Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database

Background: Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety. This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. Methods: Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. Results: A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic reaction (n = 4) and angioedema (n = 4). Time to development of symptoms ranged from 5 minutes to 1 day. The doses of andrographis used varied from 352 mg to 1,750 mg. Causality assessment of 13 case reports were certain (n = 3), probable (n = 8) and possible (n = 2). Conclusions: Our findings suggested that hypersensitivity reactions have been reported among patients receiving Andrographis paniculata. Healthcare professionals should be aware of this potential risk. Further investigation of the causal relationship is needed; meanwhile including hypersensitivity reactions for andrographis product labeling should be considered

Thai stakeholders’ awareness and perceptions of the patient adverse event reporting system for herbal medicines: a qualitative study

Background: In Thailand, the consumption of herbal medicines has been increasing. Adverse events (AEs) of herbal medicines have been identified through the spontaneous reporting system. However, the number of patients reporting AEs of herbal medicines remains limited. Aim: To explore the awareness and perceptions about the patient reporting system and to explore attitudes towards safety of herbal medicines, experiences, and intention to report AEs of herbal medicines. Method: Semi-structured in-depth interviews were conducted with stakeholders (patients, community pharmacists, village health volunteers, and consumers who had experienced submitting a complaint about health products to the Consumers Foundation). Additionally, a focus group discussion was held with stakeholders (academics, herbal medicine manufacturers, healthcare professionals, policy maker who was responsible for promoting the use of herbal medicines, pharmacovigilance staff, patient, and representative from patient organisations). The data were audio recorded, transcribed verbatim and analysed using thematic analysis. Results: Fifty participants were interviewed and the focus group discussion included 12 participants. Patients had positive attitudes towards the safety of herbal medicines. Lack of awareness of the patient reporting system was identified. Nevertheless, all stakeholders acknowledged the importance of the safety monitoring of herbal medicines and indicated a willingness to report AEs via the patient reporting system in the future. A simple reporting system, a variety of reporting channels, the provision of feedback, and providing rewards would motivate patients to report AEs. Conclusion: Although there is a lack of awareness, this provides a great opportunity to improve patient AE reporting system for herbal medicines in Thailand

Off-label use and pharmacovigilance among infants: analysis of the Thai Health Product Vigilance National Database

Background: A lack of drug safety and efficacy studies in pediatric patients is a major problem contributing to inappropriate drug use among this population. The prevalence of ‘off-label’ drug use is high in pediatric patients, leading to an increased risk of adverse events (AEs). A pharmacovigilance database is useful for healthcare providers in monitoring AEs associated with off-label drug use. Objectives: The aim of this study was to explore the characteristics of AEs reported among pediatric patients aged 1\ua0month to 2\ua0years who received off-label drugs, using information derived from the Thai pharmacovigilance database. Methods: Spontaneous reports of AEs in pediatric patients aged 1\ua0month to 2\ua0years were derived from the Thai Health Product Vigilance Center (HPVC) database for the period of January 1984 to November 2013. Off-label drug use was defined as drug use outside the age range indicated by US FDA and European Medicines Agency (EMA) drug labeling. Descriptive statistics were used to describe demographics and Anatomical Therapeutic Chemical (ATC) drug classes. Reporting odds ratios were used to evaluate associations between off-label drug use and AE seriousness and the occurrence of critical AEs. Results: A total of 22,294 AE reports were collected, with 21,390 AE reports meeting the inclusion criteria. These reports were further classified as those involving off-age drug use (5.2\ua0%), age-label drug use (65.2\ua0%), and unclear/unfound age labeling (29.6\ua0%). Of those containing off-age drug use, most were in the ATC anatomical main group of nervous system agents (24.1\ua0%), followed by systemic anti-infective agents (20.5\ua0%). There was a significant association between off-label drug use and the occurrence of critical AEs. Conclusions: Off-label drug use is associated with unwanted AEs. Therefore, assessing the risk versus benefit of each drug should be taken into consideration before prescribing off-label drugs for pediatric patients

Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database

Background: Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. Objective: This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. Methods: A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, comorbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. Results: A total of 895 cases were identified. Mean age was 59.9±12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4±13.9 vs 60.3±12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). Conclusions: RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent

Characterization of statin-associated myopathy case reports in thailand using the health product vigilance center database

HMG-CoA reductase inhibitors [statins], a widely prescribed cholesterol-lowering therapy, are associated with muscle-related adverse events. While characteristics of such events are well documented in Western countries, little data exists for the Thai population.The aim of this study was to determine the characteristics of patients, type and dosing of statin, and to identify patterns of drug use that may be associated with such adverse events using the national pharmacovigilance database known as Thai Vigibase.Muscle-related adverse events involving statins in the Thai Vigibase from 1996 to December 2009 were identified. For each report, the following information was extracted: patient demographics, co-morbidities, detailed information of adverse event, detailed information of suspected drug, treatment and outcome, as well as causality assessment and quality of reports. Descriptive statistics were performed for all study variables.A total of 198 cases of statin-associated muscle-related adverse events were identified. Mean age was 61.4 ± 12.4 years of age and 59.6% were female. Simvastatin, atorvastatin, rosuvastatin and cerivastatin were implicated as the suspected drug in 163 (82.3%), 24 (12.1%), 10 (5.1%) and 1 (0.5%) cases, respectively. Rhabdomyolysis accounted for 55.6% of all muscle-related adverse events. Drug interactions known to enhance such toxicity of statins were identified in 40.9% of the total set of reports. Similar to studies from Western countries, fibrates, HIV protease inhibitors, non-dihydropyridine calcium channel blockers, azole antifungals and macrolides were commonly found in such cases. Interestingly, colchicine has been identified as the second most common drug interaction in our database. Case fatality rates were 0.9, 1.6 and 16.7%, when there were 0, 1 and ≥2 interacting drugs, respectively.Characteristics of muscle-related adverse events with statins in the Thai population showed some similarities and differences compared with Western countries. Such similarities included advanced age, female sex, certain co-morbidities and drug interactions. While the majority of interacting drugs are well known, a big proportion of cases of statin-colchicine interaction attributed to long-term use of colchicine in Thailand was noted and should be further investigated. Based on these results, an attempt to avoid dangerous and well-known drug interactions among statin users should be implemented nationwide