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British Journal of Clinical Pharmacology Jun 2018Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in...
AIMS
Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates.
METHODS
Databases were searched up to and including September 2016. Studies were included based on PICO as follows: P: infants and neonates being treated with any medication, I: salivary TDM vs. C: traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data.
RESULTS
Twenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent/very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6-8) gave a more varied response.
CONCLUSION
There is significant potential for infantile saliva testing and in particular for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude, any compound with a pKa within physiological range (pH 6-8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.
Topics: Age Factors; Drug Monitoring; Humans; Infant; Infant, Newborn; Pharmaceutical Preparations; Pharmacokinetics; Predictive Value of Tests; Reproducibility of Results; Saliva
PubMed: 29442362
DOI: 10.1111/bcp.13553 -
Journal of Neurology, Neurosurgery, and... Jul 2014Tremor is one of the clinical manifestations of dystonia; however, there are no specific therapeutic trials evaluating the efficacy of treatments for dystonic tremor... (Review)
Review
Tremor is one of the clinical manifestations of dystonia; however, there are no specific therapeutic trials evaluating the efficacy of treatments for dystonic tremor (DT), tremor associated with dystonia or primary writing tremor (PWT). We systematically reviewed the literature available up to July 2013 on the treatment of these tremors and retrieved the data of 487 patients published in 43 papers detailing the effects of given interventions on tremor severity. Treatment outcome was highly variable, depending on the specific type of intervention and tremor distribution. No specifically designed studies were available for the treatment of tremor associated with dystonia. As for the other tremors, drug efficacy was generally disappointing and a moderate effect was only found with anticholinergics, tetrabenazine, clonazepam, β-blockers and primidone; levodopa was only efficacious on tremor due to dopa-responsive dystonia. The largest amount of data was available for botulinum toxin injections, which provided a marked improvement, particularly for the management of axial tremors (head or vocal cords). In refractory DTs, deep brain stimulation of several targets was attempted. Deep brain stimulation of globus pallidus internus, thalamus or subthalamic area led to a marked improvement of dystonic axial or appendicular tremors in most cases refractory to other treatments. Few other non-invasive treatments, for example, orthotic device in PWT, have been used with anecdotal success. In conclusion, considering the lack of good-quality studies, future randomised controlled trials are needed. In absence of evidence-based guidelines, we propose an algorithm for the treatment of DT based on currently available data.
Topics: Botulinum Toxins, Type A; Deep Brain Stimulation; Dystonia; Humans; Tremor
PubMed: 24167042
DOI: 10.1136/jnnp-2013-305532 -
The Cochrane Database of Systematic... Jan 2007The aim of drug treatment for epilepsy is to prevent seizures without causing adverse effects. To achieve this, drug dosages need to be individualised. Measuring... (Review)
Review
BACKGROUND
The aim of drug treatment for epilepsy is to prevent seizures without causing adverse effects. To achieve this, drug dosages need to be individualised. Measuring antiepileptic drug levels in body fluids (therapeutic drug monitoring) is frequently used to optimise drug dosage for individual patients.
OBJECTIVES
To review the evidence regarding the effects of therapeutic drug monitoring upon outcomes in epilepsy.
SEARCH STRATEGY
We searched the Cochrane Epilepsy Group Specialised Register (September 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 4), MEDLINE (January 1966 to April 2005) and EMBASE (1974 to May 2005). No language restrictions were imposed. We checked the reference lists of retrieved articles for additional reports of relevant studies.
SELECTION CRITERIA
Randomised controlled trials comparing the outcomes of antiepileptic drug monotherapy guided by therapeutic drug monitoring with drug treatment without the aid of therapeutic drug monitoring.
DATA COLLECTION AND ANALYSIS
We based this review on published aggregate data. The main outcomes measured were the proportions of patients achieving a 12-month remission from seizures, reporting adverse effects, and being withdrawn from the treatment they had been randomised to receive.
MAIN RESULTS
Only one study met the inclusion criteria for the review. In this open study, 180 patients with newly-diagnosed, untreated epilepsy were randomised to treatment with the antiepileptic drug selected by their physician either with or without therapeutic drug serum level monitoring as an aid to dosage adjustments. The antiepileptic drugs used were carbamazepine, valproate, phenytoin, phenobarbital and primidone. A 12-month remission from seizures was achieved by 60% of the patients randomised to therapeutic drug monitoring (intervention group) and by 61% in the control group. A total of 56% in the intervention group and 58% in the control group were seizure free during the last 12 months of follow up. Adverse effects were reported by 48% in the intervention group and 47% of the control group patients. Of those randomised to therapeutic drug monitoring, 62% completed the two-year follow up compared with 67% of the control group.
AUTHORS' CONCLUSIONS
We found no clear evidence to support routine antiepileptic drug serum concentration measurement with the aim of reaching predefined target ranges for the optimisation of treatment of patients with newly-diagnosed epilepsy with antiepileptic drug monotherapy. However, this does not exclude the possible usefulness of therapeutic drug monitoring of specific antiepileptic drugs during polytherapy, in special situations or in selected patients, although evidence is lacking.
Topics: Anticonvulsants; Carbamazepine; Drug Monitoring; Epilepsy; Humans; Phenobarbital; Phenytoin; Primidone; Valproic Acid
PubMed: 17253477
DOI: 10.1002/14651858.CD002216.pub2 -
Clinical Toxicology (Philadelphia, Pa.) Jan 2011Despite a worldwide decline in barbiturate use, cases of acute poisoning with severe toxicity are still noted, particularly in developing countries. Severe poisonings... (Review)
Review
CONTEXT
Despite a worldwide decline in barbiturate use, cases of acute poisoning with severe toxicity are still noted, particularly in developing countries. Severe poisonings often require prolonged admission to an intensive care unit, so enhanced elimination might be useful to hasten recovery. Information regarding the efficacy of these techniques for individual barbiturates is not available in standard textbooks.
OBJECTIVE
To determine the evidence supporting the effect of enhanced elimination and its role in the management of acute barbiturate poisoning.
METHODS
A systematic review was conducted using broad search criteria in three databases. All potentially relevant articles were obtained, and reference lists were manually reviewed. Ninety-four publications fulfilling inclusion criteria were located. Studies were classified as controlled or uncontrolled, and clinical and pharmacokinetic end points were manually extracted. If not directly stated, standard pharmacokinetic methods were used to calculate the clearance and efficiency of enhanced elimination techniques for each barbiturate and tabulated for direct comparison. PROSPECTIVE CONTROLLED CLINICAL TRIALS: Two of the 94 publications were prospective controlled studies (only one stated that allocation was via blinded randomisation), and both assessed the effect of multiple-dose activated charcoal for acute phenobarbital poisoning. These studies demonstrated enhanced elimination with a decrease in elimination of half-life from approximately 80 to 40?h, but only one study reported clinical benefits. UNCONTROLLED SERIES AND SINGLE CASE REPORTS: Sufficient data to determine the clearance due to enhanced elimination were available in only 52 of these papers. Barbiturate clearances by enhanced elimination varied markedly among studies. While extracorporeal modalities appeared to increase the direct clearance of many barbiturates, there was insufficient information to confirm a clinical benefit.
CONCLUSIONS
There is limited evidence to support the use of enhanced elimination in the treatment of poisoning with most barbiturates. There is no role for urine alkalinisation, while multiple-dose activated charcoal may be useful for most phenobarbital and possibly primidone poisonings. Extracorporeal techniques appear to enhance elimination, but the clinical benefits, relative to the potential complications and cost, are poorly defined. Extracorporeal techniques such as haemodialysis and haemoperfusion can be considered for patients with life-threatening barbiturate toxicity such as refractory hypotension.
Topics: Acute Disease; Adult; Barbiturates; Clinical Trials as Topic; Female; Humans; Pentobarbital; Phenobarbital; Poisoning
PubMed: 21288146
DOI: 10.3109/15563650.2010.550582 -
Seizure May 2022Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the... (Review)
Review
BACKGROUND
Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the potential adverse effects caused by exposure to antiseizure medications (ASMs).
OBJECTIVE
The objectives of this review were: to evaluate concentrations of ASMs in breastmilk of lactating WWE, qualitatively synthesize evidence that can be used to estimate theoretical doses as estimated daily intake (EDI) and relative infant dose (RID) of ASMs, and to evaluate potential risks to infants as a result of exposure to ASMs from breastmilk.
METHODS
This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020223645. The databases: MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. A qualitative synthesis was adopted in this study.
RESULTS
A total of 15 records were included in this systematic review. The included studies reported levels of 8 ASMs in the breastmilk of WWE. The highest RIDs of carbamazepine, lamotrigine, primidone, phenobarbital, gabapentin, valproic acid, ethosuximide, levetiracetam, and topiramate were 3.70%, 36.33%, 4.96%, 3.15%, 4.37%, 1.90%, 31.49%, 12.50%, and 12.18%, respectively. Breastfeeding might be limited or even discontinued when signs of excessive sedation/drowsiness and/or poor weight gain are evident on infants exposed to primidone and phenobarbital, ethosuximide/primidone, or ethosuximide/phenobarbital.
CONCLUSIONS
Concentrations of ASMs can be detected in breastmilk of WWE and plasma/serum of infants exposed via breastmilk. Healthcare providers and WWE might use the findings of this study to make informed decisions on the safety of breastfeeding while taking ASMs.
Topics: Anticonvulsants; Breast Feeding; Epilepsy; Ethosuximide; Female; Humans; Infant; Lactation; Milk, Human; Phenobarbital; Primidone
PubMed: 35427849
DOI: 10.1016/j.seizure.2022.03.017 -
Revista de NeurologiaWe discuss some controversial aspects with prescription of generic drugs (GD) and the problems concerning bioequivalence, mainly in the case of drugs with non-linear... (Review)
Review
AIM
We discuss some controversial aspects with prescription of generic drugs (GD) and the problems concerning bioequivalence, mainly in the case of drugs with non-linear pharmacokinetics and/or narrow therapeutic rank, like the antiepileptic drugs (AED).
DEVELOPMENT
There is considerable debate about GD in the treatment of epilepsy, with clearly advantages (cost saving) and disadvantages (loss of seizure control or drug toxicity) in prescribing generics anticonvulsants. We make a systematic review of the literature in primary (PubMed) and secondary (Tripdatabase and Cochrane Library) bibliographic databases in relation to GD and AED. The main information is about classical AED (phenytoin, carbamazepine, valproic acid and primidone) and we don't found studies in this area about the new AED. The level of evidence is, generally, weak, based on case-series and expert opinion without explicit critical appraisal (except in phenytoin with level of evidence moderate, based on some analytical studies). In Spain, at this moment, there are only two generic AED, one-classical (carbamazepine) and one-new (gabapentin).
CONCLUSION
The American Academy of Neurology and Epilepsy Foundation maintains that the individual and physician should be notified and give their consent before a switch in antiepileptic medications is made, whether it involves generic substitution for brand name products, or generic to generic substitutions.
Topics: Anticonvulsants; Drug Costs; Drug Prescriptions; Drugs, Generic; Epilepsy; Humans; Therapeutic Equivalency
PubMed: 16317637
DOI: No ID Found -
Der Nervenarzt Aug 2018Knowledge about the passage of various antiepileptic drugs into breast milk and its consequences for the infant is limited. Faced with this uncertainty, breastfeeding is...
BACKGROUND
Knowledge about the passage of various antiepileptic drugs into breast milk and its consequences for the infant is limited. Faced with this uncertainty, breastfeeding is often discouraged for these patients. The aim of this study was to comprehensively review the available data regarding antiepileptic drugs during breastfeeding, to compare these data with information provided by the summary of product characteristics (SmPCs), and to provide recommendations for the use of these drugs in breastfeeding women.
MATERIAL AND METHODS
We performed a systematic literature review on breastfeeding data for 23 antiepileptic drugs. A breastfeeding compatibility score was developed and validated. The estimated score based on the literature review was compared with the estimated score based on recommendations provided by the SmPCs.
RESULTS
We identified 75 articles containing exposure and safety data for 15 antiepileptic agents during breastfeeding. The comparison between the score values based on the literature review and on the SmPCs revealed a very low degree of concordance (weighted kappa: 0.08).
CONCLUSION
Phenobarbital, primidone, carbamazepine, valproate and levetiracetam are probably compatible with breastfeeding. Treatment with phenytoin, ethosuximide, clonazepam, oxcarbazepine, vigabatrin, topiramate, gabapentin, pregabalin, lamotrigine and zonisamide can be authorized during breastfeeding, provided breastfed infants are carefully monitored for side effects. Since data on the use of mesuximide, clobazam, rufinamide, felbamate, lacosamide, sultiame, perampanel and retigabine are insufficient to adequately assess the risk for breastfed infants, use in breastfeeding women is in principle not recommended and should be carefully evaluated on a case by case basis. In practice, a risk-benefit analysis should be performed for each mother under antiepileptic treatment wishing to breastfeed her child, so that individual risk factors can adequately be taken into account when counseling the patient.
Topics: Anticonvulsants; Breast Feeding; Contraindications, Drug; Epilepsy; Humans; Risk Assessment
PubMed: 29487964
DOI: 10.1007/s00115-018-0496-2 -
Neurologia I Neurochirurgia Polska 2020Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin and clonazepam) due to side effects and frequent dose limitations. Botulinum toxin type A (BoNT-A) has been widely used to treat tremor, but its efficacy and safety are uncertain.
AIMS
To evaluate the efficacy and safety of BoNT-A in the treatment of hand tremor.
METHODS
We searched the MEDLINE, EMBASE, PsycINFO and Cochrane Library databases for relevant randomised controlled trials of the effects of BoNT-A injections on tremors, up to 20 February 2020. A meta-analysis of comparative effects was performed using R studio software, and publication bias was examined using Egger's test.
RESULTS
Six studies examining a total of 245 participants with tremor were included in the meta-analysis. The primary outcome of meta-analysis showed no difference in clinical tremor scale scores between the BoNT-A group versus the placebo group (standardised mean difference (SMD): -0.42, 95% confidence interval (CI): -1.94 to 1.10; I2 = 96%). For clinical tremor scale scores, subgroup analyses suggested that the BoNT-A group may differ in terms of multiple sclerosis (MS) related tremor (SMD: -1.10; 95% CI: -2.17 to -0.04; I2 = 79%) compared to a placebo, but the difference did not exist in the outcome of essential tremor (ET) or hand tremor (MD: -1.31; 95% CI: -3.39; 1.31; I2 = 97%). Grip strength (MD: -1.25, 95% CI: -5.99 to 3.50, I2 = 97%) was slightly lower in the BoNT-A group, but the difference was not significant. The incidence of adverse events (AEs), including hand weakness (RR: 2.96, 95% CI: 1.40 to 6.24, I2 = 37%), was significantly greater in the BoNT-A group than in the placebo group. Two studies were assessed as having an overall low risk of bias.
CONCLUSIONS
Our study confirms that BoNT-A injections are unlikely to have an impact on patients with hand tremors. However, subgroup analysis suggested that BoNT-A injections could have possible benefits in MS-related tremor. While moderate to severe hand weakness AEs often limits their use in clinical practice, additional well-designed double-blind, placebo-controlled trials are needed to provide more robust conclusions.
Topics: Botulinum Toxins, Type A; Hand; Humans; Muscle Weakness; Tremor
PubMed: 33047784
DOI: 10.5603/PJNNS.a2020.0079