Journal of Clinical Pharmacy and Therapeutics (J Clin Pharm Therapeut )

Publisher: Blackwell Publishing

Description

The Journal of Clinical Pharmacy and Therapeutics has become established among pharmacists in various disciplines and areas of specialization as a forum for the communication of significant developments in clinical and hospital pharmacy. Its scope embraces: the manufacture, quality control and formulation of medicines; drug information services; pharmacokinetics; radiopharmacy; organisation and management of the hospital pharmacy; drug distribution systems including unit dose systems; clinical pharmacy education; all other aspects of clinical pharmacy.

  • Impact factor
    2.10
  • 5-year impact
    1.91
  • Cited half-life
    6.30
  • Immediacy index
    0.47
  • Eigenfactor
    0.00
  • Article influence
    0.51
  • Website
    Journal of Clinical Pharmacy and Therapeutics website
  • Other titles
    Journal of clinical pharmacy and therapeutics (Online), Journal of clinical pharmacy & therapeutics
  • ISSN
    1365-2710
  • OCLC
    45469824
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher's version/PDF cannot be used
    • On author's server, institutional server or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at www.blackwell-synergy.com")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: What is known and objectiveAmphotericin B (AmB) is commonly used to treat a broad spectrum of fungal infections and leishmaniasis. Its use is limited by numerous adverse effects. Reversible dilated cardiomyopathy associated with AmB is a rare disorder with only four previously reported cases, and all of them referring to patients who presented with a predisposing factor for heart failure.Case summaryA previously healthy 45-year-old man with visceral leishmaniasis treated with AmB developed acute dilated cardiomyopathy. Other causes of heart failure as well-known predisposing factors for this condition were ruled out. As with previously reported cases, the cardiac function of our patient returned to normal shortly after.What is new and conclusionWe describe the first case of dilated cardiomyopathy associated with the administration of AmB in a patient without any known predisposing factor for developing cardiac dysfunction. Available evidence suggests that AmB may induce cardiotoxicity. Further investigations are needed to clarify this issue.
    Journal of Clinical Pharmacy and Therapeutics 12/2014;
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    ABSTRACT: Generic manufacturers help decrease the cost of antiretroviral (ARV) and antimicrobial medications which are used to treat opportunistic infections (OIs) in developing countries. Concerns have been expressed about potential quality issues with such medications as a result of the identification of numerous counterfeit medications in developing countries. However, few studies have assessed the quality of these medications using the United States Pharmacopeia (USP) compendial standards. The goal of this study was to assess the quality of ARV and OI medications obtained from various sources, including South Africa, United States, China, Ethiopia, Thailand, Laos, Mexico, Nigeria and five Internet pharmacies.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveThe management of metastatic melanoma has changed significantly in the past decade with the development of immunotherapies and targeted molecular therapies. Trials of targeted therapies have focused mainly on patients with the most common BRAF V600 mutations, namely V600E/K substitutions, with very little information available on the benefit of targeted therapies on less commonly occurring mutations such as V600R/D and M.Case summaryWe present a 54-year-old man with metastatic melanoma harbouring a rare BRAF V600M mutation, who experienced clinical and radiological response to combined therapy with the BRAF inhibitor dabrafenib and MEK inhibitor trametinib.What is new and conclusionAs our understanding of these therapies evolves and an increasing number of patients have mutational testing performed, there is a clear imperative – as highlighted by this case – to test for rarer mutations and facilitate their inclusion both in everyday practice and in future clinical trials.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveThe reasons of clopidogrel (CLP) resistance are still unclear. The response to CLP may be influenced by both genetic and non-genetic factors. Among genetic factors, common polymorphisms in the gene coding glycoprotein-P (P-gp, MDR1 and ABCB1) are considered as potential determinants of the efficacy of CLP treatment. The aim of this study was to evaluate the influence of ABCB1 3435C>T genetic polymorphism on the pharmacokinetics and pharmacodynamics of CLP and its metabolites: diastereoisomers of thiol metabolite (the inactive H3 and the active H4) and inactive carboxylic derivative.Methods The study group included 42 patients undergoing elective coronary angiography and percutaneous coronary intervention. The plasma concentrations of CLP and its metabolites were measured by a validated HPLC-MS/MS method. Whole-blood aggregation was determined with Multiplate analyzer. For evaluation of ABCB1 3435C>T polymorphism, PCR-RFLP method was applied.Results and discussionIt was found that Exposition to the unchanged CLP, measured by AUC0–t of the drug, was significantly lower (P = 0·012) in TT homozygotes comparing to that observed in CC and CT genotypes, although no correlation was found between platelet aggregation and ABCB1 genetic polymorphism.What is new and conclusionOur findings show that the presence of 3435C>T allele has an impact on CLP pharmacokinetics but not on the drug pharmacodynamics. Therefore, the 3435C>T genotype may not be the primary determinant influencing the pharmacokinetics of the active H4 metabolite and antiplatelet effect of the drug.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveDrug eluting beads (DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2).Methods All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system and from the analytic accountability.Results and discussionOne hundred and sixty-one patients were included. Median time to treatment failure and overall survival were 13·1 and 23·8 months in Period 1 vs. 14·1 and 30·2 months in Period 2 (P = 0·45 and P = 0·40). Mean hospital durations and tariffs were 14·9 ± 7·7 days and € 11 472 ± 5901 in Period 1 vs. 12·4 ± 8·4 days and € 7654 ± 4625 in Period 2 (P = 0·03 and P < 10−4).What is new and conclusionThe possibility of using DEBs did not improve the prognosis in HCC patients treated by TACE. Nonetheless, it had a better medico-economic profile.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveTherapeutic success is characterized by undetectable viral load, immune reconstitution confirmed by CD4+ T-cell count and no clinical manifestations of disease. High treatment adherence is a major determinant of therapeutic success that needs prevention of viral replication, allowing immune reconstitution. Adherence to treatment <95% has been associated with both immune and viral failure. The objective of this study was to evaluate factors associated with therapeutic success in adult patients on highly active antiretroviral therapy (HAART) in a specialized centre for HIV-AIDS in southern Brazil, being defined therapeutic success as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm3) and adherence to HAART ≥ 95%.Methods We conducted a historical cohort study nested in the PC-HIV randomized clinical trial of PC-HIV. We included adults who were on HAART at Pelotas HIV/AIDS Assistance Service between June 2006 and July 2007 and for whom information on treatment adherence, viral load and CD4+ cell count was available. Pregnant women were excluded. We obtained clinical data from medical records and socio-demographic information in an interview. Therapeutic success was defined as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm3) and adherence to HAART ≥95%.Results and discussionWe included 136 patients (60% male) in the cohort study. Mean age was 40 ± 10 years, and median treatment duration was 59 months (IQR 25–93). Family income varied from 0 to 8 times the minimum wage (IQR 1·0–2·3). Therapeutic success was achieved by 90% (122 patients), and it was associated with previously undetectable viral load (PR = 1·30; 95% CI = 1·13–1·49) and treatment adherence prior to study entry (PR = 1·34; 95% CI = 1·07–1·69), independently of sex, age and previous immune status.What is now and conclusionWhen undetectable viral load, CD4+ cell count ≥200 cells/mm3 and treatment adherence above 95% are included in the definition of therapeutic success, the rate was elevated (90%) and the factors associated were previous history of adherence to HAART and previous undetectable viral load.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveAzole antifungals, prescribed prophylactically to avoid severe infections in immunosuppressed organ transplant recipients, can interact with drug substrates of CYP3A4. We report serious adverse effects due to interaction between orally administered voriconazole and everolimus in a renal transplant recipient.Case descriptionDespite reduction of the dose of everolimus by a third, the blood trough concentration of everolimus increased considerably in a kidney transplant recipient upon oral administration of voriconazole. Everolimus was then discontinued. Pneumonia secondary to pulmonary aspergillosis worsened, possibly due to the excessive immunosuppression.What is new and conclusionOrally administered voriconazole inhibits intestinal and hepatic cytochrome P450-3A4 activity and thereby reduces everolimus metabolism. An 80% decrease in dose or discontinuation of everolimus is required when concomitant voriconazole is introduced. Daily blood monitoring of everolimus is warranted until a steady state of concentrations is reached.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveEndocrine therapy is an effective treatment for post-menopausal women with ‘oestrogen receptor-positive’ invasive breast cancers. There are two main types of endocrine therapies: selective oestrogen receptor modulators (tamoxifen) and aromatase inhibitors (anastrozole, letrozole and exemestane). The aim of this study was to compare the patterns of use of endocrine therapies for breast cancer in women between nine developed countries.MethodsA longitudinal, cross-national drug utilization study was conducted. The endocrine therapies included were tamoxifen and the aromatase inhibitors: anastrozole, letrozole and exemestane. Annual drug utilization data were collected from Australia, Denmark, England, Finland, France, Iceland, the Netherlands, Norway and Sweden over the period 2001–2012. Utilization was measured in DDD/1000 inhabitants/day and was also adjusted for breast cancer incidence and female population statistics.Results and discussionTotal use of endocrine therapies either increased or remained steady in all countries. Total endocrine therapy usage was consistently highest in England and France. Norway showed the lowest usage of endocrine therapies overall, using only 1·80 DDD/1000 inhabitants/day in 2012. Downward trends in tamoxifen use and upward trends in aromatase inhibitors were seen across all countries over the study period. By 2012, aromatase inhibitors represented over half of total endocrine therapy use in all countries, and as high as 74% and 80% in France and Denmark, respectively.What is new and conclusionOur analysis found a shift in use of endocrine therapy from tamoxifen to aromatase inhibitors. This trend is consistent with major clinical guidelines endorsing preferential use of aromatase inhibitors in post-menopausal women. Stabilization or small increase in tamoxifen use in the recent years may reflect the recognition of tamoxifen as still an appropriate first-line treatment. The similarity in utilization patterns may be due to the relatively comparable healthcare systems in the countries, namely universal health insurance and pharmaceutical coverage. Differences in utilization observed could be due to differences in breast cancer incidence, prescribing behaviours, interpretation of new trial evidence, and timing of drug marketing approval and reimbursement between countries.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveClinical pharmacists have a challenging task when answering patients’ question about whether they can take specific drugs with grapefruit juice (GFJ) without risk of drug interaction. To identify the most practicable method for predicting clinically relevant changes in plasma concentrations of orally administered drugs caused by the ingestion of GFJ, we compared the predictive performance of three methods using data obtained from the literature.Methods We undertook a systematic search of drug interactions associated with GFJ using MEDLINE and the Metabolism & Transport Drug Interaction Database (DIDB version 4.0). We considered an elevation of the area under the plasma concentration‒time curve (AUC) of 2 or greater relative to the control value [AUC ratio (AUCR) ≥ 2·0] as a clinically significant interaction.Results and discussionThe data from 74 drugs (194 data sets) were analysed. When the reported information of CYP3A involvement in the metabolism of a drug of interest was adopted as a predictive criterion for GFJ‒drug interaction, the performance assessed by positive predictive value (PPV) was low (0·26), but that assessed by negative predictive value (NPV) and sensitivity was high (1·00 for both). When the reported oral bioavailability of ≤0·1 was used as a criterion, the PPV improved to 0·50 with an acceptable NPV of 0·81, but sensitivity was reduced to 0·21. When the reported AUCR was ≥10 after co-administration of a typical CYP3A inhibitor, the corresponding values were 0·64, 0·79 and 0·19, respectively.What is new and conclusionWe consider that an oral bioavailability of ≤0·1 or an AUCR of ≥10 caused by a CYP3A inhibitor of a drug of interest may be a practical prediction criterion for avoiding significant interactions with GFJ. Information about the involvement of CYP3A in their metabolism should also be taken into account for drugs with narrow therapeutic ranges.
    Journal of Clinical Pharmacy and Therapeutics 11/2014;
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    ABSTRACT: What is known and objectiveMedication errors (ME) in oncology are known to cause serious iatrogenic complications. However, MEs still occur at each step in the anticancer chemotherapy process, particularly when injections are prepared in the hospital pharmacy. This study assessed whether a ME simulation program would help prevent ME-associated iatrogenic complications.Methods The 5-month prospective study, consisting of three phases, was undertaken in the centralized pharmaceutical unit of a university hospital of Lyon, France. During the first simulation phase, 25 instruction sheets each containing one simulated error were inserted among various instruction sheets issued to blinded technicians. The second phase consisted of activity aimed at raising pharmacy technicians' awareness of risk of medication errors associated with antineoplastic drugs. The third phase consisted of re-enacting the error simulation process 3 months after the awareness campaign. The rate and severity of undetected medication errors were measured during the two simulation (first and third) phases. The potential seriousness of the ME was assessed using the NCC MERP® index.Results and discussionThe rate of undetected medication errors decreased from 12 in the first simulation phase (48%) to five in the second simulation phase (20%, P = 0∙04). The number of potential deaths due to administration of a faulty preparation decreased from three to zero. Awareness of iatrogenic risk through error simulation allowed pharmacy technicians to improve their ability to identify errors.What is new and conclusionThis study is the first demonstration of the successful application of a simulation-based learning tool for reducing errors in the preparation of injectable anticancer drugs. Such a program should form part of the continuous quality improvement of risk management strategies for cancer patients.
    Journal of Clinical Pharmacy and Therapeutics 10/2014;
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    ABSTRACT: What is known and objectiveFibromyalgia is a painful disease affecting 1–2% of the United States population. Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and milnacipran, are well studied and frequently used for treating this disorder. However, efficacy data are limited for the SNRI venlafaxine despite its use in nearly a quarter of patients with fibromyalgia. Accordingly, we systematically reviewed the efficacy of venlafaxine for treatment of fibromyalgia.Methods PubMed, Web of Science and the Cochrane Database were searched using the terms ‘venlafaxine’ and ‘fibromyalgia’. Results were classified as primary studies or review articles based on abstract review. References of review articles were evaluated to ensure no primary studies evaluating venlafaxine were overlooked. All clinical studies that investigated venlafaxine for the treatment of fibromyalgia were included and graded on strength of evidence.Results and discussionFive studies met the inclusion criteria, including 4 open-label cohort studies and 1 randomized, controlled trial. Study durations ranged from 6 weeks to 6 months, and study sizes ranged from 11 to 102 participants. Four of the five published studies reported improvement in at least one outcome. Generally consistent improvements were observed in pain-related outcome measures, including the Fibromyalgia Impact Questionnaire (range, 26–29% reduction; n = 2 studies), Visual Analog Scale (range, 36–45% reduction; n = 2 studies), McGill Pain Questionnaire (48% reduction; n = 1 study) and Clinical Global Impression scale (51% had significant score change; n = 1 study). However, the few studies identified were limited by small sample size, inconsistent use of outcomes and methodological concerns.What is new and conclusionStudies assessing the efficacy of venlafaxine in the treatment of fibromyalgia to date have been limited by small sample size, inconsistent venlafaxine dosing, lack of placebo control and lack of blinding. In the context of these limitations, venlafaxine appears to be at least modestly effective in treating fibromyalgia. Larger randomized controlled trials are needed to further elucidate the full benefit of venlafaxine.
    Journal of Clinical Pharmacy and Therapeutics 10/2014;
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    ABSTRACT: What is known and objectiveEvidence demonstrates that the delicate balance between pro- and anti-inflammatory cytokines determines the further progress to severe injury or recovery. Therefore, understanding which cytokines are associated with the development of drug-induced hepatotoxicity (DIH) might guide the prevention and therapeutic direction. Some polymorphisms of cytokine genes have been reported to be associated with DIH involving interleukin-4 (IL-4), interleukin-10 (IL-10) and tumour necrosis factor-α (TNF-α); however, these studies are still scanty with inconsistent results. In addition, most of these associations have not been investigated in antituberculosis drug-induced hepatotoxicity (ATDH) patients with the exception of TNF-α polymorphisms. Therefore, we aimed to investigate the association between IL-4 and IL-10 gene polymorphisms with the risk of ATDH in a Chinese population.Methods The study was designed as a nested case–control study within a prospective cohort. Each case was matched with four controls by sex, age at baseline (±5 years), treatment history, disease severity, drug dosage and place of sample collection. Genetic polymorphisms of IL-4 and IL-10 were determined by TaqMan single nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model.Results and discussionA total of 89 incident ATDH cases and 356 controls undergoing antituberculosis treatment were included. Six SNPs were selected for genotyping, which were rs2243289, rs2243250 and rs2070874 for IL-4, and rs1800896, rs1800871 and rs1800872 for IL-10. No significant difference was observed in genotypes frequencies of the six selected SNPs between case and control group, and the distributions of IL-4 and IL-10 haplotypes were similar in ATDH patients and controls.What is new and conclusionThis study is the first attempt to evaluate the associations of genetic polymorphisms of IL-4 and IL-10 genes with ATDH using a nested case–control study design. We provide preliminary evidence that there is no statistically significant association between IL-4 and IL-10 genotypes/haplotypes and the risk of ATDH in Chinese population.
    Journal of Clinical Pharmacy and Therapeutics 10/2014;
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    ABSTRACT: What is known and objectiveSeveral studies have investigated factors that may influence adherence for a given disease. The influence of disease on adherence has received limited attention. Less work has been conducted to investigate the influence of other factors in conjunction with disease on adherence. The aim of this study was to determine the independent influence of disease and other factors on adherence.MethodsA literature search was conducted to retrieve adherence studies using medication event monitoring system devices. Studies were categorized into different therapeutic areas. Only the two most commonly studied therapeutic areas were selected. Pseudopatient-level data were extracted from each study. The extracted data were analysed using a model-based meta-analysis technique. Univariate and multivariate models were developed. Model selection was based on a likelihood ratio test and visual plots.ResultsThe most commonly studied therapeutic areas were HIV and hypertension. The most commonly recorded adherence criterion was percentage of prescribed doses taken per day. Based on this adherence criterion, ultimately, 24 HIV papers and 12 hypertension papers were included for data extraction. The statistically significant factors were disease, age and dosing regimen. The independent influences of each factor on adherence were as follows: an increase in adherence of approximately 8% per 10-year increase of age, a 15–19% reduction from once to thrice daily dosing and that patients with HIV were 5% more adherent than those with hypertension.What is new and conclusionAlthough the influence of disease on adherence was significant, it was of limited clinical significance in the diseases studied here. Adherence appears to improve with age and decline with more frequent dosing. Additionally, the influence of dosing regimen wanes with increasing age. These results should be treated as exploratory and require prospective assessment.
    Journal of Clinical Pharmacy and Therapeutics 10/2014;
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    ABSTRACT: What is known and objectiveAngiotensin receptor blockers (ARBs) are medications commonly used for treating conditions such as hypertension. However, ARBs are frequently associated with hyperkalemia, a potentially critical adverse event, in high-risk patients. Although both the liver and the kidney are major elimination routes of ARBs, the relationship between hepatorenal function and ARB-related hyperkalemia has not yet been investigated. The purpose of this study was to evaluate the risk of hyperkalemia, in terms of various hepatorenal functions, for hospitalized patients newly initiated on ARB treatment.Methods We evaluated ARB-related hyperkalemia in a cohort of 5530 hospitalized patients, who had not previously used ARBs, between 12 April 2004 and 31 May 2012. Hepatorenal function was assessed by the Model for End-stage Liver Disease (MELD) score. Hyperkalemia risk was assessed by hepatorenal function, risks were categorized into the four MELD scoring groups, and the groups were compared with one another.Results and discussionThe MELD score was significantly different between the hyperkalemic and non-hyperkalemic groups (independent t-test, P < 0·001). The MELD score 10–14, 15–19 and ≥20 groups showed higher risks of hyperkalemia than the lowest MELD score group {log-rank test, P < 0·001; multiple Cox proportional hazard model, hazard ratios 1·478 (P = 0·003), 2·285 (P < 0·001) and 3·024 (P < 0·001), respectively}.What is new and conclusionThe MELD score showed a stronger predictive performance for hyperkalemia than either serum creatinine or estimated glomerular filtration rate alone. Furthermore, the MELD score showed good predictive performance for ARB-related hyperkalemia among hospitalized patients. The clinical implications and reasons for these findings merit future investigation.
    Journal of Clinical Pharmacy and Therapeutics 10/2014;
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    ABSTRACT: What is known and objectiveDrug lag is a major public concern in Japan. During the development of new drugs, some factors related to clinical trials in the marketing application package, such as trial design and the number of trials, can affect drug approval. The aim of this study was to determine whether those clinical trial factors were associated with drug lag in Japan.Methods We investigated new drug applications for new molecular entities that were approved in Japan between April 2009 and March 2012. We collected information on clinical trials in the marketing application package from review reports.Results and discussionWe constructed a multiple regression model to predict drug lag using the review period, use of foreign clinical trial data, the number of confirmatory trials, the design of the pivotal trial, failures of confirmatory trials and the death rate (n = 59). No use of foreign trial data was significantly associated with a longer drug lag (84% increase; 95% confidence interval [CI], 1·03–3·29). Compared to the open-label, one-armed design, drugs that underwent pivotal trials of placebo-controlled superiority, active-controlled superiority and active-controlled non-inferiority designs had a significantly shorter drug lag (74% decrease, 95% CI: 0·08–0·83; 74% decrease, 95% CI: 0·07–0·99; and 85% decrease, 95% CI: 0·04–0·58, respectively).What is new and conclusionOur findings suggest that new drug application packages that do not use data from foreign clinical trials and that involve pivotal trials of open-label, one-armed design contribute to drug lag in Japan. To reduce this lag, improved strategies for the development of new drugs should be identified.
    Journal of Clinical Pharmacy and Therapeutics 09/2014;
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    ABSTRACT: What is known and objectiveBipolar disorder is a common and disabling condition. Although its negative impact may be limited in some way by the use of different treatment options, lack of adherence to psychiatric treatment is still an obstacle to overcome. Because there are many factors involved in non-adherence to treatment, in this study, we sought to examine the subjective aspect of this phenomenon. We analysed perceptions of both the disease and the treatment in a group of patients with bipolar disorder.Methods We incorporated a qualitative design that included 50 outpatients diagnosed with bipolar disorder type 1. Through semi-structured interviews, we explored patients' perceptions of bipolarity and psychiatric medication management.Results and discussionThe participants reported the use of medications as one of the most troubling aspects of having bipolar disorder. The fear of becoming addicted to psychiatric drugs was repeatedly mentioned among the patients as an argument for abandoning treatment. The main expectation of treatment was to achieve stable mood, but the patients considered that drugs were not the only way to be euthymic.What is new and conclusionsThe patients expressed ambivalence between the need to take medication to remain stable and the fear of negative consequences of using psychiatric drugs. Personal beliefs and environmental influences seem to determine each individual's final choice of whether to maintain or discontinue treatment; so, in everyday clinical practice, it would be necessary to discuss perceptions of the disease with patients and their families.
    Journal of Clinical Pharmacy and Therapeutics 09/2014;
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    ABSTRACT: What is known and objectivePatients with non-valvular atrial fibrillation (NVAF) are at risk for stroke and systemic embolism (SSE), and this risk can be decreased with adjusted-dose warfarin. Warfarin, however, is cumbersome to use and requires at least monthly laboratory monitoring. Three new oral anticoagulants (NOACs) that are less cumbersome have been approved as alternatives to warfarin for SSE prevention in NVAF. Selecting a patient-specific alternative to warfarin can be confusing for pharmacists and clinicians. This review details clinical parameters to consider when choosing an alternative to warfarin for a specific patient and summarizes them in a Comparison Table.Methods Using available clinical evidence from pivotal trials, US FDA- and Health Canada-approved prescribing information and post-marketing observations, this review provides a summary of important clinical variables for clinicians to consider when choosing patient-centred anticoagulant alternatives to warfarin for prevention of SSE in NVAF.Results and discussionDabigatran, rivaroxaban and apixaban are approved alternatives to warfarin for primary and secondary prevention of SSE in patients with NVAF. Additionally, apixaban has also been compared to aspirin in patients with NVAF that were considered unsuitable for vitamin K antagonist therapy. Prospective consideration of age, weight, hepatic function, renal function and drug interactions are important clinical parameters to consider when selecting patient-centred alternatives to adjusted-dose warfarin.What is new and conclusionSeveral NOACs are now alternatives to warfarin for SSE prevention in NVAF but require providers to make a shift in strategy from tailoring anticoagulant dose based on anticoagulant effect to selection of the anticoagulant based on clinical variables that affect anticoagulant exposure. These variables and their interactions should be considered in choosing an alternative to warfarin and are summarized in a simple table comparing the new anticoagulants.
    Journal of Clinical Pharmacy and Therapeutics 09/2014;
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    ABSTRACT: What is known and objectiveFew studies have evaluated the effect of vancomycin dosing on the health outcomes in geriatric patients. Data are needed to determine whether higher vancomycin dosing strategies are more effective in geriatric patients and/or lead to excessive rates of adverse events.Methods This study used a subset of patients aged ≥65 years from a multicentre, retrospective, cohort study of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Patients received ≥ 48 h of empiric vancomycin between 1 July 2002 and 30 June 2008. We compared the incidence of nephrotoxicity and in-hospital mortality in patients who received guideline-recommended dosing (at least 15 mg/kg/dose) to patients who received lower dosing. Multivariable generalized mixed-effect models were constructed to determine independent risk factors for nephrotoxicity and in-hospital mortality.Results and discussionHalf of the cohort (46% of 92 patients) received guideline-recommended dosing. Empiric use of weight-based dosing did increase the percentage of patients achieving a vancomycin trough ≥ 15 mg/L (57% vs. 42%). Nephrotoxicity occurred in 32% of patients and 26% died during their hospitalization. Guideline-recommended dosing was not associated with significant changes in nephrotoxicity (OR 1·13; 95% CI 0·40–3·19) or in-hospital mortality (OR 1·14; 95% CI 0·41–3·18) in the multivariable analysis.What is new and conclusionIn this study of geriatric patients, guideline-recommended dosing was not associated with significant changes in nephrotoxicity or mortality. As 40% of the patients who received guideline-recommended dosing failed to achieve a target vancomycin trough of ≥ 15 mg/L, future studies should focus on dosing strategies to increase target attainment rate.
    Journal of Clinical Pharmacy and Therapeutics 09/2014;
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    ABSTRACT: What is known and objectiveVariation in the expression of drug-response-related genes contributes significantly to interindividual differences in drug response. DNA methylation is one of the most common epigenetic modifications that control gene expression. DNA methylation may occur in genes encoding drug metabolizing enzymes (DMEs), drug transporters and drug targets, and can thereby alter the pharmacokinetics and pharmacodynamics of drugs. In this review, we discuss recent advances in pharmacoepigenetics with a focus on DNA methylation.Methods The literature search focusing on DNA methylation of drug-response-related genes and DNA methylation-related SNPs in pharmacogenomics was carried out using the PUBMED database and a combination of keywords including DNA methylation, drug response, DMEs, drug transporters, drug target and SNPs.Results and discussionAn extensive range of research has contributed to our understanding of how DNA methylation of drug-response-related genes alters their function. This is particularly well studied in cancer chemotherapy and drug resistance. The impact of polymorphisms of miRNAs in these processes requires further study.What is new and conclusionDNA methylation-related genetic variation is an increasingly recognized mechanism for altered drug-response and disease susceptibility. These new discoveries require assimilation into the practice of personalized medicine.
    Journal of Clinical Pharmacy and Therapeutics 09/2014;