Pharmacy

A review of adverse event data associated with the synthetic vitamin A retinoid isotretinoin between 1997 and 2002 suggests that the acne treatment is a "probable" cause of inflammatory bowel disease (IBD) and may precipitate its presentation within a certain subset of patients who are either predisposed to the disease or have subclinical symptoms.

Approximately 17 million people in the United States have type 2 diabetes, and the prevalence continues to rise.1 More than 45% of patients with end-stage renal disease have type 2 diabetes as an etiology, and a patient with type 2 diabetes has the same risk of developing an acute coronary syndrome (unstable angina, myocardial infarction [MI]) over the next 10 years as someone who has had an acute coronary syndrome in the past.2 In addition to these complications, type 2 diabetes also increases the risk of blindness, neuropathy, and amputation.3

Drug-eluting stents (DES) represent an innovative application of pharmaceutical technology that has piqued the interest of hospital and managed care decision-makers. Since their introduction to the US market in 2004, the sirolimus- and paclitaxel-eluting stents have featured drugs employing different mechanisms of action to reduce the risk of restenosis following percutaneous coronary intervention (PCI) in an attempt to improve cardiovascular outcomes.

Despite the variety of medications available to treat type 2 diabetes, the disease is inadequately controlled in many patients. In order to improve glycemic control, manufacturers are pursuing compounds that affect the incretin hormones that stimulate insulin release in response to increased glucose levels. Although stimulation of the incretin receptors by the glucagon-like peptide-1 (GLP-1) enhances the body's ability to produce insulin in response to elevated blood glucose concentrations, the clinical usefulness of GLP-1 is limited by its rapid degradation by dipeptidyl peptidase-IV (DPP-IV). Drug companies have developed compounds intended to act as inhibitors of DPP-IV. Vildagliptin (Galvus, Novartis) is the second DPP-IV inhibitor under investigation by FDA to offer this new mechanism to achieve glycemic control. An NDA for vildagliptin was submitted to FDA in March 2006, 1 month after the submission of the first DPP-IV inhibitor, sitagliptin.

Trimipramine capsules, 25, 50, and 100 mg (equiv to Surmontil capsules)

First antifungal approved for prevention of invasive fungal infections caused by Aspergillus species

A drug use evaluation at Wake Forest University Baptist Medical Center (WFUBMC) was initiated following a change in institution-approved guidelines for the administration of amphotericin B lipid complex injection (ABLC) (Abelcet, Enzon). This study was conducted to determine compliance with the new guidelines among prescribers and to characterize the population of patients receiving ABLC. A total of 153 patients received ABLC from April 2001 through December 2002. One hundred thirty-three patients (87%) met 1 or more of the institutional criteria for ABLC administration and 20 (13%) receiving ABLC did not meet the guidelines. The mean baseline serum creatinine (SCr) value among patients meeting institutional guidelines (n=133) was 2.0 mg/dL (range, 0.5–5.0 mg/dL). Among patients who did not meet the guidelines (n=20), the mean baseline SCr level was 1.7 mg/dL (range, 0.6–2.9 mg/dL). The use of new guidelines, which were less stringent than previous guidelines, resulted in earlier administration..

This study evaluates the appropriateness and cost implications of using epoetin alpha for transfusion reduction in Hartford Hospital's (Hartford, Conn) intensive care units (ICUs), with the goal of implementing a protocol for use in this setting. We conducted a literature review to determine the efficacy, safety, and clinical outcomes of epoetin alpha for transfusion reduction in the ICU. We also evaluated the safety and supply of red blood cell (RBC) transfusions and the cost considerations of epoetin alpha. The literature review demonstrated that epoetin alpha can reduce blood transfusions in the ICU setting but its use provided no difference in mortality or any other clinical outcome. Our epoetin alpha expenditure for transfusion reduction was $112,067 annually to theoretically save $14,349 in blood transfusion costs. The pharmacy and therapeutics (P&T) committee subsequently recommended that epoetin alpha not be used for transfusion reduction in the ICUs and requested that a drug use evaluation (DUE) be performed to monitor compliance, adverse effects, and cost avoidance. One year after implementation of the epoetin alpha DUE program, the compliance rate was >90%, there were no reported adverse events with blood transfusions or problems with blood supply, and a cost avoidance of $104,562 was realized. (Formulary. 2006;41:442?449.)

FDA issued a proposed rule late last month that would allow pharmaceutical manufacturers to register and list products electronically in an effort to minimize the paper-based element of the process, allowing the agency to host a comprehensive national database of medications and to be more flexible in its role of monitoring the safety of medications for sale, according to officials.

A drug use evaluation at Wake Forest University Baptist Medical Center (WFUBMC) was initiated following a change in institution-approved guidelines for the administration of amphotericin B lipid complex injection (ABLC) (Abelcet, Enzon). This study was conducted to determine compliance with the new guidelines among prescribers and to characterize the population of patients receiving ABLC. A total of 153 patients received ABLC from April 2001 through December 2002. One hundred thirty-three patients (87%) met 1 or more of the institutional criteria for ABLC administration and 20 (13%) receiving ABLC did not meet the guidelines. The mean baseline serum creatinine (SCr) value among patients meeting institutional guidelines (n=133) was 2.0 mg/dL (range, 0.5–5.0 mg/dL). Among patients who did not meet the guidelines (n=20), the mean baseline SCr level was 1.7 mg/dL (range, 0.6–2.9 mg/dL). The use of new guidelines, which were less stringent than previous guidelines, resulted in earlier administration..

A variety of clinical approaches are utilized in the management of poor glycemic control in patients with type 2 diabetes. Sitagliptin (Januvia, Merck), a novel drug in a new medication class known as dipeptidyl peptidase-IV (DPP-IV) inhibitors, offers a new mechanism by which to achieve glycemic control. Although stimulation of receptors by the glucagon-like peptide-1 (GLP-1) enhances the body's ability to produce insulin in response to elevated blood glucose concentrations, rapid degradation of GLP-1 by DPP-IV limits its clinical effectiveness. The development of medications to reduce this degradation is being pursued by numerous manufacturers. An NDA for the first of these medications, sitagliptin, was submitted to FDA in February 2006. Currently available clinical studies have demonstrated improved glycemic control with sitagliptin therapy in patients who have not achieved target glucose levels with diet and oral medications. (Formulary. 2006;41:434–441.)

Azithromycin for oral suspension, 100 mg/5 mL and 200 mg/5 mL (equiv to Zithromax for oral suspension)

The combination of pioglitazone and glimepiride was approved on July 28, 2006, as an adjunct to diet and exercise as a once-daily combination therapy to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of pioglitazone and a sulfonylurea or whose diabetes is not adequately controlled with a sulfonylurea alone, or for those patients who have initially responded to pioglitazone alone and require additional glycemic control.

A prodrug of penciclovir, famciclovir is ultimately phosphorylated by the viral thymidine kinase and subsequently cellular kinases to a penciclovir triphosphate, which inhibits herpes simplex 2 (HSV-2) DNA polymerase in a competitive manner.

This antiplatelet agent exerts its effect through direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the lipoprotein GPIIb/IIIa complex.

New incretin-based therapies will soon enter the therapeutic armamentarium for type 2 diabetes. Two dipeptidyl peptidase (DPP)-IV inhibitors in phase 3 clinical trials, vildagliptin and sitagliptin, are oral agents that can be used once daily as monotherapy or in combination with other oral antidiabetic agents to reduce levels of hemoglobin A1c (HbA1c) with few side effects, little risk of hypoglycemia, and no promotion of weight gain, researchers reported at the 66th scientific sessions of the American Diabetes Association (ADA) in Washington, DC.

Anidulafungin (Eraxis, Pfizer) is a new echinocandin approved for the treatment of Candida infection in adults. Like other echinocandins, anidulafungin acts on the fungal cell wall by inhibiting 1,3 beta-D glucan synthesis. Studies suggest that among the echinocandins, anidulafungin may have more potent in vitro activity against Candida spp and Aspergillus spp. Further, phase 2 and 3 clinical studies with anidulafungin have supported a high end of therapy success rates for invasive candidiasis, including esophageal candidiasis. Anidulafungin appears to be well tolerated, with headache, nausea, vomiting, phlebitis, neutropenia, and hypokalemia being the most commonly reported adverse effects. Importantly, as anidulafungin is chemically degraded, it has no clinically significant drug interactions and does not require any dose adjustment for renal or hepatic impairment.

The role of cost- and pharmacoeconomic-related criteria in formulary decision-making was assessed in a literature review of 31 studies of hospital (n=18) and managed care (n=13) pharmacy and therapeutics (P&T) committees. In both settings, cost was important, although the elements of cost considered varied. Acquisition cost was mentioned more frequently than pharmacoeconomic or cost-effectiveness information. Other factors, including drug characteristics, quality of life, supply-related issues, and physician demand, also influenced decisions.

A meta-analysis of data from national hospital records in Denmark and from the country's national prescription registry showed that the use of selective cyclooxygenase-2 (COX-2) inhibitors in all doses and nonselective non-steroidal anti-inflammatory drugs (NSAIDs) in high doses raised the risk of death in patients who experienced first-time acute myocardial infarction (MI).

Metronidazole topical gel, 0.75% (equiv to Metrogel topical gel)

This fixed-dose combination tablet contains: efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI); emtricitabine, a synthetic nucleoside analog of cytidine; and tenofovir disoproxil, which is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.

Dasatinib is an inhibitor of multiple tyrosine kinases and is active in vitro against leukemic cell lines representing variants of imatinib-sensitive and -resistant disease.

A salmeterol/fluticasone combination (SFC) surpassed a formoterol/budesonide combination (FBC) in reducing the rate of moderate-to-severe exacerbations in patients with persistent asthma, according to a study published by the journal Respiratory Medicine.

Bupropion extended-release tablets

Ambrisentan, a propanoic acid type-A selective endothelin receptor antagonist, improved exercise capacity and delayed clinical worsening in patients with pulmonary arterial hypertension (PAH) in phase 3 clinical trial results presented at the annual international conference of the American Thoracic Society in San Diego, Calif.

The anticonvulsant lacosamide is effective in relieving diabetic neuropathy and produces increased pain reduction with continued treatment for 22 months, according to phase 3 study results presented during the 25th Annual Scientific Meeting of APS in San Antonio, Texas. "This is a promising treatment that maintains a long-term effect," said Tibor Hidvegi, MD, Medical Department, Petz Hospital, Gyor, Hungary.

Morphine extended-release once daily significantly reduced pain among patients with chronic, moderate-to-severe low back pain compared with oxycodone controlled-release twice daily, according to results of a study presented at the 25th Annual Scientific Meeting of the American Pain Society (APS) in San Antonio, Texas. The once-daily opioid also demonstrated significant improvement in sleep scores, said Richard L. Rauck, MD, Carolinas Pain Institute, Winston-Salem, NC.

Valsartan is associated with a reduction in the levels of high-sensitivity C-reactive protein (hs-CRP), the inflammatory marker that is highly predictive of adverse cardiovascular outcomes, independent of its blood pressure-lowering effect, said Paul M. Ridker, MD, MPH, lead investigator of a trial presented at the 21st annual meeting of ASH.

Phase 3 clinical trials demonstrated that the once-daily, highly selective beta blocker nebivolol lowers blood pressure in a dose-dependent manner and is well tolerated at all doses, according to presenters at the 21st annual scientific meeting of the American Society of Hypertension (ASH), in New York, NY.

A number of clinical approaches are utilized in managing insomnia. Indiplon (Pfizer) is a selective non-benzodiazepine sedative hypnotic under consideration by FDA for the treatment of insomnia. Like other agents in its class, indiplon binds selectively to the GABA-A receptors in the brain, promoting sleep.