Concurrent Prescription Research Articles

Long‐term, high‐dose benzodiazepine prescriptions in veteran patients with PTSD: Influence of preexisting alcoholism and drug‐abuse diagnoses

Databases from the New England Veterans Integrated Service Network were analyzed to determine factors associated with long-term, high-dose anxiolytic benzodiazepine prescriptions dispensed to patients with posttraumatic stress disorder (PTSD) and existing alcoholism and/or drug abuse diagnoses. Among 2,183 PTSD patients, 234 received the highest 10% average daily doses for alprazolam, clonazepam, diazepam, or lorazepam, doses above those typically recommended. Highest doses were more commonly prescribed to patients with existing drug abuse diagnoses. Among patients with PTSD and alcoholism, younger age, drug abuse, and concurrent prescriptions for another benzodiazepine and oxycodone/acetaminophen independently predicted high doses. Results indicate that for veteran patients with PTSD, alcoholism alone is not associated with high-dose benzodiazepines, but existing drug abuse diagnoses do increase that risk.

Factors associated with antipsychotic dosing in psychiatric inpatients: a prospective study

The persistent use of doses in excess of recommended levels is associated with increased risks of adverse reactions without evidence of additional benefits. Such treatment modality was evaluated in hospitalized psychiatric patients. During a 6-year recruitment period, a consecutive series of psychiatric inpatients receiving antipsychotic therapy were included. At admission, sociodemographic and clinical data, including antipsychotic drug use, were collected, and the 18-item version of the Brief Psychiatric Rating Scale was administered. At discharge, data on antipsychotic drug therapy were collected. Prescribed daily doses were converted into multiples of the defined daily doses. Using a cut-off score of a prescribed daily dose/defined daily dose as a ratio of more than 1.5 both at admission and at discharge assessments, a total of 62 (15.4%) patients persistently received high antipsychotic dose. With less stringent criteria (prescribed daily dose/defined daily dose as a ratio of more than 2), however, only 4.4% of the entire sample was persistently exposed to high antipsychotic doses. Bootstrapped linear regression analysis revealed that positive symptoms were positively associated with high antipsychotic dose, whereas negative symptoms were negatively associated with high antipsychotic dose. Antipsychotic polypharmacy at admission was the strongest predictor of persistently receiving antipsychotic doses in excess of recommended levels. This study showed that the use of high antipsychotic dosing is not an occasional event. Clinicians should consider that concurrent prescribing of two or more antipsychotic agents increases the probability of administering excessive dosing in the long-term.

Using Pharmacy Data on Partial Adherence to Inform Clinical Care of Patients With Serious Mental Illness

Using Pharmacy Data on Partial Adherence to Inform Clinical Care of Patients With Serious Mental Illness

As Antidepressant Use Increases, Youth Suicides Decline

Back to table of contents Previous article Next article Professional NewsFull AccessAs Antidepressant Use Increases, Youth Suicides DeclineJim RosackJim RosackSearch for more papers by this authorPublished Online:17 Nov 2006https://doi.org/10.1176/pn.41.22.0004aOn a county-by-county basis, higher levels of prescribing of SSRI antidepressants are associated with lower rates of suicide among youth aged 5 to 14. Yet the clinical significance of this finding is being debated (see article at left).The findings, which are reported in the November American Journal of Psychiatry, are similar to those in the majority of research reports published over the last several years that have looked for an association between antidepressant medications and an increased risk of suicidal thoughts or behaviors (which the U.S. Food and Drug Administration collectively labels“ suicidality”), serious suicide attempts resulting in the need for emergency medical intervention, or actual suicides. Also, several observational or ecological studies have found inverse relationships between high rates of SSRI prescribing and suicide attempts or suicides in adults or older adolescents.The findings from the new study, however, run counter to those of other studies that have found an increased risk associated with the medications, particularly in young patients. In addition, a major FDA meta-analysis of clinical trials data also found on average a twofold increase in risk of suicidality in children and adolescents who take antidepressants.What is noteworthy about the new study is that the authors focused their analysis on the youngest cohort of patients reported on so far. In addition, in analyzing the current data, the researchers used complex statistical methods in an attempt to minimize known potential biases associated with several common, yet confounding, factors.Robert Gibbons, Ph.D., a psychiatric epidemiologist and director of the Center for Health Statistics at the University of Illinois at Chicago, teamed with colleagues at the university and youth-suicide experts at Columbia University's College of Physicians and Surgeons. The work was funded primarily by grants from the National Institute of Mental Health.Gibbons and his colleagues, including J. John Mann, M.D., a professor of psychiatry and radiology at Columbia and chief of psychiatric research in the Division of Neuroscience at the New york State Psychiatric Institute, analyzed county-level suicide data gathered by the Centers for Disease Control and Prevention from 1996 through 1998. The database included all reported suicides for each county in all 50 states, with each suicide identified by sex, race, and age.The researchers compared the three years of county-level suicide data with concurrent county-level antidepressant prescription dispensing data from IMS Health Inc., a U.S.-based global health care data firm. The researchers noted that the data were obtained from IMS with the assistance of a grant from Pfizer Inc. However, they added, Pfizer played no part in study design, data analysis, or preparation of the report. In addition, Mann reported research support from GlaxoSmithKline and disclosed that he has served as an advisor to Lilly and Lundbeck. (All three companies market antidepressant medications.) Gibbons, as well as the remaining co-authors, reported no competing interests.Gibbons, Mann, and colleagues used a random sample of dispensing data from 20,000 pharmacies in the IMS database. The data did not include hospital pharmacies or mail-order facilities. For each county, data were obtained for the SSRI antidepressants citalopram, paroxetine, fluoxetine, fluvoxamine, and sertraline.The researchers found that there were 933 suicides among children aged 5 to 14 from 1996 through 1998, corresponding to an overall annual rate of 0.8 per 100,000 population.The suicide rate varied, however, by the number of SSRI prescriptions by county.The counties with the highest rate of SSRI prescribing had the lowest suicide rate (0.7 per 100,000). The counties with the second-lowest rate of SSRI prescriptions had the highest suicide rate (1.7 per 100,000).The SSRI effect remained highly significant, even after the researchers corrected for potential confounding factors, including sex and race, as well as for two important factors potentially affecting patients' access to quality mental health care: income and the number of psychiatrists and child psychiatrists in each county. (Physician data were obtained from the AMA's Physician Master File.)Gibbons and his colleagues noted in their report that “the aggregate nature of these observational data precludes a direct causal interpretation of the results... and may reflect antidepressant efficacy, treatment compliance, better quality of mental health care, and low toxicity in the event of a suicide attempt by overdose.”“The Relationship Between Antidepressant Prescription Rates and Rate of Early Adolescent Suicide” is posted at<www.ajp.psychiatryonline.org/cgi/content/full/163/11/1898>.▪ ISSUES NewArchived

Treatment of Intractable Hiccups With Olanzapine Following Recent Severe Traumatic Brain Injury

Treatment of Intractable Hiccups With Olanzapine Following Recent Severe Traumatic Brain Injury

Pharmacoutilization of anti-inflammatory and gastroprotective drugs in patients with osteoarthritis: comparison between COXIBs and conventional NSAIDs by using administrative records

The aim of the study was to analyze anti-inflammatory and gastroprotective drug utilization in patients with osteoarthritis comparing conventional non-steroidal anti-inflammatory drugs (NSAIDs) versus cyclo-oxygenase 2 (COX 2) inhibitors. A retrospective observational cohort study was conducted and health-assisted subjects from the Local Health Units of Turin and Caserta were enrolled. Data linkage techniques were used to cross demographical, pharmaceutical and nosological databases. All subjects aged ≥18 years who were hospitalized for osteoarthritis from July 1st 2002 to June 30th 2004 were enrolled in the study. Concurrent prescriptions of non-steroidal anti-inflammatory and gastroprotective drugs were considered. Other demographic and clinical characteristics were recorded. A total of 1,002 subjects with a diagnosis of osteoarthritis treated with NSAIDs were enrolled. Of these subjects, 438 patients were treated with non selective NSAIDs (80.8%), 104 with COXIBs (19.2%) and 460 with multiple therapy. There were no significant differences between the demographic and clinical characteristics of the three groups. Gastroprotective drugs were prescribed in 37.0% and 35.6% of subjects treated with NSAIDs and COXIBs, respectively. Gastroprotective drug prescriptions increased from the index date to the follow-up period (from 20.4% to 41.1% of subjects treated with NSAIDs). In high-risk subjects with gastrointestinal events, gastroprotective drug utilization was undersized and increased from the index date to the follow up period (from 19.4% to 40.8% of high-risk subjects). Evidence from this study indicated that non selective NSAIDs and COXIBs are used indiscriminately with respect to patient characteristics and gastroprotection.

Characterizations of Long-term Anxiolytic Benzodiazepine Prescriptions in Veteran Patients

To characterize long-term prescriptions for commonly prescribed anxiolytic benzodiazepines to veteran patients and to identify factors associated with high daily doses, we analyzed the linked pharmacy and administrative databases from New England Veterans Healthcare System (VISN 1). We analyzed treatment episodes of 3 months or longer with the 4 most commonly prescribed agents: alprazolam, clonazepam, diazepam, and lorazepam. Descriptive statistics and univariate and multivariate analyses described the sample and tested associations of pharmacological and clinical variables for patients prescribed the top 5% of average daily doses ("high-dose" prescriptions). From 16,630 full or partial treatment episodes for all 4 agents analyzed within a 42-month window, average daily doses were predominantly moderate, age-sensitive, and stable; refill lag intervals were short. Patients on "high-dose" prescriptions for the 4 agents combined, compared with "middle quartile" dose prescriptions, in adjusted analyses, were younger, more likely to have posttraumatic stress disorder (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.17-3.13), substance abuse (OR, 1.50; 95% CI, 1.25-1.80), and anxiety (OR, 1.33; 95% CI, 1.11-1.60) and were more likely to be receiving concurrent oxycodone/acetaminophen (OR, 2.05; 95% CI, 1.64-2.56), anxiolytic benzodiazepine (OR, 1.51; 95% CI, 1.12-2.03), antidepressant (OR, 2.15; 95% CI, 1.80-2.58), and neuroleptic (OR, 2.03; 95% CI, 1.69-2.44) prescriptions. These results indicate that veteran patients prescribed anxiolytic benzodiazepines typically receive modest, nonincreasing doses over long-term treatment episodes. However, those on the highest average daily doses, typically more than recommended guidelines, are more likely to have clinical diagnoses and concurrent prescriptions for psychoactive medications indicative of more complex and, perhaps, problematic management.

Prevalence, incidence and persistence of antipsychotic drug prescribing in the Italian general population: retrospective database analysis, 1999–2002

To investigate the prevalence, incidence and persistence with antipsychotic drug therapy in a large and geographically defined catchment area of Italian general population. All antipsychotic drug prescriptions dispensed during 1999, 2000, 2001 and 2002 were extracted from an administrative prescription database covering a population of 2 640 379 individuals. Antipsychotic drug users were defined as patients who had at least one recorded prescription in the current year. New users were defined as patients receiving a first prescription without any recorded antipsychotic drug treatment in the previous 12 months. Prevalence data were calculated by dividing users by the total number of male and female residents in each age group. Incidence data were calculated as the number of new users divided by the person-time free from antipsychotic drugs in the current year. The cumulative persistence of each medication was calculated by dividing the total prescribed amount of antipsychotic drug by the recommended daily dose, according to each agent's defined daily dose (DDD). A progressive rise in prevalence and incidence rates was observed during the 4-year period. In each census year, the prevalence and incidence of prescribing was higher in females than males, and progressively rose with age, with the highest rates in old and very old subjects. The analysis of persistence with therapy revealed that 3176 individuals (78.5%) were occasional antipsychotic drug users, and that occasional use was more frequent among individuals receiving conventional antipsychotic drugs than among individuals receiving novel antipsychotic drugs. This difference was not explained by differences in the occurrence of neurologic adverse reactions, as shown by the concurrent prescribing of anticholinergic drugs, which was fairly similar between the two groups of new drug users. Additionally, we found that conventioal antipsychotic drugs were more often used in older individuals, where occasional use is very frequent, while novel antipsychotic drugs were more often prescribed in young and adult individuals, where regular use is more frequent. An epidemiologically relevant proportion of everyday individuals is annually exposed to antipsychotic drugs. The distribution of prevalence and incidence rates by age highlighted an emerging public health issue related to the adverse and beneficial consequences of antipsychotic drug exposure in the elderly. The finding that persistence with therapy was longer in new users of novel antipsychotic drugs compared with new users of conventional agents might be explained by the different demographic and clinical characteristics of individuals receiving these two drug classes and not by the different tolerability profile of these two drug classes.

The Complexity and Cost of Drug Regimens of Older Patients Hospitalized With Heart Failure in the United States, 1998-2001

Polypharmacy-the concurrent prescription of multiple medications-is a salient consideration in the care of older patients with heart failure. Little is known, however, about the complexity and financial burden of medical therapy in this population. This is a study of the chronic medications prescribed at hospital discharge to patients 65 years or older hospitalized for heart failure in 2 cohorts separated by 27 months (April 1998-March 1999, n = 31 602; July 2000-June 2001, n = 30,774). Three utilization measures were assessed: the number of drugs, the estimated number of doses per day, and the estimated annual costs using the same cost standard (2003 average wholesale prices) for both samples. Utilization associated with population characteristics and between time frames was assessed in multivariable models. In 1998-1999, the mean number of drugs was 6.8, representing 10.1 doses daily at a cost of 3142 dollars/y, increasing to 7.5 drugs, 11.1 doses daily and 3823 dollars/y in 2000-2001 (P<.001 for all comparisons). After adjustment, the number of drugs increased by 12% and costs by 24% between samples. Factors associated with greater complexity and cost included diabetes (1.6 additional drugs and 1094 dollars/y additional cost), prior revascularization (1.3 drugs, 1154 dollars/y), and chronic lung disease (1.2 drugs, 814 dollars/y). Younger age and white race were also associated with more drugs and higher costs. The drug treatment of older patients with heart failure is characterized by rapidly increasing complexity and cost. Efforts should be directed toward optimizing the complex drug regimens of elderly patients with heart failure and multiple comorbidities.

Does concurrent prescription of selective serotonin reuptake inhibitors and non‐steroidal anti‐inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?

A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people. To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently. We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis. Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants. Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.

Concurrent Prescribing of Anticholinergic Drugs and Cholinesterase Inhibitors

Anticholinergic agents antagonize the effects of cholinesterase inhibitors, which are used to treat Alzheimer dementia. Moreover, anticholinergic drugs

Frequency of Concurrent Use of Warfarin with Potentially Interacting Drugs

To determine the rates of concomitant use of drugs known to interact with warfarin by increasing the prothrombin time expressed as the international normalized ratio (INR), decreasing the INR, or increasing bleeding risk without apparent changes in INR in a cohort of patients receiving long-term warfarin therapy. Retrospective, longitudinal cohort study. Large pharmacy benefits manager database. A total of 134,833 patients who were prescribed long-term warfarin from June 1, 1999-May 31, 2000. Longitudinal pharmacy claims from the pharmacy benefits manager database were reviewed to identify coprescription of warfarin and drugs associated with significant interactions with warfarin. Of the 134,833 patients receiving long-term warfarin therapy, 109,998 (81.6%) were prescribed a concurrent prescription for at least one potentially interacting drug, including 87,346 (64.8%) who were prescribed one or more concomitant drugs associated with interactions known to increase the INR. Acetaminophen-containing products, prescribed for 22.7% of patients receiving concomitant prescriptions, and thyroid hormones, prescribed for 17.5%, were the most commonly prescribed concurrent drugs associated with an increased INR response. The most frequently prescribed interacting agents associated with a decreased INR response were trazodone (2.2%) and carbamazepine (1.1%). The most commonly prescribed agents independently associated with increased bleeding risk were cyclooxygenase-2 inhibitors. Many patients receiving warfarin therapy are treated with concomitant drugs that may interact with the warfarin. The high percentage of patients taking drugs that may increase INR or bleeding risk is a reminder that bleeding events are a likely adverse outcome of combining drugs that interact with warfarin. Careful warfarin management is necessary to avoid adverse events associated with drug interactions.

Characterizations of Long-term Oxycodone/Acetaminophen Prescriptions in Veteran Patients

Long-term management of chronic pain with opioids may be stable over time or may be complicated by problematic dose increases, drug dependencies, and toxic effects. To determine clinical contexts in which stability or problems may occur, we examined the pharmacologic and clinical correlates of long-term prescriptions of oxycodone/acetaminophen, a commonly prescribed short-acting opioid formulation. We analyzed linked, archival outpatient pharmacy and clinical databases from the New England Veterans Integrated Service Network between January 1, 1998, and June 30, 2001. Durations, doses, and dose changes of oxycodone/acetaminophen prescriptions and concurrent use of long-acting opioids, benzodiazepines, tricyclic antidepressants, and anticonvulsants were determined. In aggregate, 2195 patients (31% with cancer diagnoses per the International Classification of Diseases, Ninth Revision, Clinical Modification) received oxycodone/acetaminophen for more than 9 months at a mean prescribed daily dose of 3.9 tablets per day (range, 0.5-13.0 tablets per day) with minimal changes in daily prescribed mean dose over time. Patients with cancer were more likely than other patients to receive concurrent long-acting opioids. For patients without cancer, a higher mean daily dose was associated with duration, older age, human immunodeficiency virus (HIV) and/or AIDS, and with prescribed benzodiazepines and long-acting opioids; concurrent benzodiazepine prescriptions were associated with anticonvulsant prescriptions and with psychogenic pain and alcohol abuse and/or dependence diagnoses. In veteran patients who received long-term oxycodone/acetaminophen prescriptions, mean daily doses were typically modest and stable, likely reflecting a selection of patients with successful, long-term management. Among patients without cancer, however, associations of higher oxycodone/acetaminophen doses with benzodiazepine prescriptions, psychogenic pain, alcohol abuse, and HIV/AIDS may portend opioid prescription management problems.

Frequency of simvastatin prescriptions with potentially interacting medications in a Veterans Affairs health care system.

The primary objective of this review is to quantify the proportion of patients on simvastatin, an HMG-CoA reductase inhibitor (commonly known as statin), who received concurrent prescriptions for potentially interacting chronicuse medications. The secondary objective is to determine the frequency with which simvastatin was prescribed above its recommended dose when administered concomitantly with known interacting medications. A retrospective review of computerized outpatient pharmacy records from a Veterans Affairs Medical Center and its associated ambulatory clinics was performed in September 2002. A total of 12,240 patients had an active prescription for a statin. The majority of patients (95%, N = 11,677) were on simvastatin therapy, and 1,231 (10.5%) of the patients on simvastatin were prescribed at least 1 potentially interacting medication. More than one half (57.8%) of simvastatin doses were above the maximum recommended daily dose when prescribed with potentially interacting medications. This analysis supports the need for vigilance in reviewing the dose of simvastatin in patients receiving interacting medications. Health care systems should consider strategies to educate health care professionals on prevention of drug interactions and adverse patient outcomes.

Alternative therapy use by elderly African Americans attending a community clinic.

To describe the use of orally ingested alternative therapies (OAT) by a community-dwelling, primarily African-American sample of elders. Face-to-face survey. University-affiliated geriatric medicine primary care clinic. One hundred two elderly OAT users and 100 nonusers who had an appointment between June and August 2000. Demographic characteristics, OAT products used, reasons for use, and influencing factors leading to use. Two hundred ninety-two subjects were screened: 102 (35%) OAT users, 100 (34%) nonusers, and 90 (31%) who refused to participate. The OAT users were 78% female and 67% African American, with a mean age+/-standard deviation of 79.7+/-6.2. They were a frail group, with an average of 5.2+/-2.3 medical conditions, 4.5+/-2.3 medications, and 52% with at least one impairment in activities of daily living. Nonusers had more documented medical conditions and medications and a lower median household income. The most popular OAT products were multivitamins (65%), vitamin E (42%), and calcium (31%). Ninety-seven percent of users reported concurrent OAT and prescription medication use. The patients took OATs to supplement their diet (23%) and stay well (15%), as well as for various medical conditions. Influencing factors for OAT use were media advertisements (37%), physicians' advice (36%), and immediate family members (19%). Sixty percent of elders discussed their OAT use with their physicians Community-dwelling, primarily African-American, elders are using OATs despite physical frailty and limited financial resources. OAT users are healthier and wealthier than nonusers. More subjects used concurrent OAT and prescription medications and discussed their use with their physicians than would be expected from the literature. A large national survey of OAT use by minority elders could explore these findings.

Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients

Purpose Many drugs prolong the QT interval and increase the risk of torsade de pointes. Concurrent use of two or more of these drugs can further increase the risk, but the prevalence of concurrent prescription of QT-prolonging drugs is not known. Methods Using the administrative claims database of a national pharmaceutical benefit manager, we conducted a retrospective cohort study in 4,825,345 subjects aged 18 years or older. After identifying 50 drugs with QT-prolonging potential, and an additional 26 drugs that inhibit the metabolic clearance of QT-prolonging drugs, we measured the frequency of overlapping prescriptions for two or more of these drugs in the outpatient setting in 1999. Results Nearly 1.1 million subjects (22.8%) filled 4.4 million prescriptions for QT-prolonging drugs. Of these, 103,119 subjects (9.4%) filled overlapping prescriptions for two or more of the drugs or for a QT-prolonging drug and another drug that inhibits its clearance; 7249 subjects (0.7%) filled overlapping prescriptions for three or more of these drugs. Twenty-two percent of subjects who filled overlapping prescriptions were aged 65 or older; 74% were women. Antidepressants were involved in nearly 50% of the cases. Conclusion Concurrent prescription of QT-prolonging drugs is common in the outpatient setting, and antidepressants are involved in half of these cases. Large pharmaceutical claims databases are useful for detecting potentially harmful prescribing behaviors, but better clinical evidence on medication safety is needed before such a system can be implemented fully.

Survey on concurrent prescriptions for quinolones with non-steroidal anti

Survey on concurrent prescriptions for quinolones with non-steroidal anti

Fatalities Associated with Therapeutic Use and Overdose of Atypical Antipsychotics

Since 1989, several novel antipsychotic drugs have become available for use including clozapine, risperidone, olanzapine, quetiapine and ziprasidone. These agents represent a substantial improvement in the treatment of schizophrenia and related disorders and are considered to have a favourable adverse effect profile relative to traditional antipsychotics. Nonetheless, in rare cases, people have died as a result of taking atypical antipsychotic drugs at therapeutic and supratherapeutic doses. Toxic doses of atypical antipsychotics are highly variable: some patients have died while taking therapeutic doses and others have survived massive overdoses. Toxicity may be increased by coingestion of other agents, particularly drugs with similar metabolic pathways. Atypical antipsychotics are metabolised predominantly by cytochrome p450 (CYP) isoenzymes, particularly CYP1A2 (clozapine and olanzapine), CYP3A4 (clozapine, quetiapine and ziprasidone) and CYP2D6 (olanzapine and risperidone). Concurrent prescription of other drugs that inhibit these isoenzymes may increase the probability of adverse events in patients taking atypical antipsychotics. Deaths due to atypical antipsychotic toxicity are often related to cardiovascular complications, but pulmonary, neurological, endocrine and gastrointestinal complications have also caused fatalities. Prevention and management of atypical antipsychotic overdose are of increased clinical relevance as prescription of these drugs increases.

High rates of adverse effects and patient unawareness of withdrawn lipid-lowering drug combination in a public hospital clinic.

Examine use, patient awareness and outcomes of concurrent cerivastatin and gemfibrozil in a public hospital clinic system 2 weeks following cerivastatin withdrawal. Electronic pharmacy records for cerivastatin prescriptions for 1 year preceding withdrawal were downloaded and linked to gemfibrozil prescriptions. Patients with concurrent prescriptions were surveyed for current use, awareness of withdrawal/warnings, adverse effects and creatine phosphokinase (CK) results. From August 2000 to August 2001, 29,377 prescriptions for cerivastatin were dispensed for 10,780 unique patients; 211 (2%) also received gemfibrozil. Prescription time frames for the two drugs overlapped for 67 patients. Interview of 47 patients revealed 35 actually taking both. 18/35 (51.4%) were still taking both drugs 2 weeks after market-withdrawal of cerivastatin. Only 7/46 (21.2%) had 'heard the news' about withdrawal. 19/46 (41.3%) described muscle-related symptoms; nine reported severe symptoms. Only 13 (28.3%) had CK monitoring. 5/8 symptomatic patients monitored had CK values > 200 U/L. (> 1000 U/L in two cases.) Despite escalating labeled warnings, nearly 2% of patients prescribed cerivastatin received gemfibrozil prescriptions, 1/3 concurrently. Most were still taking this combination 2 weeks after cerivastatin withdrawal and unaware of publicized warnings. Nearly half experienced muscle-related symptoms. More reliable methods for preventing prescription/dispensing of interacting medications and alerting patients about drug recalls are warranted.

Adverse-effects-of-herbs-and-drug-herbal-interactions

Many people have turned away from conventional medicines, with the belief that ‘natural’ substances like herbs are safer than synthetic substances. This belief is augmented by many other unwarranted claims such as herbal products do not contain chemicals while conventional medicines do, thus contributing to the latter’s side effects. The increasing use of herbal medicines has resulted in concern about the efficacy and safety of these products. Herbs can be hazardous in many ways. They may be intrinsically toxic or toxic when taken in combination with other preparations. Because herbal preparations are usually not evaluated for purity and consistency of active compounds, they often contain contaminants. Inclusion of incorrect but toxic species, allergens, pollen, insect parts, heavy metals such as lead, mercury and arsenic and scheduled poisons (drugs), whether intentional or unintentional, have been cited as the causes of herbal adverse reactions or toxicities. The increasing use of herbal medicines means that there is potential for more drug interactions, particularly between herbal products and conventional ‘Western’ medicines. Toxicity and drug-local herb interaction studies are scarcely conducted and therefore should be encouraged. Proper documentation of adverse effects of herbs should be initiated and patients should be asked about their use of herbal products in order to evaluate the potential of these products to interact with concurrent prescription medications. The public should be made aware of the adverse effects of herbal products.