Carbamazepine

Formal Name:
Total Carbamazepine

This article was last modified on November 9, 2021

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Therapeutic Drug Monitoring

At a Glance

Why Get Tested?

To determine the concentration of carbamazepine in the blood to establish an appropriate dose and maintain a therapeutic level

When To Get Tested?

At regular intervals to monitor the drug’s level; when indicated to detect low or excessive (potentially toxic) concentrations

Sample Required?

A blood sample drawn from a vein

Test Preparation Needed?

None, but you should talk to your health care provider about the timing of the sample collection. Often, the recommended time is when the level in the blood is expected to be at its lowest, just before the next dose is taken.

What is being tested?

Carbamazepine is a drug that is primarily used to treat certain seizure disorders (also called epilepsy) but is also prescribed to stabilize the moods of people with bipolar disease, to ease alcohol withdrawal, and to help alleviate some types of nerve pain. It may be prescribed by itself or in combination with other antiepileptic drugs. This test measures the level of carbamazepine in the blood.

Carbamazepine levels are monitored because the drug must be maintained within a narrow therapeutic range. If the level is too low, the drug may not be effective and the person may experience a recurrence of symptoms (i.e., seizures, mania, or pain); if the level is too high, the person may experience toxic side effects. Maintaining a therapeutic level of this drug can be a challenge to achieve for several different reasons:

Oral doses of carbamazepine are absorbed in the gastrointestinal tract at widely variable rates.
Since carbamazepine is metabolized by the liver, anything that affects liver function can affect blood levels of the drug.
Upon a long-term administration, carbamazepine induces its own metabolism.
Much of the drug is bound to plasma protein, but it is the free portion of the drug that is active. Conditions that affect protein binding of the drug may affect therapeutic effectiveness. This may occur when someone has low blood albumin, kidney failure, or when they are very young (newborn) or elderly.
The metabolite of carbamazepine, carbamazepine-10,11-epoxide, is also therapeutically active and contributes to the overall effect of the medication.
Several drugs, if taken in conjunction with carbamazepine, may interact or affect its metabolism and blood levels.

Dosages of carbamazepine must be adjusted carefully in order to reach a steady concentration in the blood. The actual amount of drug required to reach this steady state will vary from person to person and may change over time.

Carbamazepine is usually monitored long-term because it is prescribed to treat the chronic conditions epilepsy, bipolar disorder, trigeminal neuralgia, and nerve pain from diabetes.

Epilepsy affects the brain’s ability to transmit electrical impulses and to regulate nerve activity. During a seizure, a person may experience changes in consciousness, alterations in sight, smell, and taste, and may experience convulsions. The frequency of seizures varies from a single episode, to occasional seizures, to recurrent seizures. Carbamazepine is prescribed to help prevent specific types of recurrent seizures.

Bipolar disorder is a mental condition that is characterized by cycles of depression and mania that may last for days, weeks, months, or years. During a depressive episode, those affected may feel sad, hopeless, worthless, and have thoughts of suicide. During a manic episode, those affected may be euphoric, irritable, use poor judgment, and participate in risky behaviors. Carbamazepine is prescribed to help even out the moods of the person with bipolar disorder, especially mania.

Trigeminal neuralgia, a condition associated with facial nerve pain and muscle spasms, and paroxysmal choreoathetosis, a movement disorder that causes involuntary movements of the limbs, trunk, and facial muscles, are also sometimes treated with carbamazepine. So is diabetic peripheral neuropathic pain, which affects the functionality, mood, and sleep patterns of approximately 10-20% of people with diabetes mellitus.

Common Questions

How is it used?

The carbamazepine test is used to measure and monitor the amount of carbamazepine in the blood to determine whether the level of drug is within the therapeutic range. Carbamazepine is primarily used to treat certain seizure disorders (also called epilepsy) but is also prescribed to stabilize the moods of people with bipolar disease, to ease alcohol withdrawal, and to help alleviate some types of nerve pain.

Initially, the test may be used to establish the appropriate dose for an individual. Depending on the results of the blood test, the dose of drug may be adjusted up or down until the blood level reaches the therapeutic range. Subsequent tests are then used to ensure that the level remains in the therapeutic range. If a person’s health changes or if, for example, they begin taking other drugs, the test may be used to determine whether an adjustment to the prescribed dose is necessary.

A healthcare practitioner may use a carbamazepine test to help evaluate someone who is experiencing side effects or adverse reactions or a recurrence of symptoms.

A routine carbamazepine test measures total carbamazepine, both protein-bound and free portions of the drug. Sometimes a test to measure free carbamazepine or the biologically active metabolite, carbamazepine-10,11-epoxide, is ordered along with the total carbamazepine test to evaluate their contribution to a person’s therapy.

When is it ordered?

Carbamazepine tests are ordered frequently at first, then at regular intervals and as needed to ensure that therapeutic blood concentrations are maintained.

Additional total carbamazepine tests may be ordered if dosages of the drug are changed or if the treated person starts or stops taking additional medications to judge their effect, if any, on the carbamazepine level. Once blood concentrations of carbamazepine have stabilized, concentrations are monitored at regular intervals to ensure that they remain within therapeutic range.

The carbamazepine test may be ordered when a person does not appear to be responding to therapy and has a recurrence of symptoms such as seizure, nerve pain, or bipolar mood swings. The blood level may not be high enough, the person may not be taking the medication regularly, or the drug may be ineffective for that person.

Carbamazepine tests may also be ordered when a person experiences a troublesome level of side effects and/or develops complications. Side effects that may be seen at any dose but that are related to higher concentrations include:

Dizziness
Uncoordinated movement
Sleepiness
Blurred or double vision
Involuntary back and forth movement of the eyeball

Other side effects may include:

Red, itchy rash
Nausea
Diarrhea
Constipation
Headache
Confusion

A healthcare practitioner should be contacted immediately if someone has serious side effects, including:

Pale skin, rapid heart rate, trouble concentrating
Fever, chills, or sore throat
Mouth and throat ulcers
Easy bruising or bleeding
Severe tingling, numbness, pain, muscle weakness
Confusion, agitation, vision problems, or hallucinations
Shortness of breath
Swelling of the ankles or feet
Urinating less than usual
Yellowing of the skin or eyes
Severe skin reaction

Carbamazepine can also sometimes cause liver dysfunction, low sodium levels, a decrease in white blood cells, or an increase in eosinophils (a type of white blood cell). In some cases, the severity of side effects may necessitate use of a different anti-seizure, bipolar, or nerve pain medication.

A free carbamazepine test and/or a carbamazepine-10,11-epoxide test may also be ordered along with the total carbamazepine test when a health care practitioner wants to evaluate the contribution of the free drug and/or its metabolite to drug therapy. The healthcare practitioner may choose to do so when the result from a total carbamazepine test is within the therapeutic range but the treated person is experiencing side effects. Sometimes results are evaluated as a percentage of free to total carbamazepine.

What does the test result mean?

The therapeutic range for carbamazepine when it is taken by itself is about 4 to 12 mcg/mL (micrograms per milliliter). Levels above 15 mcg/mL are considered toxic. Ranges vary slightly from laboratory to laboratory, however, and may be expressed in other units such as mg/L (milligrams per liter). Health care practitioners and patients should use the therapeutic ranges and units established by the laboratory that performs the testing.

Within the therapeutic range, most people will respond to the drug without excessive side effects; however, response varies with each individual. Some people will experience seizures, mood swings, or nerve pain at the low end of the therapeutic range while some people will experience excessive side effects at the upper end. Variations in free carbamazepine and carbamazepine-10,11-epoxide can contribute to this response. People who use this medication should work closely with their health care provider to find the dosage that works the best for them.

In general, if carbamazepine test results are within the therapeutic range and the treated person is not having recurrent seizures, mood swings, or nerve pain and is not experiencing significant side effects, then the dosage of carbamazepine is considered adequate.

Is there anything else I should know?

People should not increase, decrease, or stop taking their medication without consulting with their health care provider as it can increase the risk of having a seizure and may affect other medications being taken. Dosage determinations and adjustments must be evaluated on a case-by-case basis.

Likewise, people should tell their healthcare providers about any other prescription drugs, over-the-counter medicines, or herbal supplements being taken. A very long list of prescription medicines may interact dangerously with carbamazepine. Among these are commonly prescribed medications, including warfarin, fluoxetine and other antidepressants, isoniazid, theophylline, erythromycin, ethosuximide, and benzodiazepines. Carbamazepine can also affect or be affected by over-the-counter medications such as acetaminophen and by herbal supplements such as St. John’s wort. Do not begin taking a new medication without consulting your health care practitioner.

The metabolism of carbamazepine can be increased by drugs such as phenobarbital, primidone, and phenytoin, decreasing carbamazepine concentrations in the blood. Some of these drugs may also require monitoring with other blood tests because the plasma concentrations may be decreased.

Grapefruit juice can increase the level of carbamazepine in the blood.

Some people who take carbamazepine may become more sensitive to sunlight and may need to avoid sunlight. Sunlight may cause a skin rash, itching, redness or other discoloration of the skin, or severe sunburn.

Use of carbamazepine has been associated with aplastic anemia, damage to the bone marrow and blood stem cells, and with agranulocytosis, a relatively lower number of white blood cells.

Carbamazepine can increase the risk of certain birth defects and fetal death and can decrease the effectiveness of oral contraceptives. Women of childbearing age should talk to their healthcare provider about this.

How long will I need to be on carbamazepine?

People who have epilepsy, a bipolar disorder, or chronic nerve pain will typically take carbamazepine or other medications throughout their lifetime. If carbamazepine ceases to be effective or causes adverse effects, then the person may need to be given different drug(s). If someone has seizures that are caused by a temporary condition, then the person may only need the medication for a short period of time.

Will my doctor order free carbamazepine or carbamazepine-10,11-epoxide frequently?

Generally, no. These additional tests may be ordered once or twice to help evaluate how your body is metabolizing and using carbamazepine, but they typically are not used for routine monitoring.

I heard there is another test that certain people should have before taking carbamazepine. What is it?

According to a 2007 U.S. Food and Drug Administration (FDA) alert and clinical labelling of carbamazepine, people of Asian descent should get a genetic test before starting therapy with carbamazepine. The genetic test detects for the presence of the HLA-B*1502 allele. People with the HLA-B*1502 allele who begin taking carbamazepine are at a significantly increased risk of developing rare but dangerous or even fatal skin reactions (Stevens-Johnson syndrome or toxic epidermal necrolysis). The HLA-B*1502 allele occurs almost exclusively in people with Asian ancestry. Those who test positive should avoid treatment with carbamazepine, phenytoin, or fosphophenytoin.

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