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British Journal of Clinical Pharmacology Jul 2003Status epilepticus is common in children with severe falciparum malaria and is associated with poor outcome. Phenytoin is often used to control status epilepticus, but...
AIMS
Status epilepticus is common in children with severe falciparum malaria and is associated with poor outcome. Phenytoin is often used to control status epilepticus, but its water-soluble prodrug, fosphenytoin, may be more useful as it is easier to administer. We studied the pharmacokinetics and clinical effects of phenytoin and fosphenytoin sodium in children with severe falciparum malaria and status epilepticus.
METHODS
Children received intravenous (i.v.) phenytoin as a 18 mg kg-1 loading dose infused over 20 min followed by a 2.5 mg x kg(-1) 12 hourly maintenance dose infused over 5 min (n = 11), or i.v. fosphenytoin, administered at a rate of 50 mg x min(-1) phenytoin sodium equivalents (PE; n = 16), or intramuscular (i.m.) fosphenytoin as a 18 mg x kg(-1) loading dose followed by 2.5 mg x kg(-1) 12 hourly of PE (n = 11). Concentrations of phenytoin in plasma and cerebrospinal fluid (CSF), frequency of seizures, cardiovascular effects (respiratory rate, blood pressure, trancutaneous oxygen tension and level of consciousness) and middle cerebral artery (MCA) blood flow velocity were monitored.
RESULTS
After all routes of administration, a plasma unbound phenytoin concentration of more than 1 microg x ml(-1) was rapidly (within 5-20 min) attained. Mean (95% confidence interval) steady state free phenytoin concentrations were 2.1 (1.7, 2.4; i.v. phenytoin, n = 6), 1.5 (0.96, 2.1; i.v. fosphenytoin, n = 11) and 1.4 (0.5, 2.4; i.m. fosphenytoin, n = 6), and were not statistically different for the three routes of administration. Median times (range) to peak plasma phenytoin concentrations following the loading dose were 0.08 (0.08-0.17), 0.37 (0.33-0.67) and 0.38 (0.17-2.0) h for i.v. fosphenytoin, i.v. phenytoin and i.m. fosphenytoin, respectively. CSF: plasma phenytoin concentration ratio ranged from 0.12 to 0.53 (median = 0.28, n = 16). Status epilepticus was controlled in only 36% (4/11) following i.v. phenytoin, 44% (7/16), following i.v. fosphenytoin and 64% (7/11) following i.m. fosphenytoin administration, respectively. Cardiovascular parameters and MCA blood flow were not affected by phenytoin administration.
CONCLUSIONS
Phenytoin and fosphenytoin administration at the currently recommended doses achieve plasma unbound phenytoin concentrations within the therapeutic range with few cardiovascular effects. Administration of fosphenytoin i.v. or i.m. offers a practical and convenient alternative to i.v. phenytoin. However, the inadequate control of status epilepticus despite rapid achievement of therapeutic unbound phenytoin concentrations warrants further investigation.
Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Infusions, Intravenous; Malaria, Falciparum; Male; Phenytoin; Status Epilepticus
PubMed: 12848783
DOI: 10.1046/j.1365-2125.2003.01829.x -
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.The Cochrane Database of Systematic... Dec 2017Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.
OBJECTIVES
To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).
SEARCH METHODS
We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016.
SELECTION CRITERIA
We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events.
MAIN RESULTS
IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than current first-line treatment carbamazepine and other current first-line treatment lamotrigine performed better than all other treatments (aside from levetiracetam); carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure types (moderate- to high-quality evidence).Generally, direct evidence and network meta-analysis estimates (direct plus indirect evidence) were numerically similar and consistent with confidence intervals of effect sizes overlapping.The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders.
AUTHORS' CONCLUSIONS
Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.
Topics: Adult; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fructose; Gabapentin; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Network Meta-Analysis; Oxcarbazepine; Phenobarbital; Phenytoin; Piracetam; Remission Induction; Topiramate; Triazines; Valproic Acid; Zonisamide; gamma-Aminobutyric Acid
PubMed: 29243813
DOI: 10.1002/14651858.CD011412.pub3 -
British Journal of Clinical Pharmacology Dec 2002Some children with malaria and convulsions also have concurrent bacterial meningitis. Chloramphenicol is used to treat the latter whereas phenytoin is used for... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
AIMS
Some children with malaria and convulsions also have concurrent bacterial meningitis. Chloramphenicol is used to treat the latter whereas phenytoin is used for convulsions. Since chloramphenicol inhibits the metabolism of phenytoin in vivo, we studied the effects of chloramphenicol on phenytoin pharmacokinetics in children with malaria.
METHODS
Multiple intravenous (i.v.) doses of chloramphenicol succinate (CAP) (25 mg kg-1 6 hourly for 72 h) and a single intramuscular (i.m.) seizure prophylactic dose of fosphenytoin (18 mg kg-1 phenytoin sodium equivalents) were concomitantly administered to 15 African children with malaria. Control children (n = 13) with malaria received a similar dose of fosphenytoin and multiple i.v. doses (25 mg kg-1 8 hourly for 72 h) of cefotaxime (CEF). Blood pressure, heart rate, respiratory rate, oxygen saturation, level of consciousness and convulsion episodes were monitored. Cerebrospinal fluid (CSF) and plasma phenytoin concentrations were determined.
RESULTS
The area under the plasma unbound phenytoin concentration-time curve (AUC(0, infinity ); means (CAP, CEF): 58.5, 47.6 micro g ml-1 h; 95% CI for difference between means: -35.0, 11.4), the peak unbound phenytoin concentrations (Cmax; medians: 1.12, 1.29 micro g ml-1; 95% CI: -0.5, 0.04), the times to Cmax (tmax; medians: 4.0, 4.0 h; 95% CI: -2.0, 3.7), the CSF:plasma phenytoin ratios (means: 0.21, 0.22; 95% CI: -0.8, 0.10), the fraction of phenytoin unbound (means: 0.06, 0.09; 95% CI: -0.01, 0.07) and the cardiovascular parameters were not significantly different between CAP and CEF groups. However, mean terminal elimination half-life (t1/2,z) was significantly longer (23.7, 15.5 h; 95% CI: 1.71, 14.98) in the CAP group compared with the CEF group. Seventy per cent of the children had no convulsions during the study period.
CONCLUSIONS
Concomitant administration of chloramphenicol and a single i.m. dose of fosphenytoin alters the t1/2,z but not the other pharmacokinetic parameters or clinical effects of phenytoin in African children with severe malaria. Moreover, a single i.m. dose of fosphenytoin provides anticonvulsant prophylaxis in the majority of the children over 72 h. However, a larger study would be needed to investigate the effect of concomitant administration of multiple doses of the two drugs in this population of patients.
Topics: Anti-Bacterial Agents; Anticonvulsants; Area Under Curve; Cefotaxime; Child, Preschool; Chloramphenicol; Drug Therapy, Combination; Female; Half-Life; Humans; Infant; Injections, Intramuscular; Injections, Intravenous; Malaria; Male; Models, Biological; Phenytoin; Seizures
PubMed: 12492612
DOI: 10.1046/j.1365-2125.2002.01689.x -
Neurology India 2014We observed that in patients with traumatic brain injury (TBI) who did not improve as expected, serum levels of phenytoin were in the toxic range and that their...
BACKGROUND
We observed that in patients with traumatic brain injury (TBI) who did not improve as expected, serum levels of phenytoin were in the toxic range and that their sensorium improved with modification of the dose. This led us to study the usage of phenytoin in patients with TBI.
AIMS
To determine the prevalence of phenytoin toxicity in TBI patients and to study the suitability of using ideal body weight (IBW) to guide phenytoin dosing.
SETTING AND DESIGN
Neurotrauma unit of a tertiary care centre in India. Prospective data collection from an already established protocol of drug level monitoring.
MATERIALS AND METHODS
The study cohort included 100 consecutive adult patients with mild or moderate TBI who were administered phenytoin based on IBW. Trough serum phenytoin and albumin levels were measured on day 4 after administration of the loading dose and actual body weight obtained when it was possible.
STATISTICAL ANALYSIS
Chi-square was used for comparing categorical variables, student's t-test for continuous variables and multivariate regression analysis to obtain independent risk factors.
RESULTS
Clinical toxicity was observed in 15% of patients and biochemical toxicity in 36%, with a significant association between the two (P < 0.01). Using multivariate analysis, abdominal girth ≤75 cm (P = 0.07), neck circumference ≤34 cm (P = 0.025) and IV dose proportion ≥80% (P = 0.003) were independent risk factors for biochemical toxicity. The plot between actual weight and IBW showed that toxicity occurred when IBW was higher than actual weight.
CONCLUSION
The prevalence of biochemical phenytoin toxicity was high, with independent risk factors being a higher proportion of IV administration and overestimation of weight by IBW. Clinical suspicion of phenytoin toxicity was a good predictor of biochemical toxicity.
Topics: Adult; Anticonvulsants; Body Weight; Brain Injuries; Drug Monitoring; Humans; Male; Middle Aged; Phenytoin; Prospective Studies; Risk Factors; Treatment Outcome
PubMed: 25033851
DOI: 10.4103/0028-3886.136929 -
Indian Pediatrics Mar 2020To evaluate the efficacy and tolerability of intravenous fosphenytoin in children with status epilepticus, and resulting serum total phenytoin levels. (Observational Study)
Observational Study
OBJECTIVE
To evaluate the efficacy and tolerability of intravenous fosphenytoin in children with status epilepticus, and resulting serum total phenytoin levels.
METHODS
In this prospective study, 51 children aged less than 18 years received intravenous loading dose of fosphenytoin (18-20 mg/kg). Serum total phenytoin levels were estimated at 90 -100 minutes. Outcomes studied were (i) seizure control and local and/or systemic adverse effects in next 24 hours and (ii) phenytoin levels and its correlation with dose received, seizure control and adverse effects.
RESULTS
The actual dose of fosphenytoin received varied from 15.1 to 25 mg/kg. Seizures were controlled in 45 (88%) children and, two required additional dose of 10 mg/kg. None of the children showed any local or systemic adverse effects. Serum total phenytoin levels were in the therapeutic range (10-20 µg/mL) in 12 (23.5%), sub-therapeutic in 16 (31.3%) and supra-therapeutic in 25 (49%) children. There was weak correlation of the phenytoin levels with dose of fosphenytoin received, seizure control, or adverse effects.
CONCLUSIONS
Intravenous fosphenytoin loading dose of 20 mg/kg is effective in controlling seizures in 88% of children with status epilepticus, with a good safety profile. Seizure control and adverse effects appear to be independent of serum total phenytoin levels achieved.
Topics: Administration, Intravenous; Adolescent; Anticonvulsants; Biomarkers; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Infant; Linear Models; Male; Phenytoin; Prospective Studies; Status Epilepticus; Treatment Outcome
PubMed: 32198860
DOI: No ID Found -
Journal of Neurology, Neurosurgery, and... Oct 1999To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy.
METHODS
A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased.
RESULTS
Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences.
CONCLUSION
For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.
Topics: Adult; Aged; Brain Diseases; Cognition; Craniotomy; Double-Blind Method; Epilepsy; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Phenytoin; Quality of Life; Time Factors; Valproic Acid
PubMed: 10486394
DOI: 10.1136/jnnp.67.4.474 -
Epilepsia 1998Antiepileptic drugs (AEDs) may aggravate pre-existing seizures and trigger new seizure types. However, the extent and mechanisms of this problem are unclear, for several... (Review)
Review
Antiepileptic drugs (AEDs) may aggravate pre-existing seizures and trigger new seizure types. However, the extent and mechanisms of this problem are unclear, for several reasons. AED trials are not designed to detect worsening of seizures, severe childhood epilepsies may fluctuate in severity, and worsening of seizures may be over-hastily ascribed to the introduction of a new AED. Moreover, the seizure and the epilepsy type may have been incorrectly diagnosed. The problem is identification of true aggravation of epilepsy in the absence of overdosage or toxicity. This is a common and clinically important problem that concerns both established and newer AEDs, but the biologic mechanisms involved are unknown. An increase in seizure frequency due to overdosage has been reported with phenytoin but is rare with other AEDs. Paradoxical reaction has been reported with carbamazepine (CBZ), benzodiazepines, and vigabatrin (VGB). Exacerbation of seizures may also occur during AED-induced encephalopathy or hepatopathy. An inappropriate choice of the AED (i.e., a purely pharmacodynamic mechanism) can induce worsening when CBZ or VGB is used in absence and myoclonic seizures. Further research should determine whether seizure exacerbation is associated with the type of epilepsy or with the type of EEG abnormality. Recent evidence indicates that lamotrigine is inappropriate in severe myoclonic epilepsy. Some childhood epileptic encephalopathies have been affected by certain seizure-worsening mechanisms. Whether this is due to a predisposition in specific syndromes or to an increased risk for adverse effects in patients undergoing multiple AED manipulations is unclear. Furthermore, some syndromes are not the sum of accompanying seizure types but have unique neurobiology.
Topics: Acute Disease; Anticonvulsants; Child; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Electroencephalography; Epilepsy; Humans; Phenytoin; Seizures; Severity of Illness Index
PubMed: 9593229
DOI: 10.1111/j.1528-1157.1998.tb05118.x -
The International Journal of... Aug 2006Phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. We completed a trial of phenytoin in mania and schizoaffective disorder, manic type.... (Comparative Study)
Comparative Study
Phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. We completed a trial of phenytoin in mania and schizoaffective disorder, manic type. Thirty-nine patients entered a 5-wk double-blind controlled trial of haloperidol+phenytoin vs. haloperidol+placebo; 30 patients completed at least 3 wk; 25 completed 5 wk. Significantly more improvement was observed in those patients receiving phenytoin. Phenytoin has not previously been studied prophylactically in bipolar patients. Bipolar patients were studied who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in bipolar disorder [Cox's F test for comparing survival in two groups: F(6, 18)=3.44, p=0.02]. This study suggests prophylactic effects of add-on phenytoin in bipolar illness. However, the number of patients was small and confirmation is necessary. Lamotrigine has recently been reported to have antidepressant effects. In the past, small studies showed antidepressant effects for carbamazepine and valproate. To determine if such effects could be a class property of other voltage-activated sodium channel blockers such as phenytoin, we performed a double-blind controlled trial of phenytoin vs. fluoxetine in unipolar depression. Thirty-three depressed patients entered the study, and 28 completed at least 3 weeks and were included in data analyses. Weekly Hamilton Depression Scales for 6 wk showed no difference between fluoxetine and phenytoin. Clearly pharmaceutical company funding for clinical trials or advertising for phenytoin is minimal and this must be taken into account in evaluating literature on phenytoin vs. other drugs. The present data suggests that effects on affective disorder may be common to many anticonvulsants.
Topics: Anticonvulsants; Bipolar Disorder; Double-Blind Method; Humans; Phenytoin
PubMed: 16202184
DOI: 10.1017/S1461145705006140 -
The Journal of Biological Chemistry Sep 1998Phenytoin and related xenobiotics can be bioactivated by embryonic prostaglandin H synthase (PHS) to a teratogenic free radical intermediate. The mechanism of free...
Free radical intermediates of phenytoin and related teratogens. Prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry, and photochemical product analysis.
Phenytoin and related xenobiotics can be bioactivated by embryonic prostaglandin H synthase (PHS) to a teratogenic free radical intermediate. The mechanism of free radical formation was evaluated using photolytic oxidation with sodium persulfate and by EPR spectrometry. Characterization of the products by mass spectrometry suggested that phenytoin photolyzes to a nitrogen-centered radical that rapidly undergoes ring opening to form a carbon-centered radical. PHS-1 was incubated with teratogen (phenytoin, mephenytoin, trimethadione, phenobarbital, and major metabolites) or its vehicle and the free radical spin trap alpha-phenyl-N-t-butylnitrone, and incubations were analyzed by EPR spectrometry. There was no alpha-phenyl-N-t-butylnitrone radical adduct in control incubations. For phenytoin, a putative unstable nitrogen-centered radical adduct and a stable carbon-centered radical adduct were detected. Free radical spin adducts also were detected for all other teratogens and metabolites except carbamazepine. The PHS inhibitor eicosatetraynoic acid abolished the free radical EPR signal. Incubation of 2'-deoxyguanosine with phenytoin and PHS-1 resulted in a 5-fold increase in its oxidation to 8-hydroxy-2'-deoxyguanosine. This is the first direct chemical evidence for PHS-catalyzed bioactivation of phenytoin and related teratogens to a free radical intermediate that initiates DNA oxidation, which may constitute a common molecular mechanism of teratologic initiation.
Topics: Biotransformation; Catalysis; Deoxyguanosine; Electron Spin Resonance Spectroscopy; Free Radicals; Oxidation-Reduction; Phenytoin; Photochemistry; Prostaglandin-Endoperoxide Synthases; Teratogens
PubMed: 9737965
DOI: 10.1074/jbc.273.39.25079 -
Wounds : a Compendium of Clinical... Feb 2024Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound...
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
Topics: Humans; Phenytoin; Anti-Bacterial Agents; Wound Healing; Analgesics; Pain
PubMed: 38479432
DOI: No ID Found