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Contraception Jan 2011Drug interactions between hormonal contraceptives and anticonvulsants, resulting in reduced contraceptive effectiveness and/or increased seizure activity, have been... (Review)
Review
BACKGROUND
Drug interactions between hormonal contraceptives and anticonvulsants, resulting in reduced contraceptive effectiveness and/or increased seizure activity, have been published.
STUDY DESIGN
We conducted a systematic review, searching PUBMED and The Cochrane Library for articles in any language on use of hormonal contraceptive methods among women taking anticonvulsant therapy from 1966 through 3 May 2010. Forty-three articles were identified and evaluated.
RESULTS
Evidence suggests drug interactions occur when combined oral contraceptives (COCs), the levonorgestrel implant (Norplant), or the etonogestrel implant (Implanon) are used concomitantly with carbamazepine, phenobarbital, phenytoin, topiramate or lamotrigine. Significant drug interactions were not observed during sodium valproate intake and COC use nor among women using progestogen-only contraceptives and taking lamotrigine.
CONCLUSIONS
To avoid contraceptive failure or increased seizure activity, women with epilepsy should be offered contraceptive methods that do not interact with anticonvulsant medication.
Topics: Anticonvulsants; Contraception; Contraceptives, Oral, Hormonal; Drug Interactions; Epilepsy; Female; Humans
PubMed: 21134499
DOI: 10.1016/j.contraception.2010.06.013 -
Clinical Pharmacokinetics Mar 2021Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability,...
BACKGROUND
Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy.
OBJECTIVE
The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates.
METHODS
We systematically searched the PubMed and Embase databases from inception to 30 June 2020. The information on study designs, target population, model characteristics, and identified covariates was summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults.
RESULTS
Fourteen studies were included, among which two involved neonates, four involved children, two involved both children and adults, and six involved adults only. The median value of apparent clearance for children (0.074 L/h/kg [range 0.038-0.079]) was higher than that for adults (0.054 L/h/kg [range 0.039-0.061]). Body weight was found to significantly influence the apparent clearance and volume of distribution, whereas renal function influenced the clearance. Likewise, coadministration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9-22%, whereas coadministration with valproate acid decreased it by 18.8%.
CONCLUSION
Levetiracetam dose regimen is dependent on the body size and renal function of patients. Further studies are needed to evaluate levetiracetam pharmacokinetics in neonates and pregnant women.
Topics: Adult; Anticonvulsants; Carbamazepine; Child; Female; Humans; Infant, Newborn; Levetiracetam; Phenytoin; Piracetam; Pregnancy
PubMed: 33447943
DOI: 10.1007/s40262-020-00963-2 -
The International Journal of... Jun 2012We performed this systematic review to determine whether intravenous sodium valproate was more effective or safer than other drugs in patients with status epilepticus... (Meta-Analysis)
Meta-Analysis Review
We performed this systematic review to determine whether intravenous sodium valproate was more effective or safer than other drugs in patients with status epilepticus (SE). A literature search was performed using Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). From 544 articles screened, 5 were identified as randomized controlled trials and were included for data extraction. The main outcomes were SE controlled and risk of seizure continuation. The meta-analysis was performed with the Random-effect model. The quality of the included studies was evaluated by GRADE (Grading of Recommendations Assessment, Development, and Evaluation). There was no significant statistics in SE controlled between intravenous sodium valproate and phenytoin. Compared with diazepam, sodium valproate had a statistically significant lower risk of time interval for control of refractory SE (RSE) after having drugs; however, there was no statistically significant difference in SE controlled within 30 min between the two groups. There was no statistically significant difference in cessation from status between intravenous sodium valproate and levetiracetam. Intravenous sodium valprate was as effective as intravenous phenytoin for SE controlled and risk of seizure continuation.
Topics: Anticonvulsants; Diazepam; Humans; Injections, Intravenous; Levetiracetam; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Status Epilepticus; Valproic Acid
PubMed: 22248033
DOI: 10.3109/00207454.2012.657376 -
The Cochrane Database of Systematic... Jul 2009Seizures are poorly controlled in many people with epilepsy, despite current antiepileptic treatments. Some turn to alternative or complementary therapy to treat their... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seizures are poorly controlled in many people with epilepsy, despite current antiepileptic treatments. Some turn to alternative or complementary therapy to treat their condition and the use of traditional Chinese medicinal herbs (TCMH) is increasingly popular. However, it remains unclear whether the existing evidence is rigorous enough to support its use.
OBJECTIVES
To determine the effectiveness and safety of traditional Chinese medicine in people with epilepsy.
SEARCH STRATEGY
Our search included the Cochrane Epilepsy Group's Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1950 to 2007) and EMBASE (1974 to 2007).
SELECTION CRITERIA
Randomised controlled trials evaluating traditional Chinese medicine in people of any age with any type of epilepsy, and comparing one formula of TCM with no intervention, placebo or single Western medicine (monotherapy).
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted trial data and assessed quality. We assessed the following outcomes: (a) seizure freedom for at least one year; (b) 50% or greater reduction in seizure frequency; (c) percentage reduction in seizure frequency and duration; and (d) adverse events.
MAIN RESULTS
Five short-term studies involving 1125 participants met the inclusion criteria. All the studies were of poor methodological quality and had a high probability of selection, detection and performance bias.Two studies assessed seizure freedom for one year. One found no difference between Xiaxingci granule and phenytoin for primary generalized tonic-clonic seizures (RR 1.00; 95% CI 0.07 to 14.90).The other study found no difference between Dianxianning pill and valproate (RR 13.00; 95% CI 0.74 to 227.72) for different types of epilepsy.Three studies assessed a 50% or greater reduction in seizure frequency. One found an advantage for Tianmadingxian capsule when compared to phenytoin (RR 1.37; 95% CI 1.23 to 1.53) in different types of epilepsy, the second an advantage for Zhixian I pill when compared to phenytoin (RR 1.31; 95% CI 1.16 to 1.48) in primary generalized tonic-clonic seizure, and the third an advantage for an 'Antiepilepsy capsule' when compared to phenobarbital (RR 1.21; 95% CI 1.02 to 1.43) for primary and secondary generalized tonic-clonic seizure. One study reported the incidence of adverse effects and the Peto odds ratio was 0.04 (99% CI 0.01 to 0.12, P < 0.00001) favouring TCMH compared to phenobarbital.
AUTHORS' CONCLUSIONS
The current evidence is insufficient to support the use of traditional Chinese medicine as a treatment for epilepsy. Much larger, high quality randomised clinical trials are needed to evaluate the effectiveness and safety of traditional Chinese medicinal herbs for treating epilepsy.
Topics: Anticonvulsants; Drugs, Chinese Herbal; Epilepsy; Epilepsy, Tonic-Clonic; Humans; Medicine, Chinese Traditional; Phenobarbital; Phenytoin; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 19588391
DOI: 10.1002/14651858.CD006454.pub2 -
Birth Defects Research Dec 2020To systematically identify studies of implementing risk management measures when prescribing teratogenic medicines for women of childbearing age and studies reporting... (Review)
Review
AIM
To systematically identify studies of implementing risk management measures when prescribing teratogenic medicines for women of childbearing age and studies reporting risk perceptions of teratogenic medications.
METHODS
MEDLINE, CINAHL, Scopus, EMBASE, and International Pharmaceutical Abstracts were searched. Studies were included in the risk management section if they reported any of the following risk management measures: teratogenic counseling, contraceptive counseling, pregnancy testing before starting treatment, pregnancy testing during treatment, use of contraception before starting treatment, and use of contraception during treatment. Studies were included in the perceptions section if they reported perceived teratogenic risk as numerical value.
RESULTS
Fifty-five studies were included in the risk management section and seven studies were included in the perceptions sections. Prevalence of risk management measures varied as follows: teratogenic counseling (9.5%-99.3%), contraceptive counseling (6.1%-98%), pregnancy testing before starting treatment (0%-95.1%), pregnancy testing during treatment (12.7%-100%), contraception use before starting treatment (15.7%-94%), and contraception use during treatment (1.7%-100%). A proper estimation of the teratogenic risk was reported for thalidomide (by general practitioners and obstetric/gynecologists), for etretinate (by pregnant women), and for misoprostol (by pregnant and nonpregnant women). An under-estimation was reported for warfarin and retinoids (by general practitioners and obstetric/gynecologists). And over-estimation was reported for thalidomide, valproate, lithium, isotretinoin, phenytoin, warfarin and etretinate by different populations.
CONCLUSION
Considerable variation in the implementation of risk management measures when prescribing teratogenic medicines to women of childbearing age is reported in the literature. A common tendency to over-estimate the risk of teratogenic medications was evident.
Topics: Contraception; Counseling; Female; Humans; Pregnancy; Risk Management; Teratogenesis; Teratogens
PubMed: 32918401
DOI: 10.1002/bdr2.1799 -
Neurosurgical Review Oct 2021The use of prophylactic anticonvulsants among patients with subarachnoid hemorrhage (SAH) is controversial. We sought to assess the effectiveness of different durations... (Meta-Analysis)
Meta-Analysis Review
The use of prophylactic anticonvulsants among patients with subarachnoid hemorrhage (SAH) is controversial. We sought to assess the effectiveness of different durations of prophylactic antiepileptic drug (AED) use among SAH patients. We searched the MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases until March 1, 2020. Randomized controlled trials or observational studies comparing different durations or different drugs were selected. The primary outcome was poor clinical outcomes. The secondary outcome was in-hospital seizure. Bayesian network meta-analysis was also performed to indirectly compare the effectiveness of different prophylaxes. A total of 5 papers were included. Three studies with a total of 959 patients were included in the analysis of the primary outcome; the results showed that long-term exposure to prophylactic AEDs (more than 3 days) led to poor clinical outcomes (OR 1.55; 95% CI 1.01-2.39; p = 0.045). Four studies with 1024 patients were included in the analysis of the secondary outcome; the results showed no association between the duration of prophylactic AED use and the occurrence of in-hospital seizures (OR 0.62; 95% CI 0.18-2.15; p = 0.447). In the network meta-analysis, no significant difference was found among the four different prophylaxes. Our findings suggested that, when compared with the short-term use, the long-term use of prophylactic AEDs in SAH patients has a similar effect on in-hospital seizure prevention but is associated with poor clinical outcomes. However, these findings were based on a small number of available studies with obvious heterogeneity in study design and different prescription regimens. Further well-designed studies are warranted to elucidate these questions.
Topics: Anticonvulsants; Bayes Theorem; Carbamazepine; Humans; Phenytoin; Subarachnoid Hemorrhage
PubMed: 33389342
DOI: 10.1007/s10143-020-01466-1 -
Seizure Nov 2022Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions.
OBJECTIVE
We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN).
METHODS
MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR).
RESULTS
We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of >50 and a mean score of 54.96 out of 77.
CONCLUSION
Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy.
Topics: Humans; Stevens-Johnson Syndrome; HLA-DRB1 Chains; HLA-C Antigens; Asian People; HLA-B Antigens; Anticonvulsants; HLA Antigens
PubMed: 36183454
DOI: 10.1016/j.seizure.2022.09.011 -
Bone Jul 2014It has been shown that antiepileptic drugs (AEDs) may have a detrimental effect on bone health and translate into an increased risk of bone fracture. We aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been shown that antiepileptic drugs (AEDs) may have a detrimental effect on bone health and translate into an increased risk of bone fracture. We aimed to comprehensively evaluate the association between use of AEDs and fracture risk.
METHODS
We searched NCBI (PubMed), ISI Web of Science, the Cochrane Library and EMBASE databases for studies reporting fracture risk among users of AEDs. Random-effects meta-analysis was used to pool results across studies.
RESULTS
Twenty-two studies met the inclusion criteria. Overall, there was a significant increase in fracture risk among users of AEDs involving 1,292,910 participants, with a mean/median age of 36-82 years (relative risk (RR)=1.86; 95% confidence interval (CI) 1.62-2.12). When we limited the studies to those on osteoporosis-related fractures, the RR was still significant. Both liver enzyme-inducing antiepileptic drugs (LEI AEDs) and non-LEI AEDs were associated with an increase in fracture risk, although the estimate for LEI AEDs was higher than that of non-LEI AEDs (RR=1.18; 95% CI 1.11-1.25). For some specific AEDs, use of phenobarbiturate (PB), topiramate (TPM) and phenytoin (PHT) suggested an increase in fracture risk of 78%, 39% and 70%, respectively.
CONCLUSIONS
The study suggests a robust association between use of AEDs and fracture risk (particularly for LEI AEDs). It also suggests that several specific AEDs such as PB, TPM and PHT may be associated with an increased risk of fracture.
Topics: Anticonvulsants; Fractures, Bone; Humans
PubMed: 24780876
DOI: 10.1016/j.bone.2014.04.018 -
Handbook of Experimental Pharmacology 2020Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone...
Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate - DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.
Topics: Bone Density; Bone and Bones; Fractures, Bone; Humans; Medroxyprogesterone Acetate; Pharmaceutical Preparations
PubMed: 31889220
DOI: 10.1007/164_2019_340 -
The British Journal of Dermatology Nov 2007Oral phenytoin was first introduced as an antiseizure medication in 1937. Over 60 years investigators have shown an interest in how topical phenytoin may be used to... (Review)
Review
BACKGROUND
Oral phenytoin was first introduced as an antiseizure medication in 1937. Over 60 years investigators have shown an interest in how topical phenytoin may be used to promote wound healing in a variety of chronic wounds.
OBJECTIVES
Systematically to identify, summarize and critically appraise the clinical evidence available on the effects of topical phenytoin on wound healing.
METHODS
Systematic searches were carried out in PubMed (1963-2005), Medline (1966-2005) and Cinahl (1982-2005) for the years listed and in the Cochrane Library and the University of York NHS Centre for Reviews and Dissemination. The search terms used the following key words alone and in combination: phenytoin, wounds and injuries, wound healing, and wound care. Secondary hand searching was also carried out using relevant journal articles and reference lists, historical books, conference proceedings and theses in the area of wound healing. Papers were included if they described randomized controlled trials (RCTs) on humans and if the primary aim was wound closure, with a secondary aim of measuring wound healing over time. The methodological quality of the papers in this systematic review was assessed using the van Tulder method and in addition best-evidence synthesis was carried out. The magnitude of the effect of phenytoin therapy in the studies included in the systematic review was investigated in four of the 14 trials.
RESULTS
Fourteen RCTs were included in the systematic review. Two papers were of high and 12 papers of low to moderate methodological quality. Most papers failed to describe randomization, treatment allocation and blinding techniques adequately. There was moderate evidence presented to support the use of phenytoin for the treatment of leg ulcers, leprosy wounds, chronic wounds and diabetic foot ulcers. There was a positive percentage treatment effect in favour of the phenytoin-treated group in one study investigating diabetic foot wounds and one study on chronic wounds. There was limited evidence for the use of phenytoin on burns and war wounds.
CONCLUSIONS
Overall it would appear that studies investigating the effect of topical phenytoin on wound healing are of moderate methodological quality, and these suggest that there may be a positive effect on wound healing in a variety of wounds.
Topics: Administration, Topical; Anticonvulsants; Humans; Phenytoin; Randomized Controlled Trials as Topic; Wound Healing; Wounds and Injuries
PubMed: 17854378
DOI: 10.1111/j.1365-2133.2007.08160.x