Medication review and reconciliation with cooperation between pharmacist and general practitioner and the benefit for the patient:a systematic review

This article systematically reviews the literature on the impact of collaboration between pharmacists and general practitioners and describes its effect on patients' health. A systematic literature search provided 1041 articles. After first review of title and abstract, 152 articles remained. After review of the full text, 83 articles were included. All included articles are presented according to the following variables: (i) reference; (ii) design and setting of the study; (iii) inclusion criteria for patients; (iv) description of the intervention; (v) whether a patient interview was performed to involve patients' experiences with their medicine-taking behaviour; (vi) outcome; (vii) whether healthcare professionals received additional training; and (viii) whether healthcare professionals received financial reimbursement. Many different interventions are described where pharmacists and general practitioners work together to improve patients' health. Only nine studies reported hard outcomes, such as hospital (re)admissions; however, these studies had different results, not all of which were statistically significant. Randomized controlled trials should be able to describe hard outcomes, but large patient groups will be needed to perform such studies. Patient involvement is important for long-term success

Cost-Effectiveness of Dabigatran Compared to Vitamin-K Antagonists for the Treatment of Deep Venous Thrombosis in the Netherlands Using Real-World Data

Vitamin-K antagonists (VKAs) present an effective anticoagulant treatment in deep venous thrombosis (DVT). However, the use of VKAs is limited because of the risk of bleeding and the necessity of frequent and long-term laboratory monitoring. Therefore, new oral anticoagulant drugs (NOACs) such as dabigatran, with lower rates of (major) intracranial bleeding compared to VKAs and not requiring monitoring, may be considered.To estimate resource utilization and costs of patients treated with the VKAs acenocoumarol and phenprocoumon, for the indication DVT. Furthermore, a formal cost-effectiveness analysis of dabigatran compared to VKAs for DVT treatment was performed, using these estimates.A retrospective observational study design in the thrombotic service of a teaching hospital (Deventer, The Netherlands) was applied to estimate real-world resource utilization and costs of VKA monitoring. A pooled analysis of data from RE-COVER and RE-COVER II on DVT was used to reflect the probabilities for events in the cost-effectiveness model. Dutch costs, utilities and specific data on coagulation monitoring levels were incorporated in the model. Next to the base case analysis, univariate probabilistic sensitivity and scenario analyses were performed.Real-world resource utilization in the thrombotic service of patients treated with VKA for the indication of DVT consisted of 12.3 measurements of the international normalized ratio (INR), with corresponding INR monitoring costs of €138 for a standardized treatment period of 180 days. In the base case, dabigatran treatment compared to VKAs in a cohort of 1,000 DVT patients resulted in savings of €18,900 (95% uncertainty interval (UI) -95,832, 151,162) and 41 (95% UI -18, 97) quality-adjusted life-years (QALYs) gained calculated from societal perspective. The probability that dabigatran is cost-effective at a conservative willingness-to pay threshold of €20,000 per QALY was 99%. Sensitivity and scenario analyses also indicated cost savings or cost-effectiveness below this same threshold.Total INR monitoring costs per patient were estimated at minimally €138. Inserting these real-world data into a cost-effectiveness analysis for patients diagnosed with DVT, dabigatran appeared to be a cost-saving alternative to VKAs in the Netherlands in the base case. Cost savings or favorable cost-effectiveness were robust in sensitivity and scenario analyses. Our results warrant confirmation in other settings and locations

Pharmacological aspects of neonatal antidepressant withdrawal

Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary

Implications of a clinical medication review and a pharmaceutical care plan of polypharmacy patients with a cardiovascular disorder

Background A clinical medication review, including patient involvement, is expected to improve pharmaceutical care. Objective To determine whether a clinical medication review followed by a pharmaceutical care plan decreases the number of potential drug-related problems (DRPs) and pharmaceutical care issues (PCIs) and leads to a positive effect on relevant clinical and laboratory parameters for elderly cardiovascular patients with multiple drug use. Setting Randomized controlled trial in eight primary care settings in the Netherlands. Method Elderly polypharmacy patients with a cardiovascular disorder were randomized into two groups. Intervention patients received a clinical medication review, followed by a pharmaceutical care plan developed in cooperation between these patients' pharmacists and general practitioners (GPs), and agreed to by the patients. Control patients received care as usual. Patient data were collected at the start of the study (t = 0) and after 1-year follow-up (t = 1). Main outcome measure Decrease in potential DRPs and pharmaceutical PCIs, improvement of clinical and laboratory parameters. Results 512 patients were included. An average of 2.2 potential DRPs and pharmaceutical PCIs were defined per patient in the intervention group. After 1-year follow-up, 47.2 % of potential DRPs and PCIs were resolved. In total, 156 care interventions were proposed (0.9/patient), 108 of which were implemented after 1 year (69.2 %). For control-group patients, a total of 47 proposed care interventions were documented for 255 patients (0.2/patient); after 1 year, 43 had been implemented (91.5 %). The study intervention (p <0.001) and the number of medicines used (p = 0.030) had a significant effect on the number of interventions proposed. Small biochemical changes in cardiovascular risk factors did occur, but the differences were small and not considered clinically relevant. Conclusion The integrated use of a clinical medication review with a pharmaceutical care plan in a primary care setting supports the detection of and decrease in DRPs and pharmaceutical PCIs in almost half of the patients. Its benefit in terms of control of cardiovascular risk factors and safety parameters was relatively low. Risk stratification might be necessary to decide which patients might benefit most from this type of intervention

Classification and occurrence of clinically significant drug interactions with irinotecan and oxaliplatin in patients with metastatic colorectal cancer

Background: Pharmacokinetic and pharmacodynamic drug interactions with cytotoxic drugs may significantly influence the efficacy and toxicity of chemotherapy. Objective: The purpose of this study was to identify drug interactions with irinotecan and oxaliplatin reported in the literature, to assess their clinical significance, and to examine the occurrence of these interactions in patients with metastatic colorectal cancer treated with either irinotecan or oxaliplatin or both. Methods: To obtain data on drug-drug interactions with irinotecan and oxaliplatin, a literature search of PubMed and EMBASE was conducted using the search terms irinotecan, oxaliplatin, and interactions (English-language studies only published between 1980 and August 2004). The interactions found were subsequently classified for documentation evidence and severity of clinical effect, according to a 5-level classification system of a standard reference text, by a study panel of medical oncologists and clinical pharmacists. Comedication of patients who were treated with irinotecan or oxaliplatin, or both, was then examined to determine the occurrence of clinically significant interactions. Results: Ninety-eight patients (50 women, 48 men; mean age, 60 years) were included in the study. Seventeen interactions with irinotecan were found in the literature, and 11 were classified as clinically significant. Only 1 nonspecific, clinically significant interaction was identified for oxaliplatin. Irinotecan-treated patients received a mean of 8 different comedications and oxaliplatin-treated patients received a mean of 6. Apart from antiemetic and antidiarrheal drugs that were prescribed for treatment-related toxicities, only 1 patient appeared to be exposed to a possible clinically significant interaction (between irinotecan and phenytoin). Conclusions: Eleven of the 17 interactions with irinotecan that were found in the literature were classified as clinically significant versus 1 clinically significant interaction with oxaliplatin. The occurrence of these interactions in the study patients with metastatic colorectal cancer was low. For medication surveillance purposes, however, the significant interactions should be considered in clinical practice. Copyright (c) 2005 Excerpta Medica, Inc

Tyrosine Kinase Inhibitors and Proton Pump Inhibitors:An Evaluation of Treatment Options

Tyrosine kinase inhibitors (TKIs) have rapidly become an established factor in oncology, and have been shown to be effective in a wide variety of solid and hematologic malignancies. Use of the oral administration route of TKIs offers flexibility and is convenient for the patient; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. Acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may subsequently decrease TKI solubility, bioavailability, and treatment efficacy. Clear and practical advice on how to manage PPI use during TKI therapy is currently not available in the literature. Since PPIs are extensively used during TKI therapy, prescribers are presented with a big dilemma as to whether or not to continue the combined treatment, resulting in patients possibly being deprived of optimal therapy. When all pharmacological characteristics and data of either TKIs and PPIs are considered, practical and safe advice on how to manage this drug combination can be given

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine:A Pragmatic Randomized Controlled Trial (CYSCE Trial)

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression