Carbamazepine side effects and how to avoid them

Common carbamazepine side effects | Serious side effects |  Side effects timeline | Contraindications | Warnings | Interactions | How to avoid side effects | How to treat side effects

Carbamazepine is a generic prescription anticonvulsant that controls seizures in people with epilepsy and relieves nerve pain due to trigeminal neuralgia. Many people know this drug as one of its brand-name versions: Tegretol, Tegretol XR, Epitol, or Carbatrol. There are a variety of formulations of carbamazepine available: immediate-release tablets, chewable tablets, extended-release capsules, and oral suspensions. No matter what the formulation is, carbamazepine quiets nerves by reducing their electrical activity and blocking their ability to signal other nerves. In this way, it prevents many types of seizures—partial seizures, generalized tonic-clonic seizures, and mixed seizures—as well as alleviating nerve pain. Carbamazepine is effective at quieting nerves, so it’s commonly used off-label to treat bipolar disorder, nerve pain, fibromyalgia, dementia, schizophrenia, restless legs syndrome, and similar conditions. It is, however, relatively moderate in its side effects, but it can cause problems with other drugs or pre-existing conditions.

Common side effects of carbamazepine

Carbamazepine side effects in order of incidence are:

• Dizziness
• Drowsiness
• Poor muscle control and unsteadiness
• Nausea
• Vomiting
• Tiredness
• Constipation
• Itching
• Dry mouth
• Skin rash
• Blurred vision
• Seeing double
• Elevated blood pressure
• Tremor 
• Headache
• Tingling of the skin
• Vertigo
• Low sodium
• Reduced thyroid function

Serious side effects of carbamazepine

The most serious side effects of carbamazepine include:

• Serious heart rhythm disturbances
• Blood disorders
• Liver poisoning
• Low sodium levels
• Swollen pancreas
• Fainting
• Osteoporosis
• Elevated pressure in the eye
• Suicidal thoughts and behaviors
• Severe allergic reactions
• Severe skin reactions

How soon do carbamazepine side effects start?

Many mild side effects due to carbamazepine begin early in treatment, most commonly drowsiness, dizziness, nausea, vomiting, and unsteadiness. Many of these are directly due to the drug’s effects on the nervous system. Problems with blood pressure and vision can also happen early in treatment. Some of the more serious side effects are delayed reactions that occur after the drug has been taken for a while. These include severe skin reactions and blood disorders.

How long do carbamazepine side effects last?

Mild side effects of carbamazepine may improve over time or at least feel like they’re improving. Fortunately, these side effects tend to be tolerable. If they’re not, they will usually improve when the drug is stopped, typically about two to three days after the last dose if the drug has been taken for a while. Some adverse effects, such as blood disorders, liver problems, or pancreatitis, may take longer to improve and require medical treatment. 

What are the long-term side effects of carbamazepine?

For both seizure disorder and trigeminal neuralgia, healthcare professionals will prescribe carbamazepine for as long as it works and the side effects are tolerable. Some people take this medication for years—often with other medications as well. However, long-term use of anti-seizure medications, such as carbamazepine, phenytoin, or valproic acid, can reduce bone density. In some cases, they can make bones softer, more brittle, and more vulnerable to fractures. In those cases, a healthcare provider may switch to a drug related to carbamazepine called oxcarbazepine because the evidence indicates that it does not affect bone density.

Carbamazepine contraindications

Some people with certain pre-existing medical conditions cannot take carbamazepine at all:

• Bone marrow depression (decreased ability to make blood cells)
• Any history of an allergic or drug reaction to carbamazepine
• Any history of an allergic or drug reaction to tricyclic antidepressants, such as amitriptyline

Pregnancy

Because of a known risk of birth defects, carbamazepine is not recommended for use in pregnant women. When it is used in pregnant women, regular testing for birth defects may need to be performed.

Breastfeeding

Carbamazepine is not recommended in women who are breastfeeding. Carbamazepine is present in breast milk and may cause problems in a nursing infant. Women are advised to discontinue breastfeeding or switch to a different medication.

Children

Carbamazepine is approved for use in infants, children, and adolescents to treat seizure disorders. As long as dosing is correctly calibrated to weight, the effectiveness and side effects are not significantly different for them when compared to adults. 

Seniors

Healthcare professionals use caution when prescribing carbamazepine to people older than 65 years of age. There is an increased risk of fainting, falling, low sodium, confusion, agitation, fractures, and heart problems in seniors. Regular blood tests may be required to monitor carbamazepine levels in the blood, as well as sodium levels.

Carbamazepine warnings

Carbamazepine is a powerfully effective drug. Unfortunately, this means that it may cause problems in some people with pre-existing conditions, ethnic background, or if too much drug is taken.

Black box warning

A black box warning is the FDA’s signal that a drug has a relatively high risk of causing a serious problem. For carbamazepine, there are two black box warnings listed on carbamazepine’s drug information:

• Severe skin reactions. Carbamazepine can cause severe and even life-threatening drug reactions that mainly affect the skin: Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis. People of Asian descent, particularly Han Chinese, are far more likely to carry a gene variant (HLA-B 1502) that makes them more likely to have one of these drug reactions. A genetic test may be required before treatment.
• Blood disorders. Several types of blood disorders are possible side effects of carbamazepine, but the risk of two of them, agranulocytosis and aplastic anemia, is considered relatively high. Agranulocytosis occurs when there’s a drop in one type of white blood cell (granulocytes), increasing the risk of serious infections and death. Aplastic anemia occurs when the bone marrow cannot make enough blood cells of all types, causing fatigue and vulnerability to infections and bleeding episodes. These are both serious problems, so healthcare professionals will regularly monitor blood cell counts throughout carbamazepine treatment.

Cautions

Carbamazepine can cause some problems in people with certain pre-existing conditions, including:

• Variant of the gene HLA-B 1502 (because of potential severe skin reactions)
• Asians (because of potential severe skin reactions)
• Variant of the gene HLA-A 3101 (because of potential allergic reactions)
• Depression (because of the risk of suicide when carbamazepine is taken)
• Heart problems (which can be worsened by carbamazepine) including:
  • Congestive heart failure
  • Cardiac disease
  • Coronary artery disease
  • Heart block
  • Irregular heartbeats (arrhythmias)
• Severe kidney disease (which can be worsened)
• Low sodium (which can be worsened)
• Blood disorders (which can be worsened)
• Some types of porphyria, a buildup of natural chemicals in the body related to red blood cells (which can be worsened)
• A history of high pressure in the eye (which can be worsened)
• Liver disease (which increases the risk for side effects)

Finally, carbamazepine does not help with certain types of seizures, including absence seizures (brief loss of attention), myoclonic seizures (muscle jerks or twitches), and atonic seizures (“drop attacks” or sudden loss of muscle strength).

Abuse and dependence

Carbamazepine is not considered to be a risk for drug abuse or physical dependence. 

Withdrawal

For those with a seizure disorder, carbamazepine must be discontinued with a steadily decreasing dose to prevent drug withdrawal seizures.

Overdose

If too much carbamazepine is taken, seek medical help immediately. The maximum dosage is 1600 mg per day for adults. Doubling this maximum dose could be deadly. This maximum daily dosage for adults is also enough to kill a young child. Symptoms of an overdose manifest within an hour or two of taking the medication. They include severe drowsiness, slow and shallow breathing, blood pressure changes, loss of consciousness, fast heartbeat, and coma.

Carbamazepine interactions

Carbamazepine has several drug interactions that may cause serious issues. These medications should not be prescribed with carbamazepine:

• Monoamine oxidase inhibitors (MAOIs)
• AIDS/HIV antiviral medications
• Some hepatitis C antiviral medications
• Some antifungal medications
• The antidepressant Wellbutrin (bupropion)
• The antidepressant nefazodone
• The antipsychotic Latuda (lurasidone)
• The GERD treatment metoclopramide

Other medications that may interact with carbamazepine include:

• Drugs that slow down the body’s metabolism of carbamazepine, raising the risk of carbamazepine side effects
• Drugs that speed up the body’s metabolism of carbamazepine, making treatment less effective
• Drugs that are metabolized faster when combined with carbamazepine, making them less effective—this includes hormonal contraceptives
• Drugs that are metabolized slower when combined with carbamazepine, making side effects from those drugs more likely

These four categories add up to a very long list of drugs. Healthcare providers and pharmacists can help answer questions regarding how carbamazepine interacts with these drugs. Some treatments may be altered, dosages may be changed, or, in some cases, nothing will change, but side effects will be more closely monitored.

How to avoid carbamazepine side effects

While most of carbamazepine’s side effects are tolerable, it’s still possible to avoid or minimize problems when taking this drug.

1. Give the prescriber a complete medical history

Because carbamazepine can cause problems with many different medical conditions, make sure the prescriber has a complete medical history.  Important information to share includes:

• Bone marrow depression
• Heart problems 
• Blood problems
• Liver problems
• Kidney problems
• A history of suicidal thoughts or suicide attempts
• Mental health issues such as bipolar disorder, mania, or psychosis
• Any history of high pressure in the eye
• Drinking
• Pregnancy or pregnancy plans
• Breastfeeding or breastfeeding plans

2. Tell the prescriber about all medications being taken

Many medications interact with carbamazepine. The easiest thing to do is to simply give the prescriber a complete list of all prescription drugs, over-the-counter medications, and supplements being taken. It’s very important to tell the prescriber about any of the following drugs:

• MAO inhibitors
• Nefazodone
• Birth control pills
• Lithium
• Grapefruit or grapefruit juice

If any new prescription drugs are added to the mix, be sure to tell the healthcare provider who has prescribed carbamazepine.

3. Take this drug as instructed

Only take carbamazepine as instructed. Follow the dosing schedule. Do not take extra medicine or change the dose. Do not stop taking the medicine without talking to the prescriber. A missed dose can be taken when remembered, but skip it if it’s almost time for the next dose.

4. Avoid alcohol

Alcohol will worsen many of the side effects of carbamazepine, especially drowsiness, dizziness, and unsteadiness. The combination also increases the risk of liver problems. 

5. Avoid grapefruit

Grapefruit can increase the risk of side effects when taking carbamazepine. 

6. Avoid driving or other risky activities

Drowsiness and dizziness caused by carbamazepine may affect how well a person can drive a car, operate machinery, or engage in any other activity that requires alertness and attention. It’s recommended that people taking carbamazepine take a break from driving and similar activities until it is certain that they are not impaired by the drug.

How to treat side effects of carbamazepine

Many side effects can be handled at home, but a few will require medical attention.

Suicidal thoughts and behaviors

A person thinking about or planning suicide requires immediate medical help. Contact a healthcare professional at any significant sign of suicidality including:

• Thoughts or talk about suicide or death
• New or worsening depression 
• New or worsening anxiety
• Aggressive, hostile, or violent behavior
• Panic attacks
• Agitation, restlessness, irritability, or anger
• Acting on dangerous impulses
• Extreme increase in activity or talking
• Trouble sleeping

Blood problems

Carbamazepine can cause a variety of blood problems. Some of them can be serious. Symptoms may vary depending on specific circumstances, but get medical help if any of the following symptoms are noticed:

• Frequent or long-lasting infections
• Easy bruising
• Nosebleeds
• Bleeding gums
• Purple or red spots on the skin
• Unusual tiredness
• Weakness

Liver problems

Carbamazepine can poison the liver. Over time, this can reduce liver function. Contact the prescribing healthcare provider immediately if you notice:

• Pain on the right side of the upper abdomen
• Dark urine
• Loss of appetite
• Nausea
• Vomiting
• Yellowing of the skin or eyes

Allergic reactions

An allergic reaction while taking carbamazepine requires the drug to be stopped. Immediately contact the prescriber at any sign of an allergic reaction, such as: 

• Swelling of the face, throat, or mouth
• Skin rash
• Hives
• Sore throat
• Trouble swallowing
• Trouble breathing

Skin reactions

Potentially life-threatening skin reactions are possible with carbamazepine. Some people may be more vulnerable than others. These drug reactions typically begin with a skin rash, so take this symptom seriously. Get immediate medical help if any of the symptoms of a severe skin reaction are noticed, including:

• Skin rash
• Hives
• Sores in the mouth
• Skin blisters
• Skin peeling

Sources

• Carbamazepine, Epocrates
• Carbamazepine drug summary, Prescriber’s Digital Reference
• Carbamazepine tablet prescribing information, U.S. National Library of Medicine
• Long-term anticonvulsant therapy leads to low bone mineral density — evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells, Experimental and Clinical Endocrinology & Diabetes
• Tegretol prescribing information, U.S. National Library of Medicine
• The effects of oxcarbazepine on bone metabolism, Acta Neurologica Scandinavica