Association of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis with the HLA-B75 serotype or HLA-B*15:21 allele in Filipino patients.

A case-control study was conducted to investigate the association of HLA-A alleles, HLA-B alleles including HLA-B*15:02 and HLA-B75 serotype with carbamazepine-induced SJS/TEN in Filipino patients. A retrospective review of medical records was performed. Pertinent clinical data were collected. Eight (8) carbamazepine-induced SJS/TEN cases and 32 tolerant controls were recruited. Genomic DNA was extracted from the saliva samples and genotyping was performed by employing allele-specific polymerase chain reaction. Data were analyzed using the Fisher's exact test, Mann-Whitney U test, univariate logistic regression, and multivariate logistic regression. Single allele association analysis was done. The strength of association was expressed as odds ratio with 95% confidence interval. Positive predictive value, negative predictive value, sensitivity, and specificity were computed. Of all the alleles tested, the HLA-B75 serotype (p = 0.007, OR = 23.25, 95% CI = 2.33-232.21) and HLA-B*15:21 (p = 0.026, OR = 7.53, 95% CI = 1.27-44.79) were significantly associated with carbamazepine-induced SJS/TEN. The HLA-B75 serotype or HLA-B*15:21 allele may be used as a genetic risk assessment prior to prescription for prevention of carbamazepine-induced SJS/TEN in Filipino patients.

Drug Utilization Review of Monitored Parenteral Antimicrobials in a Tertiary Care Private Hospital in Cebu City.

Background: Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for common disease-causing pathogens. In the hospital setting, antimicrobial stewardship programs have been implemented to optimize the use of antimicrobials. Drug utilization review studies provide essential feedback to improve prescribing and use of medications. Objectives: This study aimed to review drug utilization of monitored parenteral antimicrobials among patients admitted from January to December 2019. Methods: The study employed a retrospective, cross-sectional, descriptive research design. A retrospective chart review of drugs administered to patients was conducted. Results: A total of 821 patients charts met the inclusion criteria. The patients' ages ranged from 18 to 98 years old and 52% were females. General Internal Medicine practitioners (28%) were the top prescribers of monitored parenteral antimicrobials primarily for the management of moderate-risk community-acquired pneumonia (39%). They were mostly indicated for empirical treatment of infections (94%) and were given for an average of 5.73 days.Only 58% of the total cases had orders for culture and sensitivity testing. Of which, principally 47% had colony cultures. Blood (29%) and sputum (27%) were the most common specimens taken for culture and sensitivity testing. The microorganisms often isolated were Escherichia coli (19%), Klebsiella pneumoniae (18%), and Staphylococcus aureus (9%). In addition, extended-spectrum beta lactamase-producing gram-negative pathogens (4%) and methicillin-resistant S. aureus (1%) were also isolated. All the microorganisms isolated showed most resistance to ampicillin (81%) and most susceptibility to colistin (100%). There were drug therapy-related problems encountered. There was one case of an adverse drug reaction (0.1%) and two cases of contraindications (0.2%). Therapeutic duplication was also observed in 5% of the cases. Moreover, 39% had instances of drug-drug interactions.Piperacillin-tazobactam had the highest consumption (79.50 defined daily doses/1,000-patient days) among the monitored parenteral antimicrobials.Some prescriptions were deemed inappropriate upon evaluation. 12% of cases were inappropriate based on the justification indicator. As for the critical indicators, duration of therapy (78%) was the main reason. Only four components of the DUE criteria indicators have met or exceeded the established threshold level.The cost analysis indicated that the total actual cost of therapy with the monitored parenteral antimicrobials amounted to ₱17,645,601.73. Considering Department of Health National Antibiotic Guidelines recommendations, ideal total cost of treatment was ₱14,917,214.29. Potential cumulative cost savings of ₱2,728,387.44 could have been achieved for patients admitted last 2019. Conclusion: Consumption of piperacillin-tazobactam was relatively high as compared to the other monitored parenteral antimicrobials covered in this study. Physicians at the study site seldom prescribe monitored parenteral antimicrobials as recommended by the National Antibiotic Guidelines. This is evidenced in the incidence of inappropriate therapy regimens, with inapt duration of therapy as the leading explanation.From the patient's perspective, the main economic implication was on the direct medical costs, particularly the increased cost of the actual antimicrobial therapy prescribed to manage various infections. Adherence of physicians to the established guidelines and selection of the most cost-effective therapy could have resulted in considerable cost savings.

Effects of MDR1 and OPRM1 genetic polymorphisms on the pharmacodynamics of propofol-remifentanil TIVA in pediatrics.

Aims: To investigate the roles of MDR1 (1236C>T, 2677G>T/A, and 3435C>T) and OPRM1 (118A>G) gene polymorphisms on the anesthetic and adverse effects of propofol-remifentanil total intravenous anesthesia in pediatric surgery. Materials & methods: The genotypes were identified through Sanger sequencing. The clinical data including hemodynamics on anesthesia, postanesthesia pain and sedation score and the occurrence of adverse effects were recorded and compared against the genetic data. Results: A total of 72 pediatric patients undergoing surgery were recruited. A weak to no association was found between the genetic polymorphisms of MDR1 and OPRM1 and the anesthetic and adverse effects of propofol-remifentanil. Conclusion: Genetic polymorphisms in OPRM1, but not in MDR1, gene polymorphism, demonstrated plausible association with the effects of propofol-remifentanil.

Genetic polymorphisms of OPRM1 on the efficacy and safety of anesthetic and analgesic agents: a systematic review.

Aim: This systematic review aimed to outline the outcome of OPRMI (A118G) variants on the effects of anesthetic and analgesic agents used in various procedures. Materials & methods: Literature was obtained from reliable, established databases and reference tracking. Efficacy and side/adverse effects of anesthetic and analgesic drugs intraoperatively or within 48 h postsurgery were the key outcome measures for all populations. Animal studies were excluded. Results: Twenty-nine studies were chosen for inclusion. In association with the efficacy and safety of anesthetic and analgesic agents, gene polymorphism in OPRM1 displayed a strong correlation in reduced analgesic effect and protection against adverse reactions. Conclusion: This systematic review summarized the correlation between genetic polymorphism in the OPRM1 gene and anesthetic/analgesic effects.

Effects of genetic polymorphisms of ABCB1 on the efficacy of anesthetic and analgesic agents: a systematic review.

Aim: To perform a systematic review to determine the effect of ABCB1 (1236C>T, 2677G>T/A and 3435C>T) variants on the effects of anesthetic and analgesic agents in various surgical procedures. Materials & methods: Literature was obtained from established databases and reference tracking. The main outcome measures were efficacy of anesthetic and analgesic agents intraoperative or within 48 h post surgery of human population. Results: Seventeen studies were included for data extraction from 1127 screened studies. The influences of ABCB1 gene polymorphisms on analgesic effects showed conflicting results. The mutational homozygous TT genotypes of 1236C>T and 3435C>T polymorphisms demonstrated significant association with the anesthetic effects. Conclusion: The mutational homozygous TT genotype in both ABCB1 1236C>T and 3435C>T is associated with weaker anesthetic effect but there are no clearly demonstrated analgesic effects.

HLA-A*24:07 as a potential biomarker for carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Filipino patients.

Aim: A case-control study was conducted in Filipino patients to determine the association between HLA alleles and carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Materials & methods: A retrospective review of medical records and data collection were performed. A total of 10 carbamazepine-induced SJS/TEN cases and 40 tolerant controls were recruited. Genomic DNA extracted from saliva samples was genotyped. Statistical analysis was done. Results: The HLA-B75 serotype (p = 0.003; odds ratio [OR] = 13.8; 95% CI = 2.5-76.8), HLA-B*15:21 (p = 0.041; OR = 4.7; 95% CI = 1.1-20.8) and HLA-A*24:07 (p = 0.032; OR = 6; 95% CI = 1.2-30.7) were significantly associated with carbamazepine-induced SJS/TEN. Conclusion: The HLA-B75 serotype, HLA-B*15:21 or HLA-A*24:07 may be used for pharmacogenetic screening prior to prescribing carbamazepine in Filipinos.

Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm).

Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.

Southeast Asian Pharmacogenomics Research Network (SEAPharm): Current Status and Perspectives.

Pharmacogenomics (PGx) is increasingly being recognized as a potential tool for improving the efficacy and safety of drug therapy. Therefore, several efforts have been undertaken globally to facilitate the implementation process of PGx into routine clinical practice. Part of these efforts include the formation of PGx working groups working on PGx research, synthesis, and dissemination of PGx data and creation of PGx implementation strategies. In Asia, the Southeast Asian Pharmacogenomics Research Network (SEAPharm) is established to enable and strengthen PGx research among the various PGx communities within but not limited to countries in SEA; with the ultimate goal to support PGx implementation in the region. From the perspective of SEAPharm member countries, there are several key elements essential for PGx implementation at the national level. They include pharmacovigilance database, PGx research, health economics research, dedicated laboratory to support PGx testing for both research and clinical use, structured PGx education, and supportive national health policy. The status of these essential elements is presented here to provide a broad picture of the readiness for PGx implementation among the SEAPharm member countries, and to strengthen the PGx research network and practice in this region.

Carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis overlap in a Filipino with positive HLA-B75 serotype.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two related mucocutaneous disorders with different severities. Although the incidence is low, SJS and TEN are life-threatening and predominantly drug-induced conditions. There is a strong relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN in different Southeast Asian populations. Here, we report a case of Filipino with SJS/TEN overlap probably induced by carbamazepine. The condition was treated with hydrocortisone followed by prednisone. The HLA-B*1502 allele was not found in this case. The patient tested positive for the HLA-B75 serotype, suggesting that carbamazepine-induced SJS/TEN may be serotype specific. Establishing the genotype before initiation of the drug may be advantageous for some patients and will aid physicians in determining the optimal drug therapy. Prevention of adverse drug reactions (ADR) may be done if pharmacists and other healthcare professionals work as a multidisciplinary ADR team to ensure that safe medication practices are realised.

Medicines management in the Philippine public sector during the response to Haiyan.

INTRODUCTION: Health service delivery in the Philippines is constantly challenged by disasters and emergencies. This descriptive study documented existing policies for medicines management in the Philippines and then assessed these in the public sector response post-Haiyan. METHOD: We used desk a review of existing laws, regulations and related issuances and a series of interviews of key informants from various national and local health agencies. RESULTS: We found that while numerous national policies covered critical aspects of medicines management, implementation post-Haiyan was problematic at all levels of the decentralized health-care system. We identified issues of quantification, warehousing, distribution, utilization monitoring and disposal. Donated medicines also added additional burden for storage and disposal, especially for expired and unwanted medicines. DISCUSSION: While the process of managing medicines during disasters did not differ greatly from non-emergency situations, the Haiyan experience highlighted the system's weaknesses. With the current gaps in implementation, as well as the logistical obstacles brought about by disasters, there is a need to have integrated mechanisms for medicines management in the Philippines. This assessment provided an important opportunity to review the medicines management policies at national and local levels.

Acute oral toxicity of the crude aqueous extract of the whole plant of Euphorbia hirta L. (Family Euphorbiaceae)

BACKGROUND: E. hirta or tawa-tawa is a small annual herb common to tropical countries. In the Philippines, the decoction of the whole plant is used for the treatment of dengue because of its apparent platelet increasing property. While efforts are ongoing to determine the role of E. hirta for dengue, this study focused on its safety. OBJECTIVE: This study determined the median lethal dose (LD50), toxidromes and reversibility of toxic effects following the acute oral administration of the crude aqueous extract in Sprague-Dawley rats. METHODS: The Up-and-Down Procedure (Organization for Economic Cooperation and Development (OECD) Test Guideline 425) was conducted after the preliminary tests for the aqueous extract such as phytochemical and pesticide residue analyses and tests for aflatoxin and heavy metals. RESULTS: Phytochemical screening showed the presence of tannins, glycosides and alkaloids in the plant extract. The aqeous extract contained allowable aflatoxin levels. Organochlorines, organophosphates and heavy metals such as arsenic, cadmium, lead and mercury were not detected in the aqueous extract. The LD50 of the aqueous extract was greater than 5000 mg/kg. The test animals did not experience significant body weight alterations. Gross necropsy revealed a hematoma on top of the skull and in the large intestine and a small, round protrusion in the stomach of the test animals. Histopathological examination showed foci of perivascular hemorrhages and neuronal degeneration in the brain, multifocal submucosal hemorrhages in the large intestine and fragmented very dark staining nuclei and fibrin stands with red blood cells in the stomach of test animals. CONCLUSION: While the acute oral LD50 of the aqueous extract is greater than 5000 mg/kg, there is a need to pay attention to the toxidromes showing evidence of dose-dependent CNS depression. Histopathological examination showed multifocal submucosal hemorrhages and foci of perivascular hemmorrhages and neuronal necrosis indicating an acute hemorrhagic enteritis and cerebral hemorrhage, respectively. These findings and crucial in the light of the anecdotal use of E. hirta for the treatment of dengue hemorrhagic fever.