Does amiodarone impact on apixaban levels? The effect of amiodarone on apixaban level among Thai patients with non-valvular Atrial Fibrillation.

BACKGROUND: Apixaban and amiodarone are drugs used for non-valvular atrial fibrillation (NVAF) in routine practice. The evidence about apixaban plasma levels in patients who receive apixaban with amiodarone, including bleeding outcomes, has been limited. This study aimed to compare the apixaban plasma levels and bleeding outcomes between apixaban monotherapy and apixaban with amiodarone groups. METHODS: This study was a prospective, observational, and single-center research which was conducted from January 2021 to January 2022 in NVAF patients who received apixaban at a tertiary care hospital located in the center of Bangkok, Thailand. RESULTS: Thirty-three patients were measured for their median (5th-95th percentile) apixaban plasma levels. The trough of apixaban plasma level (Ctrough) were 108.49 [78.10-171.52] and 162.05 [87.94-292.88] µg/L in the apixaban monotherapy and apixaban with amiodarone groups, respectively (p = 0.028). Additionally, the peaks of apixaban plasma level (Cpeak) were 175.36 [122.94-332.34] and 191 [116.88-488.21] µg/L in the apixaban monotherapy and apixaban with amiodarone groups, respectively (p = 0.375). There was bleeding that occurred in 7 patients (21.21%); 5 patients in the apixaban monotherapy group and 2 patients in the apixaban with amiodarone group, respectively. CONCLUSIONS: Amiodarone may increase the peaks and troughs of apixaban plasma levels. The co-administration of apixaban with amiodarone is generally well tolerated. However, the careful observation of bleeding symptoms in individual cases is necessary to ensure safety.

Incidence of urticaria, angioedema, and type I hypersensitivity reactions associated with fibrinolytic agents in Thailand using the database of the health product vigilance center.

BACKGROUND: Besides hemorrhage, allergic reactions have also been observed in several clinical trials of fibrinolytic agents. These reactions might negatively affect patient outcomes, especially life-threatening type I hypersensitivity reactions such as anaphylaxis. However, there are limited data on the incidence of these reactions. OBJECTIVE: The aim of study was to analyze the incidence of urticaria, angioedema, and type I hypersensitivity reactions from fibrinolytic agents for various indications. METHODS: A retrospective analysis of data from the Thai Vigibase database was conducted. All reports of adverse drug reactions from fibrinolytic agents from 1984 to 2017 were identified using the World Health Organization adverse reaction terminology. The proportion of each suspected adverse drug reaction and the cumulative incidence were calculated. RESULTS: A total of 284 reports were identified in the Thai Vigibase database. The overall incidence of urticaria, angioedema, and type I hypersensitivity reactions for the streptokinase group was 52.64/10,000 persons, with individual incidence rates of 9.64/10,000 persons for urticaria, 8.90/10,000 persons for angioedema, and 34.11/10,000 persons for type I hypersensitivity reactions. In the alteplase group, the overall incidence for all suspected reactions was 18.90/10,000 persons, with individual incidence rates of 3.29/10,000 persons for urticaria, 5.75/10,000 persons for angioedema, and 9.86/10,000 persons for type I hypersensitivity reactions. CONCLUSIONS: Type I hypersensitivity reactions were the most common allergic reactions from fibrinolytic agents. It is necessary to take these reactions into consideration when using fibrinolytic therapy.

Do Apixaban Plasma Levels Relate to Bleeding? The Clinical Outcomes and Predictive Factors for Bleeding in Patients with Non-Valvular Atrial Fibrillation.

Apixaban can significantly prevent stroke events in patients with non-valvular atrial fibrillation (NVAF), as can be observed from the large, randomized, controlled trial conducted in the present study. However, the real-world evidence of bleeding events related to the apixaban plasma levels in Asian populations is limited. This study aimed to investigate the apixaban plasma levels and clinical outcomes among NVAF patients receiving apixaban, including determining the risk factors associated with bleeding during routine care. Seventy-one patients were included in the study. The median values were 112.79 (5-95th percentiles: 68.69-207.8) µg/L and 185.62 (5-95th percentiles: 124.06-384.34) µg/L for the apixaban trough (Ctrough) and apixaban peak plasma levels (Cpeak), respectively. Stroke and bleeding were found in 8 (11.27%) and 14 patients (19.72%), respectively. There was no statistical significance for Ctrough and Cpeak in the stroke and non-stroke groups, respectively. The median of Ctrough (139.15 µg/L) in patients with bleeding was higher than that in the non-bleeding group (108.14 µg/L), but there was no statistical significance. However, multivariate analyses showed that bleeding history (odds ratio (OR): 17.62; 95% confidence interval (CI): 3.54-176.64; and p-value = 0.002) and Ctrough (OR: 1.01; 95%: CI 1.00-1.03; and p-value = 0.038) were related to bleeding events. Almost all of the patients presented apixaban plasma levels within the expected range. Interestingly, bleeding events were associated with the troughs of the apixaban plasma levels and bleeding history.

Urticaria, angioedema, and type I hypersensitivity reactions associated with fibrinolytic agents.

BACKGROUND: Several clinical trials of fibrinolytic agents have reported the occurrence of allergic reactions, in addition to hemorrhage. These reactions might worsen patient outcomes, especially by causing life-threatening type I hypersensitivity reactions, including anaphylaxis; however, there is a scarcity of data in this regard. OBJECTIVE: This study described and characterized patients with urticaria, angioedema and type I hypersensitivity reactions caused by fibrinolytic agents. METHODS: This was a retrospective study in which cases of suspected adverse drug reactions from the use of streptokinase, alteplase, and tenecteplase were evaluated over a period of 10 years at Phramongkutklao and Ratchaburi hospitals in Thailand. In addition, patient characteristics and management were assessed. RESULTS: A total of 824 patients received fibrinolytic agents due to various indications. Of 147 patients who received streptokinase, nine (6.12%) had suspected adverse drug reactions (one case of urticaria, two cases of anaphylactic shock, and six cases of hypotension). The prescription rate of alteplase was the highest, being taken by 547 patients; however, only one patient (0.18%) reported an adverse reaction, angioedema in the face and lips. Similarly, of the 130 patients who received tenecteplase, only one patient (0.77%) developed hypotension. CONCLUSIONS: All fibrinolytic agents, either nonfibrin or fibrin-specific, can cause urticaria, angioedema, and type I hypersensitivity reactions due to their mechanism of action.

Characterization of Statin-Associated Myopathy Case Reports in Thailand Using the Health Product Vigilance Center Database.

BACKGROUND: 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. OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.