- Red, tiger or green top tube
- 5 mL of venous blood
Recommended sample collection time:
| Drug | Route of
Administration | Recommended
Collection
Time |
|---|
| Fosphenytoin | IV/IM | Trough: Just prior to when next dose is due
Peak: 10 minutes after IV or 90 minutes after IM |
| Phenytoin | IV | 2-4 hours after IV loading dose or just prior to when next dose is due |
| Phenytoin | PO | For therapeutic monitoring:
- 5-7 days after initiating therapy, change in dosing regimen, adding a second drug, or change in the patient's liver or GI function
- Again 3-5 weeks later
- For suspected toxicity: Immediately, and 6 hrs after last dose
|
Additional information
- Note the following times on the lab requisition form and the patient's chart:
- Trough specimen drawn (time)
- Peak specimen drawn (time)
- If orally (or IM) dosed, time of last dose
- If IV dosed, time drug started and completed infusion
- Handle sample gently to prevent hemolysis
- Send sample to lab immediately. If delay is expected, separate serum and refrigerate
- Phenytoin levels are obtained to measure the concentration of antiepileptic drug phenytoin in the blood
- Phenytoin is an anticonvulsant drug (sodium channel blocker) used as first-line or adjunctive treatment for partial and generalized seizures, Lennox-Gastaut syndrome, status epilepticus, and childhood epileptic syndromes
- Phenytoin may also rarely be utilized in the treatment of digoxin toxicity and alcohol withdrawal syndrome
- Antiepileptic drug levels in the therapeutic range are most effective, whereas high levels can be toxic and inadequate levels may lack therapeutic efficacy
- Measured levels are highly dependant upon dosing (amount and frequency), patient's body mass, and pharmacokinetic parameters such as bioavailability, volume of distribution, clearance, half-life, and protein binding
- After drug administration the drug concentration fluctuates between a maximum (peak) and a minimum (trough) level
Fosphenytoin Notes
- Fosphenytoin is a precursor of phenytoin used for short-term parenteral use when the oral form is unavailable or less advantageous such as to control status epilepticus and to prevent and control seizures during neurosurgery
- Fosphenytoin is preferable over phenytoin as it is compatible with glucose-containing solutions, less caustic, has minimal adverse and toxic effects, and it may be administered more rapidly as IV (or can be given IM)
- Its levels are measure as phenytoin levels with same therapeutic range
This section covers Antiseizure medication levels - Phenytoin. Other sections provide detailed information on other components of Antiseizure medication levels.
- The clinical utility of phenytoin levels include:
- To monitor compliance with therapeutic regimen in the treatment of epilepsy, prevention of seizures, and rarely as a mood stabilizer
- To monitor and evaluate change of medication or dosage
- Evaluation of overdose and prevention of toxicity, especially in combination with ethanol
- To monitor children, elderly people, and persons with poorly controlled seizures or if patient noncompliance is suspected
- To time reinstitution of chronic therapy after overdose
- The adverse effects and toxicity of phenytoin may clinically present as
- Central nervous system
- Eyes
- Gastrointestinal system
- Dermatological
- Cardiovascular (IV formulation)
- Tissue necrosis (IV formulation)
- Hematopoetic system
- Connective tissue system
- Coarsening of the facial features
- Enlargement of the lips
- Gingival hyperplasia (20%)
- Hypertrichosis
- Peyronie's disease
- Hypersensitivity reactions
- Metabolic symptoms such as osteomalacia and hypothyroidism (chronic toxicity)
- Exposure of phenytoin to the fetus may lead to fetal hydantoin syndrome, which may present as:
- Craniofacial anomalies, such as broad nasal bridge, wide fontanelle, low hairline, cleft lip/palate, epicanthal folds, low-set ears
- Short neck
- Microcephaly
- Small or absent nails
- Dislocated hip
- Hypoplasia of distal phalanges
- Impaired growth
- Mental retardation
- Congenital heart defects
- Conditions associated with the risk of developing early phenytoin toxicity include:
- Children
- Elderly patients
- Critically ill patients
- Impaired liver function (hypoalbuminemia)
- Renal disease (hypoalbuminemia)
- Elevated metabolic waste products, bilirubin, and urea (displaces phenytoin from albumin binding sites)
Additional information
- The plasma half-life after oral administration of phenytoin averages 22 hours and reaches steady state therapeutic levels by 4 to 6 days (5 to 7 half-lives) after initiation of therapy. Most of the drug is metabolized by the liver and excreted in bile as an inactive metabolite (HPPH), which is then reabsorbed from the intestinal tract and excreted in the urine
- Phenytoin is highly bound to albumin (>90%) at therapeutic concentrations, thereby patients with low serum albumin (hypoalbuminemia) have a higher percentage of free to bound phenytoin ratio and thus therapeutic or toxic reactions occur at a lower serum level
- Phenytoin is subject to drug interactions due to displacement of protein binding and extensive metabolism, and also cross-reactivity with metabolites. Thus, direct measurement of free phenytoin is selected patient, is a better index of anticonvulsant activity
- Many factors must be considered in effective dosing and monitoring of therapeutic drugs including patient age, weight, drug, route of administration, interacting medications, electrolyte balance, protein levels, water balance, conditions that affect absorption and excretion, and ingestion of other substances (foods, herbals, vitamins, and minerals) that can either potentiate or inhibit the intended target concentration
- Serum phenytoin is unaltered by dialysis
- Factors interfering with test results include
- Sample collection in serum separator tubes/gel tubes (gel slowly absorbs the drug)
- Serum frozen on cells or left standing on cells for several days
- Hepatic or renal disease
- In critically ill and uremic patients (false increase)
- Cross reacts with fosphenytoin (false increase)
- Related laboratory tests include:
This section covers Antiseizure medication levels - Phenytoin. Other sections provide detailed information on other components of Antiseizure medication levels.
Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.
| Conv. Units
(µg/mL) | SI Units
(µmol/L) |
|---|
| Total Phenytoin |
| Children/Adults | 10-20 | 40-70 |
| Neonates | 7-14 | 28-55 |
| Toxic | >25 | >100 |
| Lethal | >100 | >400 |
| Free Phenytoin |
| Therapeutic | 1-2 | 4-8 |
| Toxic | >3.5 | >14 |
This section covers Antiseizure medication levels - Phenytoin. Other sections provide detailed information on other components of Antiseizure medication levels.
Elevated serum phenytoin level is associated with incorrect dosing, overdose, poisoning and toxicity.
Drugs that may increase phenytoin levels or increase the risk of phenytoin toxicity include:
- Amiodarone
- Azapropazone
- Carbamazepine
- Chloramphenicol
- Cimetidine
- Disulfiram
- Ethanol
- Ethosuximide
- Fluconazole
- Halothane
- Ibuprofen
- Imipramine
- Isoniazid
- Levodopa
- Metronidazole
- Miconazole
- Nifedipine
- Oral anticoagulants
- Phenylbutazone
- Sulfonamides
- Trazodone
- Tricyclic antidepressants
- Trimethoprim
- Valproic acid
This section covers Antiseizure medication levels - Phenytoin. Other sections provide detailed information on other components of Antiseizure medication levels.
Decreased serum Phenytoin levels are associated with decreased therapeutic effect, inadequate dosing or non-compliance.
Drugs that may decrease phenytoin levels include:
- Antineoplastic drugs
- Bleomycin
- Calcium
- Carbamazepine
- Cisplatin
- Diazepam
- Diazoxide
- Ethanol (chronic)
- Folic acid
- Intravenous fluids containing glucose
- Nitrofurantoin
- Oxacillin
- Phenobarbital
- Rifampin
- Salicylates
- Sucralfate
- Theophylline
- Vinblastine
This section covers Antiseizure medication levels - Phenytoin. Other sections provide detailed information on other components of Antiseizure medication levels.