Carbamazepine

Carbamazepine is an aromatic anticonvulsant that is widely used in therapy for epilepsy, trigeminal neuralgia, and acute manic and mixed episodes in bipolar I disorder ¹. Carbamazepine works by decreasing nerve impulses that cause seizures and nerve pain, such as tregimenal neuralgia and diabetic neuropathy. Carbamazepine indications for epilepsy are specifically for partial seizures with complex symptomatology (psychomotor, temporal lobe), generalized tonic seizures (grand mal), and mixed seizure patterns ². Carbamazepine is not indicted for absence seizures ³. Carbamazepine is FDA indicated as first-line treatment trigeminal neuralgia or tic douloureux. Randomized control trials have shown that carbamazepine has similar efficacy to lithium in acute manic episodes.

Carbamazepine was approved for use in epilepsy in the United States in 1968 and it is still in common use with more than 2 million prescriptions being written yearly. Current indications include prevention and management of partial, complex, mixed and generalized seizures. It is used alone or in combination with other anticonvulsants. Carbamazepine is also effective in trigeminal neuralgia and peripheral neuropathies, but the mechanisms of its analgesic actions are not known. Carbamazepine is used off label for behavioral disorders and depression.

Carbamazepine is used off-label for refractory schizophrenia ¹. Simple well designed trials have shown efficacy in patients with schizophrenia with EEG abnormalities, schizophrenia with violent episodes, and schizoaffective disorder. Carbamazepine improves both positive and negative symptoms in schizophrenic patients ⁴. Other off-label uses of this drug include treatment of restless leg syndrome and decreasing agitation and aggression in patients with dementia ⁵. Another prominent off-label use of this drug is the treatment of neuropathic pain and fibromyalgia ⁶. In patients with moderate to severe alcohol withdrawal syndrome, Carbamazepine has been shown to have clinical efficacy in treatment. However, this is not approved by the FDA, and it has not been shown to prevent alcohol withdrawal seizures as compared to benzodiazepines ⁷.

Carbamazepine is available as conventional tablets, extended-release tablets (Tegretol XR), suspensions, and solutions. Tablets of 100 mg and 200 mg and extended release capsules of 100, 200 and 400 mg (Carbatrol, Equetro) are available, as are liquid formations and chewable forms for use in pediatrics. The liquid formation is absorbed faster than the other two modes of administration, and the extended-release tablet is absorbed slightly slower than conventional tablets. Carbamazepine is available in multiple generic forms and under the commercial names as Tegretol, Carbatrol, Equetro and Epitol. The recommended starting dose in adults for seizures is 200 mg twice daily in adults and 100 twice daily in children under 12 or 100 mg four times daily, with increase in dose by 100 to 200 mg at weekly intervals based upon clinical response, but generally not exceeding 1200 mg daily. Doses in children are based upon body weight. Minimum effectively levels in adults and children over 12 years is 800 mg to 1200mg daily for treatment of epilepsy. In children from six to 12 years, the effective level for treatment of epilepsy is 400 mg to 800 mg daily ⁸. Typically, lower doses are used for trigeminal neuralgia and other less established indications (restless leg syndrome, bipolar disorders, chorea).

The extended-release tablet (Tegretol XR) is usually taken twice a day with meals. The extended-release capsule (Carbatrol, Equetro) is usually taken twice a day with or without meals. To help you remember to take carbamazepine, take it at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take carbamazepine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the extended-release tablets whole; do not split, chew, or crush them. The extended-release capsules may be opened and the beads inside sprinkled over food, such as a teaspoon of applesauce or similar food. Do not crush or chew the extended-release capsules or the beads inside them.

Shake the suspension well before each use to mix the medication evenly.

Carbamazepine may help control your condition but will not cure it. It usually takes a couple of weeks for carbamazepine to work. Continue to take carbamazepine even if you feel well. Do not stop taking carbamazepine without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you have a seizure disorder and you suddenly stop taking carbamazepine, your seizures may become worse. Your doctor will probably decrease your dose gradually.

Common side effects of carbamazepine include feeling sleepy (drowsiness), sedation, dizziness, headaches, ataxia, blurred vision, nausea, vomiting, and skin rash. These are usually mild and go away by themselves.

Carbamazepine mechanism of action

Currently, the mechanism of action for carbamazepine in humans is still not understood completely by researchers. It has been proposed via animal research that this drug works by reducing polysynaptic responses and blocking the post-tetanic potentiation. Carbamazepine is an iminostilbene that is chemically related to tricyclic antidepressants and unrelated in structure to other anticonvulsants. Carbamazepine suppresses spread of seizure activity by reduction in the post-tetanic potentiation of synaptic transmission.

It was also shown to reduce pain that is caused by stimulation of an infraorbital nerve in cats and rats. Another group of findings was the reduction of the action potential in the nucleus ventralis of the thalamus and depression of the lingual mandibular reflex. This reduction of action potential occurs by carbamazepine binding to voltage-dependent sodium channels and inhibiting the generation of rapid action potentials. This effect increases with increased rates of neuronal firing ⁸.

Carbamazepine special precautions

Before taking carbamazepine:

• tell your doctor and pharmacist if you are allergic (rash, wheezing, hives, difficulty swallowing or breathing, swelling of your face, eyes, eyelids, lips, or tongue) to carbamazepine, amitriptyline (Elavil), amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor, Zonalon), imipramine (Tofranil), nortriptyline (Pamelor), oxcarbazepine (Trileptal), protriptyline (Vivactil), other medications for seizures such as phenobarbital, phenytoin (Dilantin, Phenytek), or primidone (Mysoline), any other medications, or any of the ingredients in carbamazepine preparations. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor if you are taking nefazadone or certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as delavirdine (Rescriptor). Your doctor will probably tell you not take carbamazepine with these medications. Also, tell your doctor if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate), or if you have stopped taking an MAO inhibitor within the past 14 days. Your doctor will probably tell you not to take carbamazepine. If you stop taking carbamazepine, you should wait at least 14 days before you start to take an MAO inhibitor.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: acetaminophen (Tylenol); acetazolamide (Diamox); albendazole (Albenza); alprazolam (Panax); aminophylline; anticoagulants (‘blood thinners’) such as apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa), rivaroxaban (Xarelto), and warfarin (Coumadin, Jantoven); antidepressants such as amitriptyline (Elavil), bupropion (Wellbutrin, Zyban), buspirone (BuSpar), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), mirtazapine (Remeron), nortriptyline (Pamelor); antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), ketoconazole, and voriconazole (Vfend); aprepitant (Emend); aripiprazole (Abilify); buprenorphine (Butrans, Sublocade); bupropion (Aplenzin, Wellbutrin, Zyban); cimetidine (Tagamet); ciprofloxacin; cisplatin (Platinol); corticosteroids such as dexamethasone and prednisolone (Prelone); clarithromycin (Biaxin, in Prevpac); clonazepam (Klonopin); clozapine (Clozaril); cyclophosphamide; cyclosporine (Gengraf, Neoral, Sandimmune); dalfopristin and quinupristin (Synercid); danazol (Danocrine); dantrolene (Dantrium); diltiazem (Cardizem, Diltzac, Tiazac, others); diuretics (water pills); doxorubicin (Adriamycin, Rubex); doxycycline (Vibramycin); erythromycin (E.E.S., E-Mycin, Erythrocin); eslicarbazepine (Aptiom); everolimus (Afinitor, Zortress); felodipine (Plendil); haloperidol (Haldol); HIV protease inhibitors including atazanavir (Reyataz), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Fortovase, Invirase); ibuprofen (Advil); imatinib (Gleevec); isoniazid (INH, Laniazid, in Rifater); levothyroxine (Levoxyl, Synthroid); lithium (Lithobid); loratadine (Claritin); lorazepam (Ativan); loxapine (Adasuve); certain medications to treat malaria such as chloroquine (Aralen) and mefloquine ; medications for anxiety or mental illness; other medications for seizures such as ethosuximide (Zarontin), felbamate (Felbatol), fosphenytoin (Cerebyx); lamotrigine (Lamictal), methsuximide (Celontin), oxcarbazepine (Trileptal), phenobarbital, phensuximide (Milontin) (not available in the US), phenytoin (Dilantin, Phenytek), primidone (Mysoline), tiagabine (Gabitril), topiramate (Topamax), and valproic acid (Depakene, Depakote); lapatinib; methadone (Dolophine, Methadose); midazolam; niacinamide (nicotinamide, Vitamin B3); olanzapine; omeprazole; oxybutynin; propoxyphene (Darvon); praziquantel (Biltricide); quetiapine; quinine; rifampin (Rifadin, Rimactane); risperidone; sedatives; sertraline (Zoloft); sirolimus; sleeping pills; tacrolimus (Prograf); tadalafil (Adcirca, Cialis); temsirolimus (Torisel); terfenadine (Seldane) (not available in the US); theophylline (Theo-24, Theochron, others); ticlopidine; tramadol (Ultram); tranquilizers; trazodone; troleandomycin (TAO); verapamil (Calan, Verelan); zileuton (Zyflo); ziprasidone (Geodon), and zonisamide (Zonegran). Many other medications may also interact with carbamazepine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• if you are taking any other liquid medications, do not take them at the same time as carbamazepine suspension.
• tell your doctor if you have or have ever had glaucoma (a condition in which increased pressure in the eye can lead to gradual loss of vision); or heart, kidney, thyroid, or liver disease.
• you should know that carbamazepine may decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, injections, implants, or intrauterine devices). Use another form of birth control while taking carbamazepine. Tell your doctor if you have unexpected vaginal bleeding or think you may be pregnant while you are taking carbamazepine.
• tell your doctor if you are pregnant or plan to become pregnant. Carbamazepine may harm the fetus. If you become pregnant while taking carbamazepine, call your doctor immediately.
• do not breastfeed while you are taking carbamazepine.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking carbamazepine.
• you should know that carbamazepine may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
  remember that alcohol can add to the drowsiness caused by this medication.
  you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are taking carbamazepine for the treatment of epilepsy, mental illness, or other conditions. A small number of adults and children 5 years of age and older (about 1 in 500 people) who took anticonvulsants such as carbamazepine to treat various conditions during clinical studies became suicidal during their treatment. Some of these people developed suicidal thoughts and behavior as early as one week after they started taking the medication. There is a risk that you may experience changes in your mental health if you take an anticonvulsant medication such as carbamazepine, but there may also be a risk that you will experience changes in your mental health if your condition is not treated. You and your doctor will decide whether the risks of taking an anticonvulsant medication are greater than the risks of not taking the medication. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: panic attacks; agitation or restlessness; new or worsening irritability, anxiety, or depression; acting on dangerous impulses; difficulty falling or staying asleep; aggressive, angry, or violent behavior; mania (frenzied, abnormally excited mood); talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; giving away prized possessions; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.
• if you have fructose intolerance (an inherited condition in which the body lacks the protein needed to break down fructose [a fruit sugar found in certain sweeteners such as sorbitol]), you should know that the oral suspension is sweetened with sorbitol. Tell your doctor if you have fructose intolerance.

Special dietary instructions

Talk to your doctor about eating grapefruit or drinking grapefruit juice while taking carbamazepine.

Carbamazepine in pregnancy

Studies looking at women who have taken carbamazepine during the first trimester of pregnancy have found a 1% chance (1/100 births) of neural tube defects (the spinal cord or skull do not form properly). The most common neural tube defect is spina bifida. Other studies have reported a 2 to 3 times greater chance for other major birth defects, such as heart defects or cleft lip.

Some studies have also suggested an increased chance for minor birth defects such as a small nose with a long space between the nose and upper lip, and small finger and toenails. Other studies have reported an increased chance of growth issues and small head size.

Folic acid has been found to reduce the chance for neural tube defects. Because women taking carbamazepine have a higher chance of having a baby with a neural tube defect, healthcare providers recommend that all women taking carbamazepine take extra folic acid before and during pregnancy. Speak with your healthcare provider to discuss how much folic acid you should take.

Can taking carbamazepine during pregnancy affect my baby’s development?

More studies are needed before we can be sure of the long-term effects of carbamazepine. Researchers are just beginning to look at the development of children who have been exposed to carbamazepine during pregnancy. Some studies have found a small increased chance for developmental delays. Other studies have found no differences in development or IQ.

Are there any other concerns with carbamazepine use during pregnancy?

Rarely, maternal use of carbamazepine during pregnancy has been associated with bleeding problems in the newborn due to low vitamin K levels. It has been recommended that women taking these medications receive vitamin K supplements near the end of their pregnancy and that their infants receive vitamin K supplement at birth. Women taking carbamazepine in pregnancy should discuss this with their healthcare provider and their child’s pediatrician before delivery.

Should I stop taking carbamazepine during my pregnancy?

You should contact your health care providers before becoming pregnant, or when you find out that you are pregnant, to discuss making any changes to your medication. The benefits of taking carbamazepine must be weighed against the possible risks to the developing baby.

I have been taking carbamazepine for the last few years and I just found out I am pregnant. What tests are available to see if my baby has spina bifida or other birth defects?

Screening tests are available for neural tube defects and other birth defects in your pregnancy. There are blood tests and ultrasounds. Discuss your screening options with your healthcare providers. There are no tests that can tell if there has been any effect on behavior or ability to learn.

I am taking carbamazepine, but I would like to stop taking it before becoming pregnant. How long does carbamazepine stay in your body?

Each person’s ability to break down the medication can be different. When you first start to take carbamazepine, your body breaks it down slowly. It can take 5-14 days to clear from your body. After long-term treatment, most of the carbamazepine should be gone from your body 3-5 days after the last dose.

Pregnant women should not change their medications during pregnancy without talking to a health care provider. Having a seizure while pregnant may be harmful to the baby. Women with bipolar disorder who stop taking medication during their pregnancy may be at an increased risk for episodes of depression or mania that could be harmful to both the mother and the baby.

If possible, women with seizure disorders or bipolar disorder who could become pregnant should discuss their options for treatment, including medications, with their health care provider before becoming pregnant.

I have been taking carbamazepine for many years. Can this affect my ability to get pregnant?

Studies have found that long-term use of seizure medications in women with seizure disorders is associated with menstrual irregularities and difficulty getting pregnant. Talk to your healthcare provider if you are experiencing difficulty in becoming pregnant.

What could happen to my baby if I stopped taking my carbamazepine and then had a seizure during my pregnancy?

About 1 in 3 women with epilepsy experiences an increase in frequency of seizures during pregnancy. Problems for the mother and fetus depend on how often she has a seizure and how long they last. Epileptic seizures and convulsions could cause a lack of oxygen in the blood. This could potentially lead to brain damage and developmental issues for the child, or could be life-threatening. In addition, a seizure could cause the mother to fall and physically injure herself.

Breastfeeding

Carbamazepine passes into breast milk. However, the amount of carbamazepine found in an infant’s blood is usually below a therapeutic level, meaning it would not be expected to affect the infant. There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Breastfeeding while taking carbamazepine monotherapy does not appear to affect infant growth or development. Some healthcare providers can measure levels of carbamazepine in the newborn if there is concern. Be sure to talk to your health care provider about all your breastfeeding questions.

What if the father takes carbamazepine?

One small animal study and a couple small human studies have suggested that carbamazepine might affect sperm development, but the studies did not look at whether or not this went on to cause problems getting a woman pregnant. More studies are needed to know if men who take carbamazepine have a harder time getting their partners pregnant. In general, exposures that fathers have are unlikely to increase risks to a pregnancy.

Carbamazepine Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using carbamazepine with any of the following medicines is not recommended. Your doctor may decide not to treat you with carbamazepine or change some of the other medicines you take.

• Artemether
• Atazanavir
• Boceprevir
• Clorgyline
• Cobicistat
• Daclatasvir
• Darunavir
• Dasabuvir
• Delamanid
• Delavirdine
• Doravirine
• Efavirenz
• Elbasvir
• Elvitegravir
• Furazolidone
• Grazoprevir
• Iproniazid
• Isavuconazonium
• Isocarboxazid
• Linezolid
• Lorlatinib
• Lumefantrine
• Lurasidone
• Maraviroc
• Methylene Blue
• Moclobemide
• Nefazodone
• Nialamide
• Ombitasvir
• Pargyline
• Paritaprevir
• Phenelzine
• Praziquantel
• Procarbazine
• Ranolazine
• Rasagiline
• Rilpivirine
• Ritonavir
• Selegiline
• Telaprevir
• Tenofovir Alafenamide
• Toloxatone
• Tranylcypromine
• Voriconazole

Using carbamazepine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abemaciclib
• Abiraterone Acetate
• Acalabrutinib
• Acetazolamide
• Adenosine
• Afatinib
• Alfentanil
• Almotriptan
• Alprazolam
• Amiodarone
• Amphetamine
• Amprenavir
• Apixaban
• Apremilast
• Aprepitant
• Aripiprazole
• Axitinib
• Bedaquiline
• Benzhydrocodone
• Benzphetamine
• Bictegravir
• Bosutinib
• Brexpiprazole
• Brigatinib
• Buprenorphine
• Bupropion
• Butorphanol
• Cabozantinib
• Calcifediol
• Cariprazine
• Ceritinib
• Chloroquine
• Chlorpromazine
• Cisatracurium
• Clarithromycin
• Clonazepam
• Clozapine
• Cobimetinib
• Codeine
• Conivaptan
• Copanlisib
• Crizotinib
• Cyclophosphamide
• Cyclosporine
• Dabigatran Etexilate
• Dasatinib
• Deflazacort
• Desmopressin
• Desogestrel
• Desvenlafaxine
• Dextroamphetamine
• Dienogest
• Dihydrocodeine
• Diltiazem
• Dolasetron
• Dolutegravir
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Dronedarone
• Drospirenone
• Duvelisib
• Eliglustat
• Encorafenib
• Enzalutamide
• Eravacycline
• Erdafitinib
• Erlotinib
• Erythromycin
• Escitalopram
• Eslicarbazepine Acetate
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Etravirine
• Everolimus
• Exemestane
• Ezogabine
• Felodipine
• Fentanyl
• Fluconazole
• Fluoxetine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fostamatinib
• Gefitinib
• Gestodene
• Gilteritinib
• Glasdegib
• Glecaprevir
• Granisetron
• Hemin
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Ibrutinib
• Idelalisib
• Ifosfamide
• Imatinib
• Indinavir
• Irinotecan
• Irinotecan Liposome
• Isoniazid
• Itraconazole
• Ivabradine
• Ivacaftor
• Ivosidenib
• Ixabepilone
• Ixazomib
• Ketoconazole
• Lamotrigine
• Lapatinib
• Larotrectinib
• Ledipasvir
• Levomilnacipran
• Levonorgestrel
• Levorphanol
• Linagliptin
• Lisdexamfetamine
• Lomitapide
• Lopinavir
• Loratadine
• Lorcaserin
• Loxapine
• Macimorelin
• Macitentan
• Manidipine
• Medroxyprogesterone
• Mefloquine
• Meperidine
• Mestranol
• Metaxalone
• Methadone
• Methamphetamine
• Midostaurin
• Mifepristone
• Mirtazapine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naloxegol
• Nelfinavir
• Neratinib
• Netupitant
• Nifedipine
• Nilotinib
• Nimodipine
• Nintedanib
• Norethindrone
• Norgestimate
• Norgestrel
• Olanzapine
• Olaparib
• Orlistat
• Osimertinib
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Paclitaxel
• Palbociclib
• Paliperidone
• Palonosetron
• Panobinostat
• Pazopanib
• Pentazocine
• Perampanel
• Phenytoin
• Pibrentasvir
• Piperaquine
• Ponatinib
• Propoxyphene
• Quetiapine
• Quinine
• Regorafenib
• Remifentanil
• Ribociclib
• Rivaroxaban
• Rolapitant
• Romidepsin
• Saquinavir
• Sertraline
• Simvastatin
• Sofosbuvir
• Sonidegib
• Stiripentol
• Sufentanil
• Sunitinib
• Tacrolimus
• Tamoxifen
• Tapentadol
• Tasimelteon
• Telithromycin
• Temsirolimus
• Terfenadine
• Tezacaftor
• Thioridazine
• Thiotepa
• Ticagrelor
• Tipranavir
• Tofacitinib
• Tolvaptan
• Trabectedin
• Tramadol
• Trazodone
• Ulipristal
• Valbenazine
• Vandetanib
• Velpatasvir
• Vemurafenib
• Venetoclax
• Verapamil
• Vigabatrin
• Vilazodone
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Vorapaxar
• Vortioxetine
• Voxilaprevir
• Zileuton
• Ziprasidone

Using carbamazepine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetaminophen
• Acetylcysteine
• Aminophylline
• Amitriptyline
• Amoxapine
• Anisindione
• Aripiprazole Lauroxil
• Caspofungin
• Dalfopristin
• Danazol
• Desipramine
• Dicumarol
• Doxepin
• Etretinate
• Felbamate
• Flunarizine
• Furosemide
• Ginkgo
• Haloperidol
• Hydrochlorothiazide
• Imipramine
• Influenza Virus Vaccine
• Levetiracetam
• Lithium
• Methylphenidate
• Methylprednisolone
• Metronidazole
• Mianserin
• Midazolam
• Miokamycin
• Nafimidone
• Niacinamide
• Nortriptyline
• Omeprazole
• Ospemifene
• Phenobarbital
• Phenprocoumon
• Pipecuronium
• Primidone
• Protriptyline
• Psyllium
• Quinupristin
• Remacemide
• Rifampin
• Rifapentine
• Risperidone
• Rocuronium
• Rufinamide
• Sabeluzole
• Theophylline
• Tiagabine
• Ticlopidine
• Topiramate
• Troleandomycin
• Valnoctamide
• Valproic Acid
• Vecuronium
• Viloxazine
• Warfarin

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using carbamazepine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice
• Black Tea

Other Medical Problems

The presence of other medical problems may affect the use of carbamazepine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Behavior or mood problems or
• Blood vessel disease or
• Depression, history of or
• Diabetes or
• Glaucoma, or history of or
• Heart block or
• Heart disease or
• Heart rhythm problems, history of or
• Hyponatremia (low sodium in the blood) or
• Liver disease, history of or
• Porphyria (an inherited disease) or
• Problems with urination or
• Stevens-Johnson syndrome (severe skin disease) or
• Toxic epidermal necrolysis (severe skin disease)—Use with caution. May make these conditions worse.
• Asian ancestry (eg, Chinese, Filipino, Japanese, Korean, Taiwanese)—May increase the risk for serious skin reactions. Your doctor may order a special test before prescribing this medicine.
• Bone marrow depression, history of—Should not be used in patients with this condition.
• Fructose intolerance (rare inherited problem)—Tegretol® oral liquid contains sorbitol and should not be given to patients with this condition.

What is carbamazepine used for?

Carbamazepine is an anticonvulsant medication used to control seizures in the treatment of epilepsy specifically for partial seizures with complex symptomatology (psychomotor, temporal lobe), generalized tonic seizures (grand mal), and mixed seizure patterns ². Carbamazepine is also used to treat bipolar affective disorder, schizophrenia, trigeminal neuralgia and other specific pain disorders. Carbamazepine is also sometimes used to treat mental illnesses, depression, posttraumatic stress disorder, drug and alcohol withdrawal, restless legs syndrome, diabetes insipidus, certain pain syndromes, and a disease in children called chorea.

Carbamazepine is used off-label for refractory schizophrenia ¹. Simple well designed trials have shown efficacy in patients with schizophrenia with EEG abnormalities, schizophrenia with violent episodes, and schizoaffective disorder. Carbamazepine improves both positive and negative symptoms in schizophrenic patients ⁴. Other off-label uses of this drug include treatment of restless leg syndrome and decreasing agitation and aggression in patients with dementia ⁵. Another prominent off-label use of this drug is the treatment of neuropathic pain and fibromyalgia ⁶. In patients with moderate to severe alcohol withdrawal syndrome, Carbamazepine has been shown to have clinical efficacy in treatment. However, this is not approved by the FDA, and it has not been shown to prevent alcohol withdrawal seizures as compared to benzodiazepines ⁷.

Carbamazepine administration

Take carbamazepine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects

Carbamazepine should be taken with meals to lessen unwanted effects (eg, stomach upset, nausea, vomiting).

Carbamazepine Equetro® extended-release capsules do not need to be taken with meals unless they upset your stomach. The contents of the Equetro® extended-release capsules may be sprinkled over a teaspoon of applesauce or other similar food. The capsule or its contents should not be crushed or chewed.

Tegretol® extended-release tablets must be swallowed whole and should not be crushed or chewed. Do not take Tegretol® extended-release tablets that are damaged or have chips or cracks.

Grapefruit and grapefruit juice may increase the effects of carbamazepine by increasing the amount in the body. You should not eat grapefruit or drink grapefruit juice while you are taking carbamazepine.

If you are taking carbamazepine for pain relief:

• Carbamazepine is not an ordinary pain reliever. It should be used only when a doctor prescribes it for certain kinds of pain. Do not take carbamazepine for any other aches or pains.

If you are taking Tegretol® oral liquid:

• Shake the oral liquid well before each use. Measure your dose with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.
• Do not take any other liquid medicines at the same time that you take your dose of Tegretol® without first checking with your doctor.

Tegretol® tablets work differently than the Tegretol® oral liquid, even at the same dose (number of milligrams). Do not switch from the tablets to the oral liquid unless your doctor tells you to.

Tegretol® may be used alone or together with other seizure medicines. Ask your doctor first before taking any other seizure medicine together with Tegretol®.

Do not take Equetro® capsules if you are also using Tegretol® suspension or tablets. These medicines should not be taken together because both medicines contains carbamazepine. Ask your doctor if you have any questions.

Carbamazepine dosage

The dose of carbamazepine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of carbamazepine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of carbamazepine that you take depends on the strength of the carbamazepine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take carbamazepine depend on the medical problem for which you are using carbamazepine.

For oral dosage form (extended-release capsules):

• For bipolar disorder:
  • Adults—At first, 200 milligrams (mg) 2 times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1600 mg per day.
  • Children—Use and dose must be determined by your doctor.
• For epilepsy:
  • Adults and children 12 years of age and older—At first, 200 milligrams (mg) 2 times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 500 to 800 mg 2 times a day.
  • Children younger than 12 years of age—Dose is based on body weight and must be determined by your doctor. However, the dose is usually not more than 1000 mg per day.
• For trigeminal neuralgia:
  • Adults—At first, 200 milligrams (mg) once a day. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 1200 mg per day.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (extended-release tablets):

• For epilepsy:
  • Adults—At first, 200 mg 2 times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
  • Children 6 to 12 years of age—At first, 100 mg 2 times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
  • Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is usually 10 to 20 milligram (mg) per kilogram (kg) per day, taken 2 times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 35 mg per kg of body weight per day.
• For trigeminal neuralgia:
  • Adults—At first, 100 milligrams (mg) 2 times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 1200 mg per day.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (oral liquid):

• For epilepsy:
  • Adults—100 milligrams (mg) or 1 teaspoon 4 times a day (400 mg per day). Your doctor may adjust your dose as needed. However, the dose is usually not more than 1000 to 1600 mg per day.
  • Children 6 to 12 years of age—At first, 50 milligrams (mg) or one-half teaspoon 4 times a day (200 mg per day). Your doctor may adjust your dose as needed. However, the dose is usually not more than 1000 mg per day.
  • Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken 4 times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 35 mg per kg of body weight per day.
• For trigeminal neuralgia:
  • Adults—At first, 50 milligrams (mg) or one-half teaspoon 4 times a day (200 mg per day). Your doctor may adjust your dose as needed. However, the dose is usually not more than 1200 mg per day.
  • Children—Use and dose must be determined by your doctor.

For oral dosage forms (tablets or chewable tablets):

• For epilepsy:
  • Adults—At first, 200 milligrams (mg) 2 times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 1000 to 1600 mg per day.
  • Children 6 to 12 years of age—At first, 100 mg 2 times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 1000 mg per day.
  • Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken 3 times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 35 mg per kg of body weight per day.
• For trigeminal neuralgia:
  • Adults and teenagers—At first, 100 milligrams (mg) 2 times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 1200 mg per day.
  • Children—Use and dose must be determined by your doctor.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Carbamazepine side effects

Carbamazepine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness
• thinking abnormal
• difficulty speaking
• uncontrollable shaking of a part of the body
• constipation
• dry mouth

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING and SPECIAL PRECAUTION sections, call your doctor immediately:

• confusion
• rash
• fast, slow, or pounding heartbeat
• yellowing of the skin or eyes
• dark urine
• pain on the right side of your stomach area
• loss of appetite
• nausea
• vomiting
• vision changes
• fatigue
• swelling of your face, eyes, eyelids, lips, or tongue
• difficulty swallowing or breathing
• headache, new or increased number of seizures, difficulty concentrating, confusion, weakness, or unsteadiness
• severe rash with one or more of the following: fever, muscle or joint aches, red or swollen eyes, blisters or peeling skin, mouth sores, or swelling of your face or neck

Carbamazepine may cause other side effects. Call your doctor if you have any unusual problems while taking carbamazepine.

Carbamazepine toxicity

Carbamazepine toxicity occurs at levels higher than 40 mg/L (usual therapeutic levels are 4 to 12 mg/L) ⁹. Carbamazepine toxicity can be divided into the following three levels: (1) disorientation and ataxia at levels of 11–15 mg/L; (2) aggression and hallucinations with levels of 15–25 mg/L; and (3) seizures and coma with levels above 25 mg/L ⁹. Common cause for carbamazepine toxicity is co-administration of other medications ⁹. Patients are likely to take antiepileptic drugs are likely at the same time as carbamazepine. For example, lamotrigine is a common medication used in these patients, and symptoms of carbamazepine overdose are more likely when lamotrigine is added. A similar situation is also seen with levetiracetam. Any inhibitors of cytochrome P450, such as grapefruit juice, will cause elevated levels of carbamazepine. An intentional overdose of carbamazepine is less common and usually seen with a suicide attempt in a severely depressed patient during the initial administration of the medication.

Carbamazepine overdose is not uncommon. In 2014 there were 1880 documented cases of symptomatic carbamazepine toxicity according to the American Association of Poison Control Centers report ⁹. Of those, 37% were intentional overdose while 57% were an unintentional overdose and 4% were an adverse reaction.

Symptoms of carbamazepine overdose may include the following:

• unconsciousness
• coma
• seizures
• restlessness
• muscle twitching
• abnormal movements
• shaking of a part of your body that you cannot control
• unsteadiness
• drowsiness
• dizziness
• vision changes
• irregular or slowed breathing
• rapid or pounding heartbeat
• nausea
• vomiting
• difficulty urinating

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call your local emergency services number.

Carbamazepine is significant protein bound with a high volume of distribution, Most of the drug will remain bound to plasma protein due to the high protein binding property; additionally, the drug will enter the bloodstream from tissue stores. Carbamazepine undergoes oxidation via CYP 3A4 and to a lesser extent CYP 2C8 to carbamazepine-lO, ll-epoxide, which is the active metabolite that is thought to cause toxic effects. Other metabolites also have been investigated such as the dihydroxy-derivative of the epoxide. Carbamazepine metabolism also includes hydroxylation of the 6-membered aromatic rings and N-glucuronidation of the carbamoyl side chain.

Carbamazepine is eliminated with a half-life of about 30 hours after the first dose. It usually induces cytochrome P450 enzyme for next doses and elimination increases. Peak blood concentration appears between 6 and 24 hours after ingestion a therapeutic dose; however, large overdose, whether intentional or not, will take up to 72 hours after ingestion to reach a peak level. It was found that the toxicity of carbamazepine is more likely to occur when lamotrigine is added to carbamazepine if its initial level was higher than 8mg/L; this could be due to the assumption that lamotrigine inhibits the enzyme epoxide hydrolase. Another widely used antiepileptic agent is levetiracetam; its introduction led to a marked disabling symptom of carbamazepine toxicity, and that dose had to be reduced, or levetiracetam had to be weaned off. Although there was no evidence of pharmacokinetic interaction based on serial blood tests of levels, it is thought to be pharmacodynamics mechanism. Symptoms include double vision, dizziness, nystagmus, ataxia, nausea, and vomiting and improved in some cases with a slight reduction of carbamazepine. In some cases, it required a complete cessation of levetiracetam: however, it is recommended to reduce carbamazepine and adjust levetiracetam dosages until better seizure control given the ‘’safer’’ profile of levetiracetam. Patients on carbamazepine are recommended not to drink grapefruit juice that can increase the level of carbamazepine in the blood through the inhibition of cytochrome P450 3A4 by furanocoumarins.

Patients must be observed closely and given a neurological exam due to the deterioration of symptoms. Anesthesia and an intubation kit must be bedside ready. Any sign of even minor deterioration and anticipation of worse symptoms should prompt pre-emptive patient intubation. EKG must be done. Serial carbamazepine levels must be obtained every 4 hours ¹⁰.

Carbamazepine toxicity management and treatment

Treatment ranges from physiological clearance, use of activated charcoal, or extracorporeal therapy such as hemodialysis or plasmapheresis. Activated charcoal binds to carbamazepine and prevents the absorption from the gastrointestinal tract. It also enhances the elimination of carbamazepine by interrupting the enterohepatic circulation of the drug. Caution must be taken because of the risk of aspiration of charcoal associated with worsening mental status. Charcoal hemoperfusion is another technique shown to improve clinical outcome for carbamazepine overdose. Charcoal hemoperfusion has risks such as hypoglycemia, hypocalcemia, and thrombocytopenia. Charcoal will compete with plasma proteins for carbamazepine binding. In one treatment session, the blood compartment can be exposed to the hemoperfusion column many times. Successful treatment of carbamazepine toxicity with intravenous lipid emulsion therapy also has been reported in the literature. Due to the risk of death in 13% of cases with significant toxicity, an aggressive treatment plan is required that includes hemoperfusion, hemodialysis, intravenous lipid emulsion and multiple-dose activated charcoal.

Pediatric populations are at greater risk for adverse effects and symptoms of toxicity at lower serum levels when compared to adults. Use of continuous venovenous hemodiafiltration has been reported. This technique uses both diffusion and convection which allows flexibility in enhancing clearance by increasing the volume of ultrafiltrate or the dialysate flow rates. This technique is superior over diffusive techniques alone because the convective transfer helps clear larger molecules such as drugs like carbamazepine. It is a good option for unstable patients, and this continuous procedure is controlled easily. Gastric lavage is useful if done within one hour of ingestion, but care must be taken due to anticholinergic characteristics of carbamazepine that slow down peristalsis and delay the processing of ingested medications. Whole bowel irrigation can be done safely only after securing the airway. As reported in the literature, whole body irrigation can be complicated with ileus and complete bowel obstruction that could require an ileostomy due to the anticholinergic effect of carbamazepine and its effect on peristalsis.

Carbamazepine toxicity prognosis

The severity of symptoms at the time of patient presentation correlates with the outcomes. Patients may have altered level of mental status for several days after the acute overdose, but the majority will improve. Patient education is very important for recurrence prevention. A detailed explanation is needed on coadministration of other medications and the patient also should be advised to keep all medications in a locked, secure place to prevent pediatric overdose. Of the 1880 documented cases in 2014, only 62 patients had a major outcome that included admission to the intensive care unit and mechanical ventilation, and no deaths were reported.

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