Current evidence of rituximab in the treatment of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. The immunopathology of MS involves both T and B lymphocytes. Rituximab is one of the anti-CD20 monoclonal antibody therapies which deplete B-cells. Although some anti-CD20 therapies have been approved by the Food and Drug Administration for treatment of MS, rituximab is used off-label. Several studies have shown that rituximab has a good efficacy and safety in MS, including certain specific patient conditions such as treatment-naïve patients, treatment-switching patients, and the Asian population. However, there are still questions about the optimal dose and duration of rituximab in MS due to the different dosing regimens used in each study. Moreover, many biosimilars have become available at a lower cost with comparable physicochemical properties, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Thus, rituximab may be considered as a potential therapeutic option for patients without access to standard treatment. This narrative review summarized the evidence of both original and biosimilars of rituximab in MS treatment including pharmacokinetics, pharmacodynamics, clinical efficacy, safety, and dosing regimen.

Evaluating Therapeutic Equivalence of Generic and Original Levetiracetam in Patients with Epilepsy: A Retrospective Study.

The brand interchangeability of antiepileptic drugs (AEDs) is a topic of debate, especially regarding their therapeutic equivalence. This study evaluates the efficacy and tolerability of generic levetiracetam compared to the brand-name equivalent in a routine clinical setting. We conducted a retrospective study, examining patients with stable seizure frequency who received generic levetiracetam after the brand-name drug. During the six-month substitution period, changes in seizure frequency, hospitalization due to seizure exacerbation, adverse events, composite outcomes related to adjusting the AED dosage, and switching back to original levetiracetam were analyzed. Seventy-five patients were enrolled; the majority (85.3%) had focal onset seizures, and almost half (49.3%) had refractory epilepsy. Six months after the substitution, the mean seizure frequency per month was not significantly different (3.15 ± 14.47 vs. 2.77 ± 11.41; p = 0.970). In patients with controlled seizures before the change, the seizure frequency increased significantly (0.56 ± 1.83 vs. 0.03 ± 0.16; p = 0.012). Adverse events occurred in six patients. We have observed recurrent seizures or adverse events from 14 days after the transition. The original drug return rates due to recurrent seizures and adverse events were 5.3% and 1.3%, respectively. Generic levetiracetam might not show therapeutic equivalence to the original molecule, especially in patients adequately controlled by the brand-name drug.

Barriers to generic antiseizure medication use: Results of a global survey by the International League Against Epilepsy Generic Substitution Task Force.

The objective of this study was to identify and quantify barriers to generic substitution of antiseizure medications (ASM). A questionnaire on generic ASM substitution was developed by the International League Against Epilepsy (ILAE) Task Force on Generic Substitution. Questions addressed understanding of bioequivalence, standards for generic products, experiences with substitution, and demographic data. The survey was web-based and distributed to ILAE chapters, their membership, and professional colleagues of task force members. Comparisons in responses were between ILAE regions and country income classification. A total of 800 individuals responded, with 44.2% being from the Asia-Oceania ILAE Region and 38.6% from European Region. The majority of respondents had little or no education in generic substitution or bioequivalence. Many respondents indicated lack of understanding aspects of generic substitution. Common barriers to generic substitution included limited access, poor or inconsistent quality, too expensive, or lack of regulatory control. Increase in seizures was the most common reported adverse outcome of substitution. Of medications on the World Health Organization Essential Medication list, problems with generic products were most frequent with carbamazepine, lamotrigine, and valproic acid. Several barriers with generic substitution of ASM revolved around mistrust of regulatory control and quality of generic ASM. Lack of education on generic substitution is also a concern. Generic ASM products may be the only option in some parts of the world and efforts should address these issues. Efforts to address these barriers should improve access to medications in all parts of the world.

Therapeutic drug monitoring of intravenous busulfan in Thai children undergoing hematopoietic stem cell transplantation: A pilot study.

Busulfan (Bu) is commonly used in myeloablative conditioning regimens for children undergoing hematopoietic stem cell transplantation. The standard target area under the concentration-time curve (AUC) of Bu is approximately 900-1500 µM min. In previous studies using five fixed doses (0.8-1.2 mg/kg) for Bu without dose adjustment, 75% patients achieved the target AUC. The aim of this pilot study was to determine the percentage of target AUC for intravenous (IV) Bu in Thai children. IV Bu was administered every 6 h over 16 doses. Blood samples were collected for pharmacokinetic (PK) analysis after the first, ninth, and thirteenth doses of Bu. Seven patients (2-14 years; median 6 years) were diagnosed with thalassemia (n = 4), acute myeloid leukemia (n = 2), and pure red cell aplasia. Three, two, and two patients received Bu at 1.1, 1.2, and 0.8 mg/kg, respectively. The AUC of Bu varied from 292-1714 µM min (median = 804). Nine (42.86%), eleven (52.38%), and one (4.76%) AUC values were within, below, and above the target, respectively. The median (range) Bu clearance was 5.93 (1.91-14.65) mL/min/kg. In this study, 42.86% AUC value achieved the target, which was lower than that in previous studies. Therapeutic drug monitoring (TDM) of Bu should be considered in Thai children receiving five fixed doses of IV Bu, and dose adjustment should be performed as necessary. Further PK studies for Bu with a larger sample size are warranted for confirming the necessity of TDM in every step dose of Bu.(Trial registration numbers; TCTR20190528003).

Impact of Geriatric Pharmacy Specialist Interventions to Reduce Potentially Inappropriate Medication Among Hospitalized Elderly Patients at Medical Wards: A Prospective Quasi-Experimental Study.

BACKGROUND: Elderly patients are at greater risk of receiving potentially inappropriate medications (PIMs) and developing adverse drug events. Identification and correction of PIMs is essential to maximize medication safety. OBJECTIVE: To determine the prevalence of PIMs on admission in Thai elderly patients admitted to a medical ward and to compare changes of PIMs on discharge, following comprehensive care by a ward pharmacist with or without a geriatric pharmacy specialist. PATIENTS AND METHOD: A prospective, quasi-experimental study was performed at a tertiary university hospital in Bangkok, Thailand. Patients aged ≥ 60 years who were admitted to the medical ward were recruited and allocated to one of two groups: intervention (IG) and control (CG). The CG received pharmaceutical care from the ward pharmacist. The IG received pharmaceutical care from the geriatric pharmacy specialist along with the ward pharmacist. The 2012 Beers criteria were used to identify PIMs on admission, during hospitalization, and on discharge. RESULTS: Prevalence of PIMs on admission was 43.3% (N = 187). On discharge, prevalence of PIMs in the IG decreased significantly compared to that on admission (21.3% and 43.3%, p < 0.05) and was significantly lower than in the CG (21.3% and 40.9%, p = 0.036). Moreover, the percentage of patients without PIMs on discharge in the IG was significantly higher than in the CG (78.7% and 59.1%, p < 0.0001). CONCLUSION: Use of PIMs was common among hospitalized elderly patients on admission. Pharmaceutical care provided by a geriatric pharmacy specialist in conjunction with a ward pharmacist significantly reduced the prevalence of PIMs on discharge compared with on admission.

Knowledge of stroke and medication adherence among patients with recurrent stroke or transient ischemic attack in Indonesia: a multi-center, cross-sectional study.

BackgroundThere is a limited data in Indonesia regarding the stroke knowledge and medication adherence among stroke survivors.ObjectiveTo assess the level of stroke knowledge and medication adherence along with their relationship among stroke survivors.SettingTwo tertiary-care hospitals in Surabaya, East Java, Indonesia.MethodsA prospective, cross-sectional study was conducted among 215 stroke survivors. Stroke Knowledge Test and the Morisky Green Levine Adherence Scale questionnaires were used to evaluate stroke knowledge and medication adherence, respectively. Binary logistic regression was performed to assess the rela tionship between stroke knowledge and medication adherence. Main outcome measuresRelationship between stroke knowledge and medication adherence.ResultsA total of 215 patients with mean age of 56.34 ± 8.69 years were recruited into this study. Mean Stroke Knowledge Test score was 7.89 ± 3.38 with 76.7% had low level of stroke knowledge. Mean Morisky Green Levine Adherence Scale was 3.05 ± 1.11 with 52.1% had low to medium medication adherence. Education and duration of stroke correlated with stroke knowledge level (Spearman's correlation coefficient: 0.307, p = 0.001 and 0.128, p = 0.041, respectively). Age and disability correlated with medication adherence (Spearman's correlation coefficient: 0.169; p = 0.013 and 0.171; p = 0.012), respectively. After adjustment for covariates, stroke knowledge level was independently associated with medication adherence (adjusted OR: 4.37, 95% CI 2.00-9.53; p < 0.001).ConclusionStroke knowledge was low among Indonesian stroke survivors and independently related to medication adherence. Attempts should be made to increase stroke knowledge which may improve medication adherence among stroke survivors.

Trough Level and Tacrolimus Variability of Early Converted Once-Daily Tacrolimus: 1-Year Follow-up Study.

INTRODUCTION: Long-term transplant outcomes are considered a crucial point for kidney transplantation. Follow-up studies in patients receiving early conversion to once-daily tacrolimus (TAC-OD) are still limited. We aimed to investigate tacrolimus trough level (Cmin), intrapatient variability of tacrolimus dose-normalized Cmin (TAC-Cmin/D), along with other outcomes between twice-daily tacrolimus (TAC-BID) and early converted TAC-OD. MATERIAL AND METHODS: This study was a single center, retrospective, cohort study. All new kidney transplant patients who received tacrolimus and presented an estimated glomerular filtration rate of more than 45 mL/min/1.73 m2 on the day of hospital discharge were included. Studied patients were divided into the standard TAC-BID and patients who were converted from TAC-BID to TAC-OD on the day of hospital discharge. We followed patients for 1 year after transplantation. RESULTS: At the first follow-up visit, Cmin of TAC-OD was significantly lower than that of TAC-BID. However, Cmin and estimated glomerular filtration rate were comparable between TAC-BID and TAC-OD throughout 1-year follow-up. TAC-OD also provided a lower intrapatient variability of TAC-Cmin/D compared with TAC-BID when observed after 6 months post transplantation (17.40% and 23.27% for TAC-OD and TAC-BID, respectively; P = .13). The renal function, as well as other adverse outcomes, was similar between 2 formulations. DISCUSSION: TAC-OD provided a similar Cmin with comparable renal function compared with TAC-BID during 1-year follow-up. In addition, TAC-OD is likely to have a benefit of a lower intrapatient variability of tacrolimus. CONCLUSION: Early conversion from TAC-BID to TAC-OD with 1:1 ratio can be used with close long-term monitoring.

Anticholinergic discontinuation and cognitive functions in patients with schizophrenia: a pharmacist-physician collaboration in the outpatient department.

INTRODUCTION: Cognitive impairment is a core feature and shows the highest impact on functional outcome in patients with schizophrenia. There have been no previous studies investigating the role of the pharmacist in a multidisciplinary team on cognitive outcomes in patients with schizophrenia. PURPOSE: We evaluated the impact of pharmacist intervention on cognitive outcomes in patients with schizophrenia by focusing on anticholinergic discontinuation. PATIENTS AND METHODS: A prospective, open-label, randomized, controlled study was conducted. Patients with schizophrenia were randomly assigned to either the pharmacist intervention or usual care groups. In the pharmacist intervention group, the pharmacist identified drug-related problems (DRPs) and provided a pharmacotherapy suggestion, while there was no intervention in the usual care group. The primary outcome was mean change from baseline of executive function by using Wisconsin Card Sorting Test (WCST) perseverative errors within the pharmacist intervention group at week 12. RESULTS: A total of 30 patients completed the study (13 in the pharmacist intervention group and 17 in the usual care group). WCST perseverative errors at the end of the study within the pharmacist intervention group improved significantly from baseline (P=0.003). DRPs at week 12 were reduced by 85.19% and 9.76% in the pharmacist intervention and usual care groups, respectively. The most common intervention was the discontinuation of anticholinergics in patients without extrapyramidal side effects. CONCLUSION: Added-on pharmacist intervention in a multidisciplinary team could help to improve cognitive functions in patients with schizophrenia by reducing DRPs and optimizing the drug therapy regimen, especially for anticholinergic discontinuation.

Impact of Early Versus Late Intravenous Followed by Oral Nimodipine Treatment on the Occurrence of Delayed Cerebral Ischemia Among Patients With Aneurysm Subarachnoid Hemorrhage.

BACKGROUND: Guidelines for aneurysm subarachnoid hemorrhage (aSAH) management recommend treatment with nimodipine to all patients to reduce delayed cerebral ischemia (DCI) and poor clinical outcome. However, it did not give the most beneficial time to start therapy and route of administration. OBJECTIVES: To compare the DCI occurrence and clinical outcome among aSAH patients who received nimodipine treatment at different times. METHODS: A retrospective cohort study was conducted by collecting data from medical chart reviews between August 30, 2010, and October 31, 2015, at Prasart Neurological Institute, Thailand. Patients were classified into 2 groups by time to receive nimodipine: early group and late group (<96 and >96 hours, respectively). All patients received intravenous (IV) followed by oral nimodipine to complete treatment course. Clinical outcome was graded using the Glasgow Outcome Scale at 21 days. The factors related to DCI were analyzed using multivariate logistic regression. RESULTS: A total of 149 patients were recruited: early (n = 97) and late (n = 52). No difference in baseline characteristics between groups was observed. The occurrence of DCI was not statistically significantly different between groups (early group, 18.60%, vs late group, 20.80%; P = 0.74). The World Federation of Neurosurgical Societies IV to V was associated with DCI occurrence. The proportion of patients with good outcome, poor outcome, or death did not show any difference between groups. CONCLUSIONS AND RELEVANCE: Receiving IV nimodipine 3 to 7 days following oral therapy after bleeding can be the alternative regimen in patients who did not start nimodipine within 96 hours.

Impact of pharmaceutical care on pain and agitation in a medical intensive care unit in Thailand.

Background Currently, a lack of pharmaceutical care exists concerning pain and agitation in medical intensive care units (MICU) in Thailand. Pharmaceutical care focusing on analgesics/sedatives would improve clinical outcomes. Objective To investigate the impact of pharmaceutical care of pain and agitation on ICU length of stay (LOS), hospital LOS, ventilator days and mortality. Setting The MICU of a university hospital. Method A before/after study was conducted on mechanically ventilated patients receiving analgesics/sedatives. Medical chart reviews and data collection were conducted in the retrospective group (no pharmacists involved). In the prospective group, pharmacists involved with the critical care team helped select analgesics/sedatives for individual patients. Main outcome measure ICU LOS Results In total, 90 and 66 patients were enrolled in retrospective and prospective groups, respectively. The median duration of ICU LOS was reduced from 10.00 (2.00-72.00) in the retrospective group to 6.50 days (2.00-30.00) in the prospective group (p = 0.002). The median hospital stay was reduced from 30.50 days (2.00-119.00) in the retrospective group to 17.50 days (2.00-110.00) in the prospective group (p < 0.001). Also, the median ventilator days was reduced from 14.00 days (2.00-90.00) to 8.50 days (1.00-45.00), p = 0.008. Mortality was 53.03% in the prospective group and 46.67% in the retrospective group (p = 0.432). Conclusion Pharmacist participation in a critical care team resulted in a significant reduction in the duration of ICU LOS, hospital LOS and ventilator days, but not mortality.

Effectiveness of tobacco education for pharmacy students in Indonesia.

BACKGROUND: Smoking remains the major preventable cause of death worldwide, especially cancer-related death. Evidence clearly indicates that tobacco-related morbidity and mortality is reduced by smoking cessation. Pharmacists are well-positioned to provide tobacco cessation services an involvement of pharmacists in smoking cessation is encouraged by several organizations. While Indonesia's prevalence of smoking is in the first rank in Asian countries, none of the pharmacy schools in Indonesia are currently offering tobacco-related courses in their existing curricula at present. Our study aimed to develop and to evaluate the effectiveness of tobacco education (TE) for pharmacy students in Indonesia. MATERIALS AND METHODS: A 6-hour TE was developed and evaluated using pre-test/post-test with control group design. A total of 137 fifth-year pharmacy students at Gadjah Mada University (GMU), Yogyakarta, were chosen as an intervention group while a total of 105 fifth-year students of Islamic University of Indonesia, (UII) served as the control group. Knowledge, perceived-role, self-efficacy, and ability to perform counseling using the 5A's framework were evaluated. RESULTS: A significant improvement (P < 0.001) in knowledge, perceived-role, and self-efficacy was found in the intervention group but not in the control group. In addition, we revealed that 89.7% of the intervention group were able to perform counseling using 5A's. CONCLUSIONS: The developed TE significantly improved student knowledge, perceived-rolse, self-efficacy, and created an ability to perform cessation counseling. Integration of TE education in curricula of Indonesian pharmacy schools nation-wide should be encouraged.