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Journal of the European Academy of... Apr 2024Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening mucocutaneous reactions most often induced by drugs. To date, no large...
BACKGROUND
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening mucocutaneous reactions most often induced by drugs. To date, no large pharmacovigilance study has been conducted in the paediatric population.
OBJECTIVES
To describe the spectrum of drugs associated with SJS-TEN in children through the analysis of cases reported in the WHO pharmacovigilance database (VigiBase).
METHODS
Disproportionality study using data from VigiBase. All paediatric (age under 18 years) cases reported between January 1, 1967, and July 6, 2022, were included. For each molecule, a case-non-case study was performed to assess a potential pharmacovigilance signal by computing the lower end of the 95% credibility interval for the information component (IC). We performed sensitivity analyses, (i) taking into account only cases reported by physicians and (ii) taking into account only cases reported in the last 10 years.
RESULTS
Among 31,376,783 adverse drug reactions reported in VigiBase, 2,248,727 were paediatric cases and 7342 were encoded as paediatric SJS-TEN. Significant statistical pharmacovigilance signals were observed for 165 drugs. The two most represented drug classes were antiepileptics and anti-infectious drugs. The five drugs with the highest IC were lamotrigine (IC 4.99), carbamazepine (IC 4.88), phenobarbital (IC 4.67), phenytoin (IC 4.52) and nimesulide (IC 4.23). Acetaminophen was significantly associated with paediatric SJS-TEN (IC 2.85) and we also described various new suspected drugs. Vaccines had no significant pharmacovigilance signal. These results were confirmed with the sensitivity analyses.
CONCLUSIONS
This study updates the spectrum of drugs potentially associated with paediatric SJS-TEN.
PubMed: 38682703
DOI: 10.1111/jdv.20054 -
American Journal of Medical Genetics.... Apr 2024Exposure at conception to phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) has been associated with several different effects on the fetus, including...
Exposure at conception to phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) has been associated with several different effects on the fetus, including hypoplasia of the distal phalanges, dysmorphic facial features, and structural abnormalities such as oral clefts and neural tube defects. One question is whether each of these antiepileptic drugs (AEDs) has the same effects or just similar effects. A systematic examination of the fingers of children exposed at conception to PHT, PB, or CBZ, as monotherapy, has been used to address this question. The findings in the examinations of the fingers of 115 AED-exposed children (40, PHT; 34, PB; 41, CBZ) and their parents were compared to the findings in 111 age- and sex-matched children and their parents. The evaluations used were both subjective assessments and objective measurements. Shortening and narrowing of the fifth fingernail and an increased frequency of arch patterns in the dermal ridges were more common in PHT-exposed children. A significant decrease in the length of the nail, but not width, occurred in the PB-exposed children. Stiffness of the interphalangeal joints was more common in the CBZ-exposed children. The findings in children exposed to PHT, PB, or CBZ, as monotherapy, showed that all three exposures in early pregnancy affected the fingers, but the effects were not the same. The most striking effects were present in PHT-exposed children.
PubMed: 38666724
DOI: 10.1002/ajmg.a.63620 -
Daru : Journal of Faculty of Pharmacy,... Jun 2024Drug hypersensitivity reactions (DHRs) manifested as vasculitis are rare. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), sulphonamides, diuretics,...
Drug hypersensitivity reactions (DHRs) manifested as vasculitis are rare. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), sulphonamides, diuretics, immunosupressants and anticonvulsants are the most common culprits for drug-induced leukocytoclastic vasculitis (LCV) but there is scarce information about barbiturates. We present a case of 53-year-old female with severe vasculitis after phenobarbital- and NSAIDs-containing medications use. The preliminary diagnosis of drug-induced vasculitis was made based on anamnestic and clinical data. Further examinations confirmed the diagnosis of LCV and excluded other more common causes of vasculitis. The causative significance of used medications was assessed by long-term observation of the patient after the reaction, including the drug challenge series and Naranjo's Adverse Drug Reaction Probability Scale. It was concluded that phenobarbital is the most probable culprit drug. The patient's data were included in the Armenian Registry of Patients with Severe DHRs. Since then, the patient has avoided only barbiturate-containing drugs and no reactions were noted. Thus, the case indicates that even with limited diagnostic capabilities, the final diagnosis of rare drug-induced LCV and even rarer culprit drug can be established by comparing the available data. Awareness about phenobarbital and proper recording of the case are important in the management and prevention of DHRs manifested as vasculitis.
Topics: Humans; Female; Phenobarbital; Middle Aged; Vasculitis, Leukocytoclastic, Cutaneous; Anticonvulsants; Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity
PubMed: 38658483
DOI: 10.1007/s40199-024-00515-0 -
Epilepsy & Behavior : E&B Jun 2024Epilepsy is a chronic disease that requires long-term monitoring and treatment. It is suspected that there is a interaction between the use of anti-seizure medications...
OBJECTIVE
Epilepsy is a chronic disease that requires long-term monitoring and treatment. It is suspected that there is a interaction between the use of anti-seizure medications and the risk of cardiovascular disease. The aim of the study is to investigate the association between the intake of phenobarbital, carbamazepine and valproic acid and their serum drug concentrations (SDC) with various cardiovascular risk parameters (homocysteine, folic acid, vitamin B12, total cholesterol (TC), triglycerides, high- and low-density lipoprotein (LDL)).
METHODS
This is a cross-sectional study. Data (demographic characteristics and laboratory results) of patients treated for epilepsy in a tertiary care hospital between January 2020 and February 2022 were analyzed retrospectively (n = 2014). Kruskal Wallis, Mann-Whitney U, correlation analysis was used, p < 0.05 was considered statistically significant.
RESULTS
The median age of patients was 15 years (IQR:8-31) and 48.3 % were women. The highest homocysteine level was found in patients receiving valproic acid, but it was not statistically significant. Patients receiving phenobarbital had the highest levels of folic acid and B12 and the lowest levels of total cholesterol and low-density lipoprotein cholesterol, which was statistically significant. In patients receiving carbamazepine, a moderately negative significant association was found between serum drug concentration and folic acid levels and a moderately positive significant association was found between TC and LDL levels.
CONCLUSION
In our study, the majority of patients were children and adolescents. Regular monitoring of drug serum concentrations and metabolic parameters may be useful to select the safest drug in terms of cardiovascular disease risk. Randomized controlled trials on the long-term effects of anti-seizure treatment are needed.
Topics: Humans; Female; Anticonvulsants; Cross-Sectional Studies; Male; Adult; Epilepsy; Adolescent; Young Adult; Valproic Acid; Cardiovascular Diseases; Child; Carbamazepine; Homocysteine; Phenobarbital; Retrospective Studies; Vitamin B 12; Heart Disease Risk Factors; Folic Acid
PubMed: 38657483
DOI: 10.1016/j.yebeh.2024.109802 -
Therapeutic Drug Monitoring Jun 2024The authors described tacrolimus dosing in a kidney transplant patient concurrently treated with phenobarbital, where measuring the tacrolimus area under the curve was...
The authors described tacrolimus dosing in a kidney transplant patient concurrently treated with phenobarbital, where measuring the tacrolimus area under the curve was necessary to achieve adequate drug exposure and improve kidney function.
Topics: Humans; Area Under Curve; Drug Interactions; Drug Monitoring; Immunosuppressive Agents; Kidney Transplantation; Phenobarbital; Tacrolimus
PubMed: 38648637
DOI: 10.1097/FTD.0000000000001203 -
Cureus Mar 2024Background Organ and body development greatly varies in pediatric patients from year to year. Therefore, the incidence of each adverse event following phenobarbital (PB)...
Analysis of Adverse Events Following Phenobarbital Administration for Pediatric Patients Categorized by One-Year Age Increments Using the U.S. Food and Drug Administration Adverse Event Reporting System.
Background Organ and body development greatly varies in pediatric patients from year to year. Therefore, the incidence of each adverse event following phenobarbital (PB) administration would vary with age. However, in clinical trials, increasing the sample size of pediatric patients in each age group has been challenging. Therefore, previous studies were conducted by dividing pediatric patients into three or four age groups based on the development stage. Although these results were useful in clinical settings, information on adverse events that occurred at one-year age increments in pediatric patients could further enhance treatment and care. Objectives This study investigated in one-year age increments the occurrence tendency of each adverse event following PB administration in pediatric patients. Methods This study used data obtained from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Two inclusion criteria were set: (1) treatment with PB between January 2004 and June 2023 and (2) age 0-15 years. Using the cutoff value obtained using the Wilcoxon-Mann-Whitney test by the minimum p-value approach, this study explored changes in the occurrence tendency of each adverse event in one-year age increments. At the minimum p-value of <0.05, the age corresponding to this p-value was determined as the cutoff value. Conversely, at the minimum p-value of ≥0.05, the cutoff value was considered nonexistent. Results This study investigated all types of adverse events and explored the cutoff value for each adverse event. We identified 34, 16, 15, nine, five, five, eight, three, and eight types of adverse events for the cutoff values of ≤3/>3, ≤4/>4, ≤5/>5, ≤6/>6, ≤7/>7, ≤8/>8, ≤9/>9, ≤10/>10, and ≤11/>11 years, respectively. Conclusions This study demonstrated that adverse events requiring attention in pediatric patients varied with age. The findings help in the improvement of treatment and care in the pediatric clinical settings.
PubMed: 38638715
DOI: 10.7759/cureus.56418 -
Basic and Clinical Neuroscience 2023Drug-resistant epilepsy is an unmet medical condition that impacts 30% of epileptic patients. Numerous antiseizure drugs have already been developed but they provide...
INTRODUCTION
Drug-resistant epilepsy is an unmet medical condition that impacts 30% of epileptic patients. Numerous antiseizure drugs have already been developed but they provide only symptomatic relief and do not target the underlying pathogenesis. Preclinical models provide opportunities to gain insights into obscure mechanisms of drug-resistant epilepsy. Current animal models possess lacunae that need rectification and validation to discover novel antiepileptic drugs. The present study aims to validate 3 different doses of phenobarbital at 2 different periods.
METHODS
Pentylenetetrazole was given at a sub-convulsive dose (30 mg/kg/day/intraperitoneal [IP]) for 28 days to develop kindling in male Wistar rats. Further, kindled rats were divided into the following four groups: Pentylenetetrazole control, pentylenetetrazole and phenobarbital (20 mg/kg), pentylenetetrazole and phenobarbital 40 mg/kg, and pentylenetetrazole and phenobarbital (60 mg/kg). They were assessed on days 14 and 28 post-kindling. Seizure scoring, oxidative stress, phenobarbital plasma levels, and histopathology of hippocampal neurons were analyzed.
RESULTS
The results showed that the combination of pentylenetetrazole and phenobarbital (40 and 60 mg/kg) remarkably decreased seizure score, elucidated higher antioxidant effect, and prevented neuronal injury on day 14, whereas increased seizure score, oxidative stress, and neuronal death was observed with chronic administration of pentylenetetrazole and phenobarbital in kindled rats at day 28. Moreover, phenobarbital levels in blood were significantly increased at day 28 of phenobarbital treatment compared to day 14.
CONCLUSION
The adapted protocol with phenobarbital 40 mg/kg dose could be of great potential in screening antiseizure drugs in refractory epilepsy.
PubMed: 38628829
DOI: 10.32598/bcn.2022.3904.1 -
Iranian Journal of Child Neurology 2024Jaundice occurs in 60% of full-term and 80% of pre-term newborns. This study compared the effect of phototherapy with and without phenobarbital on icteric newborns.
OBJECTIVES
Jaundice occurs in 60% of full-term and 80% of pre-term newborns. This study compared the effect of phototherapy with and without phenobarbital on icteric newborns.
MATERIALS & METHODS
This study is a randomized clinical trial conducted from July until March 2018 at Imam Reza Hospital, Mashhad University of Medical Science, Iran. Full-term and near-term neonates with more than 2000 grams who were hospitalized in the mentioned period for jaundice were entered into the study. The newborns were divided into two groups using block randomization. Data were analyzed by SPSS version 19.
RESULTS
The average gestational age was 36.4 weeks (SD 2.39) in the intervention group and 36.9 weeks (SD 2.16) in the control group, with no significant difference between them. The mean hospital stay for the intervention group was 72 hours (SD 1.66), compared to 55 hours (SD 1.88) for the control group. At discharge, the serum bilirubin level in the intervention group was 11.53 mg/dL (SD 0.77), while it was 10.80 mg/dL (SD 1.09) in the control group, a statistically significant difference.
CONCLUSION
According to this study, phototherapy with phenobarbital is not more effective than phototherapy alone in neonatal hyperbilirubinemia.
PubMed: 38617400
DOI: 10.22037/ijcn.v18i2.36848 -
Materials (Basel, Switzerland) Mar 2024The removal of pharmaceutically active compounds present in relatively low concentration in wastewater is critical. This is because they have a severe, negative impact...
The removal of pharmaceutically active compounds present in relatively low concentration in wastewater is critical. This is because they have a severe, negative impact on life and the environment. To address this issue, adsorption was used, which is an effective wastewater treatment method for removing substances found in low concentrations in water. This study compared the adsorption performance of active carbon to three biosorbents derived from Adansonia digitata shells. The adsorbents were prepared and characterized using TGA, SEM, EDX, and FTIR analyses and pH. To better understand the adsorption process, equilibrium and reaction kinetics studies were conducted. The effect of contact time, initial phenobarbital concentration, adsorbent mass, and pH was investigated in static conditions. The adsorption results revealed that the biosorbent B3 has a higher affinity for the eliminated compound, with an equilibrium time of 60 min and an adsorption capacity of 47.08 mg/g at an initial concentration of 50 mg/L. The experimental data are consistent with Langmuir and Sips adsorption isotherm models, and with the pseudo-second order and Elovich models for kinetics description. This indicates strong interactions between the adsorbent materials and the pharmaceutical micropollutant. Based on these findings, it appears that, among the tested materials, B3 biosorbent is the most efficient for removing phenobarbital present in low concentrations in water.
PubMed: 38612106
DOI: 10.3390/ma17071591 -
Healthcare (Basel, Switzerland) Apr 2024The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for...
OBJECTIVES AND AIM
The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizure management. This study was designed to measure and compare the incidence of adverse effects and to determine the discharge and mortality rates associated with the use of these antiseizure medications (ASMs). Through this comparison, this research sought to provide insights to optimise care for neonates experiencing seizures.
MATERIALS AND METHODS
This retrospective cohort study evaluated 104 neonates treated for seizures at Zeynep Kamil Hospital from 2015 to 2020 after excluding those on non-PB/LEV antiseizure medications. Seizures were characterised using electroencephalogram (EEG) and categorised according to aetiology and frequency. Treatment efficacy was gauged by seizure cessation, as confirmed using EEG. Adverse effects and demographic data were recorded. Statistical analyses were conducted using SPSS, employing the Shapiro-Wilk, independent -test, Mann-Whitney U test, and chi-square test, with a significance threshold of < 0.05.
RESULTS
Overall, 104 neonates treated with first-line ASM were evaluated for efficacy; PB was administered in 68.26% of the cases, while LEV was utilised in 31.74%. The total complete response rate was 40.38%, with no significant difference between the PB and LEV groups ( = 0.309). The incidence rate ratios (IRRs) demonstrated that seizure frequency profoundly influenced treatment effectiveness, with IRRs of 2.09 for rare seizures, 3.25 for frequent seizures, and 4.01 for status epilepticus, indicating a higher treatment response rate with increasing seizure frequency. For second-line treatment, among a subset of 62 patients, PB had a slight, non-significant advantage over LEV, with an odds ratio of 1.09, suggesting a marginally better response to LEV. Adverse events were significantly more frequent in the PB group, affecting 19 of 67 neonates (28.36%), compared to only 2 of 71 neonates (2.82%) in the LEV group ( < 0.001). No significant difference was observed in the discharge rates between the two groups (PB, 67.61%; LEV, 75.76%; = 0.674). Interestingly, the mortality rate was significantly higher in the LEV group (45.45%) than that in the PB group (22.54%; = 0.045).
CONCLUSION
This study underscores LEV's superior safety profile over PB in neonatal seizure management, evidenced by a significantly lower rate of adverse events. PB seems to be more effective in the second-line treatment of neonatal seizures. Despite the lack of significant differences in the discharge rates, the higher mortality rate associated with LEV warrants further investigation. These findings advocate the cautious selection of antiepileptic drugs in neonatal care, with a preference for LEV based on its safety profile.
PubMed: 38610222
DOI: 10.3390/healthcare12070800