Information comparison of the effects of drugs on laboratory tests in drug labels and Young's book.

BACKGROUND: The effects of drugs on laboratory tests may lead to misinterpretation of laboratory data, unnecessary tests, higher costs and missed diagnoses. This study compared the information on drug-laboratory effects (DLE) described in 200 drug labels with that in Young's book. METHODS: Information on DLE was searched in the drug labels of 200 frequently prescribed drugs using the keywords 'interfer*', 'influence', and 'laborator*'. This information was compared with the information in Young's book. Each item of information scored 1 point if it was specific and exactly the same. Primary outcome was the percentage of DLE with completely the same information. RESULTS: In 23 (11.5%) of the 200 drug labels 83 DLE were described. Most DLE were described in drug labels of contraceptives (71%) and antibacterials (15%). The most frequently affected laboratory tests were adrenal gland (17%), urine tests (15%), liver tests (10%) and renal function tests (10%). Comparison of six DLE with Young's book was not possible because the information was not described in the book. Twelve (14.5%) DLE of the information in the drug label was identical to that in Young's book. Detailed information about nature of the effect, strength of the effect and body fluid was not described in the drug labels. CONCLUSIONS: In a limited number of DLE in the drug labels the information was the same as in Young's book. Overall, the information on DLE provided in drug labels is unclear, inconsistent and incomplete and does not support healthcare professionals in making evidence-based monitoring decisions.

A pharmacy medication alert system based on renal function in older patients.

BACKGROUND: Patients with diabetes or cardiovascular disease are at risk of reduced renal function and frequently use drugs that interact with renal function. GPs monitor renal function in these patients. Computerised prescription systems produce alerts in patients labelled as having chronic kidney disease, but alerts are often ignored. If pharmacists use a pharmacy medication alert system (PMAS) based on renal function, they can provide the GP with therapeutic advice to optimise the medication. The extent of this advice and the feasibility in the clinical context are unknown. AIM: To assess the therapeutic advice formulated by pharmacists with help of a PMAS based on the renal function of patients aged ≥70 years with diabetes or cardiovascular disease. DESIGN AND SETTING: Observational study in primary health care in the Netherlands. METHOD: GPs provided pharmacists with the renal function of older patients with diabetes or cardiovascular disease who were using target drugs, that is, drugs requiring therapeutic advice in patients with reduced renal function. With the help of a PMAS, pharmacists assessed the actual medication. The GP weighed the advice in relation to the clinical context of the individual patient. RESULTS: Six hundred and fifty patients were prescribed 1333 target drugs. Pharmacists formulated 143 therapeutic recommendations (11% of target drugs) concerning 89 patients (13.7% of study population). In 71 recommendations in 52 patients (8.0% of study population), the GP agreed immediately. CONCLUSION: The use of a PMAS resulted in therapeutic advice in 11% of the target drugs. After weighing the clinical context, the GP agreed with half of the advice.

Instructions on laboratory monitoring in 200 drug labels.

BACKGROUND: Monitoring drug treatment is important to assess the therapeutic effects and to prevent adverse drug reactions. Unfortunately, the clinical evidence for monitoring is often missing. To attain evidence-based laboratory monitoring and to improve patient safety it is mandatory for the clinical chemist to develop effective and rational methods for monitoring. The legal source for this evidence-based information is the drug label. We analysed frequency, nature, and applicability of instructions on laboratory monitoring described in 200 drug labels. METHODS: The applicability of instructions was assessed with an adapted Systematic Information for Monitoring score. Seven items of information were evaluated: why to monitor, what to monitor (essential), when to start or stop monitoring, how frequently to monitor, critical value (essential) and how to respond (essential). Each item scored one point when information was described specifically, otherwise the score was zero. Instructions were applicable if all three essential items scored. RESULTS: In 131 drug labels, 566 instructions on laboratory monitoring were identified, an average of 2.8 per drug label. Kidney, liver, electrolyte, and drug monitoring were important biomarker categories (71%). The median applicability score was 2.1 (0-6) and 95 (17%) instructions were applicable. Six determinants were associated with applicable instructions: kidney (OR 7.0; 95% CI 4.4-11.3), creatine phosphokinase (4.5; 1.5-13.6), drug selection (6.8; 4.0-11.7), dose adjustments (2.4; 1.5-3.7), year on the market 2000-2007 (2.6; 1.1-6.1) and statins (4.8; 2.5-9.0). CONCLUSIONS: Drug labels frequently describe instructions on laboratory monitoring, but these are ambiguous and incomplete and clinical applicability for the professional is limited.

Preventing hospital admissions by reviewing medication (PHARM) in primary care: design of the cluster randomised, controlled, multi-centre PHARM-study.

BACKGROUND: Medication can be effective but can also be harmful and even cause hospital admissions. Medication review or pharmacotherapy review has often been proposed as a solution to prevent these admissions and to improve the effectiveness and safety of pharmacotherapy. However, most published randomised controlled trials on pharmacotherapy reviews showed no or little effect on morbidity and mortality. Therefore we designed the PHARM (Preventing Hospital Admissions by Reviewing Medication)-study with the objective to study the effect of the total pharmaceutical care process on medication related hospital admissions and on adverse drug events, survival and quality of life. METHODS/DESIGN: The PHARM-study is designed as a cluster randomised, controlled, multi-centre study in an integrated primary care setting. Patients with a high risk of a medication related hospital admission are included in the study with randomisation at GP (general practitioner) level. We aim to include 14200 patients, 7100 in each arm, from at least 142 pharmacy practices.The intervention consists of a patient-centred, structured, pharmaceutical care process. This process consists of several steps, is continuous and occurs over multiple encounters of patients and clinicians. The steps of this pharmaceutical care process are a pharmaceutical anamnesis, a review of the patient's pharmacotherapy, the formulation and execution of a pharmaceutical care plan combined with the monitoring and follow up evaluation of the care plan and pharmacotherapy. The patient's own pharmacist and GP carry out the intervention. The control group receives usual care.The primary outcome of the study is the frequency of hospital admissions related to medication within the study period of 12 months of each patient. The secondary outcomes are survival, quality of life, adverse drug events and severe adverse drug events. The outcomes will be analysed by using mixed-effects Cox models. DISCUSSION: The PHARM-study is one of the largest controlled trials to study the effectiveness of the total pharmaceutical care process. The study should therefore provide evidence as to whether such a pharmaceutical care process should be implemented in the primary care setting. TRIAL NUMBER: NTR 2647.

Laboratory tests in the clinical risk management of potential drug-drug interactions: a cross-sectional study using drug-dispensing data from 100 Dutch community pharmacies.

BACKGROUND: Patient safety and the life cycle of a drug are negatively influenced by the still increasing occurrence of potential drug-drug interactions (DDIs). Clinical risk management of potential DDIs is required in patients using drugs to influence the benefit-risk profile positively. Information about laboratory test results, in particular, may be useful in the assessment of potential DDIs for the individual patient. OBJECTIVE: The objective of this study was to examine the frequency and nature of laboratory tests required for the assessment of the clinical relevance of potential DDIs in Dutch community pharmacies. In addition, the nature and clinical relevance of these potential DDIs is analysed. METHODS: All patients from 100 Dutch community pharmacies using, according to dispensing information, two or more drugs concomitantly on a specified date (Wednesday, 4 April 2007), were included (n = 223,019). The anonymous dispensing data of the included patients were analysed against a list of DDIs requiring laboratory tests for the assessment of their clinical relevance. The number of patients at risk for these potential DDIs with severe adverse reactions was calculated. The frequency of potential DDIs requiring laboratory tests were stratified by age, sex and degree of polypharmacy. RESULTS: Of the included patients, 24.4% had one or more potential DDIs (n = 54,427). In 9.0% of the included patients, one or more laboratory tests for the assessment of clinical relevance of the potential DDI were required (n = 19,968). The frequency of DDIs requiring laboratory tests increased with increasing age and number of drugs, but was not related to sex. The most commonly required laboratory tests were for renal function (42.2%), electrolytes (20.1%) and coagulation (13.1%). The percentage of patients at risk for potential DDIs requiring laboratory tests with adverse reaction category F (serious, irrecoverable disablement or death) was 2.5%; category E (increased risk of failure of life-saving therapy) was 0.6%; and category D (inconvenience with residual symptom and failure of therapy concerning serious but non-fatal diseases) was 3.8%. CONCLUSIONS: A large number of patients in Dutch community pharmacies are at risk for potential DDIs requiring laboratory tests for the assessment of the clinical relevance of the interaction. There is a strong relationship between the frequency of DDIs requiring laboratory tests and age and the number of drugs concomitantly used. In the clinical risk management of potential DDIs, information about laboratory test results is of additional value. Future research is necessary in order to obtain more evidence on using laboratory tests in terms of which tests should be linked to pharmacy data, in which patients they should be done, how often and what actions should be taken when an abnormal value is found.

Pharmacist-based medication review reduces potential drug-related problems in the elderly: the SMOG controlled trial.

BACKGROUND: The high prevalence of drug-related problems (DRPs) in the elderly, occurring as a result of multiple drug use combined with age-related changes in pharmacokinetics and pharmacodynamics, is a well known phenomenon. However, effective intervention strategies are uncommon. OBJECTIVE: A pharmacy-based controlled trial (SMOG [Screening Medicatie Oudere Geneesmiddelgebruiker; Screening Medications in the Older Drug User]) was performed to investigate whether a community pharmacist-led intervention reduces the number of potential DRPs in patients aged > or = 65 years using six or more drugs concomitantly. METHODS: This intervention study was conducted from June 2002 until June 2003 in 16 community pharmacies in the Netherlands. Medication assessment was undertaken in elderly patients aged > or = 65 years using six or more drugs concomitantly on the date of inclusion. Ten types of potential DRPs were determined and grouped into the following three categories: (i) patient-related potential DRPs: non-compliance; (ii) prescriber-related potential DRPs: expired indication, therapeutic duplication, inappropriate dosage (over- and under-dosage), off-label use, undertreatment, inconvenience of use; and (iii) drug-related potential DRPs: contraindications, drug-drug interactions, drug treatment of adverse drug reactions. A list of recommended changes in medication was compiled by the pharmacist for the patients in the intervention group. Recommendations for medication change were discussed with the general practitioner (GP). Four months after the date of inclusion, the medications of each patient were again reviewed and screened for potential DRPs. The primary outcome corresponded to the change in the number of potential DRPs; the secondary outcome was related to the change in number of used medications between the intervention group and the control group at baseline and 4 months later. RESULTS: A total of 174 patients were analysed: 87 patients in the intervention arm and 87 patients in the usual care arm. After a 4-month period, we observed a significant reduction in the mean number of DRPs per patient (mean difference -16.3%; 95% CI -24.3, -8.3). The mean number of drugs per patient was not significantly reduced (mean difference -4.7%; 95% CI -9.6, 0.2). CONCLUSION: This study showed a positive influence of the community pharmacist in reducing potential DRPs in the elderly. Future interventions should also focus on actual outcomes, including quality of life, morbidity and mortality.

Association between hospitalization and discontinuity of medication therapy used in the community setting in the Netherlands.

BACKGROUND: Transitions from one healthcare setting to another often parallel transitions in health status and can be associated with intentional as well as unintentional changes in patient care. Hospitalization may put patients at increased risk of discontinuity of medication use. OBJECTIVE: To assess the association between hospitalization and medication therapy discontinuities. METHODS: A retrospective follow-up study was conducted using data obtained from the PHARMO Record Linkage System. We randomly selected patients who had been hospitalized (index date) between July 1, 1998, and June 30, 2000. For each hospitalized patient, one nonhospitalized patient was matched for age, sex, and geographic area, and was assigned the same index date as the corresponding hospitalized patient. The primary study outcome was the incidence of one or more medication therapy discontinuities at the index date and at several control moments during a period of 18 months before and 18 months after hospital admission. We defined 4 mutually exclusive types of discontinuities: generic-brand substitution, product substitution, therapeutic switch, and stop. RESULTS: The study population comprised 8681 hospitalized patients and an equal number of age/sex-matched nonhospitalized patients. Of all hospitalized patients on drug therapy at the index date (n = 5265) 3322 (63.1%) had one or more medication therapy discontinuities at the index date, compared with 1390 (33.5%) of the nonhospitalized patients taking medication at the index date (n = 4147; RR 1.82; 95% CI 1.71 to 1.94). The highest risk estimate was found for therapeutic switch (RR 5.34; 95% CI 3.93 to 7.26), followed by product substitution (RR 2.32; 95% CI 1.88 to 2.86) and stop (RR 1.98; 95% CI 1.85 to 2.13). There was no significantly increased risk for generic-brand name substitution (RR 0.87; 95% CI 0.72 to 1.06). CONCLUSIONS: Hospitalization is associated with discontinuity of drugs used in the community setting. Medication stops were observed most frequently. Hospital safety programs should focus attention on medication therapy discontinuities at times of transition to ensure continuity of care in relation to drug therapy.

The association between antidepressant use and disturbances in glucose homeostasis: evidence from spontaneous reports.

OBJECTIVES: Depression is common in patients with diabetes, and the use of antidepressants may impair glycaemic control. We assessed the association between antidepressant use and hyper- and hypoglycaemia. METHODS: Based on spontaneous reports listed in the World Health Organization (WHO) Adverse Drug Reaction Database, a case-control study was conducted. The study base consisted of all adverse drug reactions (ADRs) ascribed to antidepressants, antipsychotics and benzodiazepines between 1969 and 2005. Cases were defined as reported ADRs classified as hyper- or hypoglycaemia and separated in different study populations. All other reports were considered as controls. Exposure to antidepressants was the primary determinant investigated. Benzodiazepines and antipsychotics were chosen as reference groups. Potential confounding factors, namely, age, gender, use of antidiabetic medication, use of hyper- or hypoglycaemia-inducing comedication and reporting year, were determined on the index date. Multivariate logistic regression was used to evaluate the strength of the association, which was expressed as reporting odds ratios (RORs) with 95% confidence intervals (95% CI). RESULTS: Overall, the use of antidepressants was associated with hyperglycaemia [ROR 1.52 (95% CI: 1.20-1.93)] and of hypoglycaemia [ROR 1.84 (95% CI: 1.40-2.42)]. The association with hyperglycaemia was most pronounced for antidepressants with affinity for the 5-HT(2c) receptor, histamine-(1) receptor and norepinephrinic (NE) reuptake transporter. The association with hypoglycaemia was most pronounced for antidepressants with affinity for the serotonin reuptake transporter. CONCLUSION: The results of this study strengthen the findings in individual case reports that the use of antidepressants is associated with disturbances in glucose homeostasis.

Identification of potential drug-related problems in the elderly: the role of the community pharmacist.

OBJECTIVE: The high prevalence of multiple drug use combined with age-related changes in pharmacokinetics and pharmacodynamics makes older adults more vulnerable to drug-related problems (DRPs). This pharmacy-based study was performed to identify potential DRPs from prescription records of the elderly and the role of the pharmacist in this process. METHOD: The study was performed from June 2002 to February 2003 in 16 community pharmacies in the Netherlands. Medication assessment of elderly patients aged 65 and over using six or more drugs concomitantly took place on the date of inclusion. Ten types of potential DRPs, grouped into three categories, were determined. The three groups were patient-related, prescriber-related or drug-related potential DRPs. We looked at the occurrence, nature and determinants of differential potential DRPs. RESULTS: The mean number of prescriptions per patient was 8.7. In total 3.9 potential DRPs per elderly person were identified. The distribution of the potential DRPs over the three categories was: patient related 4.7%, prescriber related 55.7% and drug related 39.6%. Use of NSAIDs (OR 29.9; 95% CI 4.1-219) and digoxin (OR 15.7; 95% CI 4.9-50.5) were associated with the highest risk for potential DRPs. CONCLUSION: In this vulnerable group of elderly patients potential DRPs frequently occur. Community pharmacists can play an important role in the identification, assessment and prevention of potential DRPs in the elderly. It is useful to investigate which part of potential DRPs can be avoided by the intervention of the community pharmacist in collaboration with the prescriber and the patient.