How Genes Influence The Breakdown Of Carbamazepine?

What Is Carbamazepine?

Carbamazepine is an anticonvulsant or antiepileptic medication used to treat seizures and nerve pain.

It is commonly prescribed for epilepsy patients.

This drug is one of the World Health Organization’s Essential medicines for 2021.

This drug is sold under the brand names Tegretol, Neurotol, and Epitol.

Is Carbamazepine A Sedative?

Sedation is a common side effect of most anticonvulsant medicines, including carbamazepine.

What Is Carbamazepine Used For?

Carbamazepine is used to treat epilepsy (a neurological condition that causes seizures and abnormal sensations).

It is also used to treat neuropathic pain (pain caused due to nervous system damage).

Different metabolic disorders, conditions like diabetes and multiple sclerosis, physical injury or wound, and even nutritional deficiencies can cause neuropathic pain.

Carbamazepine is also used to treat certain mood disorders and episodes of mania.

Carbamazepine may also be used to treat bipolar disorder in some patients.

Studies show that this drug, by itself or in combination with other drugs, helps treat and handle the signs of bipolar disorder.

How Does Carbamazepine Work?

Neurons in the brain are responsible for sending electrical pulses (messages) that control movements.

During a seizure, the electrical activities in the brain fire up, and there is a sudden burst of pulses sent randomly, with no pattern.

This causes problems like jerking of limbs, stiffening of the body, uncontrolled movements, and even loss of consciousness.

Neurons have sodium channels, and these channels help these electrical pulses move from one cell to another.

Carbamazepine acts as a sodium channel blocker.

By slowing down or turning off these channels, the drug prevents random pulses from being triggered and gives the brain time to recover.

How Long Does Carbamazepine Stay In Your System?

The half-life of carbamazepine is about 35 hours. It may stay in the system for up to 4 days.

Side Effects Of Carbamazepine

Some of the common side effects of carbamazepine are:

Dizziness
Drowsiness
Nausea
Migraines
Vomiting
Dry mouth
Mild skin rashes
Constipation

Some of the more severe side effects of carbamazepine are:

Abnormal heartbeats
Increased risk of anemia
Decrease in sodium levels
Liver damage, causing symptoms like darker urine, yellowing of the skin, and upper stomach pain
Increased risk of suicides

Does Carbamazepine Cause Weight Gain?

Yes. Weight gain can be a possible side effect of carbamazepine.

A study shows that the expected weight gain while on this drug can be between 7 and 15 kg in some patients.

Can Carbamazepine Cause Tinnitus?

Studies suggest that there could be a certain degree of hearing loss (tinnitus) in some patients who had overdosed on carbamazepine.

This adverse effect has not been noticed in people who take regular doses.

Can Carbamazepine Affect Your Memory?

Carbamazepine does not seem to cause memory dysfunction.

However, according to a study, carbamazepine levels in the blood may make it difficult to carry out long-term and complex memory access tasks.

Carbamazepine: Interactions With Other Drugs

Carbamazepine may interact with other drugs, leading to changes in drug efficacy or worsened side effects.

Notify your doctor if you are on any of the below medications along with carbamazepine.

Heart medicines like rivaroxaban
Blood thinners like warfarin
Antibiotics and antifungals like erythromycin and fluconazole
HIV medications
Calcium Channel Blockers (drugs that reduce blood pressure)
Other epilepsy medications like phenobarbital
Immunosuppressants
Monoamine Oxidase Inhibitors (MAOIs) (antidepressants)
Anti-anxiety medications like amitriptyline

Can You Take Vitamin D With Carbamazepine?

Studies show that carbamazepine decreases vitamin D levels in the body.

Therefore, doctors may suggest vitamin D supplementation when you are on this drug. Talk to your doctor about this.

Can You Take Carbamazepine With Topiramate?

Combining carbamazepine with topiramate, another epilepsy medication, may lead to carbamazepine intoxication.

Therefore, talk to your doctor before combining these medications.

Carbamazepine: Gene-Drug Interactions

The BAG6 Gene

The BAG cochaperone 6 gene (BAG6 gene) provides instructions for producing a protein that plays a role in cell death.

rs750332 is a Single Nucleotide Polymorphism (SNP) in the BAG6 gene.

People with the CC and CT genotypes of this SNP have an increased risk of developing Stevens-Johnson Syndrome (SJS) when treated with carbamazepine compared to those with the TT genotype.

Genotype	Implications
CC	Increased risk of developing Stevens-Johnson Syndrome (SJS) when treated with carbamazepine.
CT	Increased risk of developing Stevens-Johnson Syndrome (SJS) when treated with carbamazepine.
TT	Decreased risk of developing Stevens-Johnson Syndrome (SJS) when treated with carbamazepine.

The MICA Gene

The MHC Class I Polypeptide-Related Sequence A gene (MICA gene) produces a stress-induced antigen protein.

Changes in the gene may lead to skin conditions like psoriasis.

rs2848716 is an SNP in the MICA gene.

People with the C allele of this gene are associated with an increased risk of developing Stevens-Johnson Syndrome (SJS) when treated with carbamazepine than those with the G allele.

Allele	Implications
C	Increased risk of developing Stevens-Johnson Syndrome (SJS) when treated with carbamazepine.
G	Decreased risk of developing Stevens-Johnson Syndrome (SJS) when treated with carbamazepine.

The HSPA1L Gene

The Heat shock 70 kDa protein 1L gene (HSPA1L gene) provides instructions for producing the HSPA1L protein.

This protein is associated with cell growth, multiplication, differentiation, and death.

rs2227956 is an SNP in the HSPA1L gene.

People with the G allele of this SNP have a lesser severity of hypersensitivity when treated with carbamazepine compared to those with the A allele.

Allele	Implications
G	Decreased severity of hypersensitivity when treated with carbamazepine
A	No such protection present when treated with carbamazepine

The HLA-A Gene

The Human Leukocyte Antigen-A gene (HLA-A gene) provides instructions for producing the HLA-A protein.

This protein plays a role in determining the outcomes of infectious diseases.

rs1061235 is an SNP in the HLA-A gene.

People with the T allele of this SNP have an increased adverse response to carbamazepine compared to those with the A allele.

Allele	Implications
T	Increased adverse response to carbamazepine
A	Decreased adverse response to carbamazepine

Recommendations To Use Carbamazepine

Carbamazepine Allergy

Some people may be allergic to carbamazepine and experience the below signs immediately after consumption.

Breathing difficulties
Hives
Excessive itching and redness in the skin
Swelling of the face, nose, and lips
Tightness in the chest and throat while breathing

Call 911 or rush to the nearest ER if you experience these symptoms.

Risk Of Stevens-Johnson Syndrome (SJS)

SJS is a severe skin condition that causes blisters and rashes in the skin, death of the top layer of skin, and severe pain.

Carbamazepine-induced SJS is a rare yet serious side effect of this drug.

If you notice flu-like symptoms and the development of rashes in the skin after using the drug, contact your nearest hospital right away to rule out SJS.

Risk Of Low White Blood Cell Levels

Carbamazepine treatment may decrease White Bood Cell (WBC) count, including the levels of neutrophils, monocytes, and lymphocytes.

Very rarely, it may cause a condition called leukopenia (very low WBC count, increasing risk of infections).

Doctors may recommend getting a complete blood count test done periodically for people on carbamazepine long-term.

Risk of Bone Loss

A study analyzed changes in vitamin D levels in 47 epileptic children on carbamazepine.

After six months of treatment, the mean vitamin D levels in the children had reduced.

Lack of vitamin D makes it difficult for the body to absorb calcium and, as a result, leads to bone loss.

Doctors may suggest vitamin D supplementation for those on carbamazepine.

Pregnancy And Breastfeeding

Though carbamazepine is considered one of the safer antiepileptic medications, it may increase the risk of neural tube defects (defects in the brain, spine, and spinal cord) in the fetus.

If you are pregnant and on carbamazepine, talk to your doctor to understand the risks.

Though carbamazepine may pass on in the breastmilk, there are no studies to show that it affects the growth and development of the baby.

Talk to your doctor and understand the risks of breastfeeding while on this drug.

Suicidal Thoughts

According to the FDA, all antiepileptic drugs risk creating suicidal thoughts.

Studies show that carbamazepine may cause 5.6 to 44.8 suicide attempts per 1000 person-years.

The risk may be higher for people with existing mental health conditions.

If you have suicidal thoughts, dial 911 and get help right away.

Can I Drink Alcohol With Carbamazepine?

Alcohol can make the symptoms of carbamazepine worse, including dizziness, nausea, and difficulty in concentration.

It is recommended you don’t combine alcohol and carbamazepine.

Genetic Testing

Genetic testing will help doctors predict the severity of side effects when a patient is put on carbamazepine.

It will further help plan the right doses to prevent hypersensitivity symptoms and adverse effects.

Analyze Your Genetic Response to Carbamazepine

Summary

Carbamazepine is an anticonvulsant medication used to treat epilepsy symptoms and nerve pain. It is also prescribed to treat mood disorders, including bipolar disorder.
Carbamazepine works as a sodium channel blocker and reduces the speed at which electrical impulses are sent from the brain.
Some of the side effects of carbamazepine are dizziness, nausea, vomiting, abnormal heartbeat, and suicidal tendencies.
Carbamazepine may interact with heart medications, blood thinners, antibiotics, antifungal medications, immunosuppressants, and anti-anxiety medications, leading to drug efficacy changes or worse side effects.
Changes in the BAG6, MICA, HSPA1L, and HLA-A genes can all increase or decrease a person’s adverse effects on using carbamazepine.
Carbamazepine may cause severe allergies, bone loss, and Stevens-Johnson Syndrome (SJS) in rare cases.
Studies show that carbamazepine may lead to neural tube defects in babies when consumed during pregnancy.
Genetic testing will help understand the risk of adverse effects of using carbamazepine.