Number Of Concurrent Medications Research Articles

Polypharmacy and antidepressant acceptability in comorbid depression and type 2 diabetes: a cohort study using UK primary care data.

Polypharmacy may increase the risk of drug interactions, side effects, and poor adherence; however, the impact of polypharmacy on antidepressant acceptability in individuals with type 2 diabetes (T2DM) is unknown. To investigate the association between number of prescribed medications and early antidepressant discontinuation in adults with T2DM. Cohort study using UK primary care data from the Clinical Practice Research Datalink between 1 January 2000 and 31 December 2018. Cox regression with penalised B-splines was used to describe the association between the number of concurrently prescribed medications at the time of starting antidepressant treatment and each of the outcomes. A total of 73 808 individuals with comorbid depression and T2DM starting antidepressant treatment for the first time were identified. A median of 7 concurrent medications were prescribed. Within 32 weeks, 44.26% (n = 32 665) of participants discontinued antidepressant treatment altogether, and 11.75% (n = 8672) of participants switched antidepressant agents. An inverse relationship between the number of concurrent medications and discontinuing antidepressant treatment altogether was found. The median of 7 concurrent medications was associated with a 65.06% decrease in early antidepressant discontinuation; hazard ratio 0.45, 95% confidence interval = 0.37 to 0.55. No evidence of an association between the number of concurrent medications and switching antidepressant agents was found. Early discontinuation of antidepressants is common in adults with T2DM; however, individuals with higher levels of concurrent polypharmacy may be more adherent to treatment. These are likely to represent individuals with worse physical or mental health. Individuals with lower levels of concurrent polypharmacy may benefit from adherence support.

Determination of potential drug-drug interactions in prescription orders dispensed in a community pharmacy setting using Micromedex® and Lexicomp®: a retrospective observational study.

Background Community pharmacists have a role in identifying drug-drug interactions (DDIs) when processing prescription orders and dispensing medications to patients. The harmful effects of DDIs can be prevented or minimized by using an electronic DDI checker to screen for potential DDIs (pDDIs). However, different DDI checkers have variable rates of detecting pDDIs. Aim To estimate the prevalence of pDDIs in prescriptions dispensedina community pharmacy setting using two electronic DDI databases and to evaluate the association between thepDDIs and contributory factors. Method Eligible prescription orders dispensed by a community pharmacy chain in Qatar from January to July 2020 were included in this retrospective observational study. For each prescription, Micromedex® and Lexicomp® were simultaneously used to identify pDDIs, and the interactions categorized based on severity and risk rating. Results Seven hundred-twenty prescriptions met the inclusion criteria, of which Micromedex® and Lexicomp® respectively identified 125 prescriptions (17.4%) and 230 prescriptions (31.9%) as having at least one pDDI. Moderate strength of agreement was found between Lexicomp® and Micromedex® in identifying pDDIs (Cohen's Kappa = 0.546). Micromedex® classified 61.6% of DDIs as major severity, while Lexicomp® classified 30.8% as major severity. The number of concurrent medications per prescription was significantly and positively associated with pDDI. Conclusion This study demonstrates a high prevalence of pDDIs among prescriptions dispensed in a community pharmacy setting.It is advisable that community pharmacists in Qatar, who typically do not have access to computerized patient profiles, use these DDIcheckers to ensure all pDDIs are communicated to respective prescribers for appropriate action.

Abstract PS10-25: Tolerability and efficacy of palbociclib in combination with an aromatase inhibitor (AI) in older women (≥75 years) with ER +ve, HER2-ve metastatic breast cancer. A large ‘real world’ UK multi-centre study

Abstract IntroductionThe management of metastatic oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer has evolved with the introduction of CDK4/6 inhibitors improving disease outcomes when added to an AI in the first line setting. The FDA evaluated toxicity of all CDK4/6 inhibitors in women ≥75 years (n=198), and found increased toxicity and dose modifications [1], however, toxicity profiles differ between the CDK4/6 inhibitors. Palbociclib has been shown to be well tolerated in patients ≥75 years (n=83) [2] and ≥ 70 years (n=92) [3], however, more real-world data is essential to inform prescribing practices in larger datasets.MethodsWe undertook a national multi-centre retrospective study with 15 cancer centres participating. All patients aged ≥75 years with ER+/HER2- advanced breast cancer who had received at least 1 cycle of Palbociclib + AI as part of a patient access scheme or NICE approved by 1st December 2019 were included. Data collected included baseline characteristics, comorbidities, disease characteristics, toxicities with palbociclib, dose modifications, dose delays, discontinuation and response to treatment.ResultsData from 123 patients aged ≥75 years are included in this analysis from 3 UK cancer centres. Median age was 79 years (range 75 - 90). 98% had an ECOG performance status of 0-2. Co-morbidities were scored using Charlston comorbidity index (CCI - higher score signifies more co-morbidities). 102 patients had a CCI of ≤10 and 18 had a CCI >10. The starting dose of palbociclib was 125mg in 115 patients, but 8 (6.5%) patients started at a lower dose, a third of whom had a CCI of >10. The average number of concurrent medications was 4 (range 0-12). Visceral metastases were present in 52% of patients, and 33 patients (26.8%) had bone only metastases. The median number of cycles received was 10 (range 1 -36). 60 (48.8%) patients required one dose reduction, 18 patients required a 2nd dose reduction and 2 patients required a 3rd dose reduction. The most common cause for dose reductions was neutropenia G3-4 (n=31) and fatigue G1-3 (n=12). 75 patients (61%) required a dose delay and 9% of patients discontinued treatment due to toxicity. The rate of all grade neutropenia was 88.6% with only 1 patient (0.8%) developing febrile neutropenia. Other all grade common toxicities were fatigue (62.6%), anaemia (61.8%) and thrombocytopaenia (57.7%). 12 (9.7%) patients required hospital admission due to side effects of treatment. At the time of data analysis, 111 patients had had a radiological response assessment and the best response was stable disease in 57.7%, partial response in 32.4% and complete response in 0.9% (1 patient) with a clinical benefit rate (CR+PR+SD ≥24 weeks) of 83.8%. 10 patients (9%) had disease progression. The median progression free survival is immature, but at the time of this analysis was 13 months (range 1-36 months).ConclusionOur real world data contributes to the existing smaller published datasets in the over 75s to reassure clinicians that palbociclib is an effective and manageable treatment choice in older women. Compared to published data in older patients [2, 3], febrile neutropenia rates from palbociclib were lower. Despite a higher dose reduction and delay rate than published data [3], the clinical benefit rate was not adversely affected and the early PFS signal is reassuring. Citation Format: Salma El Badri, Daniel Hills, Alicja Synowiec, Catherine Harper-Wynne, Maung Moe, Caroline Wilson. Tolerability and efficacy of palbociclib in combination with an aromatase inhibitor (AI) in older women (≥75 years) with ER +ve, HER2-ve metastatic breast cancer. A large ‘real world’ UK multi-centre study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-25.

ADHERENCE TO INSULIN IN SINGAPOREAN PEDIATRIC TYPE 1 DIABETES PATIENTS AND ITS IMPACT ON GLYCEMIC CONTROL AND HEALTH-CARE UTILIZATION

Objective: Optimizing glycemic control is challenging with insulin non-adherence. This study aimed to characterize the prevalence of non-adherence among Singaporean pediatric patients with type 1 diabetes mellitus (T1DM) and investigate its associated outcomes.
 Methods: Singaporean patients with T1DM aged ≤18 years old with ≥1 year of insulin prescription between 2012 and 2016 were included in this retrospective, single-center longitudinal study. Patients on insulin pumps were excluded from the study. Non-adherence was defined as medication possession ratio (MPR) <100%. Glycemic control was defined using mean hemoglobin A1c (HbA1c) within the study period. Health-care utilization was defined as the number of outpatients, inpatient, and emergency visits. The t-test, Chi-square test, logistic regression, and Poisson regression were used to analyze means, proportions, factors associated with non-adherence, and association of non-adherence and health-care utilization, respectively. Sensitivity analyses were performed for MPR thresholds of 80% and 95%.
 Results: A total of 206 patients were included in this study. Non-adherent patients were older, had a longer duration of diabetes since diagnosis and shorter duration of follow-up. Gender, race, financial class, and number of concurrent medications were comparable between groups. The prevalence of non-adherence was 34.0% (95% confidence interval [CI]: 27.9–40.7%). Non-adherent patients had a higher average HbA1c (non-adherent: 9.6% [2.1] vs. adherent: 8.6% [1.3], p<0.001). Non-adherence was not associated with health-care utilization. Patients with >5 years of diabetes were more likely to be non-adherent.
 Conclusion: Non-adherence defined as MPR <100% is associated with poorer glycemic control. Further interventions may focus on patients with >5 years of diabetes to improve their adherence to insulin therapy.

Prevalence of and factors associated with primary medication non-adherence in chronic disease: A systematic review and meta-analysis.

Primary medication non-adherence (PMN), defined as failure to obtain newly prescribed medications, results in adverse clinical and economic outcomes. We aimed to (a) assess the prevalence of PMN in six common chronic diseases: asthma and/ or chronic obstructive pulmonary disease, depression, diabetes mellitus, hyperlipidaemia, hypertension and osteoporosis; (b) identify and categorise factors associated with PMN; (c) explore characteristics that contributed to heterogeneity between studies. We performed a systematic search in MEDLINE, Embase, Cochrane Library, CINAHL and PsycINFO. Studies published in English between January 2008 and August 2018 assessing PMN in subjects aged ≥18years were included. We used the Cochrane risk of bias tool, Newcastle-Ottawa Scale and National Heart, Lung and Blood Institute Quality Assessment Tool to assess the quality of randomised controlled trials, cohort and cross-sectional studies, respectively. Findings were reported using the PRISMA checklist. PMN rates were pooled using a random effects model. We summarised factors associated with PMN descriptively. Subgroup analysis was performed to explore sources of heterogeneity. We screened 3083 articles and included 33 (5 randomised controlled trials, 26 cohort and 2 cross-sectional studies, n=539156), of which 31 (n=519971) were used in meta-analysis. The pooled PMN rate was 17% (95% CI: 15%-20%). Pooled PMN rates were highest in osteoporosis (25%, 95% CI: 7%-44%) and hyperlipidaemia (25%, 95% CI: 18%-32%) and lowest in diabetes mellitus (10%, 95% CI: 7%-12%). Factors commonly associated with PMN include younger age, number of concurrent medications, practitioner specialty and higher co-payment. Type of chronic disease, age, study setting and PMN definition contributed to heterogeneity between studies (all P<0.001). Primary medication non-adherence is common among patients with chronic diseases and more needs to be done to address this issue in order to improve patient outcomes. Future PMN studies could benefit from greater standardisation to enhance comparability.

CONTRIBUTION FACTORS ON ACHIEVEMENT RATE OF TREATMENT GOALS OF BP AND LDL-C BY 3 MONTHS’ THERAPY OF ROVELITO (FIXED DOSE COMBINATION PILL OF IRBESARTAN AND ATORVASTATIN)

Objective: Coexistence of hypertension (HTN) and hypercholesterolemia is the major synergistic and modifiable risk factor for cardiovascular disease (CVD). A fixed-dose combination (FDC) of anti-HTN drug and stain may be valuable in terms of improving drug compliance especially for statin. Because renin angiotensin system activation and hypercholesterolemia are accompanied with obesity and angiotensin receptor blocker is more advantageous for Asians as it does not cause dry cough due to the angiotensin converting enzyme inhibitors, FDC of irbesartan and atorvastatin (Rovelito) may improve the treatment success rate. Design and method: Patients with comorbid HTN and hypercholesterolemia were screened for this prospective, observational, descriptive, multi-center, phase IV study. Eligible patients were administered with Rovelito for 3 months. Dose adjustment was allowed per physician's discretion. Primary purpose of this study was to evaluate the variables that affect treatment success rate for blood pressure (BP) and/or LDL-cholesterol (LDL-C). In addition, the compliance with the therapeutic lifestyle modification and the safety of the study drug were evaluated. Results: Among the total of 2,801 patients enrolled in the study, 945 patients were analyzed for clinical efficacy. BP and LDL-C goals were achieved in 813 (86.03%) and 811 (85.82%), respectively. Higher baseline BP and body mass index (BMI) were the factors for poor treatment success rate of BP goal. Baseline LDL-C level, number of concurrent medications and drinking status were the factors for poor treatment success rate for LDL-C goal. Of the total of 945 study participants, 706 (74.71%) reached the both treatment goals BP and LDL-C, diabetes and higher baseline LDL-C levels and number of concurrent medications were the factors for poor treatment success rate for both BP and LDL-C. Adherence with Rovelito was 97.87 ± 6.06% and incidence of AEs was 4.15%. Conclusions: FDC of irbesartan and atorvastatin (Rovelito) can be very helpful for managing patients with both HTN and hypercholesterolemia in Asian perspectives. Poor metabolic profile itself is as well the reason to choose Rovelito as the factor for poor treatment success rate. Therapeutic life style modification still should be underscored even with 75% treatment success rate for both conditions.

Implementation of a Community Pharmacy–Based Falls Prevention Program

Background Falls are the leading cause of fatal and nonfatal unintentional injury among older adults in the United States. Multifaceted falls prevention programs, which have been reported to reduce the risk for falls among older adults, usually include a medication review and modification component. Based on a literature search, no randomized trials that have examined the effectiveness of this component have been published. Objective The aim of this article was to report on a retrospective process evaluation of data from a randomized, controlled trial conducted to examine the effectiveness of a medication review intervention, delivered through community pharmacies, on the rate of falls among community-dwelling older adults. Methods Patients were recruited through 32 pharmacies in North Carolina. Participants were community-dwelling older adults at high risk for falls based on age (≥65 years), number of concurrent medications (≥4), and medication classes (emphasis on CNS-active agents). The process evaluation measured the recruitment of patients into the study, the process through which the intervention was delivered, the extent to which patients implemented the recommendations for intervention, and the acceptance of pharmacists' recommendations by prescribing physicians. Results Of the 7793 patients contacted for study participation, 981 (12.6%) responded to the initial inquiry. A total of 801 (81.7%) participated in an eligibility interview, of whom 342 (42.7%) were eligible. Baseline data collection was completed in 186 of eligible patients (54.4%), who were randomly assigned to the intervention group (n = 93) or the control group (n = 93). Pharmacists delivered a medication review to 73 of the patients (78.5%) in the intervention group, with 41 recommendations for changes in medication, of which 10 (24.4%) were implemented. Of the 31 prescribing physicians contacted with pharmacists' recommendations, 14 (45.2%) responded, and 10 (32.3%) authorized the changes. Conclusions Based on the findings from the present study, coordination of care between community pharmacists and prescribers needs to be improved for the realization of potential beneficial effects of medication management on falls prevention.

Safety Profile of the Fluoroquinolones

Fluoroquinolones are widely used both in primary care and in hospital settings. Since the last comparison performed in Italy on the safety profiles of different fluoroquinolones, a new molecule, prulifloxacin, has been introduced into the market and several warnings concerning this class of drugs have been released. The aim of this study was to reassess the safety profiles of fluoroquinolones using the database of the Italian Interregional Group of Pharmacovigilance (IGP) and the administrative data of fluoroquinolone prescriptions. All adverse drug reactions (ADRs) reported in four Italian regions (Lombardy, Veneto, Emilia Romagna and Tuscany) were retrieved from the IGP database. Consumption data (defined daily dose [DDD]/1000 inhabitants/day) were used as denominators. Both single reports and all ADRs (classified by System Organ Classes and MedDRA Preferred Term [PT]) due to fluoroquinolones were considered as numerators of each analysis, comparing two periods (2005 vs 2006). All fluoroquinolones with at least ten reports per year were included in the analysis. On the basis of 272 reports (532 single ADRs or PTs), patients did not show any statistically significant differences between 2005 and 2006 in terms of sex, age and number of concurrent medications. After adjustment for drug consumption, moxifloxacin showed the highest reporting rate (84.6 reports/DDD/1000 inhabitants/day; 15.4 serious reports/DDD/1000 inhabitants/day) followed by prulifloxacin (72.2; 22.2 serious) and levofloxacin (55.3; 30.6 serious) in 2005. An increment of ADR/report rates was observed over the 2 years for all fluoroquinolones except prulifloxacin, which had the lowest ADR reporting rate in 2006 (25.0; 12.5 serious). In 2006, the rate of serious ADRs associated with prulifloxacin was lower than with ciprofloxacin, while in 2005 serious events were almost equal for both compounds (55.6 vs 47.6 serious ADRs/DDD/1000 inhabitants/day). Ciprofloxacin showed the highest proportion of cutaneous PTs (e.g. rash, exanthema). Tendinopathies were mainly due to levofloxacin. These data suggest that different fluoroquinolones are characterized by different rates and types of ADRs. Among them, prulifloxacin was associated with more ADRs than other fluoroquinolones in 2005 but with fewer ADRs in 2006, when its consumption increased. Although these findings may represent an encouraging perspective towards a more appropriate use of fluoroquinolones because of their individual safety profiles, further pharmacoepidemiological studies must be performed to substantiate these results.

Comparison of orlistat and sibutramine in an obesity management program: Efficacy, compliance, and weight regain after noncompliance

To describe the comparative efficacy of orlistat and sibutramine in an obesity management program, with specific attention to compliance and weight regains after noncompliance. We prospectively evaluated 182 obese patients who were randomized to treatment with orlistat (n=98) or sibutramine (n=84) along with the diet and exercise prescriptions. Compliance (or compliant patient) was defined as adherence to scheduled visit times (at 3- month intervals) and following the prescribed drug regimen. A telephone survey was conducted in case of noncompliance. Significant body weights improvements were seen in both treatment groups. Patients lost a mean of 7.6+/-2.8% and 10.5+/-2.9% of initial body weights after a mean drug use of 8.8+/-5.7 and 8.3+/-3.7 months in the orlistat and sibutramine groups, respectively (p<0.05 vs. initial body weight). Patients in the sibutramine group lost more weight than the orlistat group (p<0.05). A total of 102 patients (56%) were compliant (53.1% in the orlistat group and 59.5% in the sibutramine group). Factors associated with compliance included weight reduction of more than 5% in the first 3 months and adherence to physical activity. Higher initial body weight, prior anti-obesity therapy, number of concurrent medications, and comorbidity were associated with noncompliance. Weight regains in noncompliant patient were a mean of 5.2+/-5.1 kg after a mean period of 9.2+/-4.2 months in the orlistat group, and a mean of 6.1+/-3.8 kg after a mean period of 9.1+/-3.9 months in the sibutramine group (p<0.05 vs. last visit for both groups, p>0.05 between groups). Both drugs in an obesity management program can achieve substantial weight loss. However, noncompliance and rebound weight regain after noncompliance are considerable problems.

Cognitive toxicity of drugs used in the elderly

The aged are an extremely heterogeneous population that is growing worldwide, included are healthy and agile individuals in their early sixties, as well as an increasing number of people over the age of 35. Pharmacotherapy is expected to continue its prominent role in the medical management of a wide range of conditions that affect older people. Adverse consequences of all kinds complicate the use of medications, and such events seem to increase in incidence with polypharmacy. Cognitive impairment can occur during the course of treatment with a wide range of medications and can have a variety of presentations, Both the number of concurrent medications that older individuals routinely use and physiologic changes in these patients render them more susceptible to developing cognitive toxicity. Most of the frequently implicated medications carry documentation of their ability to cause cognitive disturbances in their package labeling, suggesting that the level of vigilance for adverse effects during the course of their use should always be high. Such caution can be used to guide appropriate drug treatment of the aged so that clinicians do not need to opt for undertreatment to avoid toxicity.

Aging effects on drug disposition and effect.

Drug therapy in older individuals has generally been summarized in the phrase "start low and go slow". As better understanding of the effects and disposition of drugs in the aged has evolved, the concept of "therapeutic burden" which encompasses the number of concurrent medications as well as the dose of medications administered has assumed considerable importance. Epidemiologic and surveillance data demonstrate that drug therapy, in addition to offering improvement in quality and quantity of life, is also a major source of morbidity for the aged patient. These data and advances in understanding the pathophysiology of aging for individual patients which contribute to understanding of age related changes in drug response are discussed.

Pharmacist Review to Simplify Medication Regimens in a VAMC Primary Care Clinic

Objective: To assess the effect of a clinical pharmacist's prospective medication review of patients receiving multiple drug therapy, using the pharmaceutical care process, as determined by the number of concurrent medications the patient is receiving before and after clinic visits. Design: Assigned groups. Setting: Outpatient primary care clinic of a tertiary healthcare Veterans Affairs (VA) medical facility. Patients: Seven hundred twenty-seven patients who had eight or more active medication orders were selected. Four hundred forty-one patients (aged 67.2 ± 10.4 y) were in the intervention group; 286 others (aged 66.6 ± 11.9 y), whose medical records were not available, were assigned to the control group and received no clinical pharmacist intervention. Intervention: Medication regimens of VA ambulatory patients with eight or more active medications were reviewed by a clinical pharmacist, and a written communication to the prescriber was attached to the medical record. Main Outcome Measures: The number of active concurrent medications before and after clinic visits was measured. Results: There was a decrease in the medications in the intervention group from an average of 12.1 ±4 to 11.5 ± 4.2 (p &lt; 0.05). The medications in the control group rose from an average of 11.8 ± 4.44 to 12.2 ± 4 (p = NS). A decrease of 0.6 prescriptions per patient was highly significant (p &lt; 0.05). During the study, 1,336 recommendations were made to practitioners. From this group, 41% of the recommendations were accepted, and 477 medications were discontinued, the quantity dispensed or dosage was reduced, or an alternative medication was prescribed. Conclusions: These data suggest that clinical pharmacist intervention in an ambulatory care setting can affect practitioner prescribing habits and significantly decrease the number of medications prescribed.

Use of prescription-refill records to assess patient compliance

Prescription-refill records were used to assess patient compliance, to evaluate factors previously associated with compliance, and to determine the association between selected drugs and compliance. Records were selected from a computerized database containing prescription-coverage claims, based on the following criteria: (1) the prescriptions were refilled during 1987-1989 and within two times the days' supply after the dispensing date, (2) they involved any of 12 drugs selected for study, (3) they required one to four doses per day, and (4) at least 20 records with the same regimen were available. Compliance was defined as refill within 0.2 times the days' supply after the refill-due date, and it was assessed by calculating the compliance rate and the compliance index (which describes the relationship between the refill-due date and the actual refill date). Data from 19,118 prescription-refill records were analyzed. The compliance index improved slightly as the number of concurrent medications increased, worsened as the number of doses per day increased, and improved as the immediacy of the risk of noncompliance increased. Different medications and indications were associated with different degrees of compliance. Medication compliance generally improves as the number of daily doses decreases, may improve slightly as the number of concurrent medications increases, and varies with the particular drug and indication.

Efficacy and safety of vigabatrin in the long‐term treatment of refractory epilepsy.

1. The long term safety and efficacy of vigabatrin has been studied in 254 patients with refractory epilepsy (82% with partial seizures) in 23 different clinics in eight European countries. 2. This was an open multicentre study in which patients who had experienced a significant benefit from vigabatrin and had continued to take the drug for 1 year or longer were eligible for evaluation. The mean duration of therapy in the 254 patients was 22.7 months; 72 patients received vigabatrin for more than 2 years. 3. Patients were severely affected by epilepsy with a median monthly seizure frequency of 15.7 despite taking an average of 2.2 antiepileptic drugs. On vigabatrin, the median seizure frequency was about 35% of baseline, remaining stable over time despite a 10% reduction in the number of concurrent medications. 4. The lack of tachyphylaxis to the antiepileptic effect of vigabatrin is shown by the small number of patients who discontinued for insufficient efficacy (11%), two thirds of them during the first 6 months of follow-up. Maintenance of efficacy is also clearly demonstrated by analysis of 2 year and 3 year cohorts of patients. 5. Clinical and biological tolerability was excellent. There was a very low rate of drop out for adverse events (1.6%). Adverse events, mainly sedation, irritation and weight gain were mostly mild and transient. 75% of patients reported no adverse event at all. 6. Safety evaluation included serial neurological, ophthalmological and general examinations: no new abnormal clinical feature or adverse event emerged with long term therapy.