Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Dilantin fda prescribing information, side effects and uses. Phenytoin is a potent inducer of hepatic drug metabolizing enzymes. Therapeutic drug monitoring of antiepileptic medications 5 useful dasgupta, 2007. Translating phenytoin therapeutic drug monitoring for potential. At toxic doses, patients experience vertical nystagmus, double vision, sedation, slurred speech, cerebellar ataxia, and tremor. To prevent its toxicity and ensure efficacy, continuous therapeutic monitoring is required. For selected drugs therapeutic drug monitoring aims to enhance drug efficacy, reduce toxicity or assist with diagnosis. Also, the therapeutic drug monitoring tdm laboratory provides an electronic report of all completed serum drug concentrations of patients admitted to. Abstract therapeutic drug monitoring of phenytoin is carried out to ensure effective and safe levels.
Properly applied therapeutic drug monitoring tdm is a proven method of reducing adverse drug events and hence healthcare costs. Phenytoin pht, sold under the brand name dilantin among others, is an antiseizure medication. Drug monitoring in patients with epilepsy should not be routinely performed unless. Out of 95 samples tested for valproic acid, 62% had therapeutic level and 20% had subtherapeutic and 18% had toxic level of drug. Patients with serum drug concentrations on noncovered services are identified on a daily basis utilizing sunrise clinical manager scm. Pdf therapeutic drug monitoring of phenytoin is carried out to ensure effective and safe levels. Additionally, our data show that even in patients without known causes. In hospitalized patients with status epilepticus, intravenous lorazepam is the drug of choice for initial emergency therapy. Therapeutic drug monitoringantiepileptic drugs eadie. Therapeutic drug monitoring can aid dosage adjustment see section 3 for further advice.
Useful strategies exist for these drugs such that concentrations can be deter. Therapeutic drug monitoring phenytoin has a narrow therapeutic index and has nonlinear kinetics. Therapeutic drug monitoring tdm, pharmacist, effectiveness introduction therapeutic drug monitoring tdm is defined as the measurement of the concentration of a prescribed xenobiotic or endogenous compound made in the laboratory that, with appropriate interpretation, may directly influence prescribing procedures watson et al. Clinical guideline for the use of phenytoin in epilepsy page 4 of 12 3. Introduction therapeutic drug monitoring aims to individualise drug therapy and avoid both sub therapeutic and toxic plasma drug concentrations. Evidencebased implementation of free phenytoin therapeutic. Summary guideline for therapeutic drug monitoring tdm in adults. Therapeutic drug monitoring therapeutic drug monitoring tdm is the use of drug concentration measurements in body fluids as an aid to the management of drug therapy for the cure, alleviation or prevention of disease. Appropriate therapeutic drug monitoring of phenytoin. Evidencebased implementation of free phenytoin therapeutic drug monitoring. Pharmacokinetics, phenytoin, therapeutic drug monitoring. Summary guideline for therapeutic drug monitoring tdm in. Section 6 therapeutic drug monitoring kieran hand consultant pharmacist antiinfectives the objectives of this section are. Antiepileptic drug pharmacokinetics and monitoring in children.
It may also be used for certain heart arrhythmias or neuropathic pain. Therapeutic drug monitoring of phenytoin showed wide fluctuation in its plasma level. So, when talking about therapeutic drug levels, its important to know that there are many therapeutic or drugs that we generally measure therapeutic levels with. However, for the nclex, theres really four that you really kinda need to know. It is useful for the prevention of tonicclonic seizures and focal seizures, but not absence seizures. Phenytoin clearance showed a timedependent increase. Therapeutic drug monitoring of phenytoin is carried out to ensure effective and safe levels. Director, neuroscience institute and le bonheur comprehensive epilepsy program. Each antacid was administered as 160 meq at 1 and 3 hr after each meal and at bedtime on the day phenytoin was given. Therapeutic drug monitoring therapeutic drug monitoring tdm is the use of drug concentration measurements in body fluids as an aid to the management of drug therapy. Epilepsy, therapeutic drug monitoring, valproic acid. At therapeutic doses, phenytoin may produce nystagmus on lateral gaze. Therapeutic drug monitoring of phenytoin by measurement of plasma concentrations is often employed to optimize clinical efficacy while avoiding adverse effects.
Pdf therapeutic drug monitoring of antiepileptic drugs. Dual effects of carbamazepinephenytoin interaction. With such drugs, small increases in dose or in bloodserum concentrations could lead to toxic effects. Apr 22, 2019 inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Therapeutic drug monitoring of antiepileptic medications. Timedependent decline in serum phenytoin concentration. Clinical decision support of therapeutic drug monitoring of phenytoin. Phenytoin is an antiepileptic drug, also called an anticonvulsant. Nhs grampian acute sector summary guideline for therapeutic drug monitoring tdm in adults version 2 antibiotic assays on the microbiology request card for serum levels, please supply details of the antibiotic level required, the time and date of the sample. Therapeutic drug monitoring tdm involves tailoring a dose regimen to an individual patient, by maintaining plasma or blood concentrations within a particular range therapeutic range or therapeutic window. Phenytoin works by slowing down impulses in the brain that cause seizures. It is hard to get a simple, accurate, rapid, easily available, economical and highly sensitive assay in.
Evaluation of fosphenytoin therapeutic drug monitoring in. Some of the factors complicating phenytoin dosing include a narrow therapeutic window, high degree of. Phenytoin is 90% bound to serum proteins, mainly albumin, and does not show any concentrationdependent binding within the therapeutic range. Also, the therapeutic drug monitoring tdm laboratory provides an electronic report of all completed serum drug concentrations of patients admitted to the hospital twice daily. Despite its apparent advantages, it has inherent limitations. Monitoring of free phenytoin or free valproate may be indicated in the following situations. Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in scandinavia. This can result in difficulties in dose adjustment and interpretation of levels. It is highly protein bound about 90%, primarily to albumin. Antiepileptic drug aed pharmacokinetics and therapeutic drug monitoring in children james w. Therapeutic drug monitoring of phenytoin is necessary to ensure therapeutic and nontoxic levels. Serum protein concentrations of drug can vary due to factors such as drug interactions, liver disease, pregnancy and old age.
A guide to therapeutic drug monitoring melissa faye. Phenytoin has very challenging pharmacokinetic properties. Because of this, many physicians monitor serum concentrations of phenytoin to assist in optimising therapy. Phenytoin and the prodrug fosphenytoin are frequently used in the treatment of critically ill patients experiencing seizures or as prophylaxis in neurologically injured patients 1,2,3. A patient with a drug concentration within the therapeutic range is exhibiting unexpected toxicity. Therapeutic drug monitoring is defined as the measurement made in the laboratory of a parameter that, with appropriate interpretation, will directly influence prescribing procedures. Some of the factors complicating phenytoin dosing include a narrow therapeutic window, high degree of pr. Fosphenytoin and phenytoin adultpediatric inpatient. Phenytoin is a potent inducer of hepatic drugmetabolizing enzymes. Capitals indicate lifethreatening, underlines indicate most frequent. Introduction therapeutic drug monitoring aims to individualise drug therapy and avoid both subtherapeutic and toxic plasma drug concentrations.
Fosphenytoin and phenytoin adultpediatric inpatient clinical. Therapeutic drug monitoring of phenytoin showed wide fluctuation. The maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration was simulated to be 779. Monitoring of plasma or serum or sometimes, in earlier years, whole blood concentrations of the older antiepileptic drugs phenobarbitone and phenytoin began to come into use in the late 1960s, initially as a research procedure which seemed as if it might find a. Therapeutic drug monitoring an overview sciencedirect. Therapeutic drug monitoring some drugs have a narrow therapeutic index, which means that there is only a small difference between the minimum effective concentrations and the minimum toxic concentrations in the blood. Therapeutic drug monitoring of 21day oral etoposide in. By intrapatient comparison at constant phenytoin put dose, the effect of increased carbamazepine cbz dose was studied in 32 epileptic outpatients treated with a combination of pht and cbz. Some of the factors complicating phenytoin dosing include a narrow therapeutic window, high degree of protein binding, and nonlinear. The international association of therapeutic drug monitoring and clinical toxicology adopted the following definition for drug monitoring. Therapeutic drug monitoring of antiepileptic drugs. Phenytoin exhibits nonlinear elimination pharmacokinetics and has been known to have high interpatient dosing variability, with therapeutic drug monitoring being the standard of care in patients receiving. Dec, 2012 phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt.
Nhs tayside phenytoin prescribing and monitoring guideline. Clinically important displacement can be caused by. Clinical guideline for the use of phenytoin in epilepsy final. Wheless, md professor and chief of pediatric neurology. It has a narrow therapeutic range and has nonlinear pharmacokinetics. It is hard to get a simple, accurate, rapid, easily available, economical and highly sensitive assay in one method for therapeutic monitoring of phenytoin. The intravenous form is used for status epilepticus that does not improve with benzodiazepines.
In a clinical trial of adults with inhospital status epilepticus, intravenous lorazepam was superior to intravenous phenytoin. Phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt. Once the decision to monitor the concentration of a therapeutic drug has been made, it is important that a biological sample is collected to provide a clinically meaningful measurement. Therapeutic drug monitoring of phenytoin in critically ill patients. However, serum drug levels should only be taken when there is a clear indication to guide patient management. Where this cannot be done, therapeutic drug monitoring is used in two major situations 3. To test your ability to monitor serum levels for drugs with a narrow therapeutic index. Guide for drug level monitoring of commonly used medications. Clinical pharmacokinetics of phenytoin springerlink. Therapeutic drug monitoring free download as powerpoint presentation. Hypoalbuminemia, renal failure, and interactions with other highly protein. Clinical guideline for the use of phenytoin in epilepsy.
Some large hospitals have services which provide support with drug monitoring and interpretation of results. Therapeutic drug monitoring kieran hand consultant pharmacist antiinfectives the objectives of this section are. Route onset peak duration phenytoin itoyn po 224hr1wk. Phenytoin has a narrow therapeutic range, with potentially significant adverse events associated with under or overmedicating a particular patient. Monitoring of phenytoin serum levels is recommended when a drug interaction is suspected. Therapeutic drug monitoring an overview sciencedirect topics. It does not treat all types of seizures, and your doctor will determine if it is the right medicine for you. This has serious implications for the management of epilepsy with phenytoin and for therapeutic drug monitoring of phenytoin. However, serum drug levels should only be taken when there is a clear indication to. The drug has a moderately large volume of distribution and is approximately 90% bound to plasma proteins. Therapeutic drug monitoring of phenytoin by simple, rapid. If phenytoin is stopped abruptly, this may result in increased seizure frequency, including status epilepticus. Clinical decision support of therapeutic drug monitoring.
Aug 01, 2000 this has serious implications for the management of epilepsy with phenytoin and for therapeutic drug monitoring of phenytoin. Therapeutic monitoring of vancomycin in adult patients. Amitava dasgupta, in clinical challenges in therapeutic drug monitoring, 2016. This is most commonly accomplished by measurement of total phenytoin plasma concentrations. A small change in dosing can result in a large change in blood levels. Therapeutic drug monitoring of phenytoin is carried out to ensure effective and.
Updated with approvals from wirral drug and therapeutics committee. Phenytoin levels may take up to an hour to be reported and treatment in status. The mean pht plasma concentration, as well as the concentrationdose ratio for pht, became significantly higher secondary to increased doses of cbz 14. Clinical guideline for the use of phenytoin in epilepsy page 1 of 12.
Practical issues in therapeutic drug monitoring ideally, a quality drug assay should be performed within a time frame that is clinically useful. Therapeutic drug monitoring of phenytoin rationale and current. A guide to therapeutic drug monitoring sage journals. Some of the factors complicating phenytoin dosing include a narrow therapeutic window, high degree of protein binding, and nonlinear pharmacokinetics. Phenytoin preparations are not bioequivalent and care must be taken. Introduction measurements of drugs like aminoglycosides, digoxin, phenytoin, or theophylline for making decisions during treatment are accepted practice in internal medicine.
Therapeutic drug monitoring abbott core laboratory. Therapeutic drug monitoring of phenytoin in critically ill. Feb 14, 2012 therapeutic drug monitoring of phenytoin by measurement of plasma concentrations is often employed to optimize clinical efficacy while avoiding adverse effects. Guidelines for therapeutic drug monitoring q pulse reference no. Therapeutic drug monitoring wirral medicines management. Indications for monitoring free drug concentrations. However, there is often overfrequent or inappropriate. To test your ability to monitor serum levels for drugs with a narrow therapeutic.
It is suggested that the dose of phenytoin should be adjusted. Clinically important displacement can be caused by bilirubin and. All phenytoin results are reported in the following panel, with an adjusted phenytoin value. Thus, for some anticonvulsants, notably phenytoin, antiinfective agents antimalarial, antimicrobial, and. A guideline on safe prescribing, administration and monitoring of iv phenytoin on paediatric wards was written recently. Usefulness of monitoring free unbound concentrations of therapeutic drugs in patient management. Pharmacokinetic monitoring of antiepileptic drugs grupo aula. The therapeutic efficacy of phenytoin in adult patients is associated with a wide range of serum levels. However, many published papers have indicated that free phenytoin concentration correlates better with. Monitoring of plasma or serum or sometimes, in earlier years, whole blood concentrations of the older antiepileptic drugs phenobarbitone and phenytoin began to come into use in the late 1960s, initially as a research procedure which seemed as if it might find a future application in the management of epilepsy. Its toxic and subtherapeutic levels were quite high.