biologics and biosimilar developers should closely follow the regulatory and litigation landscape to successfully navigate through the challenges. Focusing on the US landscape, this article provides a brief review of the regulatory framework for biosimilar products, market exclusivities, and patent issues under the Biologics Price Control and Innovation Act (BPCIA), analyzes emerging issues in the biosimilar litigation landscape, and provides recommendations for companies entering the biosimilars market.

Systemic Market and Organizational Changes: Impact on P&T Committees.

The authors consider market stakeholder consolidation, market-driven efficiency demands, consumerism, and legal enforcement of patient rights related to access to appropriate drugs and posit how future P&T committees may approach these issues.

Incorporating a Drug Information Consult into a Pharmacy Practice Course to Build Literature Search and Evaluation Skills Through a 3-Stage Model.

OBJECTIVE: Pharmacy students need to be equipped with skills to research and evaluate literature to effectively apply evidence-based medicine (EBM) in practice. To prepare them, a 3-stage approach to writing a drug information consult (3sDIC) was incorporated into a pharmacy course. The primary objective was to assess students' abilities to retrieve and analyze literature pursuant to a drug information consult. Secondary objectives were to examine feasibility of faculty participation and continuation of the assignment. DESIGN: Ninety students were given a clinical scenario about a patient. The assignment consisted of 3 stages incorporating use of the Population, Intervention, Comparison intervention, Outcome (PICO) method and modified systematic approach (MSA) for stage 1, evaluation of primary literature to write a draft for stage 2, and stage 3, the final consult. All 3 stages were reviewed and graded by faculty. ASSESSMENT: All students completed the 3sDIC, with no grade failures. The rubric employed by faculty was effective, providing students the opportunity to improve the consult. The 3sDIC was found to be feasible with adequate faculty support. CONCLUSION: The 3sDIC, although not a substitute for a complete drug information course, demonstrated a streamlined approach for Pharmacy year 2 (P2) students to acquire and develop drug information skills.

Biosimilars: Still Not Quite Ready for Prime Time.

Biosimilars represent a potential savings opportunity for both payers and patients, but how and when the new agents will be accepted and prescribed is uncertain.

Medication Repurposing in Pediatric Patients: Teaching Old Drugs New Tricks.

OBJECTIVES: Gaps in pediatric therapeutics often result in off-label use and specifically, novel uses for existing medications, termed "drug repurposing." Drug Information (DI) queries to a Pediatric Medication Resource Center of a large metropolitan pediatric hospital in New York and inherent difficulties in retrieving evidence-based information prompted a review of current medication repurposing for pediatric patients. The objective included characterization of innovative off-label use of medications Food and Drug Administration (FDA)-approved for 1 or more indications to treat a totally different disorder or indication in pediatric patients. METHODS: A systematic literature review was conducted to retrieve publications describing repurposed medications in pediatric patients. Excluded was FDA-approved indications used off-label in pediatric patients (e.g., different dose), preclinical data, adult use only, and experimental use. Evidence quality was classified using a modified American Academy of Neurology Level of Evidence. Results were analyzed using χ(2) at p < 0.05. RESULTS: Over 2000 references were retrieved and reviewed. A total of 101 medications repurposed for novel off-label uses for pediatric patients were identified: 38 for neonates, 74 for children, and 52 for adolescents. Neonates and infants were least likely to receive a medication for a repurposed use. Strong or intermediate evidence existed in 80.2% of cases. The evidence was weak in 19.8%. No significant relationship was observed between the pediatric age group and strength of the literature. Most repurposed uses pertained to generic or widely used medications. Less than 5% of medications were first marketed after 2011. CONCLUSIONS: While not exhaustive, the present study represents the most comprehensive listing of novel uses exclusive to pediatric patients. Further research is needed to identify the frequency of repurposed uses. The valuable DI role of pharmacists in assessing repurposed uses is of expanding and increasing importance to ensure such uses are evidence-based.

The Course Syllabus: Legal Contract or Operator's Manual?

A course syllabus provides a roadmap for pharmacy students to achieve course learning objectives and develop lifelong learning skills. For several decades the literature has referred to syllabi as legal documents and/or contracts between students and professors. A review of the legal precedents reveals that syllabi are not considered contracts because the courts refuse thus far to recognize educational malpractice or breach of contract as a cause of action. Syllabi do, however, represent a triggering agent for instructional dissent and grade appeals, may be binding in student appeal proceedings, and are used in judicial hearings. Pharmacy faculty members should review their syllabi and follow process improvement strategies to construct legally sound syllabi that can both enhance learning and minimize risks of student grievances and appeals.

3-in-1 vs 2-in-1 parenteral nutrition in adults: a review.

Parenteral nutrition (PN) provides a means of nourishment for patients in whom oral or enteral nutrition is not possible or practical. Initial formulations consisted of carbohydrates (dextrose), amino acids, vitamins, trace minerals, electrolytes, and water. A stable intravenous fat emulsion (IVFE) permitted the combination of all 3 macronutrients in the same admixture (3-in-1 or total nutrient admixture [TNA]). Many institutions have adopted these TNAs as the standard formulation. Others, due to a variety of concerns (including historical concerns regarding stability), continue to administer PN as a formulation of dextrose and amino acids (2-in-1) with separate IVFE infusions. The aim of this article is to review the literature regarding the use of TNA vs 2-in-1 formulations. The published data were critically analyzed, and a preferred strategy was suggested based on an interpretation of the data. Concerns surrounding the safety of 2-in-1 vs 3-in-1 PN formulations can be grouped with respect to those regarding infections, emulsion instability ("cracking"), and precipitant formation. These concerns are largely historical and would seem to be no longer relevant to adult PN formulations. We believe that the available (limited) data support the safe transition to the 3-in-1 formulation as the standard of care in adult PN.

Hydroxyprogesterone caproate injection (makena) one year later: to compound or not to compound that is the question.

Preterm births have increased by 27% over the last decade in the U.S. The main ingredient in Makena, 17P, is less expensive at compounding pharmacies, but this method is not FDA-approved. The authors discuss the quality, safety, and use of Makena and compounded 17P; the potential for liability; cost considerations; and recommended restrictions for the product's use.

Metoclopramide-induced cardiac arrest.

The authors report a case of cardiac arrest in a patient receiving intravenous (IV) metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV) injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG) revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT) associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs) related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s) underlying metoclopramide's cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and reporting of bradydysrrhythmias and cardiac arrest in patients receiving metoclopramide.

Dietary tyramine restriction for hospitalized patients on linezolid: an update.

Linezolid is a weak, reversible monoamine oxidase inhibitor. The current practice at most hospitals is to place patients receiving linezolid on a tyramine-restricted diet. This process typically involves both the hospital's pharmacy department and the food and nutrition department. A literature search assessing the interaction between linezolid and tyramine was conducted, and the amount of tyramine in a typical unrestricted diet for a hospitalized patient was reviewed. Although patients receiving linezolid should avoid consuming large amounts of foods containing high concentrations of tyramine, such foods in large amounts are not components of meals for inpatients. Therefore, dietary tyramine restriction in hospitalized patients is not generally required.

Potential role of salicylates in type 2 diabetes.

OBJECTIVE: To review the evidence base supporting the use of salicylates for glucose level control in patients with type 2 diabetes and provide a comprehensive review of available information describing the potential role of salicylates and, in particular, salsalate, for glucose control in type 2 diabetes prevention and treatment. DATA SOURCES: A literature search using MEDLINE (1966-March 2010), PubMed, and Google Scholar was conducted using the search terms salicylates, salicylic acid, aspirin, salsalate, acetylsalicylic acid, insulin, glucose, glycemic control, diabetes, hyperglycemia, and nuclear factor. The bibliographies of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language information on the pharmacology, efficacy, and safety of salicylates for glucose control related to insulin resistance or diabetes prevention were reviewed. Preclinical data, clinical trials, and case reports were identified, evaluated, and included in this systematic review. DATA SYNTHESIS: Treatment of inflammation may be a potential novel strategy in prevention and treatment of type 2 diabetes, in which the body is resistant to the effects of insulin. Previous and recent studies reveal a possible relationship between inflammation and obesity. The chronic activation of the immune system due to low-grade inflammation was found in several studies to be associated with obesity, and this, in turn, can promote development of insulin resistance and impaired glucose tolerance. Administration of salicylates was shown over a century ago to lower glucose levels in patients with diabetes. Many in vitro and in vivo pharmacologic studies have demonstrated a glucose-lowering effect of salicylates. Salicylates, especially salsalate, were found in several clinical studies and case reports to be potential agents for diabetes treatment with a favorable safety profile. Although these studies had inherent limitations, such as small numbers of patients and short duration, the vast majority showed significant glucose-lowering effects. A large randomized trial, the National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D) trial, recently concluded that salsalate lowers hemoglobin A(1c) levels and improves glycemic control in patients with type 2 diabetes. CONCLUSIONS: Salicylates, especially salsalate, appear to be a promising treatment option for prevention or treatment of diabetes by lowering glucose levels. More extensive studies are needed to confirm the mechanisms involved and whether the effects are sustainable with continued administration of these agents. Further studies are warranted.

Clinical efficacy of antihistaminics as analgesics.

This paper reviews the clinical information on antihistaminic agents as analgesics and as analgesic adjuvants. The evidence indicates a direct analgesic effect of various antihistaminics. In clinical studies, diphenhydramine, hydroxyzine, orphenadrine and pyrilamine have been shown to produce analgesia as simple entities but chlorpheniramine has not and results with phenyltoloxamine have been equivocal when tested alone. Analgesic adjuvant effects of several antihistaminics have been reported. Clinically, orphenadrine and phenyltoloxamine have shown adjuvant effects with acetaminophen and aspirin. The mechanism of action remains speculative. The most recent trends in the classification of histamine receptors and how these receptors may interact with pain modulation are also considered.