Carbamazepine

What is being measured?
This test measures the concentration of carbamazepine in the blood. Carbamazepine is a medicine used mainly to treat some seizure disorders (particularly epilepsy), but it is also prescribed for bipolar disorder and to relieve some types of nerve pain. It can be prescribed on its own or in combination with other antiepileptic medicines.

During an epileptic seizure a patient may have changes in consciousness, sight, smell and taste, and may have convulsions. Seizures can also be associated with serious conditions, such as high fever and head injury, or with chronic diseases, such as metabolic disorders and brain tumours. In many cases the cause is not known. Seizures can range from a single episode to recurrent attacks. Seizures are classified according to the areas of the brain involved. Carbamazepine is prescribed to prevent certain types of recurrent seizures.

Bipolar disorder is a condition characterised by alternating episodes of depression and mania that can last days, weeks, months or years. During a depressive episode, people may feel sad, hopeless and lacking in energy, and may have thoughts of suicide. During a manic episode, people may be euphoric or irritable, lose their judgement and take risks. Carbamazepine is also prescribed for patients with bipolar disorder, particularly in the manic phase.

Trigeminal neuralgia, a condition associated with pain in the facial nerve, muscle spasms and paroxysmal choreoathetosis are sometimes treated with carbamazepine.

Carbamazepine levels are monitored because the medicine must be kept within a narrow therapeutic range. If levels are too low, the patient may have symptoms of the condition being treated (for example seizures, manic episodes or pain); levels that are too high can lead to toxic side effects. This balance is difficult to achieve for several reasons:

• Oral doses of carbamazepine are absorbed from the gut to varying degrees.
• Since carbamazepine is metabolised by the liver, anything that affects liver function can also affect levels of the medicine.
• Most of the medicine binds to plasma proteins, but the active form is the free form. Conditions that affect the binding of the medicine to protein can therefore affect how well the treatment works.
• A metabolite of carbamazepine, carbamazepine-10,11-epoxide, is also active and contributes to the effect of the medicine.
• Many medicines taken together with carbamazepine can interact with it or affect its metabolism and blood levels.

Carbamazepine doses must be adjusted until a steady concentration is reached. The dose needed to reach this steady concentration varies from person to person and can change over time.

How is the sample collected for testing?
The sample is taken from a vein, usually in the arm.

Is any special preparation needed to ensure the quality of the sample?
No preparation is needed.

How is it used?
When is it requested?
How are the results interpreted?
Is there anything else I should know?

How is it used?
The carbamazepine test measures “total” carbamazepine, both the protein-bound and the free portion. It is requested to measure and monitor the concentration of carbamazepine in the blood to make sure it stays within the therapeutic range. Free carbamazepine or carbamazepine-10,11-epoxide may sometimes also be requested, together with total carbamazepine, to assess their contribution to the patient’s treatment.

A doctor may request the test to help assess side effects and adverse reactions during initial dosing or after changes in treatment over time. Side effects that can occur at any dose but are more noticeable at higher concentrations include:

• Dizziness
• Uncoordinated movements
• Drowsiness
• Blurred or double vision
• Nystagmus (involuntary movement of the eyeball)

Other side effects can include:

• Itchy skin rash
• Nausea
• Diarrhoea
• Constipation
• Headache
• Confusion

Carbamazepine can sometimes cause liver dysfunction, low sodium, a fall in white blood cells (WBCs) or an increase in eosinophils (a type of WBC). In some cases the severity of the side effects may lead the patient and doctor to look for an alternative treatment for epilepsy, bipolar disorder or nerve pain.

When is it requested?
Carbamazepine tests are often requested at the start of treatment and at regular intervals as needed, to make sure therapeutic concentrations are maintained. An additional total carbamazepine test may be requested if the dose is changed, if a patient starts or stops taking other medicines (to judge their effect in combination with carbamazepine), or if symptoms return (for example a seizure, neuralgia or mood changes). Once carbamazepine blood levels have stabilised, they are monitored at regular intervals to make sure they stay within the therapeutic range.

The carbamazepine test may be requested when there seems to be no response to treatment. Concentrations may not be high enough, the patient may not have been taking the medicine regularly, or the medicine may not work for that person. The test may also be requested when a patient has troublesome side effects and/or develops complications. Free carbamazepine and/or carbamazepine-10,11-epoxide may also be requested together with total carbamazepine to assess their contribution to treatment. Results are sometimes assessed as the ratio of free to total carbamazepine.

Patients should ask their doctor how often the test should be done. The recommended time is often just before taking the medicine.

How are the results interpreted?
The therapeutic range of carbamazepine when taken on its own is 4-12 µg/mL. Levels above 15 µg/mL are considered toxic. Reference ranges may vary slightly from laboratory to laboratory and may be expressed in other units, such as mg/L. Doctors and patients should use the therapeutic range and units set by the laboratory doing the test.

Within the therapeutic range most patients do not have significant side effects; however, responses vary from person to person. Some people have seizures, mood changes or neuralgia even with concentrations at the lower end of the therapeutic range, while others have significant side effects at high values. Changes in free carbamazepine and carbamazepine-10,11-epoxide may contribute to these effects. Patients should work closely with their doctor to find the dose and concentration that suit them best.

In general, if carbamazepine values are within the therapeutic range and the patient has no recurrent seizures, mood changes or nerve pain and no significant side effects, the dose of carbamazepine being taken is considered adequate. Patients should not increase, reduce or stop taking their medicines without consulting their doctor, as such changes could increase the risk of a seizure and affect the action of other medicines they are taking. Doses and treatment adjustments must be assessed case by case.

Is there anything else I should know?
Carbamazepine can affect or be affected by other medicines such as paracetamol (acetaminophen), warfarin, fluoxetine, isoniazid, theophylline, erythromycin, ethosuximide and benzodiazepines. The metabolism of carbamazepine can be increased by medicines such as phenobarbital, primidone and phenytoin, which lower carbamazepine levels in the blood. Some of these medicines may also need their blood levels monitored. Some herbal supplements can also affect carbamazepine levels. You should tell your doctor if you use any of these substances.

In December 2007 the US Food and Drug Administration (FDA) announced the importance of including, when prescribing carbamazepine to Asian patients, a genetic test to be carried out before starting treatment. The genetic test, which detects the HLA-B*1502 gene variant, can identify a significantly increased risk of developing a rare but serious skin disease. This gene variant is found almost exclusively in people of Asian descent. Patients who test positive should avoid treatment with carbamazepine.

Carbamazepine can increase the risk of birth defects and foetal death, and can reduce the effect of oral contraceptives. Women of childbearing age should discuss this with their doctor.

1. How long will I need to stay on carbamazepine?
Patients with seizure disorders, bipolar disorder or chronic neuralgia will take carbamazepine or other medicines for life. If carbamazepine stops working or causes side effects, the patient may need to take other medicines. If a person has seizures caused by a temporary condition, they may need the medicine only for a short time.

2. Will my doctor often request carbamazepine and carbamazepine-10,11-epoxide tests?
Generally not. These additional tests may be requested once or twice to understand how carbamazepine is metabolised, but they are not routine tests.