To determine phenytoin concentration in the blood, to maintain an appropriate level, and to detect phenytoin toxicity
At regular intervals to monitor, as needed to detect low or toxic concentrations
A blood sample taken from a vein in your arm
This test measures the amount of phenytoin in the blood. Phenytoin is a drug that is used to treat some seizure disorders (also called epilepsy). Seizure disorders affect the brain’s ability to transmit electrical impulses and to regulate nerve activity. During a seizure, a patient may experience changes in consciousness, alterations in sight, smell, and taste, and may experience uncontrolled muscular convulsions of one or more parts of the body.
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 tumours. Seizures may also be seen in newborns as a result of head trauma that occurred in the womb or during birth. 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 UK since it was developed in 1938. It is still being prescribed but is gradually being replaced by newer drugs. Blood levels of phenytoin 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 may be difficult to maintain. The drug is metabolized by the liver and excreted in the urine. Enzymes in the liver process phenytoin at a rate that varies from patient to patient and that is affected by a patient's age (children metabolize it more quickly, the elderly metabolize it more slowly) and also by the health of their liver. When the body has reached its maximum 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:
Swelling of the gums and/or lymph nodes
Excess hair growth (hirsutism)
Insomnia (not sleeping properly)
In some cases, the severity of side effects may cause the 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 requested to measure and monitor the amount of phenytoin in the blood and to determine whether drug concentrations are in the appropriate (therapeutic) range. It may be requested every few days when a patient first begins taking phenytoin to help adjust the dose to the desired blood level. The test is then requested at regular intervals, and as needed, to monitor blood concentrations. One or more phenytoin tests may be requested if a patient starts or stops taking additional medications (to judge their effect, if any, on phenytoin levels) and may be requested if the patient has a seizure or if a doctor suspects toxicity.
Usually, a total phenytoin test is requested. 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.
When is it requested?
Phenytoin is requested frequently when a patient is starting phenytoin treatment and when/if a patient's treatment changes (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 requested when a patient's condition does not appear to be responding to phenytoin and they continue to have seizures, this is to determine whether concentrations are too low and the medication is ineffective or to determine if the patient is not taking the phenytoin regularly. It may also be requested when a patient experiences a troublesome level of side effects and/or exhibits symptoms that the doctor suspects may be due to toxicity.
What does the test result mean?
The therapeutic ranges for adults taking phenytoin have been established at approximately 5.0-20.0 mg/L for total phenytoin (bound plus unbound). Within this range, most people will respond to the drug without symptoms of toxicity. Response and side effects varies between individuals. 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, bone deformation related to vitamin D deficiency (osteomalacia), weakness and numbness in extremities (peripheral neuropathy), acne, and a thickening of facial features. Rarely, a patient may develop a severe rash and skin condition that requires hospitalisation.
Women who use phenytoin during pregnancy are at an increased risk of several birth defects. Women who wish to become pregnant should talk to their doctors prior to conception.
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.
Various 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, carbamazepine (can raise or lower), alcohol, aspirin (large doses), chloramphenicol, oestrogen, isoniazid, omeprazole, trimethoprim, and warfarin. Drugs that can decrease phenytoin include: antacids (when taken with phenytoin), folic acid, chronic alcohol abuse, rifampicin, and methotrexate. There are also a variety of other 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?
Phenytoin or another anti-seizure medication is usually taken every day (sometimes several times a day) for a patients lifetime. An exception to this may be patients 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 patient has status epilepticus (an acute, continuing seizure), then phenytoin may be given intravenously for rapid action.
Can I test my phenytoin level at home?