Formal Name
Phenytoin, total and free
This article was last reviewed on
This article waslast modified on September 22, 2020.
At a Glance
Why Get Tested?

To determine the level of the drug phenytoin in your blood in order to maintain a therapeutic level and to detect potential for toxicity

When To Get Tested?

At regular intervals to monitor; as needed to detect low or toxic concentrations

Sample Required?

A blood sample drawn from a vein

Test Preparation Needed?

None; however, be sure your healthcare practitioner knows about all medications (prescribed and over-the-counter), herbs, and supplements you are taking.

What is being tested?

This test measures the amount of phenytoin in the blood.

Phenytoin is a drug prescribed to treat or prevent the recurrence of certain types of seizures (see Epilepsy), including complex partial seizures (impaired consciousness that is preceded, accompanied, or followed by psychological symptoms) or generalized tonic-clonic seizures (involve abrupt loss of consciousness, respiratory arrest, muscle rigidity). It has been widely used in the United States since its development in 1938. It is still being prescribed but is beginning to be replaced by newer drugs. Phenytoin may be used alone or with phenobarbital or other anticonvulsants.

Phenytoin blood testing is ordered because phenytoin blood levels must be maintained within a narrow therapeutic range. If levels are too low, the affected person may experience seizures; if they are too high, the person may experience symptoms associated with phenytoin toxicity. These may include loss of balance and falling, involuntary eye movement from side to side (nystagmus), confusion, slurred speech, tremors, and low blood pressure.

Maintaining a therapeutic level of phenytoin in the blood can be a challenge due to several reasons:

  • The absorption rates vary among different preparations of the drug.
  • Phenytoin is metabolized by the liver enzymes. Enzymes in the liver process phenytoin at rates that differ from person to person and are affected by age (children metabolize it more quickly while the elderly metabolize it more slowly) and by the health of the liver. When the body has reached its capacity to process phenytoin, small increases in the dose can cause large increases in blood concentration, increasing the severity of side effects and causing phenytoin toxicity.
  • Most phenytoin is bound to protein in the bloodstream. But it is the unbound "free" portion that is active. If a person has a lower than normal amount of protein in their blood, such as low albumin in liver failure or in elderly, then the person may have an excess of active phenytoin.
  • A number of drug interactions could cause alteration of phenytoin levels.

Phenytoin's total effect can be unpredictable. Dosages must be adjusted slowly until a steady concentration in the blood is reached. The time to attain a steady-state level of phenytoin may vary from several days to several weeks because of substantial variations among patients in the amount of time it takes to metabolize phenytoin. Healthcare practitioners must also watch for side effects and adverse reactions during initial dosage adjustment and over time. In some cases, the severity of side effects may make it necessary to consider treating a patient with an alternative anti-seizure medication.

Accordion Title
Common Questions
  • How is the test used?

    The phenytoin test is used to optimize drug therapy, monitor the amount of phenytoin in the blood, determine whether drug concentrations are in the therapeutic range, and to monitor patient adherence.

    It may be ordered every few days when a person first begins taking phenytoin to help adjust the dose to the desired blood level. The test is then ordered at regular intervals and as needed to monitor blood concentrations. One or more phenytoin tests may be ordered if a person starts or stops taking additional medications (to judge their effect, if any, on phenytoin levels) and may be ordered if the person has a seizure or if a healthcare practitioner suspects toxicity.

    Under normal conditions, a total phenytoin test is appropriate for monitoring therapeutic levels because the balance between bound and unbound phenytoin in the blood is relatively stable.

    In certain conditions and disease states (e.g., renal disease, low blood levels of albumin), a free phenytoin test may be considered. These conditions and disease states can lead to an increase of "free" phenytoin and thus patients may experience symptoms of toxicity even though their total phenytoin results fall within the therapeutic range.

  • When is it ordered?

    Phenytoin is ordered frequently when a person begins phenytoin treatment and when/if a person's medications change (other drugs are started, stopped, or changed) or if there is a change in the status of the person's health. Once stable blood concentrations in the therapeutic range have been achieved, phenytoin is monitored at regular intervals to ensure that it remains in this range.

    The test may be ordered when a person's condition does not appear to be responding to phenytoin (e.g., the person continues to have seizures) to determine whether the concentration is too low, the medication is ineffective, and/or to determine if the person is complying with therapy (taking the phenytoin regularly).

    The test may also be ordered when a person experiences side effects or exhibits symptoms that the healthcare practitioner suspects may be due to toxicity. Toxic symptoms can affect the mouth, cardiovascular and nervous systems, and the eyes and include:

    • Swelling of the gums and/or lymph nodes
    • Excess facial and body hair (hirsutism)
    • Insomnia
    • Nausea
    • Vomiting
    • Confusion and irritability
    • Difficulty swallowing
    • Fatigue
    • Fever
    • Rashes
    • Involuntary eye movement
    • Abnormal heartbeat
    • Low blood pressure
    • Coma
    • Osteoporosis

    A free phenytoin level may be ordered when a person has a condition in which the percentage of free or active phenytoin may be increased. Some examples of these conditions include:

  • What does the test result mean?

    Test results may vary depending on the person's age, gender, health history, the method used for the testing and co-administrated medications.

    The therapeutic ranges for most adults have been established at 10.0-20.0 mcg/mL for total phenytoin (bound plus unbound) and 1.0-2.0 mcg/mL for free phenytoin (unbound only). This reference range for unbound phenytoin (free) was established based on an assumed 10% unbound drug fraction. However, the free fraction of phenytoin can vary from 3% to 37% among patients.

    In general, when phenytoin results are in the therapeutic range, most patients will respond to the drug without symptoms of toxicity. Response and side effects will be individual, however. Some people will experience seizures at the low end of the therapeutic range and some people will experience excessive side effects at the upper end. People should work closely with their healthcare practitioner to find the dosage and concentration that works the best for them. Dosage determinations and adjustments must be evaluated on a case-by-case basis.

  • Is there anything else I should know?

    People who take phenytoin long-term may develop vitamin D deficiency, numbness in their extremities due to nerve damage (peripheral neuropathy), acne, excessive hair on their face or body, a thickening of facial features, or weakness of their bones. Rarely, a person may develop a severe rash and skin condition that requires hospitalization.

    Women who use phenytoin during pregnancy are at an increased risk of having babies born with several types of birth defects, such as growth problems, heart defects, and cleft palate. Women who want to become pregnant should talk to their healthcare practitioner.

    Phenytoin is sometimes prescribed for other conditions such as trigeminal neuralgia, which causes episodes of sharp pain along the jaw, and other causes of nerve pain. This use must also be monitored.

    Phenytoin is not effective for patients with absence seizures (impaired consciousness, often abrupt onset and brief).

    A large variety of prescribed drugs, over-the-counter medications, and supplements can increase, decrease, or interfere with the concentration of phenytoin in the blood and its effects.

    • Drugs whose effects and/or levels are reduced by phenytoin include corticosteroids (e.g., prednisone), estrogens (for hormone replacement), warfarin, antidepressants, antilipidemic agents (e.g., atorvastatin, fluvastatin, and simvastatin), calcium channel blockers (e.g., nifedipine, verapamil), azoles (e.g., variconazole), oral contraceptives and other forms of birth control such as Depo-Provera or implants.
    • Drugs that may increase phenytoin blood levels include antiepileptic drugs (e.g., ethosuximide, oxcarbazepine, methsuximide), antidepressants (e.g., fluoxetine, fluvoxamine, sertraline), gastric acid reducing agents (e.g., H2 antagonists, omeprazole), sulfonamides (e.g., sulfamethizole, sulfaphenazole, and sulfamethoxazole) and others (e.g., amiodarone, methylphenidate, and isoniazid).
    • Drugs that may reduce phenytoin blood levels include antiepileptic drugs (e.g., carbamazepine), antiviral agents (e.g., fosamprenavir, ritonavir), others (e.g., diazepam, rifampin, theophylline) and chronic alcohol abuse.
    • The oral absorption of phenytoin can be reduced by antacids containing magnesium, calcium carbonate, calcium salts, or enteral feeding products.

    Many more drugs interact with phenytoin, so tell your healthcare practitioner about any prescription or over-the-counter drugs, supplements, or herbal products you take. Patients should not increase, decrease, or stop taking their medication without consulting with their healthcare provider as it can increase their risk of having a seizure and may affect other medications that they are taking.

  • How long will I need to be on phenytoin?

    Phenytoin or another anti-seizure medication is usually taken every day (sometimes several times a day) for a person's lifetime. An exception to this may be people whose seizures are caused by a temporary condition; they may only need the medication for a short period of time.

  • How is phenytoin taken?

    It may be taken as a pill or a liquid. When a person has status epilepticus (an acute, continuing seizure), then phenytoin is given intravenously for rapid action.

  • Can I test my phenytoin level at home?

    No, it requires specialized equipment. Blood samples are collected from a vein in the arm and tested in the laboratory.

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