American Pharmacists Association

About: American Pharmacists Association is a other organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Pharmacist & Pharmacy. The organization has 2413 authors who have published 1969 publications receiving 30470 citations. The organization is also known as: APhA & American Pharmaceutical Association.

Tacrolimus-itraconazole interaction in a kidney transplant patient.

Abstract: TO THE EDITOR: Tacrolimus is an immunosuppressive agent that is metabolized by the cytochrome P450 enzyme system in the liver.1 3 Its metabolism is similar to that of cyclosporine and suggests the same interactive profile.1 Itraconazole is an antifungal agent and, in our hospital, is administered for prophylaxis of Aspergillus infections during a period of approximately five or six months. Itraconazole is highly metabolized by the same form of cytochrome P450 (CYP3A4) as cyclosporine and tacrolimus; it is also known to inhibit the metabolism of cyclosporine.4 , 5 These arguments favor the existence of a potential drug interaction between itraconazole and t a c r o l i m u s . We report an interaction between tacrolimus and itraconazole in a patient who received a kidney transplant. Case Report. A 21-year-old woman (56 kg) with end-stage renal disease received a single kidney transplant. The initial immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate. Three months after transplantation, cyclosporine was stopped because of hirsutism, and tacrolimus was added to the patient’s daily treatment regimen, which consisted of prednisone 15 mg, azathioprine 100 mg, ranitidine 150 mg, itraconazole 200-mg capsules, and trimethoprim/sulfamethoxazole (160 mg/800 mg). The patient began receiving itraconazole fungus prophylaxis after the transplantation. The initial tacrolimus oral dose was 0.1 mg/kg/d (3 mg bid). The tacrolimus dosage was adjusted based on trough whole blood concentrations using a microparticle enzyme immunoassay and an IMx analyzer. The recommended therapeutic range for this drug is 5–15 ng/mL. Laboratory data were closely monitored. Four days after beginning tacrolimus therapy, the trough tacrolimus concentration was 20 ng/mL, blood urea nitrogen (BUN) was 73 mg/dL, serum creatinine was 1.3 mg/dL, and serum potassium was 4.2 mEq/L. At this time, the tacrolimus dosage was reduced to 0.067 mg/kg/d (2 mg bid), but the tacrolimus concentrations remained high (19.5 ng/mL on hospital day 7, 21.4 ng/mL on hospital day 11). Laboratory data were also increased (BUN 77 mg/dL, serum potassium 4.9 mEq/L). Dosage reduction of tacrolimus to 0.033 mg/kg/d (1 mg bid) was effective in achieving trough concentrations in therapeutic range (13.8 ± 1.5 ng/mL). BUN and serum potassium returned to normal values. The coadministration of itraconazole and tacrolimus was continued for 58 days. When itraconazole was withdrawn, low trough concentrations (3.4 ng/mL) were noted on hospital day 61, and the tacrolimus doses had to be gradually increased to 0.133 mg/kg/d (4 mg bid) to obtain trough concentrations of 9.0 ± 1.1 ng/mL. The changes in the tacrolimus concentrations and doses are shown in Figure 1. The variations in tacrolimus concentrations were attributed to concomitant itraconazole therapy because no other drugs and dosage forms were modified. In addition, the patient was compliant with her tacrolimus dosing schedule because she was admitted to the hospital after the transplantation when her trough tacrolimus concentrations were in therapeutic range (1 mg bid); during her hospitalization the patient had no gastrointestinal problems that would affect absorption of tacrolimus. No significant changes were noted in the patient’s laboratory values, except for BUN concentrations and serum potassium. These increased BUN concentrations and serum potassium could be associated with elevated tacrolimus concentrations. Based on the changes in tacrolimus blood concentrations, the itraconazole–tacrolimus interaction was considered highly probable on the Naranjo probability s c a l e .6 Discussion. Based on our observations, we recommend that blood concentrations of tacrolimus be monitored. To maintain therapeutic concentrations and minimize toxicity in patients receiving this agent, we suggest that close and appropriate dosage adjustments be made when the two drugs are administered concomitantly or when itraconazole is discontinued.

Oxymorphone Extended-Release Tablets (Opana ER) For the Management of Chronic Pain: A Practical Review for Pharmacists.

Abstract: Whether in a dedicated pain-management clinic or in a community pharmacy, pharmacists can provide valuable education and treatment recommendations to patients and clinicians. Pain programs, jointly managed by pharmacists, nurse practitioners, specialists in behavioral medicine and functional restoration, and specialty pain physicians, can enhance the satisfaction of patients and health care professionals, improve clinical outcomes, and minimize the need for secondary pain referrals.1 Pharmacists who become knowledgeable in pain pharmacotherapy can facilitate safe, effective, and cost-beneficial equianalgesic opioid conversions in primary care settings.2 Long-acting (LA) opioids are recommended for moderate-to-severe chronic cancer and non-cancer pain.3,4 In their most recent evidence review, the American Pain Society and American Academy of Pain Medicine concluded that there is insufficient evidence to recommend that LA opioids be used in place of short-acting opioids for chronic non-cancer pain, but they acknowledge that LA opioids might provide more consistent pain control, improve adherence, and reduce the risk of addiction or abuse.4 Additional research is needed to evaluate these proposed advantages.5 Differences among opioids influence individual patient response and tolerability, risks and benefits in specific disease states, the likelihood of drug interactions, and ease of monitoring. Differences among patients with respect to genetic factors, age, sex, and the prior use of opioids also contribute to variability of response to individual opioids.6 Consequently, when selecting LA opioids, clinicians cannot reliably predict how a given patient will respond. Patients with chronic pain usually require consecutive trials of several LA opioids before they find one that provides adequate analgesia with acceptable tolerability.7–9 For this reason, it is essential to have multiple LA opioids from which to choose. In 2006, the FDA approved extended-release oxymorphone HCl (Opana ER, Endo) for the control of moderate-to-severe chronic pain. At that time, morphine (MsContin, Purdue); Oramorph SR, Xanodyne; oxycodone (OxyContin, Purdue); methadone (Dolophine, Roxane); and transdermal fentanyl (Duragesic, Ortho-McNeil-Janssen) were the only LA opioids approved in the U.S., and they remain the primary alternatives to oxymorphone ER today. Some pain specialists do not consider LA tramadol (Ultram, PriCara) to be an equivalent alternative to these drugs because of its predominantly non-opioid mechanism of action10 and relatively weak analgesic potency, compared with other more potent opioids. LA hydromorphone (Palladone, Purdue) was withdrawn from the U.S. market in 2005 because of a potentially fatal interaction with alcohol.11 A new formulation (Exalgo, Covidien) has received FDA approval.12,13 Transdermal buprenorphine (e.g., Transtec, Butrans, or Norspan in Europe) is being studied for the management of chronic pain. It will probably represent another LA opioid choice if it receives FDA approval.14 Tapentadol (Nucynta, PriCara) combines mu-opioid receptor agonism with norepinephrine reuptake inhibition. It is available as an immediate-release (IR) tablet, and a long-acting preparation is being investigated.15 Tapentadol is featured in this month’s Drug Forecast column on page 330. A Schedule II controlled substance (CII), oxymorphone ER is a selective mu-opioid agonist16 that is embedded in an agglomerated hydrophilic matrix to provide sustained activity over a 12-hour dosing interval.17 This article describes the agent’s pharmacology, pharmacokinetics, efficacy and safety, and clinical considerations of significance to pharmacists, clinicians, and members of P&T committees.

Cost-Effectiveness Analysis of Anticoagulation Strategies in Non–ST-Elevation Acute Coronary Syndromes

Abstract: Background:Contemporary studies document the outcomes of unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS). It remains unclear which anticoagulant regimen is the most cost-effective.Objective:To perform a cost-effectiveness analysis comparing 4 anticoagulant regimens in NSTE-ACS.Methods:A decision analysis was conducted from a healthcare provider perspective. Data sources included the SYNERGY, OASIS-5, and ACUITY trials, including 2 subgroup analyses. A decision tree model was created incorporating the outcomes associated with 4 antithrombotic approaches: UFH with eptifibatide, enoxaparin with eptifibatide, bivalirudin alone, and fondaparinux with eptifibatide. The percentage of eptifibatide use in each arm was consistent with clinical trials. Probabilities of complications (eg, myocardial infarction, revascularization, major/minor bleeding at 30 days) were calculated. Costs were assigned to each outcome, incorporat...

Special features of topical and systemic dermatologic therapy in children

Abstract: Summary Since children differ greatly from adults in terms of physiology and pathophysiology, which in turn influences pharmacokinetics and pharmacodynamics, pediatric clinical trials on the effectiveness and safety of drugs must be supported. Such studies are still lacking. To avoid excluding pediatric patients from the benefit of optimal treatment, treatment strategies for children are often derived from trials with adult patients. Pediatric prescribing is also assisted by years of experience in the use of drugs and empirical data found in the literature. This article discusses typical side effects that can occur with pediatric topical and systemic drug use. Salicylic acid and lindane intoxication are discussed as are Reye syndrome after taking acetylsalicylic acid to treat viral infection. Additional examples and tables listing drugs often used in pediatric dermatology as well as general information on prescribing off-label pharmaceuticals should help children with skin disorders benefit from effective and tolerable treatment.

Ivabradine: a new rate-limiting therapy for coronary artery disease and heart failure.

Abstract: Ivabradine is a new bradycardic agent acting on the If channels of sinoatrial nodal cells to decrease the rate of diastolic depolarization and thus heart rate. The benefit of ivabradine over other negatively chronotropic agents is its absence of negative inotropy. Effective management of coronary artery disease, in terms of reducing morbidity and mortality, is reliant on controlling heart rate. Ivabradine has been shown to safely and effectively reduce heart rate without compromising cardiac function in patients with coronary artery disease and more recently in patients with heart failure and raised heart rate. Furthermore, ivabradine has been shown to have a favourable side-effect profile compared with alternative bradycardic agents. This article reviews the evidence for ivabradine in coronary artery disease and heart failure and compares its safety with alternative bradycardic agents for these conditions.