Rev Prat. 2021 Jan;71(1):48-51.

ABSTRACT

Drug strategy in schizophrenia Antipsychotic drugs have been shown to be relevant to treat schizophrenia. Moreover, these drugs are more effective to improve positive than negative and cognitive symptoms of schizophrenia. Antipsychotic drugs are associated with neurologic and metabolic side effects that have to be monitored.

PMID:34160938

Clin Transl Allergy. 2021 Jun;11(4):e12035. doi: 10.1002/clt2.12035.

ABSTRACT

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long-term safety study of berotralstat in patients with HAE.

METHODS: APeX-S is an ongoing, phase 2, open-label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE-C1-INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long-term safety and the secondary objective was to evaluate effectiveness.

RESULTS: Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11-540) and 307 (14-429) days for the 150-mg and 110-mg groups, respectively. Treatment-emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug-related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug-related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline.

CONCLUSIONS: In this analysis, both berotralstat doses, 150 and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE.

TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT03472040).

PMID:34161665 | DOI:10.1002/clt2.12035

Rev Prat. 2021 Apr;71(4):408-410.

NO ABSTRACT

PMID:34161007

Rev Prat. 2021 Apr;71(4):400-407.

ABSTRACT

"Management of adverse events associated with cancer immunotherapy.The role of anti-CTLA4 and anti-PD1/PD-L1 immunotherapies in the treatment of cancers is constantly evolving. Given the latest data on their use in combination with «conventional» treatments, their use should increase in the coming years, exposing a significant number of patients to immunomediated toxicities. By lifting the brakes of the immune system, these immune checkpoints blockers can induce prolonged anti-tumor responses and increase patient survival. These new immunotherapies also have a different toxicity profile compared to conventional anti-cancer treatments, known as immune-related adverse events (irAEs). They result from the activation of the immune system against normal tissues and can trigger autoimmune diseases. This singular profile of toxicity prompts us to modify our clinical practice: this is the topic of this review that will describe the different adverse events and their management."

PMID:34161006

Rev Prat. 2021 Apr;71(4):359.

NO ABSTRACT

PMID:34160997

Rev Prat. 2021 Feb;71(2):223.

NO ABSTRACT

PMID:34160988

Rev Prat. 2021 Feb;71(2):193-197.

ABSTRACT

"Renal toxicity of antineoplasic agents Renal toxicity of antineoplasic agents is a common complication faced by oncologists and nephrologists whose incidence depends on therapeutic classes used and patient's comorbidities. Nephrotoxicity is variable, according to mecanisms, chronology and potential reversibility. Besides acute kidney injury and/or chronic kidney disease, clinical features include several urinary abnormalities (mainly proteinuria). The onset of renal toxicity may directly compromise vital prognosis and may lead to the interruption of medications affecting cancer-specific mortality. Nephrotoxicity prevention (when feasible) and rapid diagnosis are essential to optimize cancer-patient medical care."

PMID:34160983

Rev Prat. 2021 Feb;71(2):160-163.

ABSTRACT

"Food supplements: real food or fake medicine? Food supplements are regulatorily considered as food. As such, they are just supposed to bring nutrients to people whose diet would not cover their nutritional needs. Ideally, they should only be consumed after a nutritional check-up. In practice, consumers consider them as safe drugs but in reality, the Nutrivigilance scheme shows they are at risk and should not be consumed without a medical advice."

PMID:34160972

Dig Dis Sci. 2021 Jun 23. doi: 10.1007/s10620-021-07112-0. Online ahead of print.

ABSTRACT

BACKGROUND: Complementary and alternative medicine (CAM) use has become increasingly common. It is also prevalent in patients with chronic liver disease, but the scope, depth, and safety of use is not well known.

AIMS: This study aimed to evaluate the prevalence and patterns of CAM use in autoimmune hepatitis (AIH) patients.

METHODS: Electronic invitation to complete a 22 item CAM-specific questionnaire was posted weekly to well-established AIH Facebook communities (combined membership of 4700 individuals) during a 6-week study period. Age ≥ 18 years and AIH diagnosis made by a treating physician were the eligibility criteria.

RESULTS: The prevalence of ever CAM use among participants was 56.4%, and nearly 42% used CAM after AIH diagnosis. Among those reporting CAM use after diagnosis, 53.7% (51/95) indicated CAM was used to mitigate AIH-related phenomenon, most often targeting liver inflammation/fibrosis (67.7%), fatigue (51%), joint pain (47.1%), and sleep issues (45.1%). Most frequent physical CAM strategies were exercise (49.5%) and yoga (34%), whereas most frequent consumable CAM included healthier eating (45.3%), cannabidiol preparations (45.3%), and probiotics (44.3%). Seventy-five percent reported that CAM improved AIH symptoms and no severe adverse events were reported.

CONCLUSIONS: CAM use in AIH patients is prevalent, yet providers have historically failed to document their patient's CAM strategies. Beyond inherent drug-induced liver injury risk, drug-drug interactions remain a concern and could alter baseline immunosuppression levels in AIH. Despite a majority found CAM approaches that improved targeted symptoms, all were unable to alter the course of chronically prescribed medications by physicians.

PMID:34160734 | DOI:10.1007/s10620-021-07112-0

Eur J Cancer. 2021 Jun 19;153:142-152. doi: 10.1016/j.ejca.2021.05.023. Online ahead of print.

ABSTRACT

BACKGROUND: This phase 1 study evaluated safety, pharmacokinetics (PK), maximum tolerated dose (MTD), and antitumour activity of regorafenib in paediatric patients with solid tumours.

PATIENTS AND METHODS: Patients (aged 6 months to <18 years) with recurrent/refractory solid tumours received oral regorafenib once daily for 3 weeks on/1 week off. The starting dose (60 mg/m2) was derived from an adult physiology-based PK model and scaled to children; dose escalation was followed by safety expansion of the MTD cohort. Treatment-emergent adverse events (TEAEs) were evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Regorafenib PK was evaluated using a population PK model.

RESULTS: Forty-one patients (median age 13 years) received regorafenib (four cohorts: 60-93 mg/m2). Five of 23 evaluable patients experienced dose-limiting toxicities (Grade 4 thrombocytopenia, Grade 3 maculopapular rash, pyrexia, hypertension, and exfoliative dermatitis [each n = 1]). The MTD was defined as 82 mg/m2. The most common Grade ≥3 drug-related TEAE was thrombocytopenia (10%). The incidence and severity of hypertension, diarrhoea, fatigue, hypothyroidism, and hand-foot skin reaction were lower than reported in adults. Regorafenib exposure increased with dose, with substantial overlap because of moderate-to-high interpatient variability. One patient with rhabdomyosarcoma experienced an unconfirmed partial response; 15 patients had stable disease, five for >16 weeks.

CONCLUSIONS: The recommended phase 2 dose of single-agent regorafenib in paediatric patients with solid malignancies is 82 mg/m2. Regorafenib demonstrated acceptable tolerability and preliminary antitumour activity, supporting further investigation in paediatric patients.

CLINICAL TRIAL NUMBER: NCT02085148.

PMID:34157616 | DOI:10.1016/j.ejca.2021.05.023

J Card Fail. 2021 Jun 19:S1071-9164(21)00243-8. doi: 10.1016/j.cardfail.2021.06.007. Online ahead of print.

ABSTRACT

BACKGROUND: There are limited data available concerning the safety, optimal administration and benefits of contemporary heart failure therapy in patients after left ventricular assist device (LVAD) implantation.

METHODS: Between 2015 and 2019, 257 patients underwent LVAD implantation and were included in this observational study. Oral heart failure therapy was initiated and up-titrated during the further course. After propensity matching and excluding patients with immediate postoperative treatment in an affiliated center with different medical standards, hospitalization rates and mortality within 12 months after LVAD implantation were compared between 83 patients who received medical therapy including an angiotensin receptor neprilysin inhibitor (ARNI) and 83 patients who did not receive an ARNI.

RESULTS: The overall use of heart failure medication after 12 months was high (prescription: beta-blockers 85%, angiotensin inhibiting drugs 90% [angiotensin-converting-enzyme inhibitors 30%, angiotensin receptor blockers 23%, ARNI 37%], mineralocorticoid receptor antagonists 80%). No serious drug-related adverse events occurred. The conditional one-year survival in the group with an ARNI was 97% (95% CI: 94-100%) compared to 88% in the group without an ARNI (95% CI: 80-96%); p=0.06.

CONCLUSIONS: Contemporary heart failure therapy is safe in LVAD patients. No increase in serious adverse events was seen in patients receiving an ARNI. No significant difference in the conditional one-year survival was seen between the ARNI group and the non-ARNI group.

PMID:34157393 | DOI:10.1016/j.cardfail.2021.06.007

Pharmacogenomics J. 2021 Jun 21. doi: 10.1038/s41397-021-00246-4. Online ahead of print.

ABSTRACT

One in every ten drug candidates fail in clinical trials mainly due to efficacy and safety related issues, despite in-depth preclinical testing. Even some of the approved drugs such as chemotherapeutics are notorious for their side effects that are burdensome on patients. In order to pave the way for new therapeutics with more tolerable side effects, the mechanisms underlying side effects need to be fully elucidated. In this work, we addressed the common side effects of chemotherapeutics, namely alopecia, diarrhea and edema. A strategy based on Random Forest algorithm unveiled an expression signature involving 40 genes that predicted these side effects with an accuracy of 89%. We further characterized the resulting signature and its association with the side effects using functional enrichment analysis and protein-protein interaction networks. This work contributes to the ongoing efforts in drug development for early identification of side effects to use the resources more effectively.

PMID:34155353 | DOI:10.1038/s41397-021-00246-4

BMC Vet Res. 2021 Jun 21;17(1):220. doi: 10.1186/s12917-021-02927-5.

ABSTRACT

BACKGROUND: 5-fluorocytosine is a pyrimidine and a fluorinated cytosine analog mainly used as an antifungal agent. It is a precursor of 5-fluorouracil, which possesses anticancer properties. To reduce systemic toxicity of 5-fluorouracil during chemotherapy, 5- fluorocytosine can be used as a targeted anticancer agent. Expression of cytosine deaminase by a viral vector within a tumor allows targeted chemotherapy by converting 5-fluorocytosine into the cytotoxic chemotherapeutic agent 5-fluorouracil. However, little is known about the tolerance of 5-fluorocytosine in dogs after prolonged administration.

RESULTS: In three healthy Beagle dogs receiving 100 mg/kg of 5-fluorocytosine twice daily for 14 days by oral route, non-compartmental pharmacokinetics revealed a terminal elimination half-life of 164.5 ± 22.5 min at day 1 and of 179.2 ± 11.5 min, after 7 days of administration. Clearance was significantly decreased between day 1 and day 7 with 0.386 ± 0.031 and 0.322 ± 0.027 ml/min/kg, respectively. Maximal plasma concentration values were below 100 µg/ml, which is considered within the therapeutic margin for human patients. 5-fluorouracil plasma concentration was below the limit of detection at all time points. The main adverse events consisted of depigmented, ulcerated, exudative, and crusty cutaneous lesions 10 to 13 days after beginning 5-fluorocytosine administration. The lesions were localized to the nasal planum, the lips, the eyelids, and the scrotum. Histological analyses were consistent with a cutaneous lupoid drug reaction. Complete healing was observed 15 to 21 days after cessation of 5-fluorocytosine. No biochemical or hematological adverse events were noticed.

CONCLUSIONS: Long term administration of 5-fluorocytosine was associated with cutaneous toxicity in healthy dogs. It suggests that pharmacotherapy should be adjusted to reduce the toxicity of 5-fluorocytosine in targeted chemotherapy.

PMID:34154593 | DOI:10.1186/s12917-021-02927-5

Ann Palliat Med. 2021 Jun 18:apm-21-1224. doi: 10.21037/apm-21-1224. Online ahead of print.

ABSTRACT

BACKGROUND: Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) are the four most common drugs for the first-line treatment of tuberculosis (TB). Although chemotherapy drugs are widely used in the treatment of TB, and achieved good results, But the side effects, especially antituberculosis drug-induced liver injury (ATDILI), cannot be overlooked. Many researchers have made efforts to uncover the association of cytochrome P450 (CYP) enzyme genetic polymorphisms with ATDILI. In this study, we systematically reviewed and meta-analyzed the relationship between CYP polymorphism and susceptibility to ATDILI.

METHODS: We carried out literature searches of PubMed, Ovid, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI). Medical Subject Headings (MeSH) terms including "cytochrome P450 enzyme", "drug-induced liver injury", "polymorphism", "tuberculosis", and "hepatotoxicity" were used as keywords for our searches.

RESULTS: The pooled odds ratio (OR) of all studies for CYP2E1 to the risk of ATDILI was 1.18 [95% confidence interval (CI): 0.82-1.71]. The articles in this meta-analysis were observed to be mildly heterogeneous. Further subgroup analysis revealed that the patients who receiving a four-drug protocol (INH + RIF + PZA + EMB) or three-drug protocol (INH + RIF + PZA) regimens showed a higher risk of ATDILI than those who receiving INH alone. However, subgroup analyses according to participants' ethnic origin, study type, and the definition of ATDILI produced no statistically significant results. Associations between other genes in the CYP family and ATDILI were indistinct and equivocal.

CONCLUSIONS: Our meta-analysis has uncovered an association between CYP2E1 RsaI/PstI polymorphisms and ATDILI, especially among patients who receive a four-drug (INH + RIF + PZA + EMB) or three-drug (INH + RIF + PZA) anti-TB treatment regimen.

PMID:34154362 | DOI:10.21037/apm-21-1224

PLoS One. 2021 Jun 21;16(6):e0253021. doi: 10.1371/journal.pone.0253021. eCollection 2021.

ABSTRACT

INTRODUCTION: Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear.

PATIENTS AND METHODS: This single-center retrospective cohort study used electronic health record data of patients with metastatic castration-resistant prostate cancer and bone metastases who were treated with radium-223 between April 1, 2014 and February 19, 2019. Patients who received radium-223 monotherapy were compared to patients who received a combination of radium-223 plus either abiraterone or enzalutamide. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, time to symptomatic skeletal event, symptomatic skeletal event-free survival, and incidence of drug-related adverse events. Time-to-event analyses were estimated by log rank tests using Kaplan-Meier curves. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards models. Chi-square tests evaluated difference in serious adverse events between the two arms.

RESULTS: A total of 60 patients met inclusion criteria (n = 41 in the monotherapy arm, n = 19 in the combination arm). Differences in median overall survival were not observed (12.7 vs. 12.8 months; HR 1.15, 95% CI 0.59-2.23; P = 0.68), but median progression-free survival was significantly longer in the combination arm (7.6 vs. 4.9 months; HR 1.94, 95% CI 1.11-3.40; P = 0.02). Significant differences were not observed in time to first SSE (P = 0.97), SSE-free survival (P = 0.16), or in the overall incidence of serious adverse events (P = 0.45).

CONCLUSION: Combination radium-223 plus abiraterone or enzalutamide did not improve overall survival, but prolonged progression-free survival without increasing the incidence of serious adverse events in metastatic castration-resistant prostate cancer patients with bone metastases. However, these results are limited by small numbers and patient selection inherent in retrospective analysis.

PMID:34153052 | DOI:10.1371/journal.pone.0253021

J Dermatolog Treat. 2021 Jun 21:1-7. doi: 10.1080/09546634.2021.1937476. Online ahead of print.

ABSTRACT

When prescribing low-dose methotrexate, frequent serological testing is recommended in the dermatologic literature, although much of the supporting data is extrapolated from non-dermatologic conditions. We performed a retrospective cohort study to determine the cumulative incidence and timing of low-dose methotrexate-associated serological abnormalities over the first year of therapy, in a pragmatic cohort of patients with dermatologic compared to non-dermatologic diagnoses. Laboratory values recorded included white blood cell count, hemoglobin, platelet count, estimated glomerular filtration rate, alanine aminotransferase, and aspartate aminotransferase. Among 1376 patients, there were no cases of methotrexate-associated grade 4/very severe lab abnormality or fatality. Baseline risk factors associated with moderate-to-severe lab abnormalities included non-dermatologic diagnoses, low hemoglobin, low estimated glomerular filtration rate, and elevated transaminases. The incidence of moderate-to-severe lab abnormalities was 4.4% among all patients, 3.1% among patients with dermatologic diagnoses, and 2.3% among patients with normal baseline lab values. Lab abnormalities led to discontinuation of therapy in 0.8% of patients. Serious changes did not occur in the first two weeks of therapy. We conclude that the cumulative incidence of low-dose methotrexate-associated lab abnormality was lower in patients with dermatologic diagnoses or normal baseline testing and these factors may be used to adjust monitoring practices.

PMID:34148493 | DOI:10.1080/09546634.2021.1937476

Expert Rev Gastroenterol Hepatol. 2021 Jun 21. doi: 10.1080/17474124.2021.1940956. Online ahead of print.

ABSTRACT

INTRODUCTION: : Current available therapies in pediatric Inflammatory Bowel Disease (IBD) target the immune system and often fail to sustain long term remission. Therefore, there is a high need for development of alternative treatment strategies such as antibiotics in pediatric IBD.

AREAS COVERED: : This study systematically assessed efficacy and safety of antibiotics in pediatric IBD. CENTRAL, EMBASE (Ovid) and Medline (Pubmed) were searched for Randomized Controlled Trials (RCTs). Quality assessment of included articles was conducted with the Cochrane risk-of-bias tool.

EXPERT OPINION: : Two RCT's (n=101, 4.4-18 years, 43% male) were included. Both studies had overall low risk of bias. In mild-to-moderate Crohn's disease, azithromycin+metronidazole (AZ+MET) (n=35) compared to metronidazole (MET) alone (n=38) did not induce a significantly different response (PCDAI drop ≥12.5 points or remission) (p=0.07). For induction of remission (PCDAI≤10), AZ+MET was more effective than MET (p=0.025). In Acute Severe Colitis, mean 5-day PUCAI was significantly lower in the antibiotic (vancomycin, amoxicillin, metronidazole, doxycycline)+intravenous corticosteroids (IVCS) group (n=16) compared to IVCS (n=12) alone (p=0.037), whereas remission (PUCAI<10) did not differ (p=0.61). No significant drug-related adverse events were reported. Results of this systematic review of antibiotic use highlight the lack of evidence in pediatric IBD. More evidence is needed before widespread implementation in daily practice.

PMID:34148466 | DOI:10.1080/17474124.2021.1940956

Breast Cancer Res Treat. 2021 Jun 20. doi: 10.1007/s10549-021-06240-5. Online ahead of print.

ABSTRACT

PURPOSE: Equivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years' follow-up.

METHODS: Following neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up.

RESULTS: Most patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78-1.93) for DFS, 1.31 (0.86-2.01) for PFS, and 1.10 (0.57-2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups.

CONCLUSION: The similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab. ClinicalTrials.gov: NCT02162667 (registered June 13, 2014).

PMID:34148205 | DOI:10.1007/s10549-021-06240-5

BMJ Case Rep. 2021 Jun 18;14(6):e243191. doi: 10.1136/bcr-2021-243191.

ABSTRACT

We describe a married couple who both presented with hypertension and hypokalaemia. Both patients were diagnosed with pseudohyperaldosteronism triggered by the widely used antifungal drug itraconazole. This effect appears to be dose-dependent, where a daily intake of 100 mg itraconazole is enough to induce pseudohyperaldosteronism. Clinicians should be aware of pseudohyperaldosteronism as a possible adverse effect of itraconazole, and we recommend monitoring potassium levels and blood pressure in all patients receiving this drug over a longer period of time. Voriconazole is probably an alternative antifungal treatment to itraconazole but also with this drug potassium levels should be monitored.

PMID:34144953 | DOI:10.1136/bcr-2021-243191

World J Clin Cases. 2021 Jun 16;9(17):4310-4317. doi: 10.12998/wjcc.v9.i17.4310.

ABSTRACT

BACKGROUND: Sodium valproate is widely used in the treatment of epilepsy in clinical practice. Most adverse reactions to sodium valproate are mild and reversible, while serious idiosyncratic side effects are becoming apparent, particularly hepatotoxicity. Herein, we report a case of fatal acute liver failure (ALF) with thrombotic microangiopathy (TMA) caused by treatment with sodium valproate in a patient following surgery for meningioma.

CASE SUMMARY: A 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue, severe jaundice accompanied by oliguria, soy sauce-colored urine, and ecchymosis. His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level, severe liver and kidney dysfunction, and disturbance of the coagulation system. He was diagnosed with drug-induced liver failure combined with TMA. After plasma exchange combined with hemoperfusion, pulse therapy with high-dose methylprednisolone, and blood transfusion, his liver function deteriorated, and finally, he died.

CONCLUSION: ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.

PMID:34141795 | PMC:PMC8173405 | DOI:10.12998/wjcc.v9.i17.4310