Showing papers in "European Journal of Clinical Pharmacology in 2012"
TL;DR: This review has collected available evidence on the nephrotoxicity of vancomycin, particularly in terms of its mechanism, incidence, predisposing factors and special target populations and included all relevant animal and human studies up to the date of publication.
Abstract: Purpose
Treatment failures following vancomycin therapy in patients with methicillin-resistant Staphylococcus aureus infections have led to the utilization of higher doses of this antibiotic to achieve the trough concentrations of 10–20 μg/mL recommended by the Infectious Diseases Society of America clinical practice guideline. However, many questions remain on the safety of such high doses of vancomycin, specifically their nephrotoxic effects. In this review, we have collected available evidence on the nephrotoxicity of vancomycin, particularly in terms of its mechanism, incidence, predisposing factors and special target populations.
334 citations
TL;DR: This class of antibiotics is efficacious with respect to controlling exacerbations of underlying respiratory problems, such as cystic fibrosis, asthma, bronchiectasis, panbrochiolitis and cryptogenic organising pneumonia.
Abstract: Macrolides have long been recognised to exert immunomodulary and anti-inflammatory actions. They are able to suppress the “cytokine storm” of inflammation and to confer an additional clinical benefit through their immunomodulatory properties. A search of electronic journal articles was performed using combinations of the following keywords: macrolides, COPD, asthma, bronchitis, bronchiolitis obliterans, cystic fibrosis, immunomodulation, anti-inflammatory effect, diabetes, side effects and systemic diseases. Macrolide effects are time- and dose-dependent, and the mechanisms underlying these effects remain incompletely understood. Both in vitro and in vivo studies have provided ample evidence of their immunomodulary and anti-inflammatory actions. Importantly, this class of antibiotics is efficacious with respect to controlling exacerbations of underlying respiratory problems, such as cystic fibrosis, asthma, bronchiectasis, panbrochiolitis and cryptogenic organising pneumonia. Macrolides have also been reported to reduce airway hyper-responsiveness and improve pulmonary function. This review provides an overview on the properties of macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin), their efficacy in various respiratory diseases and their adverse effects.
253 citations
TL;DR: The prevalence of PIP was high among the study cohort, increased with polypharmacy and was associated with significant cost, and the gross cost was estimated to be €6,098,419.
Abstract: We sought to estimate the prevalence of potentially inappropriate prescribing (PIP) in the Northern Ireland (NI) population aged ≥70 years, to investigate factors associated with PIP and to calculate total gross cost of PIP. A retrospective cross-sectional population study was carried out in those aged ≥70 years in 2009/2010 who were in primary care in NI. Data were extracted from the Enhanced Prescribing Database, which provides details of prescribed and dispensed medications for each individual registered with a general practitioner. Twenty-eight PIP indicators from the Screening Tool of Older Persons potentially inappropriate Prescriptions (STOPP) criteria were applied to these data. PIP prevalence according to individual STOPP criteria and the overall prevalence of PIP were estimated. The relationship between PIP and polypharmacy, age and gender was examined using logistic regression. Gross cost of PIP was ascertained. The overall prevalence of PIP in the study population (n = 166,108) was 34 %. The most common examples of PIP identified were proton pump inhibitors at maximum therapeutic dose for >8 weeks (17,931 patients, 11 %), non-steroidal anti-inflammatory drugs >3 months (14,545 patients, 9 %) and long-term long-acting benzodiazepines (10,147 patients, 6 %). PIP was strongly associated with polypharmacy, with those receiving seven different medications being fivefold more likely to be exposed to PIP than those on zero to three medications (odds ratio 5.04, 95 % confidence interval 4.84–5.25) The gross cost of PIP was estimated to be €6,098,419 Consistent with other research, the prevalence of PIP was high among the study cohort, increased with polypharmacy and was associated with significant cost.
172 citations
TL;DR: A fatal buprenorphine poisoning is typically accidental, and the average victim is a 27-year-old male addict, according to a retrospective analysis of data on opioid-associated deaths in the Finnish comprehensive postmortem toxicology database.
Abstract: Background
Although buprenorphine therapy has proved to be successful in opioid maintenance treatments, the drug is also widely abused in many countries by intravenous injection or sniffing (“snorting”). In Finland, buprenorphine is the most important abused opioid causing fatal poisonings.
115 citations
TL;DR: Adherence in COPD patients is influenced more by patients’ perception of their health and medication effectiveness, the presence of depressed mood and co-morbid illness than by demographic factors or disease severity.
Abstract: To investigate the effect of a range of demographic and psychosocial variables on medication adherence in chronic obstructive pulmonary disease (COPD) patients managed in a secondary care setting. A total of 173 patients with a confirmed diagnosis of COPD, recruited from an outpatient clinic in Northern Ireland, participated in the study. Data collection was carried out via face-to-face interviews and through review of patients’ medical charts. Social and demographic variables, co-morbidity, self-reported drug adherence (Morisky scale), Hospital Anxiety and Depression (HAD) scale, COPD knowledge, Health Belief Model (HBM) and self-efficacy scales were determined for each patient. Participants were aged 67 ± 9.7 (mean ± SD) years, 56 % female and took a mean (SD) of 8.2 ± 3.4 drugs. Low adherence with medications was present in 29.5 % of the patients. Demographic variables (gender, age, marital status, living arrangements and occupation) were not associated with adherence. A range of clinical and psychosocial variables, on the other hand, were found to be associated with medication adherence, i.e. beliefs regarding medication effectiveness, severity of COPD, smoking status, presence of co-morbid illness, depressed mood, self-efficacy, perceived susceptibility and perceived barriers within the HBM (p < 0.05). Logistic regression analysis showed that perceived ineffectiveness of medication, presence of co-morbid illness, depressed mood and perceived barriers were independently associated with medication non-adherence in the study (P < 0.05). Adherence in COPD patients is influenced more by patients’ perception of their health and medication effectiveness, the presence of depressed mood and co-morbid illness than by demographic factors or disease severity.
114 citations
TL;DR: These three analytically confirmed cases demonstrate that acute methoxetamine-related toxicity is associated with both “dissociative” and “sympathomimetic” clinical features, and is useful to clinical pharmacologists, not only in managing individuals with acute methxetamine toxicity but also in advising the appropriate legislative authorities on the risk of acute harm related to methoxETamine use.
Abstract: Purpose
Long-term regular use of ketamine has been reported to be associated with severe symptomatic urinary tract problems. Methoxetamine, an arylcyclohexylamine derivative of ketamine, is marketed as a “bladder safe” derivative of ketamine, and no cases of acute toxicity following analytically confirmed methoxetamine use have been reported to date. We report here a case series of three individuals with acute toxicity related to the analytically confirmed use of methoxetamine.
110 citations
TL;DR: This narrative review has evaluated the use of off-label and unlicensed medicines in children and whether and how frequently this predisposes to adverse drug reactions.
Abstract: The use of unlicensed and off-label medicines in children is common because trials in children have not usually been performed during the drug development process. Consequently, the information available to paediatricians may not always be as detailed or as robust as that available when prescribing a medicine that is licensed for an approved indication. This has led to concerns that children may be receiving drugs at dosages that either lack efficacy or present safety problems. The latter in particular has received a great deal of attention. In this narrative review, we have evaluated the use of off-label and unlicensed medicines in children and whether and how frequently this predisposes to adverse drug reactions.
109 citations
TL;DR: CYP2D6 genotypes did not influence pain control, the adverse symptoms nausea and sedation or the risk for cognitive failure in patients treated with oxycodone for cancer pain, and had no pharmacodynamic consequence.
Abstract: Objective
Opioids are recommended by the World Health Organization for moderate to severe cancer pain. Oxycodone is one of the most commonly used opioids and is metabolized in the liver by CYP3A4 and CYP2D6 enzymes. The aim of this cross-sectional study was to assess the relationship between oxycodone pharmacokinetics, pharmacodynamics and the CYP2D6 genotypes “poor metaboliser” (PM), “extensive metaboliser” (EM) and “ultra-rapid metaboliser” (URM) in a cohort of patients with cancer pain.
102 citations
TL;DR: Although much still needs to be done, it’s clear that with concerted efforts and appropriate resources, change is possible but slow, and Retaining and fostering public and political interest in paediatric medicines is challenging, but pivotal for success.
Abstract: Purpose
This review was conducted to examine the current status of paediatric medicines initiatives across the globe.
95 citations
TL;DR: The incidence of DDI-related ADRs in elderly outpatients is high; most events presented important clinical consequences and were preventable or ameliorable.
Abstract: Purpose
Although the prevalence of drug–drug interactions (DDIs) in elderly outpatients is high, many potential DDIs do not have any actual clinical effect, and data on the occurrence of DDI-related adverse drug reactions (ADRs) in elderly outpatients are scarce. This study aimed to determine the incidence and characteristics of DDI-related ADRs among elderly outpatients as well as the factors associated with these reactions.
95 citations
TL;DR: Clinicians and pharmacists should aim to minimise polypharmacy and be aware of higher ADR risks associated with some drug groups to reduce the risk of ADRs in children.
Abstract: Understanding the epidemiology and risk factors of adverse drug reactions (ADRs) is important in order to develop appropriate prevention strategies. This study aimed to identify risk factors associated with ADRs in hospitalised children and recommend strategies to minimise ADRs. A prospective multicentre cohort study was conducted on paediatric general medical wards in five European and non-European hospitals. ADRs were identified by intensive chart review. Multivariable logistic regression was used to investigate risk factors associated with ADRs. For the risk factor analysis, prescribed drugs were divided into high-risk and low-risk drug groups. Analgesics, anti-epileptics, antibacterials and antimycotics for systemic use, corticosteroids for systemic use and immunosuppressant agents were considered as high-risk groups whereas the remaining drug classes were defined as low-risk drug groups. A total of 1,253 paediatric patients were identified [Australia (n = 145), Germany (n = 372), Hong Kong (n = 138), Malaysia (n = 291), UK (n = 307)]. A total of 328 ADRs were observed in 16.7% of patients (186/1,115). Use of five or more low-risk drugs per patient or three or more high-risk drugs was a strong predictor for ADRs (OR 4.7, 95% CI 2.4–9.3; OR 6.5, 95% CI 2.7–16.0 respectively; p < 0.001). Older children were more likely to experience ADRs; gender was not significantly associated. To reduce the risk of ADRs in children, clinicians and pharmacists should aim to minimise polypharmacy and be aware of higher ADR risks associated with some drug groups.
TL;DR: There is a less than proportional dose-exposure relationship between nilotinib 300 mg and 400 mg twice-daily doses, and blood level testing is unlikely to play an important role in the general management of patients with newly diagnosed CML treated withnilotinib.
Abstract: Purpose
We investigated the population pharmacokinetics and exposure-response relationship of nilotinib in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase.
TL;DR: Vorapaxar provided rapid and sustained dose-related inhibition of platelet aggregation without affecting bleeding or clotting times and was generally mild, transient, and unrelated to dose.
Abstract: Purpose
The aim of our study was to evaluate the pharmacology of vorapaxar (SCH 530348), an oral PAR-1 antagonist, in healthy volunteers.
TL;DR: Repeated administration of berberine decreased CYP2D6, 2C9, and CYP3A4 activities and the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Abstract: Purpose
Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interactions between berberine-containing products and cytochromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
TL;DR: The findings of this analysis are mostly reassuring, with the data indicating a seemingly stagnant incidence and prevalence rate and lacking evidence of heavy users, however, the prescriber profile for incident users and the large regional variances raise concerns.
Abstract: Purpose
The purpose of the study was to characterize the utilization of medication against attention deficit hyperactivity disorder (ADHD) in Denmark between 1995 and 2011 from a national perspective, by using population-based prescription data.
TL;DR: Considering that osteoblasts may be involved in bone disorders, such as osteoporosis, osteopetrosis, osteogenesis imperfecta, and Paget’s disease, and that bisphosphonates may stimulate proliferation of osteoblast and inhibit apoptosis of osteocytes and osteoblAST, it is conceivable that a role for bisph phosphonates exists in these diseases beyond merely the osteoclast influence.
Abstract: Purpose
Bisphosphonates are synthetic analogues of pyrophosphate usually used in treating bone disorders such as osteoporosis, Paget’s disease, fibrous dysplasia, hypercalcemia of malignancy, and inflammation-related bone loss. Though therapeutic effects of bisphosphonates depend primarily on their inhibitory effect on osteoclasts, increasing attention is being given to other effector cells, such as osteoblasts. This review focuses on the presumed effect of bisphosphonates on osteoblasts.
TL;DR: EGb 761® has no relevant effect on the in vivo activity of the major CYP enzymes in humans and therefore has norelevant potential to cause respective metabolic drug–drug interactions.
Abstract: Purpose
We assessed the human in vivo metabolic drug interaction profile of Ginkgo biloba extract EGb 761® with respect to the activities of major cytochrome P450 (CYP) enzymes
TL;DR: About one-third of the elderly Norwegian population is exposed to potentially inappropriate medications, and elderly females are at particular risk, and women were more frequently exposed to PIMs than men.
Abstract: Purpose
The elderly often use several drugs on a regular basis and are especially at risk for drug-related harm from side effects and interactions. The aim of this study was to explore the overall prevalence of and predictors for potentially inappropriate medication use among Norwegian elderly outpatients.
TL;DR: The results demonstrate the importance of the interaction among genetic and clinical factors in conditioning tacrolimus disposition, with corticosteroid weight-based dose being the only modifiable risk factor for tacro Limus requirement.
Abstract: The aim of this study was to evaluate the effect of different clinical covariates on tacrolimus dose requirements in adult kidney transplant patients with a specific focus on drug interactions. Tacrolimus dosing requirement, normalized by drug levels and expressed as the concentration/dose (C/D) ratio as a surrogate index of tacrolimus bioavailability, was employed to identify four categories of tacrolimus dosing requirement, namely, very high, high, small, and very-small, in very fast, fast, slow, and very slow metabolizers, respectively. Steroid weight-based doses were analyzed instead of fixed doses, and genetic analysis of cytochrome P450 (CYP) 3A5*1/*3 and multi-drug resistance 1 (MDR1) C3435T and C1236T polymorphisms were performed Multivariate analysis on 450 adult transplant patients identified six risk factors for being slow metabolizers and therefore requiring small tacrolimus doses: male sex (OR 1.615, p = 0.020); age >60 years (OR 2.456, p = 0.0005); body mass index ≥25 (OR 1.546, p = 0.046), hepatitis C virus positivity (OR 2.800, p = 0.0004); low steroid dose <0.06 mg/kg (OR 3.101, p < 0.0001). Patients with a small tacrolimus requirement were at increased risk for multiple infections (OR 1.533, p = 0.0008) and higher systolic blood pressure (OR 1.385, p = 0.022) and showed a significant association with the CYP3A5*3/*3 genotype adjusted by MDR1 polymorphisms C3435T and C1236T (OR 8.104, p = 0.0001). Our results demonstrate the importance of the interaction among genetic and clinical factors in conditioning tacrolimus disposition, with corticosteroid weight-based dose being the only modifiable risk factor for tacrolimus requirement. As the tacrolimus dosing requirement increases with increasing tacrolimus clearance through concomitant steroid use, undesirable changes in tacrolimus levels may occur when steroid doses are tapered, predominantly in slow metabolizers. This often neglected drug interaction has to be monitored to optimize tacrolimus exposure in kidney transplant patients.
TL;DR: It is reaffirmed that the SLCO1B1 genetic risk appears to be greater in those patients receiving simvastatin compared with those receiving atorvastsatin, and suggests that the importance of S LCO1 B1 haplotypes depends on the specific statin that has been used.
Abstract: Recent studies reported the association of SLCO1B1 haplotypes with the development of musculoskeletal side effects during simvastatin use. The aim was to evaluate the pharmacogenetic association of SLCO1B1 haplotypes with atorvastatin-induced myalgia in a sample of individuals on high-dose atorvastatin regimens. One hundred and forty-three patients with familial hypercholesterolemia were followed for at least 12 months while receiving atorvastatin. Genotypes for the rs2306283 (c.A388G) and rs4149056 (c.T521C) polymorphisms were detected by high-resolution melting analysis. These markers form four distinct haplotypes (*1A, *1B, *5 and *15). During the follow-up period, 14 (9.8%) patients developed myalgia and 16 (11.2%) presented CK levels more than 3 times the upper limit of the normal range. No association of the SLCO1B1 rs2306283 and rs4149056 genotypes or haplotypes with the presence of myalgia or creatine kinase (CK) values was found. Presence of rs2306283 AG + GG genotypes was not associated with increased risks of myalgia or abnormal CK values (OR 2.08, 95% CI 0.62–7.00, p = 0.24 and OR 0.51, 95% CI 0.21–1.26, p = 0.15 respectively). The presence of rs4149056 TC + CC genotypes was also not associated with increased risk of myalgia or abnormal CK values (OR 2.24, 95% CI 0.47–10.72, p = 0.31 and OR 1.51, 95% CI 0.57–3.96, p = 0.41 respectively). Our findings reaffirm that the SLCO1B1 genetic risk appears to be greater in those patients receiving simvastatin compared with those receiving atorvastatin. This suggests that the importance of SLCO1B1 haplotypes depends on the specific statin that has been used.
TL;DR: There was a pronounced effect of sex, a finding that indicates an important factor for the previously described sex difference in systemic clearance of propofol seen, and was supported by in vitro data showing similar variability of prop ofol 4-hydroxylation in liver microsomes.
Abstract: The basis of high intersubject variability of propofol metabolism is unclear. Therefore, we examined the influence of genetic polymorphisms of the key metabolizing enzymes cytochrome P450 2B6 (CYP2B6) and uridine diphosphate (UDP)-glucuronosyltransferase 1A9 (UGT1A9), age, and sex on propofol biotransformation in vitro and in vivo. Plasma concentrations of propofol, 4-hydroxypropofol, and their glucuronides were measured over 20 min in 105 patients after a single intravenous bolus of propofol. Propofol 4-hydroxylation activity, genotypes, and content of CYP2B6 protein in 68 human livers were determined. The common single nucleotide polymorphisms (SNPs) for the CYP2B6 and UGT1A9 genes were analyzed by polymerase chain reaction (PCR). Plasma levels of propofol metabolites showed high interindividual variability (range of coefficient of variation 89–128%). This was supported by in vitro data showing similar variability of propofol 4-hydroxylation in liver microsomes and 1.9-fold higher CYP2B6 protein content in the livers from women. No significant relationships were revealed between the SNPs studied and propofol metabolism. However, patients’ sex had a pronounced effect on propofol metabolism. Thus, women had higher amounts of propofol glucuronide (1.25-fold; p = 0.03), 4-hydroxypropofol-1-glucuronide (2.1-fold; p = 0.0009), and 4-hydroxypropofol-4-glucuronide (1.7-fold; p = 0.02) as shown by the weight-corrected area under the time–plasma concentration curve of metabolites. Additionally, the sexual dimorphism in 4-hydroxypropofol glucuronidation was prominent in the 35- to 64-year-old subgroup. No significant effects of CYP2B6 and UGT1A9 SNPs or age on propofol metabolism were revealed in this pilot study, but there was a pronounced effect of sex, a finding that indicates an important factor for the previously described sex difference in systemic clearance of propofol seen.
TL;DR: Fasudil greatly reduces the occurrence of CVS and cerebral infarction in SAH patients, significantly improves the clinical outcomes of the patients, and needs to be validated with results from large randomized, controlled clinical trials.
Abstract: Cerebral vasospasm (CVS) is a frequent and unpredictable complication in patients with subarachnoid hemorrhage (SAH) and often leads to poor outcomes. This study was aimed at evaluating the efficacy and safety of fasudil in the treatment of CVS in patients with SAH. A search was conducted using the full-text database of Chinese scientific journals, the Wanfang Database (January 1999 to November 2010), the Chinese Medical Association Digital Journal Database, PubMed, the Cochrane library, OVID, and EMBase (searching through November 2010). A total of 8 studies met the inclusion criteria. The incidence rates of symptomatic CVS and CVS confirmed by angiography among the patients in the fasudil group were only 48% (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.32–0.72, P = 0.0005) and 40% (OR = 0.40, 95% CI: 0.24-0–67, P = 0.0004) respectively of that of the control group. The odds ratios of cerebral infarction for all cases and cerebral infarction for CVS cases in the fasudil group were only 50% (OR = 0.50, 95% CI: 0.34–0.76, P = 0.0009) and 43% (OR = 0.43, 95% CI: 0.26–0.70, P = 0.0008) respectively of that of the control group. Fasudil greatly reduces the occurrence of CVS and cerebral infarction in SAH patients, significantly improves the clinical outcomes of the patients (as assessed by the Glasgow Outcome Scale). Because of the limited number of trials and samples available for analysis, the conclusions from the present study still need to be validated with results from large randomized, controlled clinical trials.
TL;DR: This study confirms known ITP risks for glycoprotein IIb/IIIa receptor antagonists and sulphonamides and generates signals for several other drugs and vaccines and indicates new onset of ITP should not only direct attention to drugs as possible aetiological agents, but also to vaccines that are known to cause autoimmune phenomena.
Abstract: Drug-induced immune thrombocytopaenia is a rare, serious condition that can be triggered by numerous medications To characterize the spectrum of drugs associated with immune thrombocytopaenia (ITP) in the Berlin Case–Control Surveillance Study (FAKOS) Adult hospitalized patients with new onset idiopathic, secondary or drug-induced acute ITP and hospital control patients were ascertained by active surveillance in 50 Berlin hospitals (>180 clinical departments) between 2000 and 2009 Drug exposures were obtained in a personal interview Chronic cases were excluded in a follow-up after 6 or more months A standardized causality assessment was conducted for each ITP patient to assess possible drug aetiology Drug risks were quantified in a case–control design with unconditional logistic regression analysis Ninety out of 169 validated cases of acute ITP were assessed as being at least possibly drug-related (n = 85 different drugs overall, n = 30 drugs with certain or probable causality) Drugs involved in ≥2 cases with a probable or certain relationship were tirofiban (n = 10 cases), abciximab (n = 4), trimethoprim/sulphamethoxazole (n = 4), influenza vaccine (n = 3), and citalopram (n = 2) Pneumococcal and poliomyelitis vaccine were assessed as probably causing ITP in one case each In the case–control analyses, significantly increased risks were observed for tirofiban, abciximab, trimethoprim/sulphamethoxazole, gentamicin, triamterene/hydrochlorothiazide, drospirenone/ethinylestradiol, and influenza vaccination Our study confirms known ITP risks for glycoprotein IIb/IIIa receptor antagonists and sulphonamides and generates signals for several other drugs and vaccines New onset of ITP should not only direct attention to drugs as possible aetiological agents, but also to vaccines that are known to cause autoimmune phenomena
TL;DR: The results suggest that UGT1A3*5 may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase VPA dose for UGT2B7 carriers to ensure its therapeutic range of 50–100 μg/mL.
Abstract: The aim of this study was to investigate the genetic polymorphisms of UGT1A3, UGT1A6, and UGT2B7 in Chinese epilepsy patients and their potential influence on the pharmacokinetics of valproic acid (VPA). The genetic architectures of UGT1A3, UGT1A6, and UGT2B7 in 242 epilepsy patients were detected by DNA sequencing and PCR-restriction fragment length polymorphism. Steady-state plasma concentrations of VPA in 225 patients who had received VPA (approx. 250–1,000 mg/day) for at least 2 weeks were determined and associated with UGT polymorphisms. The allelic distribution of UGT1A3 in our Chinese epilepsy patients was significantly different from that in healthy subjects based on reference data. The standardized trough plasma concentration (CS) of VPA was much lower in our patients with the UGT1A3*5 variant than in the wild type carriers (3.24 ± 1.05 vs. 4.68 ± 1.24 μg·kg·mL-1·mg-1, P < 0.01). UGT polymorphisms had no influence on the pharmacokinetic interactions between carbamazepine and VPA. Our results suggest that UGT1A3*5 may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase VPA dose for UGT1A3*5 carriers to ensure its therapeutic range of 50–100 μg/mL.
TL;DR: Grapefruit juice decreases exposure of aliskiren partially via inhibition of intestinal OATP1A2 through the role of organic anion transporting polypeptide (OATP) transporter-mediated uptake.
Abstract: Purpose
To conduct a mechanistic investigation of the interaction between aliskiren and grapefruit juice in healthy subjects.
TL;DR: Efforts to reduce the use of BZD/Zs in nursing homes should concentrate on insomnia, with interventions aimed at reducing too high prevalence of chronic use and too high daily dosages in this indication.
Abstract: (1) To describe the prevalence of benzodiazepine use in Belgian nursing homes, with specific attention to indications and dosages. (2) To compare actual and recommended dosages of benzodiazepines for anxiety and insomnia. (3) To explore the risk profile for chronic benzodiazepine use in institutionalised older adults. Medication charts of 1,730 residents from 76 nursing homes in Belgium were collected and analysed, using the ATC classification. Drug name, indication and daily dosage were recorded. From authoritative international sources, we extracted for each drug and each indication a daily dosage recommended not to be exceeded in older adults for comparison with observed actual dosages. Among the chronic benzodiazepine or z-drug (BZD/Z) users (50% of the residents), the leading indication was ‘insomnia’ (59% of the users) followed by ‘anxiety’ (17%) and ‘unrest’ (10%). In the chronic prescriptions of BZD/Zs indicated for insomnia, the actual daily dose exceeded the geriatric upper limit in 95% of lormetazepam prescriptions, 82% of zolpidem, 78% of zopiclone and 35% of lorazepam prescriptions. For anxiety, daily doses also exceeded the limit but not to the same extent. Multivariate analysis showed BZD/Z use was positively associated with pain (OR 1.58, 95% CI 1.27–1.97), constipation (OR 1.43, 95% CI 1.16–1.76) and depression (OR 1.68, 95% CI 1.35–2.08). Residents with dementia were less likely to receive a BZD/Z (OR 0.60, 95% CI 0.48–0.74). Efforts to reduce the use of BZD/Zs in nursing homes should concentrate on insomnia, with interventions aimed at reducing too high prevalence of chronic use and too high daily dosages in this indication.
TL;DR: Hematologists should know the principles of dose adjustment in cirrhosis and renal failure, but also the most important pDDIs of the drugs used to treat liver disease and comorbidities in this population.
Abstract: Patients with liver cirrhosis may be at risk for potential drug-drug interactions (pDDIs) and/or adverse drug reactions (ADRs) due to the severity of their disease and comorbidities associated with polypharmacy. We performed a cross-sectional retrospective study including 400 cirrhotic patients and assessed diagnoses, medication patterns, pDDIs, and ADRs at hospital admission. The median (range) age of the patients was 60 (21–88) years; 68.5% were male. They had a total of 2,415 diagnoses, resulting in 6 (1–10) diagnoses per patient. Frequent were diagnoses of the digestive system (28.4%), circulatory system (14.2%), blood and blood-forming organs (8.7%), and psychiatric disorders (7.5%); 60.7% of the diagnoses were not liver-associated. The median number of drugs per patient was 5 (0–18), whereof 3 (0–16) were predominantly hepatically eliminated. Drugs were primarily indicated for gastrointestinal, cardiovascular, or nervous system disorders, reflecting the prevalent diagnoses. In 112 (28%) patients, 200 ADRs were detected, mainly associated with spironolactone, torasemide, furosemide, and ibuprofen. In 86 (21.5%) patients, 132 pDDIs were detected. Seven of these pDDIs were the direct cause of 15 ADRs, whereof 3 resulted in hospital admission. Patients with ADRs were older, had more comorbidities, were treated with more drugs, and had a worse renal function and more pDDIs than patients without ADRs. Pharmacotherapy is complex in cirrhotic patients. Hepatologists should know the principles of dose adjustment in cirrhosis and renal failure, but also the most important pDDIs of the drugs used to treat liver disease and comorbidities in this population.
TL;DR: Drug-related problems were common in the hospitalised children in this study; the most frequent were dosing problems and drug choice problems; the majority of them were preventable.
Abstract: Drug-related problems (DRP) are “an event or circumstance involving drug therapy that actually or potentially interferes with the desired health outcome”. The extent and characteristics of DRPs in children in the UK and the Kingdom of Saudi Arabia (KSA) are unknown. Our aim was to determine the epidemiology of and identify risk factors for DRPs in hospitalised children. A prospective cohort study was carried out in children aged 0–18 years, admitted to the medical ward, paediatric intensive care unit (PICU) and neonatal intensive care unit (NICU) during a 3-month period in two hospitals. Patients’ charts, medical records and laboratory data were reviewed daily to identify DRPs; their preventability and severity were assessed. Logistic regression was used to analyse the potential risk factors associated with DRP incidence. Seven hundred and thirty-seven children (median age 2.3 years, interquartile range 6 months to 8 years, 58.1% male) were included. Three hundred and thirty-three patients suffered from 478 DRPs. Overall DRP incidence was 45.2% (95% CI, 41.5–48.8); KSA (51.1%; 95% CI, 45.8–56.3), UK (39.4%; 95% CI, 34.4–44.6). Incidence was highest in the PICU (59.7%; 95% CI, 47.0–71.5). Dosing problems were the most frequently reported DRPs (n = 258, 54%). 80.3% of DRP (n = 384) cases were preventable; 72.2% (n = 345) of DRPs were assessed as minor; 27% (n = 129) as moderate. Number of prescriptions and type of admission (transferred) were potential risk factors for DRP occurrence in children. Drug-related problems were common in the hospitalised children in this study; the most frequent were dosing problems and drug choice problems; the majority of them were preventable. Polypharmacy and transferred admission (another hospital or ward) were potential risk factors. To improve prescribing practices and minimise the risk of DRPs in hospitalised children, paediatric pharmacology and pharmacotherapy are important in medical education.
TL;DR: Concomitant rifampicin-containing tuberculosis treatment reduced apparent EFV clearance with a corresponding increase in EFV exposure, and cytochrome P450 2B6 polymorphisms in the population studied may provide some explanation.
Abstract: Purpose
Drug interactions are of concern when treating patients co-infected with human immunodeficiency virus (HIV) and tuberculosis. Concomitant use of efavirenz (EFV) with the enzyme inducer rifampicin might be expected to increase EFV clearance. We investigated the influence of concomitant tuberculosis treatment on the plasma clearance of EFV.
TL;DR: Observational studies, specifically using large databases, can complement findings from randomized clinical trials (RCTs) by assessing treatment effectiveness in patients encountered in daily clinical practice, although they are more exposed to bias and certainly are lower on the hierarchy of evidence than RCTs.
Abstract: Pharmacoepidemiology is the study of the utilization and effects of drugs in clinical and population settings, and the outcomes of drug therapy. The growing trend of recording computerized data that will increasingly be automated into health care delivery is making the use of large datasets more and more common in pharmacoepidemiologic research. Most retrospective databases offer large populations and longer observation periods with real-world practice and can answer a variety of research questions quickly and cost-effectively. Observational studies, specifically using large databases, can complement findings from randomized clinical trials (RCTs) by assessing treatment effectiveness in patients encountered in daily clinical practice, although they are more exposed to bias and certainly are lower on the hierarchy of evidence than RCTs. Furthermore, careful defining of the research question with appropriate design and application of advanced statistical techniques, e.g., propensity-score analysis or marginal structural models, can yield findings with validity and improve causal inference of treatment effects. Some existing guidelines for comparative effectiveness help decision makers to evaluate the quality of observational studies comparing the effectiveness of various medical products and services. Thus, the trend for utilization of databases for pharmacoepidemiology will continue to grow in coming years.