Anyone at any age can experience a seizure. Seizures can be caused by high fevers, decreased oxygen supply, head trauma, exposure to certain toxins and drugs, withdrawal from alcohol after heavy abuse, severe infections, extremely low blood sugar, metabolic disorders, and brain tumors. Seizures may also be seen in newborns as a result of head trauma that occurred in utero or during the birthing process. In many cases, the cause of seizures is not known and the frequency and severity in those affected varies from patient to patient and may change over time. Patients may experience a single seizure and never have another, may have occasional seizures, or may have recurrent seizures. In rare cases, a patient may have a seizure that starts and does not stop without prompt medical intervention. Most patients do not experience residual damage from seizures, but muscle contractions during attacks may cause acute injuries, and losses in consciousness can lead to falls. In some cases, recurrent seizures can eventually lead to progressive brain damage.
Phenytoin is prescribed to help prevent the recurrence of certain types of seizures. 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 levels must be maintained within a narrow therapeutic range. Too little and the patient will experience seizures; too much and the patient will experience symptoms associated with phenytoin toxicity, such as: loss of balance and falling, nystagmus (eye movement from side to side), confusion, slurred speech, tremors, and low blood pressure.
Keeping a constant level of phenytoin in the blood can be complicated. The drug is metabolized by the liver and excreted in the urine. Enzymes in the liver process phenytoin at a rate that will vary from patient to patient and that it is affected by a patient’s age (children metabolize it more quickly, the elderly metabolize it more slowly) and by the health of their liver. When the body has reached its capacity to process phenytoin, small increases in the dose can cause large increases in blood concentrations, increasing the severity of side effects and causing phenytoin toxicity. Most phenytoin is bound to protein in the bloodstream; it is the unbound “free” portion that is active. If a patient has a lower than normal amount of protein in their blood, then they may have an excess of active phenytoin. Adding to the complexity is the fact that phenytoin often interacts with other drugs, increasing or decreasing the other medication’s effectiveness and/or increasing or decreasing phenytoin’s effectiveness.
The total effect can be unpredictable. Dosages of phenytoin must be adjusted slowly until a steady concentration in the blood is reached. The actual amount of drug that it takes to reach this steady state will vary from person to person and may change over time. Doctors must also evaluate their patient for side effects and adverse reactions during initial dosage adjustment and over time. These may include:
In some cases, the severity of side effects may cause patient and doctor to seek another anti-seizure medication.
How is the sample collected for testing?A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?No test preparation is needed.
How is it used?The phenytoin test is ordered to measure and monitor the amount of phenytoin in the blood and to determine whether drug concentrations are in the therapeutic range. It may be ordered every few days when a patient 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 patient starts or stops taking additional medications (to judge their effect, if any, on phenytoin levels) and may be ordered if the patient has a seizure or if a doctor suspects toxicity.
Usually, a total phenytoin test is ordered. In the blood, phenytoin is highly bound to serum proteins. Only the portion of phenytoin that is unbound or “free” is pharmacologically active. Under normal conditions, the balance between bound and unbound phenytoin in the blood is relatively stable, so measuring the total phenytoin (bound plus unbound) is appropriate for monitoring therapeutic levels. However, in certain conditions and disease states, that balance can be upset, the percentage of free or active phenytoin can increase and the patient may experience symptoms of toxicity even though their total phenytoin result falls within therapeutic range. In such cases, doctors may order a free phenytoin test to monitor the patient’s levels.
When is it ordered?Phenytoin is ordered frequently when a patient is starting phenytoin treatment and when/if a patient’s medications change (other drugs are started, stopped, or changed). Once stable blood concentrations in the therapeutic range have been achieved, then phenytoin is monitored at regular intervals to ensure that it remains in this range.
The test may be ordered when a patient’s condition does not appear to be responding to phenytoin (continues to have seizures) to determine whether concentrations are too low, the medication is ineffective, and/or to determine if the patient is complying with therapy (taking the phenytoin regularly). It may also be ordered when a patient experiences a troublesome level of side effects and/or exhibits symptoms that the doctor suspects may be due to toxicity.
A free phenytoin level may be ordered when a patient has a condition where the percentage of free or active phenytoin may be increased. Some examples include:
- Kidney failure
- Hepatic (liver) disease
- Hypoalbuminemia (low levels of albumin, a type of protein present in the blood)
- If the patient is taking other medications such as aspirin, naproxen or ibuprofen
What does the test result mean?The therapeutic ranges for adults taking phenytoin have been established at 10.0-20.0 µg/mL for total phenytoin (bound plus unbound) and 1.0-2.0 µg/mL for free phenytoin (unbound only). The range for percent free phenytoin is 8-14%. Within these ranges, most people 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. Patients should work closely with their doctor to find the dosage and concentration that works the best for them.
In general, when phenytoin results are in the therapeutic range, the patient is not having recurrent seizures, and the patient is not experiencing significant side effects, then the dosage of phenytoin a patient is receiving is adequate. Patients should not increase, decrease or stop taking their medication without consulting with their doctor as it can increase their risk of having a seizure and may affect other medications that they are taking. Dosage determinations and adjustments must be evaluated on a case-by-case basis.
Is there anything else I should know?Patients who take phenytoin long-term may develop vitamin D deficiency, osteomalacia, peripheral neuropathy (weakness and numbness in extremities), acne, and a thickening of facial features. Rarely, a patient may develop a severe rash and skin condition that requires hospitalization.
Women who use phenytoin during pregnancy are at an increased risk of several birth defects. Women who want to become pregnant should talk to their doctors about this subject.
Phenytoin is sometimes prescribed for other conditions, such as to help treat trigeminal neuralgia (which causes episodes of sharp pain along the jaw) and other causes of nerve pain. This use must also be monitored.
A variety of prescribed drugs, over-the-counter medications, and supplements can increase, decrease, or interfere with the concentrations of phenytoin in the blood. Drugs that can increase phenytoin in the body include: diazepam, carbamezepine (can raise or lower), alcohol, aspirin (large doses), chloramphenicol, estrogen, isoniazid, omeprazole, trimethoprim, and warfarin. Drugs that can decrease phenytoin include: antacids (when taken with phenytoin), folic acid, chronic alcohol abuse, rifampin, and methotrexate. There are also a variety of drugs that are affected by phenytoin. Patients should talk to their doctors about all of the drugs and supplements that they are taking and about the medication(s) that are right for them. Phenytoin is not effective for every kind of seizure and will not work for every patient.
How long will I need to be on phenytoin?
How is phenytoin taken?
Can I test my phenytoin level at home?