Phenytoin

The phenytoin test is requested to measure 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, 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 phenytoin 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.

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 the concentration remains stable.

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 (either because the dose is inadequate or the patient is not taking the phenytoin regularly) or the medication is ineffective and an alternative drug should be considered. Phenytoin testsmay 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.

The usual therapeutic range for adults taking phenytoin has been established at approximately 5.0-20.0 mg/L (20 – 80 µmol/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 vary 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. Others are well controlled on concentrations outside the therapeutic range. Patients should work closely with their doctor to find the dosage and concentration that works 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 considered to be 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.

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. Vitamin D supplements should be considered in patients who are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium. Rarely, a patient may develop a severe rash and skin condition that requires hospitalisation (more common in individuals of Han Chinese or Thai origin).

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 phenytoin), 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 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.

Phenytoin or another anti-seizure medication is usually taken every day (sometimes twice daily) for a patient’s lifetime. An exception to this may be patients whose seizures are caused by a temporary condition, who may only need the medication for a short period of time.