Feasibility of point-of-care creatinine testing in community pharmacy to monitor drug therapy in ambulatory elderly patients.

WHAT IS KNOWN AND OBJECTIVE: It is often necessary to adjust drug therapy if renal function is impaired in elderly patients taking drugs for diabetes and/or cardiovascular disease that are cleared by the kidneys. Although clinical guidelines recommend regular monitoring of renal function in these patients, in practice adherence to these recommendations varies from 28% to 75%. To determine whether drug dosing is appropriate, pharmacists need have up-to-date information about patients' renal function. In this study, the feasibility of point-of-care creatinine testing (POCCT) in a community pharmacy was evaluated as part of monitoring the drug therapy of ambulatory elderly patients. METHODS: Elderly patients on maintenance therapy with renally excreted drugs for diabetes or cardiovascular disease were eligible for POCCT. After informed consent was obtained, POCCT was performed by trained personnel. A pharmacist assessed the clinical relevance of electronically generated drug alerts based on the patient's calculated renal function and the Dutch guidelines for adjusting drug dosage in patients with chronic kidney disease. If appropriate, the patient's general practitioner (GP) was consulted and adjustments to treatment were communicated to the patient. The feasibility of POCCT was evaluated by means of questionnaires completed by patients and healthcare professionals (GPs and pharmacists). RESULTS: Of 338 potentially eligible patients, 149 (44%) whose renal function was not known were asked, by letter, to participate in the study. Of these individuals, 46 (31%) gave their informed consent and underwent POCCT. Response rates for completing the patient and professional questionnaires were 87% and 100%, respectively. More than half of the patients who underwent POCCT had mild-to-moderate renal impairment. On the basis of information provided by patients and healthcare professionals, POCCT would appear to be feasible in community pharmacies. WHAT IS NEW AND CONCLUSION: POCCT improves the management of drug therapy by community pharmacists and is feasible in daily practice.

Non-puerperal lactation associated with antidepressant drug use.

AIMS: The aim of the present study was to estimate the relative risk of non-puerperal lactation in patients using antidepressants in general, and specifically for serotonergic (selective serotonin reuptake inhibitors (SSRIs) and clomipramine) and non-serotonergic antidepressants. METHODS: All suspected adverse drug reactions in women and reported from January 1986 until August 1996 to the Netherlands Pharmacovigilance Foundation, a spontaneous adverse drug reaction reporting programme, were analysed. Adverse drug reaction (ADR) reporting odds ratios, defined as the ratio of the exposure odds among reported cases of non-puerperal lactation to the exposure odds of reported other ADRs, were calculated adjusted for age and year of reporting. RESULTS: Thirty-eight cases of non-puerperal lactation were reported, of which 15 were associated with the use of antidepressant drugs. In general, antidepressants were associated with a higher risk of non-puerperal lactation in comparison with other drugs (ADR reporting odds ratio 8.3 [95%CI: 4.3-16.1]). Serotonergic antidepressants (selective serotonin reuptake inhibitors (SSRIs) and clomipramine) were associated with a higher risk (OR 12.7 [95%CI: 6.4-25.4]), whereas other antidepressants were not (OR 1.6 [95%CI: 0.2-11.6]), compared with all other drugs. CONCLUSIONS: Our results indicate that serotonergic antidepressants are associated with an approximately eight times higher risk of non-puerperal lactation compared with other antidepressants. This effect is probably mediated by an indirect inhibition effect of serotonin on the dopaminergic transmission. This finding is in line with the occurrence of other antidopaminergic effects, such as extrapyramidal symptoms, in patients using serotonergic antidepressants.

ADR related questions received by a telephone medicines information service and ADRs received by a spontaneous ADR reporting system: a comparison regarding patients and drugs.

A telephone medicines information service (telephone service) has been available in the Netherlands since 1990. Patients can anonymously and free of charge ask a pharmacist all kinds of questions related to medication use. An analysis of the questions (n=7541) received by this service in 1994 showed that 28% of the questions predominantly related to adverse drug reactions (ADRs). A comparison was made between questions concerning ADRs received by the telephone service and suspected ADRs reported to the regionalized ADR reporting system LAREB regarding characteristics of the associated patients and medicines. In both systems approximately two out of three patients were women. LAREB received relatively more reports concerning patients of 60 years and older, whereas the telephone service received relatively more questions from patients aged 20-40 years. For most classes of medicines the observed proportion of encounters at both systems differed from the expected proportion estimated by the number of prescriptions in the same year. Antidepressants in particular were more frequently encountered at both systems than expected. There were clear differences between the telephone service and LAREB regarding the classes of medicines encountered. Reports of suspected ADRs submitted to LAREB more frequently involved antibiotics, antirheumatic products, anti-asthmatics, antihypertensives and topical antifungals, whereas questions concerning ADRs received by the telephone service significantly more frequently concerned drugs acting on the central nervous system (anxiolytics/hypnotics/sedatives, antidepressants and antipsychotic drugs) and corticosteroids. We are setting up further studies to investigate whether telephone services can serve as an additional tool in postmarketing surveillance for identifying potential drug safety issues.

Channeling of three newly introduced antidepressants to patients not responding satisfactorily to previous treatment.

The demand for knowledge about differences in effectiveness, tolerability, safety, and economic outcomes between and within groups of antidepressant drugs when used in routine daily clinical practice is growing. For gaining this knowledge, observational pharmacoepidemiologic studies are often the most feasible option. However, the results of such studies can only be valid if either patient baseline characteristics associated with the outcome under study are similar or if differences can be adjusted for in the analysis. The aim of this study was to evaluate to what extent and for what type of patients three antidepressant drugs recently introduced in The Netherlands (mirtazapine, sertraline, and venlafaxine) were prescribed during the first year after their introduction and whether there were differences compared with longer-available antidepressant drugs. For this purpose, prescription drugs histories from 20 pharmacies serving a population of approximately 200,000 persons were analyzed. One year after their introduction, the newly introduced antidepressant t drugs accounted for approximately 6% of new uses of all antidepressant drugs. In comparison to longer-available antidepressant, the newly introduced antidepressant drugs were more often prescribed for patients with prior prescriptions of another antidepressant drug (rate ratio [RR] 2.7 [95% confidence interval [CI], 2.3-3.0]), for patients with prior prescriptions of other psychotropic medicines (RR 1.3 [95% CI, 1.1-1.4), and by psychiatrists (RR 1.9 [95% CI, 1.6-2.2]). In addition, the newly introduced antidepressant drugs seemed to be more often, although not significantly, prescribed for patients who had been hospitalized on a psychiatric ward (RR 1.5 [95% CI, 0.9-2.5]). No differences were observed with regard to age and gender distribution, the total number of medicines prescribed, and prescriptions of any cardiovascular or gastrointestinal medicine. These finding suggest that a significant proportion of the patients receiving one of the newly introduced antidepressant drugs did not respond satisfactorily to previous pharmacologic treatment. This channeling phenomenon may have important consequences for the interpretation of observational comparisons between different antidepressant drugs after their introduction.

Principles of signal detection in pharmacovigilance.

Adverse drug effects are manifold and heterogenous. Many situations may hamper the signalling (i.e. the detection of early warning signs) of adverse effects and new signals often differ from previous experiences. Signals have qualitative and quantitative aspects. Different categories of adverse effects need different methods for detection. Current pharmacovigilance is predominantly based on spontaneous reporting and is mainly helpful in detecting type B effects (those effects that are often allergic or idiosyncratic reactions, characteristically occurring in only a minority of patients and usually unrelated to dosage and that are serious, unexpected and unpredictable) and unusual type A effects (those effects that are related to the pharmacological effects of the drug and are dosage-related). Examples of other sources of signals are prescription event monitoring, large automated data resources on morbidity and drug use (including record linkage), case-control surveillance and follow-up studies. Type C effects (those effects related to an increased frequency of 'spontaneous' disease) are difficult to study, however, and continue to pose a pharmacoepidemiological challenge. Seven basic considerations can be identified that determine the evidence contained in a signal: quantitative strength of the association, consistency of the data, exposure response relationship, biological plausibility, experimental findings, possible analogies and the nature and quality of the data. A proposal is made for a standard signal management procedure at pharmacovigilance centres, including the following steps: signal delineation, literature search, preliminary inventory of data, collection of additional information, consultation with the World Health Organization Centre for International Drug Monitoring and the relevant drug companies, aggregated data assessment and a report in writing. A better understanding of the conditions and mechanisms involved in the detection of adverse drug effects may further improve strategies for pharmacovigilance.