Utilization review of concomitant use of potentially interacting drugs in Thai patients using warfarin therapy

PURPOSE: In Thailand, there has been no study determining the concomitant use of medications, known to potentially interact with warfarin, in patients receiving warfarin therapy. This paper examined the frequency of which specific interacting drugs were concomitantly used in warfarin users. METHODS: We retrospectively examined the database of warfarin outpatient medical records from a regional 756-bed hospital located in the north of Thailand. All patients receiving warfarin from 10 June 1999 to 4 August 2004 were reviewed to identify all drugs possessing interaction potential with warfarin. The potential of significant interactions were divided into high, moderate and low, according to the extent of evidence documented in textbooks and literature. RESULTS: Among 1093 patients receiving warfarin therapy, 914 (84%) patients received at least one potentially interacting drug and half of them (457 patients) received at least one drug with high potential for interaction. The most frequently concomitant drug that increased INR was acetaminophen (63%, 316/457). Propylthiouracil was the most frequently concomitant drug that decreased INR response (4%, 19/457), while diclofenac was the most frequently concomitant drug that increased bleeding risk (16%, 73/457). CONCLUSIONS: About a half of patients receiving warfarin therapy was prescribed concomitant drug(s) that has a high potential of interactions with warfarin. These patients should be closely monitored and counselled to watch for signs and symptoms of bleeding and thrombosis to avoid adverse events associated with drug interactions.     

心血管内科患者华法林与其他药物联用相关的血发生情况分析

目的了解联用华法林与其他药物的心血管内科患者因药物相互作用相关的出血发生情况并探讨控制措施。方法收集北京大学第一医院心血管内科2012年1月至2013年6月住院期间应用华法林患者的病历资料进行回顾性分析,记录患者合并用药情况及可能由于药物相互作用而导致的出血发生情况,筛选与华法林存在相互作用的心血管内科常用药物。结果纳入分析的患者141例,男性90例,年龄21～83岁,平均（63±13）岁;女性51例,年龄43～85岁,平均（65±11）岁;原发病以心房颤动居多,为112例,占79．4％。141例患者中,可能由于华法林与合并用药相互作用而发生轻微出血者14例,占9．9％。其中,大便潜血5例,皮肤瘀斑3例,手术切口渗血、口腔黏膜及痰中带血、阴道出血、鼻出血、血尿和牙龈出血各1例。14例患者出血发生共涉及9种药物,包括低分子肝素（相关9例）、阿托伐他汀（相关6例）、胺碘酮（相关4例）、阿卡波糖（相关3例）、阿司匹林（相关4例）、普罗帕酮（相关3例）、奥美拉唑（相关2例）、氯吡格雷（相关2例）和莫西沙星（相关1例）;其中,以低分子肝素最多,约占64．2％。这9种药物在141例患者中与华法林的联用率以低分子肝素最高,为73．1％（103／141）;联用相关出血发生率以莫西沙星最高,为1／5。结论华法林与部分临床常用心血管药物联用可因药物相互作用而导致患者发生出血。积极开展华法林临床药学监护对预防出血发生具有重要意义。     

Diagnosis of gout in general practice

Summary

In a general practice survey of gout, an analysis was made of the criteria relating to the diagnosis in 604 patients. Approximately 60% of diagnoses were made within 1 month of the patient presenting with symptoms; in the remainder, there was often a considerable time lag before diagnosis and half of these patients had been wrongly diagnosed initially. Of the total cases, approximately 8% were diagnosed in hospital and only about 20 % of cases were referred for diagnosis or subsequent management advice. Most diagnoses were based on the presentation by the patient of a typical acute arthritis, and a raised serum urate level was used as a confirmatory factor. Few patients presented with tophi and response to colchicine was infrequently used in diagnosis, as were diagnostic X-rays or synovial fluid examination for crystals.     

The introduction of repeat dispensing for 600 patients in one general practice

Objectives The aim was to survey the introduction of repeat dispensing in one general practice to discover any generalisable lessons. Methods Serial repeat‐prescribing workload (GPs and receptionists) surveys were performed each day for whole, non‐holiday weeks five times in the year and a patient satisfaction survey was undertaken mid‐way through the year. The opinions of the community pharmacist were sought and prescribing costs were checked at the start and end of the year. Key findings There were substantial savings of time for the practice once the initial increases in effort had been overcome. These were estimated to be equivalent to a week saved annually for each general practitioner, as well as substantial amounts of staff time. Conclusions Repeat dispensing offers clear benefits to patients, practices and pharmacists. In this practice 45% of items were repeat‐dispensed after one year, in comparison to less than 1% nationally. There is potential for the scheme to be much more actively promoted.     

Serum digoxin levels in patients of a general practice in Germany

Summary Serum digoxin levels were determined in 33 outpatients of a general practice in the countryside, on three occasions at intervals of 8 weeks. All the patients were on long term digoxin treatment, about 2 years on average. About 14 days after the first and the second visits the results of the measurements were sent to the patients, with a comment about their reliability in taking treatment according to the serum digoxin level. At the first visit half of the serum digoxin level were lower than 0.5 ng/ml; the mean serum concentration was 0.52 ng/ml. There was no correlation between serum concentration and age, dose or creatinine level; but there was with replies to the question about regularity of drug intake. The mean serum level at the second and the third visits was 0.88 ng/ml and 0.89 ng/ml, respectively. A correlation was found between the dose and the serum digoxin level. From these results it seems that compliance by the patient plays a major role in producing steady state levels of drugs.Dedicated to Professor Dr. R. Aschenbrenner on the occasion of his 70th birthday     

The use of antidepressant drugs in general practice

Summary The aim of this study was to examine the antidepressant drug prescribing preferences and habits of a population of general practitioners. The method used was that of a questionnaire survey, including case vignettes. The response rate exceeded 70% Data are presented outlining the attitudes of the respondents to the use of antidepressant drugs in the management of common psychiatric presentations in the primary care setting.The majority of general practitioners (G.P.'s) had received little or no post-graduate education in psychiatry. The antidepressants most frequently prescribed were amitriptyline, clomipramine, trazodone and lofepramine. Despite recognition of the alarming frequency of serious self-poisoning incidents with some of these compounds, 26% of respondents confessed to an inability to make an informed choice of antidepressant drug, with 14% using the same drug with every patient with no attempt to select according to individual patient requirements.The management of depressive neurosis generates considerable clinical confusion with a variety of interventions favoured. The use of a sedating antidepressant is popular. There is greater accord for the management of endogenomorphic depression. The use of the benzodiazepine drugs in the management of anxiety disorders is infrequent, with appropriate recognition of the merits of behavioural approaches. However, the role for antidepressant drugs in the management of anxiety disorders is under-recognized.We conclude that general practitioners are required to undertake a significant body of work for which they may be inadequately trained.     

A double-blind Study of flupenthixol ('Fluanxol') in general practice

Summary

A double-blind crossover trial was carried out in general practice to compare the effectiveness of flupenthixol and placebo in 43 patients with mild to moderate anxiety I depression states. Patients received either 0.5 mg flupenthixol or identical placebo tablets 2 to 4-times daily for 2 weeks and were then crossed over to the alternative preparation for a further 2 weeks. A simple 5-point rating scale was used to assess patients⁷ symptoms at first visit and at subsequent follow-up. Even though there was a high placebo response, the results showed flupenthixol to be significantly more effective than placebo in relieving symptoms. Few side-effects were reported and were mild in nature.     

Effects of a medicine review and education programme for older people in general practice

AIMS: To determine whether a medicine review and education programme influences the compliance and knowledge of older people in general practice. METHODS: Older people taking at least three medicines were randomly allocated to a control or intervention group. Both groups received three visits from a clinical pharmacist: Visit 1: Assessment and patients' medicines rationalized in intervention group. Visit 2: Intervention group given medicines education. Visit 3: Knowledge and compliance in both groups assessed by structured questionnaire RESULTS: Compliance in the intervention group was 91.3%, compared with 79.5% in the control group (P < 0.0001). The number of intervention group patients correctly understanding the purpose of their medicines increased from 58% to 88% on the second visit, compared with 67% to 70% in the control group (P < 0.0005). CONCLUSIONS: A general practice based medication review and education programme improved medicine compliance and knowledge of older people in the short term.     

Use of anxiolytic or hypnotic drugs and total mortality in a general middle-aged population

PURPOSE: The aim of the study was to evaluate the effect of the consumption of anxiolytic or hypnotic drugs on total mortality in a general population. METHODS: We followed a cohort of 7225 men and 7726 women aged 40-42 years who underwent health surveys in 1985-1989 in two Norwegian counties, with respect to deaths. Mean follow-up period was 18 years. The subjects were categorised according to frequency of anxiolytic or hypnotic drug use during the last month: daily, every week, less than every week and not used during the last month. RESULTS: The proportion of anxiolytic or hypnotic drug users was 6.6% among men and 16.2% among women. Altogether 402 men and 290 women died. There was an increase in risk of death with an increase in frequency of use. Crude hazard ratios for men and women daily using anxiolytics or hypnotics were 3.1 (95%CI 2.0, 4.8) and 2.7 (1.9, 4.0), respectively, as compared with non-users last month. After adjusting painkiller use and smoking the hazard ratios were lowered, being 2.4 (1.5-4.0) (men) and 2.1 (1.4-3.2) (women). After additional adjustments for other possible confounders the hazard ratios were further attenuated to 1.5 (0.9-2.7) for men and 1.7 (1.1-2.6) for women. CONCLUSIONS: Daily users of anxiolytic or hypnotic drugs in our study showed higher crude mortality than non-users. However, after adjusting lifestyle and socio-economic variables the difference was markedly reduced suggesting that the remaining excess mortality is due to residual confounding.     

Warfarin-associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system

AIMS

To study warfarin associated bleeding events reported to the Norwegian spontaneous reporting system and evaluate the differences in assessment of potentially interacting medicines between reporters and evaluators.

METHODS

Data on bleeding events on warfarin were retrieved from the Norwegian spontaneous reporting system database. Key measurements were time to bleeding, use of concomitant medications and the evaluation done by reporters.

RESULTS

In 289 case reports a total of 1261 medicines (median 4.0 per patient, range 1–17) was used. The evaluators (authors of this article) identified 546 medicines including warfarin (median 2.0 per patient, range 1–7) that could possibly cause bleeding alone or in combination. Reporters assessed 349 medicines (median 1.0 per patient, range 1–4) as suspect. Evaluators identified 156 pharmacokinetic and 101 pharmacodynamic interactions, compared with 19 pharmacokinetic and 56 pharmacodynamic interactions reported as suspected by the reporters. Time to bleeding was stated in 224 reports. Among the early bleeding events, the reports on warfarin without interacting medicines showed the highest INR (international normalized ratio). Heparin was used in 17/21 reported bleeding events during the first week on warfarin. Among the late bleeding events, reports with pharmacokinetic interacting medicines had the highest INR.

CONCLUSIONS

Concomitant use of potentially interacting medicines was involved in the majority of the warfarin-associated bleeding events reported to the Norwegian spontaneous reporting system. Reporters assessed mostly warfarin as the only contributor to bleeding. In particular, pharmacokinetically interacting medicines were not suspected as contributing to bleeding.