Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

ABSTRACT

Objective: To evaluate the safety and tolerability of prolonged-release nicotinic acid (Niaspan) added to statin therapy in patients at increased cardiovascular risk.

Methods: This was a 6-month, prospective, observa­tional, multicentre, open-label evaluation of prolonged-release nicotinic acid (maximum dose 2000?mg/day) in statin-treated patients with cardiovascular disease and/or type 2 diabetes. The primary endpoint was the safety and tolerability of prolonged-release nicotinic acid, with special regard to treatment-related adverse drug reactions (ADRs). Secondary endpoints were changes in lipids and 10-year cardiovascular risk (Prospective Cardiovascular Münster (PROCAM) score).

Results: The study population included 1053 patients: 50% had hypertension, diabetes and/or metabolic syndrome (National Cholesterol Education Program/Adult Treatment Panel III criteria) and 80% had cardiovascular disease. Flushing (mostly mild or moderate) occurred in 430 patients (40.8%). Other ADRs occurred in 125 patients (12.5%), most commonly pruritus (2.7%), gastro­intestinal symptoms (3.8%) and nervous system-related complaints (3.8%). Serious ADRs were uncommon (0.6%). All patients recovered completely from these ADRs after treatment discontinuation. In total, 11.1% of the patients discontinued study medication for flushing and 8.4% for other ADRs. There was no evidence of hepatotoxicity or myopathy. New-onset hyperglycaemia was negligible. Overall tolerability of prolonged-release nicotinic acid treatment (n = 734 patients at closeout) was ‘very good’ in 130 (17.7%), ‘good’ in 262 (35.7%), and ‘acceptable’ in 144 (19.6%) patients. High-density lipoprotein (HDL) cholesterol increased by 23%, triglycerides decreased by 15% and LDL-C decreased by 4%.

Conclusions: Prolonged-release nicotinic acid was safe and generally well tolerated and effective in combination with statin therapy in patients at high risk of cardio­vascular events, with a side-effect profile consistent with previous clinical experience.     

Neuromuscular Effects of Rocuronium Bromide in Patients in Statin Therapy for at least Three Months

Statins cause skeletal muscle myopathy. However, the neuromuscular effects of non‐depolarizing neuromuscular‐blocking agent in patients in long‐term statin therapy remain unclear. Hence, we investigated the neuromuscular effects of rocuronium and muscle injury in patients in long‐term statin therapy. Eighteen statin users using statins for at least 3 months were included in the statin group and 18 non‐statin users were included in the non‐statin group. General anaesthesia was induced with intravenous midazolam, etomidate, sufentanil and rocuronium 0.9 mg/kg (3ED₉₅) for intubation. Anaesthesia was maintained with 1% propofol and remifentanil. The onset time and duration 10% T₁ and 25% T₁ of rocuronium were recorded. Blood samples were obtained before induction and 5 min., 1 hr, 2 hr, 4 hr, 12 hr and 24 hr after rocuronium administration to measure creatine kinase (CK), myoglobin and potassium. Myalgia was determined at 2 and 24 hr after surgery. There were no significant differences in the basic clinical characteristics between the two groups. The onset time of the statin group was significantly shorter than that of the non‐statin group (p = 0.02), while the duration 10% T₁ and duration 25% T₁ of the statin group were significantly longer than those of the non‐statin group (p = 0.006; p = 0.045). The myoglobin and CK concentrations increased after rocuronium administration as compared to baseline in both groups. CK concentration in the statin group was significantly higher than in the non‐statin group just at 24 hr (p = 0.000003). However, myoglobin showed no significant difference between the two groups. The onset time of rocuronium decreases and its duration time increases in patients in long‐term statin therapy.     

Nervous system adverse responses to topiramate in the treatment of neuropsychiatric disorders

Importance of the field: Nervous system adverse drug reactions (NS-ADRs), such as cognitive complaints and paresthesia, are among the most frequent and clinically important ADRs of topiramate. Studying ADR profiles across disorders is clinically relevant because treatment decision-making in neuropsychiatry is highly guided by ADR profiles.

Areas covered in this review: We used medline searches (until July 2009) to review the NS-ADRs of topiramate across the most investigated topiramate indications: alcohol dependence, essential tremor, binge-eating disorder, bulimia nervosa, migraine and epilepsy. We compared NS-ADRs between these disorders but did not carry out meta-analysis.

What the reader will gain: ADR profiles greatly differed between disorders. Drop-outs due to ADRs highly varied between disorders: from 2% in the bulimia nervosa group to 29% in the migraine group. Paresthesia was the most common NS-ADR for all disorders but frequencies also differed between disorders. Cognitive complaints were frequent and were reported in comparable proportions.

Take home message: When prescribing topiramate in neuropsychiatry, physicians should be aware that NS-ADR profiles have been found to differ between disorders. Differences in drop-out rates due to ADRs and in frequencies of specific NS-ADRs across disorders must be taken into account when evaluating the potential harm of topiramate in clinical practice.     

Antihypertensive-related adverse drug reactions among older hospitalized adults

Background Antihypertensive medications are commonly used for a wide range of indications, yet it is unknown to what extent older adults are at risk of adverse drug reactions (ADRs) associated with their antihypertensive medication use. Objective The aim of this study was to determine the prevalence and characteristics of antihypertensive-related ADRs on hospital admission. Setting Metropolitan teaching hospital in Sydney, Australia. Method A retrospective cross-sectional audit of 503 older patients (≥ 65 years) admitted to hospital was conducted. Potential ADRS were identified from the medical record. Two independent clinical pharmacists reviewed each potential ADR using validated tools for causality, severity, preventability and contribution to hospitalization. Characteristics associated with an increased ADR risk among antihypertensive users were identified via logistic regression. Main outcome measure Antihypertensive related ADRs. Results Antihypertensives were used on admission by 68% of the cohort and the prevalence of ‘definite/probable’ antihypertensive-related ADRs among antihypertensive users was 16.4%. Antihypertensive medications were associated with a threefold ADR risk (OR = 3.09, 95% CI 1.85–5.16). Angiotensin II Receptor Blockers (ARB), impaired renal function, recent medication changes and previous history of allergy or ADR were all associated with an increased risk of experiencing an ADR. Conclusions ADRS associated with antihypertensive medicines were relatively common among older adults admitted to hospital. Increased awareness of those older persons who are most at risk of experiencing an antihypertensive-related ADR in the clinical setting may lead to early detection and minimization of ADR associated harms.     

老年人药品不良反应的监测和预防

摘 要 老年人药品不良反应（adverse drug reactions,ADR）监测及预防是老年医学临床实践的重要内容。由于罹患多种疾病、多重用药以及药动学和药效学的改变等因素的影响,老年人更易发生ADR。老年人ADR表现的不典型性加大了其识别的难度,GerontoNet ADR风险指数是一个用于识别ADR高风险老年患者的一种实用又简便的评估方法,进而加强对ADR高风险老年患者的监护可以减少其ADR的发生。加强老年临床药理学知识的宣教可提高医生和患者对ADR的认知程度,另外,医院可采取多种措施预防ADR的发生。对于病情复杂的老年患者,通过老年综合评估进行个体化评估来简化患者用药和患者用药需求的优先度,促进患者合理用药。     

Influence of HCV or HBV coinfection on adverse drug reactions to antiretroviral drugs in HIV patients

Objective To compare the profile of adverse drug reactions (ADRs) to antiretroviral (ARV) drugs in patients coinfected with hepatitis C virus (HCV) or hepatitis B virus (HBV) versus non-coinfected patients with human immunodeficiency virus (HIV) infection. Methods We used the French Pharmacovigilance Database from 2000 to 2002. Selected patients were classified into four groups: HIV+HCV, HIV+HBV, HIV+HBV+HCV and HIV patients. We compared patients’ characteristics and profiles of ADRs to ARV drugs between the four groups. Results We identified 1,068 HIV, 172 HIV+HCV, 72 HIV+HBV and 26 HIV+HBV+HCV patients with 2,398, 446, 183 and 70 ADRs related to ARV drugs, respectively. The “seriousness” of these ADRs was similar in HIV and coinfected patients but death related to the ADRs was more frequent in HIV+HCV (9.4%) than in HIV (3.6%) patients (p<0.001). “Liver and bile system disorders” were more frequently reported in HIV+HCV and HIV+HBV patients than in HIV patients (17.3% and 20.8%, respectively, versus 8.9%, p<0.001). In HIV+HBV patients, the occurrence of these ADRs was independently associated in a logistic regression model to male gender [odds ratio (OR): 9.28, 95% confidence interval (CI): 2.74–31.36], exposure to zalcitabine (OR: 17.82, 95% CI: 1.49–212.95) or efavirenz (OR: 5, 95% CI: 1.44–17.33). “Red blood cell disorders” were also more frequent in HIV+HCV (7.4%) than in HIV (4.4%) patients (p<0.01). Conclusion Hepatic or haematological (mainly anaemia) ADRs to ARV drugs are more frequent in coinfected patients than in HIV patients. This study underlines the importance of hepatitis B or C in the occurrence of ADRs in HIV patients on ARV drugs.     

Identifying over-the-counter information to prioritize for the purpose of reducing adverse drug reactions in older adults: A national survey of pharmacists

BackgroundOver-the-counter (OTC) medication use is associated with risks of adverse drug reactions (ADRs), particularly among older adults. The Drug Facts Label (DFL) is supposed to provide consumers with information that would avoid ADRs, yet research suggests that consumers frequently fail to interact with this critical information. We postulate that emphasizing critical information by placing it on the front of the package may increase its usage. Before doing so, the most critical information from the DFL needs to be identified.ObjectivesThis study aimed to determine which information from the DFL is most critical in reducing ADRs at the time of purchase or use by older adults.MethodsA national survey of practicing pharmacists knowledgeable about OTC medication use by older adults asked participants to rank order the importance of the DFL sections to reduce ADRs in older adults. Open-ended questions focused on identifying ways of improving OTC medication labeling. Quantitative rankings were used to calculate the content validity ratio and analyzed using Wilcoxon signed rank tests. Qualitative results were categorized into themes.ResultsA total of 318 responses (12% response rate) were analyzed. There was high consensus that uses and purpose, active ingredient, warnings, and directions for use were the most important sections of the DFL. Within the warning section, 2 specific warnings, “Do not use” and “Ask a doctor or pharmacist,” were deemed most important. Similarly, qualitative themes focused on seeking health care provider assistance or were specific to age-related precautions.ConclusionsPrioritizing warnings that highlight the importance of possible drug-drug and drug-disease precautions and the need to seek medical advice before taking OTC medications were deemed most critical. Moving this type of information to the front of the package may help reduce ADRs among older adults.     

奥氮平所致药物不良反应的发生率及相关影响因素研究

目的：调查奥氮平所致药物不良反应的发生情况,并探讨其影响因素,为预防和减少ADRs的发生提供科学依据。方法：选取厦门市精神卫生中心接受治疗的1691例精神障碍患者,监测治疗过程中奥氮平不良反应的发生情况,采取单因素和多因素分析方法,研究奥氮平不良反应发生的相关影响因素。结果：奥氮平不良反应发生率较高,为33.83%。多因素非条件 Logistic 回归分析发现有肝病史、服用高剂量药物 (＞10mg)是奥氮平所致ADRs发生的危险因素,OR值分别为1.837(95% CI:1.162~2.905)和4.841(95% CI:3.874~6.049)。结论：有肝病史及服用高剂量药物 (＞10mg)的精神疾病患者是奥氮平ADRs发生的高危人群。     

Important Aspects of Pharmacist‐led Medication Reviews in an Acute Medical Ward

In some hospitals, clinical pharmacists review the medication to find drug‐related problems (DRPs) in acutely admitted patients. We aimed to identify the nature of identified DRPs and investigate factors of potential importance for the clinical implementation of pharmacist suggestions. In 100 randomly selected medication review (MR) notes, we retrospectively evaluated the clinical implementation and classified (1) timing and communication of the review; (2) DRPs and related suggestions for the physician; and (3) DRPs’ potential clinical relevance to patients as ‘beneficial’, ‘somewhat beneficial’, ‘no relevance’ or ‘other relevance’. Of 327 DRPs (0–13 DRPs per patient), 42% were implemented. The clinical implementation was higher if the MR note was made prior to (instead of after) the physician's admission, and even higher if the suggestions were communicated verbally (instead of only in writing) to the physicians (44% versus 79%, p < 0.05). The clinical relevance of the DRPs was either ‘beneficial’ (16%), ‘somewhat beneficial’ (43%), ‘no relevance’ (22%) or ‘other relevance’ (19%). The ‘beneficial’ DRPs had a higher clinical implementation (53%) than ‘no relevance’ (34%) (p < 0.05). The most frequently implemented suggestions were based on DRPs concerning ‘indication for drug treatment not noticed’, ‘inappropriate drug form’ and ‘drug dose too low’, with implementation rates of 83%, 67% and 63%, respectively. In our sample, the pharmacist's MR suggestions were only implemented by physicians in 42% of the cases, but review prior to physician contact and verbal communication of the suggestions, higher clinical relevance and specific types of DRPs were associated with a higher implementation rate.     

Risk factors for impaired health-related quality of life in functional dyspepsia

Aliment Pharmacol Ther 2011; 33: 261–274

Summary

Background The influence of patient characteristics on HRQoL in functional dyspepsia is poorly understood. Aim To determine the contribution of gastric sensorimotor function, psychosocial factors & ‘somatization’ to HRQoL in functional dyspepsia. Methods In 259 tertiary care functional dyspepsia patients, we studied gastric sensorimotor function with barostat. We measured psychosocial factors and ‘somatization’ using self‐report questionnaires. HRQoL was assessed using the SF‐36 physical and mental composite scores (PCS, MCS). Bivariate associations between gastric sensorimotor function, psychosocial factors and ‘somatization’ on the one hand and PCS and MCS on the other were estimated. Variables significantly associated with PCS or MCS in bivariate analysis were entered into hierarchical multiple linear regression models. Results Mean PCS was 40.1 ± 9.5; mean MCS was 45.1 ± 10.8. ‘Somatization’ (P < 0.0001) and chronic fatigue (P = 0.002) were significantly associated with impaired PCS (R² = 0.52, P < 0.0001). The effects of abuse history and depression were ‘mediated’ by ‘somatization’. Trait anxiety (P = 0.02), alexithymia (P = 0.06), depression (P = 0.06), positive affect (P < 0.0001), negative affect (P = 0.002) and generalised anxiety disorder (P = 0.01) were significantly associated with impaired MCS (R² = 0.67, P < 0.0001). Conclusions ‘Somatization’ is the most important risk factor for impaired physical HRQoL in functional dyspepsia; it ‘mediates’ the effect of abuse history and depression. Mental HRQoL is mainly explained by psychosocial factors.     

Haemodynamic Influences of Bisoprolol in Hypertensive Middle‐Aged Men: A Double‐Blind,Randomized, Placebo‐Controlled Cross‐Over Study

Treatment with beta‐blockers appears to show inferior reduction in central versus peripheral blood pressure. We aimed to examine simultaneous changes in central and peripheral blood pressure, vascular resistance, cardiac function and arterial stiffness during beta‐blockade. Haemodynamics were investigated after 3 weeks of bisoprolol treatment (5 mg/day) in a double‐blind, randomized, placebo‐controlled cross‐over trial in never‐treated 16 Caucasian males with grade I–II primary hypertension using continuous tonometric pulse wave analysis and whole‐body impedance cardiography. Bisoprolol decreased radial (134/80 versus 144/89 mmHg) and aortic blood pressure (122/80 versus 130/90 mmHg) and heart rate (57 versus 68 beats/min) when compared with placebo (p < 0.05 for all). Ejection duration (336 versus 316 ms) and stroke volume (109 versus 98 ml) were increased (p < 0.01 for all), while cardiac output was not significantly changed (6.2 versus 6.6 l/min). Bisoprolol decreased pulse wave velocity (7.8 versus 8.9 m/s, p < 0.001), but after adjustment for blood pressure, the decrease was not significant (8.16 versus 8.52 m/s, p = 0.464). The treatment reduced pulse pressure amplification from central to peripheral circulation (30 versus 38%, p = 0.002). No differences were observed in systemic vascular resistance, augmentation index, aortic characteristic impedance or total arterial stiffness after bisoprolol versus placebo. Bisoprolol decreased central and peripheral blood pressure and pulse wave velocity in male individuals with grade I to grade II hypertension. The decrease in pulse wave velocity was related to the antihypertensive effect. Reduced pulse pressure amplification indicates that peripheral blood pressure was reduced more efficiently than central blood pressure.     

Women encounter ADRs more often than do men

Background  Several publications indicate that the female gender experiences a higher incidence of adverse drug reactions (ADRs) than does the male gender. The reasons, however, remain unclear. Gender-specific differences in the pharmacokinetic and pharmacodynamic behaviour of drugs could not be identified as an explanation. The aim of this study was to analyse ADR risk with respect to gender, age and number of prescribed drugs. Methods  A prospective multicenter study based on intensive pharmacovigilance was conducted. Information on patient characteristics and evaluated ADRs was stored in a pharmacovigilance database—KLASSE. Results  In 2,371 patients (1,012 female subjects), 25,532 drugs were prescribed. In 782 patients, at least one ADR was found. A multivariate regression analysis adjusting for age, body mass index (BMI) and number of prescribed drugs showed a significant influence of female gender on the risk of encountering ADRs [odds ratio (OR) 1.596, confidence interval (CI) 1.31–1.94; p < 0.0001). Dose-related ADRs (51.8%) were the dominant type in female subjects. Comparing system organ classes of the World Health Organisation (SOC-WHO), cardiovascular (CV) ADRs were particularly frequent in female subjects (OR 1.92, CI 1.15–3.19; p = 0.012). Conclusion  Our data confirm the higher risk of ADRs among female subjects compared with a male cohort. Several explanations were investigated. No single risk factor could be identified.     

Chitosan‐Fe (III) Complex as a Phosphate Chelator in Uraemic Rats: A Novel Treatment Option

Phosphate retention and hyperphosphataemia are associated with increased mortality in patients with chronic kidney disease (CKD). We tested the use of cross‐linked iron chitosan III (CH‐FeCl) as a potential phosphate chelator in rats with CKD. We evaluated 96 animals, divided equally into four groups (control, CKD, CH‐FeCl and CKD/CH‐FeCl), over 7 weeks. We induced CKD by feeding animals an adenine‐enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks). We administered 30 mg/kg daily of the test polymer, by gavage, from the third week until the end of the study. All animals received a diet supplemented with 1% phosphorus. Uraemia was confirmed by the increase in serum creatinine in week 4 (36.24 ± 18.56 versus 144.98 ± 22.1 μmol/L; p = 0.0001) and week 7 (41.55 ± 22.1 versus 83.98 ± 18.56 μmol/L; p = 0.001) in CKD animals. Rats from the CKD group treated with CH‐FeCl had a 54.5% reduction in serum phosphate (6.10 ± 2.23 versus 2.78 ± 0.55 mmol/L) compared to a reduction of 25.6% in the untreated CKD group (4.75 ± 1.45 versus 3.52 ± 0.74 mmol/L, p = 0.021), between week 4 and week 7. At week 7, renal function in both CKD groups was similar (serum creatinine: 83.98 ± 18.56 versus 83.10 ± 23.87 μmol/L, p = 0.888); however, the CH‐FeCl‐treated rats had a reduction in phosphate overload measured by fractional phosphate excretion (FEPi) (0.71 ± 0.2 versus 0.4 ± 0.16, p = 0.006) compared to the untreated CKD group. Our study demonstrated that CH‐FeCl had an efficient chelating action on phosphate.     

Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study

Objective: In this pharmacovigilance study, we aimed to determine the incidence of spontaneously reported suspected adverse drug reactions (ADRs) related to oral anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA)

Research design and methods: In this retrospective observational study, we extracted all the individual case safety reports related to oral anticoagulants recorded in the Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual incidence of suspected ADRs was estimated using drug exposure data. Disproportionality of reporting ADR was addressed through reporting odds ratio (ROR) and 99% confidence intervals.

Results: We appraised 794 suspected ADR (78% related to NOACs). The annual number of ADRs increased overtime with 9 ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs ADRs decreased from 2012 onwards. VKA showed a disproportion in ‘Investigation’ (ROR 0.10, 99%CI 0.05–0.22) and ‘Injury, poisoning and procedural complications’ (ROR 0.36, 99%CI 0.19–0.69) ADRs compared with NOACs. NOACs had a higher significant disproportion of ‘Nervous system disorders’ related ADRs (ROR 3.98, 99%CI 1.50–10.53).

Conclusions: Reporting of ADRs associated with oral anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses showed an increase of reports of nervous system ADRs with NOACs, and INR-related ADRs with VKA.     

Efficacy and safety evaluation of intensive statin therapy in older patients with coronary heart disease: a systematic review and meta-analysis

Purpose

To reveal and evaluate the efficacy and safety of intensive statin therapy in older patients (age ≥ 65 years) with coronary heart disease (CHD).

Methods

Electronic databases were searched for randomized controlled trials (RCTs) that involved intensive statin therapy use in older patients with CHD. Data was extracted and used to calculate risk ratios (RR) by software Revman 5.1.

Results

Five RCTs and 11,132 patients were included in. Compared with non-intensive statin therapy, intensive statin therapy had significant effect on reducing low density lipoprotein cholesterol (LDL-C) levels (55.4 %) and total cholesterol (TC) and triglyceride (Tg). Although the results showed that intensive statin therapy had no superior effect on reduction of mortality (both all-cause mortality [RR?=?0.97, p?=?0.65] and cardiac death [RR?=?0.95, p?=?0.57]) and cardiac arrest (RR?=?1.09, p?=?0.81), it possessed significant effects on prevention of nonfatal myocardial infarction (MI) (RR?=?0.78, p?=?0.008), stroke (RR?=?0.72, p?=?0.02) and coronary revascularization (RR?=?0.69, p?=?0.007). In terms of side effects, intensive statin therapy was associated with small absolute increase in incidence of drug discontinuation, due to adverse events (3.9 %) and liver enzymes abnormalities (1.7 %). And the occurrence rates of myopathy, rhabdomyolysis and creatine kinase (CK) elevation were very low.

Conclusions

This results show that intensive statin therapy has excellent effects on reduction of serum lipid level including LDL-C, TC, Tg, and also on prevention of nonfatal MI, stroke and coronary revascularization with small absolute increased risk of side effects. Our analysis supports the use of intensive statin therapy in patients ≥?65 years old with CHD.     

Initiation of a pharmacovigilance programme at a tertiary care hospital in South India

Objective India is a country with the availability of a large number of pharmaceutical preparations as branded generics. At the time of this study there was no established pharmacovigilance system at the national level except a co‐ordinating centre at the national capital. The study site was a tertiary care teaching hospital with a bed capacity of 500 and with an average of 200 outpatient visits and 50 inpatient admissions per day. The hospital did not have any system of monitoring and documenting adverse drug reactions. The objective of the study was to introduce an adverse drug reaction (ADR) monitoring programme at a tertiary care teaching hospital and assess ADR‐related issues in both inpatient and outpatient departments. Method All departments willing to report ADRs were included in the study, which was carried out for one year. Physicians and nurses filled in the notification forms when they encountered suspected ADR cases. These cases were then assessed by a panel of four judges. According to Naranjo's algorithm, the ADRs were assessed and classified based on World Health Organization (WHO) classification. Key findings A total of 288 suspected cases were reported and 264 ADRs were confirmed by the panel. According to Naranjo's probability scale, 83 cases were categorized as ‘probable’, 181 cases were classified as ‘possible’, and none were classified as ‘unlikely’ or ‘definite’. The most common classes of drugs involved were antibiotics (25%), psychotropics (20%), analgesic and cardiovascular agents (14% each). Generalised itch and rash, tremors, urticarial drug reaction, oral ulcer, gastritis and akathesia and extrapyramidal symptoms were found to be the most common ADRs observed; 2.1% of the patients in the studied departments had ADRs. Conclusion The ADR reporting system was initiated at the hospital and was well received by the physicians. Appreciable participation of physicians was noted during the study in reporting ADRs. The study also gave an insight into the awareness of physicians about ADR‐related issues. The number of ADRs reported was reasonably comparable with the findings of other authors from India.     

The impact of gamma hydroxybutyrate (GHB) legal restrictions on patterns of use: Results from an International Survey

Aims: To conduct an Internet-based survey of gamma hydroxybutyrate (GHB) use and identify differences by respondent residence.

Methods: We recruited GHB-knowledgeable persons via ‘social networking Internet sites’. Individuals (n = 314) or groups (n = 66) were approached based on GHB-use testimonials. Data collected: location, use and reason for cessation (if applicable).

Findings: We recruited 155 GHB users. The US respondents (53 of the 70; 76%) compared to the non-US respondents (38 of 85; 45%) were older and more highly educated (p < 0.05) but manifest a three-fold greater adjusted odds of GHB cessation (odds ratio [OR] 3.1; 95% confidence interval [CI] 1.4–6.9; p < 0.05). Of the 80 respondents stating reason for cessation, 36 (45%) cited legal risk, price, or access; 44 (55%) cited health or related concerns. The US compared to the non-US respondents more frequently invoked legal and related concerns (OR 2.5; 95% CI 0.99–6.3; p = 0.05). In a nested analysis, narrowly stated legal (n = 4/5 the US) versus health (n = 6/18 the US) reasons differed by location (p = 0.048, one-tailed).

Conclusions: In the US, where GHB has stricter legal penalties, GHB cessation is more likely, with legal and related reasons more commonly invoked for cessation. These findings support a link between the declining US GHB abuse and more stringent restrictions, although other un-assessed factors may also explain this association.     

Improving medication safety in oncology care: impact of clinical pharmacy interventions on optimizing patient safety

Background Adverse drug reactions (ADRs) monitoring in cancer patients is important to ensure early detection, effective management and possible prevention subsequently. Objectives This study was conducted to detect and monitor ADRs to anti-cancer agents, and to assess impact of clinical pharmacists (CPs)’ interventions in minimizing ADRs to anti-cancer agents. Setting Private, specialty oncology care hospital in South India. Methods CPs prospectively followed cancer patients admitted to inpatient wards and treated at ambulatory care in order to identify ADRs, for a period of 3 years. Identified/reported ADRs were discussed with concerned oncologists and/or nurses, documented electronically and assessed further for their causality, severity, preventability and grading. Based on study findings during year 1, interventions (educational, therapeutic and system based) were developed by CPs and implemented in order to minimize preventable ADRs. Impact of CPs’ interventions was studied during year 2 and year 3. Main outcome measure(s) Preventable factors contributing to ADRs and percentage of preventable ADRs before and after CPs’ interventions. Results A total of 1279 ADRs were reported in 1133 patients from a cohort of 1328 patients. Vomiting (23.22%), alopecia (9.53%), diarrhoea (8.67%) and myelosuppression (7.42%) were the common ADRs reported. Inappropriate administration frequency and regimen of anti-emetics (22%), lack of/suboptimal supportive care (18%) and administration errors (16%) were identified as common contributing (preventable) factors for ADRs in year 1. Percentage of preventable ADRs was 81% during year 1 (pre-intervention), and 45% and 34% in year 2 and year 3 respectively (post-interventions). Conclusion Interventions by CPs helped to minimize preventable ADRs to anti-cancer agents.

     

Factors associated with adverse drug reactions in older inpatients in teaching hospital

Background Adverse drug reactions (ADRs) occur frequently during hospital stays and are an important public health problem, particularly in the care of the older. Objectives This study aimed to determine the prevalence of ADRs among older inpatients and the factors associated with their occurrence. Setting Brazilian teaching hospital. Methods This was a cross-sectional study with older inpatients in the internal medicine ward of a teaching hospital. The dependent variable was the occurrence of an ADR during hospitalization. The independent variables were gender, age, length of hospitalization, number of health problems, medications, and potentially inappropriate medications for the older. Logistic regression was performed to analyze the association between an ADR and the independent variables. Main outcome measure Factors associated with ADR in older inpatients. Results Among the 237 inpatients investigated, 50 (21.1%) developed at least one ADR. The total number of ADRs observed was 62 and the most frequent were acute kidney injury, hypotension, and cutaneous adverse reactions A multivariate analysis demonstrated a positive and independent association between the occurrence of an ADR and the presence of heart failure [odds ratio (OR) 2.4; 95% confidence interval (CI) 1.2–4.6], and with hospitalization time exceeding 12 days (OR 2.3; 95% CI 1.2–4.4). Conclusions The study showed a high prevalence of ADRs among the older and a positive association with hospitalization time and heart failure. Understanding the factors associated with the occurrence of ADRs among older inpatients provides elements for improving the safety of care and optimization of pharmacotherapy.     

Impact of Ageing on Serum Concentrations of Risperidone and Its Active Metabolite in Patients with Known CYP2D6 Genotype

The aim of this study was to investigate the impact of ageing on serum concentrations of risperidone and 9‐hydroxyrisperidone in patients with known CYP2D6 genotype. We included retrospective therapeutic drug monitoring data from 464 genotyped patients with measured serum concentrations of risperidone and 9‐hydroxyrisperidone after oral administration. Patients were divided into two age subgroups, that is ≤65 (n = 396) and >65 years (n = 68), and dose‐adjusted concentrations (C:D ratios) were compared using multiple linear regression analyses with CYP2D6 genotype and gender as covariates. Moreover, absolute concentrations and prescribed daily doses were compared between age subgroups by simple, univariate Mann–Whitney tests. Age had no effect on C:D ratio of risperidone (p > 0.4), but C:D ratios of 9‐hydroxyrisperidone and risperidone + 9‐hydroxyrisperidone (total active moiety) were estimated to be 2.6 and 2.0 times higher in patients >65 versus ≤65 years (p < 0.001). Female gender and a CYP2D6 poor metabolizer (PM) genotype were also associated with significantly higher C:D ratio of the total active moiety (p < 0.01). Despite lower dosing in patients >65 versus ≤65 years (median 1.5 versus 3.0 mg/day, p < 0.0001), absolute concentration of the total active moiety did not differ between the age subgroups (median 52.5 versus 47.0 nmol/L, p > 0.6). In conclusion, ageing implies significantly increased dose‐adjusted serum concentration of risperidone active moiety, and treatment intensity is not generally reduced by halving the oral dose in the elderly. Tolerability of risperidone therapy should therefore be closely monitored in older patients, and female CYP2D6 PMs >65 years might be a particularly vulnerable subgroup of adverse effects.