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Pharmacotherapy 1996Fosphenytoin is a phenytoin prodrug that received an approvable letter from the Food and Drug Administration in February 1996. It was designed to overcome many of the... (Comparative Study)
Comparative Study Review
Fosphenytoin is a phenytoin prodrug that received an approvable letter from the Food and Drug Administration in February 1996. It was designed to overcome many of the shortcomings associated with parenteral phenytoin sodium. Specifically, fosphenytoin is a highly water-soluble, phosphate ester of phenytoin that has no known pharmacologic activity before its conversion to phenytoin. Dosing of fosphenytoin uses phenytoin equivalents (PE) to minimize dosage errors when converting from the conventional formulation. Pharmacokinetic studies documented that the agent is rapidly and completely converted to phenytoin after intravenous and intramuscular dosing. Reported conversion half-lives after intravenous administration range from 8-15 minutes. The absorption rate appears to be the rate-limiting step in the conversion of fosphenytoin to phenytoin after intramuscular administration (half-life range 22-41 min). Bioavailability of phenytoin derived from both intravenous and intramuscular fosphenytoin is essentially 100%. As a consequence of concentration-dependent protein binding, fosphenytoin is bioequivalent to phenytoin sodium at intravenous infusion rates of 100-150 mg PE/minute and 50 mg/minute, respectively. In clinical studies to date, fosphenytoin is safe and significantly better tolerated than phenytoin sodium when administered intravenously. It is also well tolerated when given intramuscularly, and this is a valuable alternative route of administration when intravenous access or cardiographic monitoring is unavailable. Its pharmacoeconomic advantages over phenytoin have not been documented in formal studies to date, although the likelihood of savings based on cost-effectiveness analyses is high. Hence, fosphenytoin has the potential as a safe, well-tolerated, and effective means of delivering phenytoin parenterally in a variety of clinical settings.
Topics: Animals; Anticonvulsants; Biological Availability; Clinical Trials as Topic; Half-Life; Humans; Phenytoin; Prodrugs; Randomized Controlled Trials as Topic; Seizures
PubMed: 8888074
DOI: No ID Found -
Journal of Neurology, Neurosurgery, and... Mar 1986
Topics: Carbamazepine; Epilepsy; Humans; Phenytoin; Valproic Acid
PubMed: 3083052
DOI: 10.1136/jnnp.49.3.334 -
Drug and Chemical Toxicology Apr 2014Phenytoin sodium (PHT Na(+)) is a potent antiepileptic drug against epileptic seizures and is used as a prophylactic treatment in traumatic brain injury. PHT Na(+) leads...
Phenytoin sodium (PHT Na(+)) is a potent antiepileptic drug against epileptic seizures and is used as a prophylactic treatment in traumatic brain injury. PHT Na(+) leads to the formation of reactive oxygen species (ROS), and DNA is a crucial molecular target of ROS-initiated toxicity. Melatonin and its metabolites possess free-radical-scavenging activity. We therefore designed this study to investigate the potential protective effect of melatonin against PHT Na(+)-induced DNA damage by using the comet assay in a rat model in vivo. Thirty-three 3-month-old male Wistar rats were divided into five groups of control treated with isotonic sodium chloride (a single injection of isotonic sodium chloride and 100 µL in drinking water for 10 days), ethanol treated (in drinking water for 10 days containing 100 µL of ethanol in each 300-mL drinking bottle), melatonin treated (4 mg/kg body weight [b.w.] intraperitoneally [i.p.] at the start, in drinking water for 10 days), PHT Na(+) treated (a single i.p. injection of 50 mg/kg) and PHT Na(+) (50 mg/kg b.w., single i.p.) and melatonin (4 mg/kg b.w. i.p. at the start and 4 mg/kg in drinking water for 10 days) cotreated. To determine the protective effects of melatonin, the comet assay was performed using lymphocytes isolated in different time intervals (0, 15, 30, 45 and 60 minutes) from each group of animals. On days 1, 3, 7 and 10, blood samples were taken and the comet assay technique was performed. Our present data suggest that melatonin reversed PHT Na(+)-induced DNA damage.
Topics: Animals; Anticonvulsants; Comet Assay; DNA Damage; Ethanol; Free Radical Scavengers; Injections, Intraperitoneal; Lymphocytes; Male; Melatonin; Oxidative Stress; Phenytoin; Rats; Rats, Wistar; Reactive Oxygen Species; Time Factors
PubMed: 24171672
DOI: 10.3109/01480545.2013.838777 -
The Canadian Journal of Hospital... 1984Until recently, phenytoin sodium injection was not recommended for dilution in intravenous fluids because insolubility results in precipitation of phenytoin acid. The...
Until recently, phenytoin sodium injection was not recommended for dilution in intravenous fluids because insolubility results in precipitation of phenytoin acid. The formation of rod-shaped crystals primarily reflects the failure to maintain the pH of the admixture above 9.5 to 10. Investigations have clarified this problem and point out that stable solutions of phenytoin sodium can be prepared which are safe for intravenous infusion provided the injection is diluted in small volumes of 0.9 percent sodium chloride or Ringer's. Lactate injection and administered freshly prepared. Specific guidelines are suggested for the preparation and administration of phenytoin sodium infusions.
Topics: Drug Compounding; Infusions, Parenteral; Phenytoin
PubMed: 10269318
DOI: No ID Found -
Annals of Neurology Aug 1986Phenytoin is a major anticonvulsant drug that is very effective in controlling a wide variety of seizure disorders while impairing neurological function little, if at... (Review)
Review
Phenytoin is a major anticonvulsant drug that is very effective in controlling a wide variety of seizure disorders while impairing neurological function little, if at all. Early work suggested the hypothesis that the drug's effects were due to a selective block of high-frequency neuronal activity. This theory is reevaluated in the light of accumulated observations on the effects of phenytoin in many neuronal and synaptic preparations. Most of these observations can be explained by a use- and frequency-dependent suppression of the sodium action potential by phenytoin, with a consequent filtering out of sustained high-frequency neuronal discharges and synaptic activity. The molecular mechanism for this is a voltage-dependent blockade of membrane sodium channels responsible for the action potential. Through this action, phenytoin obstructs the positive feedback that underlies the development of maximal seizure activity, while normal brain activity, proceeding at lower neuronal firing rates, is spared its depressant action. Other mechanisms of action that may contribute to the drug's efficacy and selectivity are also discussed.
Topics: Action Potentials; Animals; Anticonvulsants; Anura; Aplysia; Brain; Calcium; Crustacea; Guinea Pigs; Hippocampus; In Vitro Techniques; Ion Channels; Lampreys; Mice; Neural Conduction; Neural Inhibition; Neuromuscular Junction; Neurotransmitter Agents; Phenytoin; Potassium; Seizures; Sodium; Synaptic Transmission
PubMed: 2428283
DOI: 10.1002/ana.410200202 -
The Journal of the Association of... Apr 1999
Topics: Aged; Diabetes Insipidus; Humans; Male; Phenytoin; Seizures
PubMed: 10778541
DOI: No ID Found -
Clinical Pharmacy Sep 1987A case of phenytoin-induced hepatitis with mononucleosis is reported, and syndromes associated with phenytoin hypersensitivity reactions are discussed. A 23-year-old...
A case of phenytoin-induced hepatitis with mononucleosis is reported, and syndromes associated with phenytoin hypersensitivity reactions are discussed. A 23-year-old black woman with a two-month history of seizure disorder was admitted to a hospital with nausea, vomiting, fever, lymphadenopathy, diffuse maculopapular rash, left-upper-quadrant tenderness, and hepatomegaly. She was receiving phenytoin sodium 300 mg/day; carbamazepine 200 mg four times daily had been discontinued four days before admission because of leukopenia. Phenytoin was discontinued after admission; however, phenytoin 1 g i.v. was given for a tonic-clonic seizure two days after admission, after which swelling of the face and legs and pruritus developed. Over the next few days, signs and symptoms of hepatotoxicity progressed, and she became comatose. Seizures were treated with diazepam. She began to recover after 10 days of supportive therapy and was discharged several weeks later on primidone therapy. Serious phenytoin hypersensitivity reactions may appear as dermatologic, lymphoid, or hepatic syndromes. Fever, rash, and lymphadenopathy often accompany hepatic injury. Encephalopathy and death may occur. Proposed mechanisms for phenytoin hypersensitivity include antigen-antibody reactions, alteration of lymphocyte function, and an enzyme abnormality causing the production of toxic metabolites. Treatment is supportive; phenobarbital and carbamazepine may be used with caution as alternate anticonvulsant therapy. The possibility of phenytoin hypersensitivity reactions should be considered when patients receiving phenytoin have unusual symptoms, particularly fever, rash, and lymphadenopathy.
Topics: Adult; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Female; Humans; Lymphatic Diseases; Phenytoin; Seizures
PubMed: 3677571
DOI: No ID Found -
BMJ Clinical Evidence Feb 2012About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. (Review)
Review
INTRODUCTION
About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of monotherapy in newly diagnosed generalised epilepsy (tonic clonic type)? What are the effects of additional treatments in people with drug-resistant generalised epilepsy? What are the effects of surgery in people with drug-resistant generalised epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 8 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: monotherapy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs (lamotrigine or levetiracetam) for drug-resistant epilepsy; and hemispherectomy for drug-resistant epilepsy.
Topics: Anticonvulsants; Carbamazepine; Epilepsy; Epilepsy, Generalized; Humans; Incidence; Phenytoin; Remission Induction; Valproic Acid
PubMed: 22348419
DOI: No ID Found -
BMJ Clinical Evidence May 2011About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. (Review)
Review
INTRODUCTION
About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of starting antiepileptic drug treatment following a single seizure? What are the effects of drug monotherapy in people with partial epilepsy? What are the effects of additional drug treatments in people with drug-resistant partial epilepsy? What is the risk of relapse in people in remission when withdrawing antiepileptic drugs? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or generalised epilepsy who are in remission; behavioural and psychological treatments for partial or generalised epilepsy (biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, relaxation therapy (alone or plus behavioural modification therapy, yoga); and surgery for drug-resistant temporal lobe epilepsy ( lesionectomy, temporal lobectomy, vagus nerve stimulation as adjunctive therapy).
Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Humans; Phenytoin; Vigabatrin
PubMed: 21549021
DOI: No ID Found -
American Journal of Hospital Pharmacy Mar 1981The use of rapid intravenous infusions of phenytoin sodium to achieve prompt plasma therapeutic concentrations of phenytoin was studied in adult epileptic patients. Six...
The use of rapid intravenous infusions of phenytoin sodium to achieve prompt plasma therapeutic concentrations of phenytoin was studied in adult epileptic patients. Six adult patients who experienced recent tonic-clonic seizures were selected for study. Four of them had not been treated with phenytoin before the study; two were on chronic phenytoin therapy but had subtherapeutic serum levels. A leading dose of phenytoin sodium (15 mg/kg in 100 ml of 0.9% sodium chloride injection) was infused at 30-50 mg/min. Blood samples were drawn before phenytoin administration, every five minutes during the infusion, and at 1, 2, 4, 8, 12, 18, and 24 hours after completion of the infusion. Adverse effects were monitored during the infusion. Pharmacokinetic variables were calculated. Patients received from 750 to 1500 mg phenytoin sodium (mean +/- S.D. = 1040.8 +/- 297.3 mg). From 5 to 30 minutes were required to reach therapeutic (10-20 micrograms/ml) serum phenytoin concentrations; concentrations peaked at 31.1 +/- 10.0 micrograms/ml. Four of the six patients had therapeutic serum concentrations at 18 hours after completion of the infusion. Adverse effects were minimal and not severe; no cardiotoxicities were noted. Phenytoin half-life was 31.2 +/- 8.4 hours, total plasma clearance was 47.2 +/- 10.7 ml/kg/hr, and volume of distribution was 1.96 +/- 0.46 liters/kg. It is concluded that rapid intravenous infusion of phenytoin appears to be a reasonably safe and effective method of rapidly reaching therapeutic phenytoin concentrations.
Topics: Blood Pressure; Epilepsy; Half-Life; Humans; Infusions, Parenteral; Phenytoin
PubMed: 7223748
DOI: No ID Found