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Pharmaceutics Oct 2020Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have...
Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have been reported in several previous studies when they are coadministered, there are no studies of the interactions between these drugs. Therefore, our study was conducted to solve this lack of information. The potential effects of CBZ/PHT were investigated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RIV between the control group (RIV alone) and the test groups (RIV administered with CBZ/PHT) in rats using the noncompartmental analysis (NCA) and the compartmental model approach. The NCA results indicate that of RIV decreased by 57.9% or 89.7% and of RIV decreased by 43.3% or 70.0% after administration of CBZ/PHT, respectively. In addition, both CBZ and PHT generally reduced the effects of RIV on the prothrombin times of the blood samples. PK profiles of RIV were most properly described by a two-compartment disposition model with a mixed first- and zero-order absorption kinetics and a first-order elimination kinetics. The compartmental model approach showed that a 211% or 1030% increase in of RIV and a 33.9% or 43.4% increase in 2 of RIV were observed in the test groups by the effects of CBZ/PHT, respectively. In conclusion, CBZ and PHT significantly reduced RIV exposure and therefore reduced the therapeutic effects of RIV. Consequently, this might result in adverse events due to insufficient RIV concentration to attain its therapeutic effects. Further studies are needed to validate this finding.
PubMed: 33143037
DOI: 10.3390/pharmaceutics12111040 -
Cureus May 2024Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious...
Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious adverse effect of phenytoin. This case report presents the case of a patient with severe thrombocytopenia induced by phenytoin for the treatment of tonic-clonic seizures. A 63-year-old male received 300 mg/day of phenytoin for the treatment of tonic-clonic seizures. Seven days after receiving the first dose of phenytoin, he was diagnosed with severe thrombocytopenia (platelet count 44 x 10/L) without hemorrhage. Phenytoin was discontinued, and seizures were controlled with levetiracetam. Seven days after stopping phenytoin, his daily platelet count improved from 44 to 177 x 10/L. The Naranjo algorithm score of 7 was at a probable level for phenytoin-induced thrombocytopenia. Thrombocytopenia is a serious adverse drug reaction that can result in life-threatening bleeding. Phenytoin-induced thrombocytopenia commonly begins 1-90 days after administration, and the recovery time is 3-21 days. The potential mechanism of phenytoin-induced thrombocytopenia is drug-induced immune thrombocytopenia. Drugs that enhance the concentration of phenytoin epoxide may be a contributing factor in phenytoin-induced thrombocytopenia. Phenytoin-induced thrombocytopenia is a rare but serious hematological complication. It should be recognized early, particularly in patients with a high risk of hemorrhage or concurrently with medications that increase phenytoin epoxide. Regularly consecutive complete blood count tests may be essential in order to detect an early decrease in platelet count in these patients.
PubMed: 38899236
DOI: 10.7759/cureus.60669 -
Seizure Oct 2021To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a meta-analysis of RCTs.
METHODS
We systematically searched PubMed, Embase, Cochrane, FDA.gov, and ClinicalTrials.gov for RCTs (published before July 31, 2020; no language restrictions). Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO: CRD42020202736. Eleven studies fulfilled the established criteria. We assessed pooled data by using a random-effects model. Quality analysis was performed by using version 2 of the Cochrane risk-of-bias tool (RoB 2). RevMan v.5.3 was used to perform statistical analyses, and publication bias (egger's test) was assessed with Stata MP v.14.0.
RESULTS
Levetiracetam was similar to (fos)phenytoin in seizure termination rate (risk ratio [RR] 0.94; 95% CI 0.87 to 1.01), time of seizure termination (mean difference [MD] 0.44; -0.60 to 1.49), and drug resistance ([RR] 1.12, 0.86 to 1.45). The safety outcome showed a significant statistical difference between fosphenytoin group and levetiracetam group ([RR] 1.44, 1.14 to 1.81), while there was no significant difference observed between phenytoin treatment and levetiracetam treatment ([RR] 1.26, 0.99 to 1.60).
CONCLUSION
Levetiracetam was similar to (fos)phenytoin in cessation rate convulsive status epilepticus, and drug resistance, while it was superior (fos)phenytoin in pooled safety outcome. Further exploration is still needed as to whether it is the first choice for second-line drugs.
Topics: Anticonvulsants; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 34284302
DOI: 10.1016/j.seizure.2021.07.012 -
BMC Neurology Sep 2021Many antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels. Polymorphisms of sodium channel genes may affect the response to ASMs...
BACKGROUND
Many antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels. Polymorphisms of sodium channel genes may affect the response to ASMs due to altering the effect of ASMs on blocking sodium channels.
METHODS
We conducted a retrospective study of epilepsy patients followed up at the Neurological Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan between January 2010 and December 2018. We categorized the patients into response, partial response, and failure to sodium channel blocking ASM groups. Sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, lacosamide, zonisamide, topiramate, and valproic acid. A subgroup of predominant sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, and lacosamide. Associations between the response of ASMs and single-nucleotide polymorphisms of SCN1A, SCN1B, SCN2A, and SCN9A were analyzed.
RESULTS
Two hundred Taiwanese patients and 21 single-nucleotide polymorphisms among SCN1A, SCN1B, SCN2A, and SCN9A were evaluated. We found allele C of rs55742440 in SCN1B was statistically significantly associated with not achieving seizure-free with sodium channel blocking ASMs. For the predominant sodium channel blocking ASMs group, no SNPs were associated with the response of ASMs.
CONCLUSION
Single-nucleotide polymorphism in SCN1B was associated with the response to sodium channel blocking ASMs. This highlights the possibility that beta subunits may affect the function of sodium channels and resulted in different responsiveness to ASMs.
Topics: Anticonvulsants; Epilepsy; Humans; Lamotrigine; NAV1.7 Voltage-Gated Sodium Channel; Retrospective Studies; Sodium Channels
PubMed: 34556045
DOI: 10.1186/s12883-021-02395-2 -
Frontiers in Neurology 2022Phenytoin is widely used as primary seizure prophylaxis in hematopoietic stem cell transplantation in patients undergoing myeloablative conditioning with busulfan....
BACKGROUND
Phenytoin is widely used as primary seizure prophylaxis in hematopoietic stem cell transplantation in patients undergoing myeloablative conditioning with busulfan. Because of the negative side effects of phenytoin, we abandoned phenytoin use in these patients. To assess the effect of this change, we performed a retrospective cohort study on all patients receiving busulfan.
METHODS
We included 139 patients who underwent conditioning with busulfan for hematopoietic stem cell therapy. We registered the use of phenytoin, as well as the occurrence of seizures, until 7 days after busulfan administration. We compared seizure incidence between patients who received phenytoin and those who did not.
RESULTS
Of the 43 patients who received phenytoin prophylaxis, four patients (9.3%) had a seizure during the conditioning regimen, of which two patients had cerebral non-Hodgkin lymphoma. Furthermore, all these 4 patients had very high levels of phenytoin (intoxication). Of the 96 patients that did not receive phenytoin prophylaxis, three patients (3.1%) had a seizure, and one of these patients had an undefined cerebral lesion. Phenytoin did not relate to seizure prevention in a logistic regression analysis.
CONCLUSION
We conclude that phenytoin prophylaxis in patients treated with busulfan is obsolete and possibly harmful, as phenytoin intoxication can occur. We recommend discontinuing the use of phenytoin as primary seizure prophylaxis in these patients.
PubMed: 36071908
DOI: 10.3389/fneur.2022.928550 -
Journal of Pediatric Neurosciences 2021Common first-line antiepileptic drugs (AEDs) used in children are valproate, phenytoin, and levetiracetam. Many side effects for these AEDs are reported including...
BACKGROUND
Common first-line antiepileptic drugs (AEDs) used in children are valproate, phenytoin, and levetiracetam. Many side effects for these AEDs are reported including obesity, atherosclerosis, and metabolic syndrome. The aim of our study was to evaluate changes in carotid artery intima-media thickness (CIMT) in epileptic children and to correlate with lipid profile of those who are on long-term antiepileptic therapy.
MATERIALS AND METHODS
This case-control study was done over 18 months in department of pediatrics. Sample size was 84 with equal number of cases and controls. Epileptic children between 1 and 18 years of age receiving monotherapy with valproate, phenytoin, or levetiracetam for at least 6 months were included in the study. Measurement of CIMT was done by B mode ultrasonography. Lipid profile was analyzed. Statistical analysis was performed using one-way analysis of variance (ANOVA) test and Pearson correlation.
RESULTS
Among 42 cases of epilepsy, 30 were on valproate, 9 on phenytoin, and 3 on levetiracetam monotherapy. No significant difference was noted in body mass index (BMI) among children receiving AED compared with that of controls ( = 0.82). Mean value for CIMT was significantly higher among valproate (0.43 ± 0.04, ≤ 0.001), phenytoin (0.44 ± 0.04, 0.001), and levetiracetam group (0.43 ± 0.03, = 0.01) compared to controls (0.39 ± 0.01). Significant correlation was noted between CIMT and total cholesterol ( = 0.034), triglyceride ( = 0.011), low-density lipoprotein ( = 0.008), and very low-density lipoprotein ( = 0.011).
CONCLUSION
Children on long-term monotherapy with valproate, phenytoin, and levetiracetam have significantly abnormal CIMT. This might be associated with atherosclerotic changes, and these children may require close follow-up to prevent cardiovascular and cerebrovascular risks.
PubMed: 35018181
DOI: 10.4103/jpn.JPN_84_20 -
Pharmaceutics Mar 2021Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in... (Review)
Review
Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients' quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were "topical AND pain", "topical AND neuropathic", "topical AND treatment", "topical AND mechanism", "peripheral neuropathic", and "mechanism". The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy.
PubMed: 33810493
DOI: 10.3390/pharmaceutics13040450 -
Cureus Jul 2023Stevens-Johnson syndrome (SJS) is a dreaded hypersensitivity reaction and a rare immune disorder. We present a Stevens-Johnson syndrome induced by herbal kadha, which...
Stevens-Johnson syndrome (SJS) is a dreaded hypersensitivity reaction and a rare immune disorder. We present a Stevens-Johnson syndrome induced by herbal kadha, which may be the first case. A ten-year-old boy presented with massive sloughing, redness, oedematous skin, an oral ulcer, and an inability to feed or drink for two days. The present symptoms started after 12 hours of consuming herbal Kadha, given by a private practitioner in clinics where he was treated for fever. After not responding to earlier treatment, the patient was referred to the present Institute. The patient had a history of seizure disorder and had been on tablet phenytoin for seven months with no history of adverse reactions to it. He was treated in the intensive care unit. Fortunately, he responded to treatment and recovered fully. He received treatment in the form of immunoglobulin and steroids. Phenytoin and herbal kadha were withdrawn, and Clobazam was continued. Natural herbal medicines can develop severe adverse effects. Physicians should remain aware that drug interactions can likely be seen with drugs with a narrow therapeutic index combined with herbal preparations. Clinicians should do more research on the interaction between herbal and prescription medications.
PubMed: 37637620
DOI: 10.7759/cureus.42407 -
Experimental Neurology Feb 2023Over 30 antiseizure medicines (ASMs) have been uncovered in a diversity of preclinical seizure and epilepsy models, with several critical inflection points in the 20th... (Review)
Review
Over 30 antiseizure medicines (ASMs) have been uncovered in a diversity of preclinical seizure and epilepsy models, with several critical inflection points in the 20th century fundamentally transforming ASM discovery. This commentary aims to review the historical relevance of cannabidiol's (CBD; Epidiolex) approval for epilepsy in the context of other ASMs brought to market. Further, we highlight how CBD's approval may represent an inflection point for 21st century ASM discovery. CBD is one of the main phytocannabinoids of Cannabis sativa. Unlike its related phytocannabinoid, Δ9-tetrahydrocannabinol, CBD does not exert any euphorigenic, tolerance, or withdrawal effects at anticonvulsant doses. CBD also possess marked anti-inflammatory effects, offering the tantalizing potential of a new pharmacological approach in epilepsy. For decades, hints of the anticonvulsant profile of CBD had been suggested with a small handful of studies in rodent seizure models, yet difficulties in formulation, compounded by the social and regulatory pressures related to medical use of cannabis plant-derived agents constrained any clinical implementation. Nonetheless, CBD possesses a broad antiseizure profile in preclinical seizure and epilepsy models, but the transformative impact of CBD'-s approval came because of studies in a rodent model of the orphan disease Dravet syndrome (DS). DS is a pediatric developmental epileptic encephalopathy with high mortality, frequent spontaneous recurrent seizures, and marked resistance to conventional ASMs, such as phenytoin and carbamazepine. CBD was approved for DS by the US Food and Drug Administration in 2018 after convincing efficacy was established in randomized, placebo-controlled trials in children. Because of the clinical approval of CBD as a novel, cannabis plantderived ASM for DS, CBD has revealed a new strategy in ASM discovery to reignite 21st century therapeutic development for epilepsy. In this commentary, we review the major preclinical and clinical milestones of the late 20th century that made CBD, a compound historically subjected to regulatory restrictions, a key driver of a new discovery strategy for epilepsy in the 21st century.
Topics: Humans; Cannabidiol; Anticonvulsants; Epilepsy; Seizures; Epilepsies, Myoclonic; Cannabinoid Receptor Agonists
PubMed: 36471511
DOI: 10.1016/j.expneurol.2022.114288 -
Indian Journal of Critical Care... Mar 2021Mahajan C, Singh BP, Kapoor I, Prabhakar H. Phenytoin Sodium and Acetate-Maleate Buffered Balanced Salt Solutions are Physically Incompatible! Indian J Crit Care Med...
Mahajan C, Singh BP, Kapoor I, Prabhakar H. Phenytoin Sodium and Acetate-Maleate Buffered Balanced Salt Solutions are Physically Incompatible! Indian J Crit Care Med 2021;25(3):352.
PubMed: 33790524
DOI: 10.5005/jp-journals-10071-23756