Carbamazepine (Tegretol)
Anticonvulsant used for epilepsy, trigeminal neuralgia, and alcohol withdrawal
📊 Quick facts about carbamazepine
💡 Key takeaways about carbamazepine
- Primary uses: Carbamazepine treats epilepsy, trigeminal neuralgia, and alcohol withdrawal by stabilizing sodium channels in the brain
- Serious skin reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis can occur, especially in patients of Han Chinese or Thai ancestry carrying the HLA-B*1502 allele
- Many drug interactions: Carbamazepine is a potent CYP3A4 inducer and reduces the effectiveness of hormonal contraceptives, warfarin, statins, and many other drugs
- Pregnancy risk: Up to 3 times higher risk of birth defects including neural tube defects — effective contraception is essential during treatment
- Regular monitoring required: Blood counts, liver function, sodium levels, and drug levels should be checked regularly during treatment
What Is Carbamazepine and What Is It Used For?
Carbamazepine is an anticonvulsant medication that works by blocking voltage-gated sodium channels in the brain, preventing the spread of abnormal electrical signals. It is primarily prescribed for epilepsy, trigeminal neuralgia (severe facial nerve pain), and alcohol withdrawal syndrome.
Carbamazepine belongs to a group of medicines called anticonvulsants, also known as antiepileptic drugs (AEDs). It was first introduced in the 1960s and has since become one of the most widely prescribed antiepileptic medications worldwide. The World Health Organization (WHO) includes carbamazepine on its Model List of Essential Medicines, recognizing it as one of the most effective and safe medicines needed in a health system.
The medication works by stabilizing the inactivated state of voltage-gated sodium channels in nerve cell membranes. In simple terms, it reduces the ability of nerve cells to fire rapidly in an uncontrolled manner, which is what happens during an epileptic seizure. This mechanism also explains its effectiveness in treating nerve pain conditions like trigeminal neuralgia, where nerves send inappropriate pain signals.
Approved indications
Carbamazepine is approved for the treatment of several conditions:
- Epilepsy: Partial seizures (with or without secondary generalization) and generalized tonic-clonic seizures. It is considered a first-line treatment option for focal epilepsy according to major international guidelines including NICE and the International League Against Epilepsy (ILAE).
- Trigeminal neuralgia: Severe, stabbing facial pain caused by irritation of the trigeminal nerve. Carbamazepine remains the first-line pharmacological treatment for this condition, with response rates of 70-80% according to systematic reviews.
- Alcohol withdrawal: Used to manage symptoms of alcohol withdrawal including seizures, anxiety, and tremors, particularly in settings where benzodiazepines may not be appropriate.
In addition to its approved uses, carbamazepine is sometimes prescribed off-label for bipolar disorder (particularly for manic episodes), neuropathic pain conditions, and certain psychiatric disorders. However, these uses should be discussed with a specialist who can weigh the benefits against potential risks.
Carbamazepine is available only by prescription and should only be taken under medical supervision. The dosage is carefully adjusted for each patient based on their condition, response to treatment, and blood drug levels. Never change your dose without consulting your doctor.
What Should You Know Before Taking Carbamazepine?
Before starting carbamazepine, inform your doctor about all medical conditions, allergies, and current medications. Carbamazepine must not be used if you have AV block, porphyria, bone marrow disorders, or are taking MAO inhibitors. Genetic testing (HLA-B*1502) is recommended for patients of Asian ancestry.
Contraindications
You should not take carbamazepine if any of the following apply to you:
- Allergy to carbamazepine or any of its ingredients, or to chemically related drugs such as tricyclic antidepressants (e.g., amitriptyline, imipramine)
- Porphyria: A group of rare metabolic disorders affecting the production of porphyrins, which are important for liver function and blood formation
- Atrioventricular (AV) block: A certain type of heart conduction disorder
- History of bone marrow suppression: Including agranulocytosis or aplastic anemia
- Current use of MAO inhibitors: Treatment with monoamine oxidase inhibitors must be discontinued at least 14 days before starting carbamazepine
- Neonates under 4 weeks: Unless no other treatment alternative exists (oral suspension formulation)
Warnings and precautions
Talk to your doctor before taking carbamazepine if you have any of the following conditions or concerns:
- Heart or vascular disease: Carbamazepine can affect heart rhythm and blood pressure
- Liver or kidney disease: Dose adjustments may be necessary, and more frequent monitoring is required
- Glaucoma or urinary difficulties: Carbamazepine has mild anticholinergic effects that may worsen these conditions
- Previous hypersensitivity to oxcarbazepine or phenytoin: Approximately 25% of patients who are allergic to carbamazepine will also react to oxcarbazepine
- Low sodium levels (hyponatremia): Carbamazepine can lower sodium levels in the blood, particularly in elderly patients or those taking diuretics
Life-threatening skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with carbamazepine use. These reactions are significantly more common in patients carrying the HLA-B*1502 allele, which is found predominantly in people of Han Chinese, Thai, Malaysian, Filipino, and other Southeast Asian ancestry.
The FDA, EMA, and other regulatory agencies recommend genetic testing for HLA-B*1502 before initiating carbamazepine in at-risk populations. Patients who test positive should not receive carbamazepine unless the benefit clearly outweighs the risk.
Stop taking carbamazepine and seek immediate medical attention if you develop a rash, blistering, peeling skin, mouth sores, or flu-like symptoms during the first months of treatment.
A small number of people treated with antiepileptic drugs, including carbamazepine, have had thoughts of self-harm or suicide. If you ever experience such thoughts, contact your doctor immediately. This risk applies to all antiepileptic medications and is not specific to carbamazepine.
Pregnancy and breastfeeding
Carbamazepine poses significant risks during pregnancy. If taken during pregnancy, the baby has up to 3 times higher risk of birth defects compared to babies of women not taking antiepileptic medication. Reported malformations include:
- Neural tube defects (spina bifida — opening in the spine)
- Facial malformations including cleft lip and palate
- Skull abnormalities and microcephaly (small head)
- Heart defects
- Hypospadias (abnormal urethral opening in males)
- Finger and limb malformations
Studies have also shown that babies exposed to carbamazepine during pregnancy may be smaller and weigh less than expected at birth. In one study, approximately 13 out of 100 babies born to mothers taking carbamazepine were small for gestational age, compared with 11 out of 100 babies born to mothers not taking antiepileptic drugs.
Some studies have reported potential effects on neurological development in children exposed to carbamazepine in the womb, although findings are inconsistent. The possibility that carbamazepine may affect cognitive development in the child cannot be excluded.
Women of childbearing potential should use effective contraception during treatment with carbamazepine and for two weeks after the last dose. Note that carbamazepine reduces the effectiveness of hormonal contraceptives (see Drug Interactions section). Discuss appropriate contraceptive methods with your doctor.
If you are planning a pregnancy, speak with your doctor before stopping contraception to discuss switching to alternative treatments that carry lower risks during pregnancy.
If you are already pregnant or suspect pregnancy, inform your doctor immediately. Do not stop taking carbamazepine on your own, as uncontrolled seizures can be dangerous for both you and your baby. Your doctor will assess whether the treatment should be modified.
Breastfeeding: Carbamazepine passes into breast milk. Consult your doctor or pharmacist before taking carbamazepine while breastfeeding. Your healthcare provider will help you weigh the benefits of breastfeeding against the potential effects on your baby.
Driving and operating machinery
Carbamazepine may cause drowsiness, dizziness, blurred vision, double vision, or impaired coordination, particularly at the start of treatment or after dose increases. These effects can impair your ability to drive or operate machinery safely. Do not drive or use machines until you know how carbamazepine affects you. You are personally responsible for assessing whether you are fit to drive or perform tasks requiring alertness.
How Does Carbamazepine Interact with Other Drugs?
Carbamazepine is a potent inducer of CYP3A4 liver enzymes and interacts with a very large number of medications. It reduces the effectiveness of hormonal contraceptives, warfarin, many statins, and numerous other drugs. MAO inhibitors must be stopped at least 14 days before starting carbamazepine. Grapefruit juice and St. John's wort should be avoided.
Carbamazepine is one of the most significant enzyme-inducing drugs in clinical practice. It accelerates the metabolism of many other medications by inducing cytochrome P450 enzymes, particularly CYP3A4. This means that other drugs may be broken down more quickly in the body, reducing their effectiveness. Conversely, some medications can increase or decrease carbamazepine levels, potentially leading to toxicity or reduced seizure control.
Always inform every healthcare provider about your carbamazepine treatment when being prescribed new medications, including over-the-counter drugs and herbal supplements.
Major interactions
| Drug / Class | Effect | Clinical Significance | Action Required |
|---|---|---|---|
| MAO inhibitors | Risk of serotonin syndrome and hypertensive crisis | Potentially life-threatening | Stop MAO inhibitor at least 14 days before starting carbamazepine |
| Hormonal contraceptives (pills, patches, implants) | Reduced contraceptive effectiveness | Risk of unintended pregnancy | Use non-hormonal or additional contraception |
| Warfarin | Reduced anticoagulant effect | Risk of thromboembolism | Monitor INR closely; dose adjustment needed |
| Simvastatin and other statins | Reduced statin levels | Reduced cholesterol-lowering effect | May need higher statin dose or alternative |
| Midazolam and other benzodiazepines | Reduced sedative effect | Inadequate sedation | Dose adjustment may be needed |
| Ivabradine | Reduced ivabradine levels | Reduced heart rate control | Combination may not be appropriate |
Other notable interactions
- Other antiepileptic drugs (phenytoin, valproic acid, lamotrigine): Complex mutual interactions may require dose adjustments for both drugs. Therapeutic drug monitoring is recommended.
- Dextropropoxyphene and other opioid analgesics: May increase carbamazepine levels, leading to toxicity symptoms.
- CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, grapefruit juice): Can increase carbamazepine blood levels, increasing risk of side effects. Avoid grapefruit juice during treatment.
- St. John's wort (Hypericum perforatum): Should not be used with carbamazepine as it may reduce carbamazepine levels unpredictably. If already taking St. John's wort, consult your doctor before stopping.
- Immunosuppressants (ciclosporin, tacrolimus): Carbamazepine reduces their levels significantly, potentially causing organ rejection in transplant patients.
- Antiretroviral drugs: Carbamazepine may reduce the effectiveness of certain HIV medications.
Alcohol: You should not drink alcohol during treatment with carbamazepine as the drug may reduce your tolerance to alcohol, increasing the risk of drowsiness and impaired coordination. Grapefruit juice: Avoid grapefruit juice as it inhibits CYP3A4 enzymes and can increase carbamazepine blood levels to potentially toxic levels.
What Is the Correct Dosage of Carbamazepine?
Carbamazepine dosage is individualized by your doctor. Treatment starts with a low dose that is gradually increased. The typical maintenance dose for adults is 800–1200 mg per day divided into 2–3 doses. For children, the dose is 10–20 mg/kg/day. Take with or after meals.
The dose of carbamazepine is carefully determined by your doctor and tailored to your individual needs. It is critically important for epilepsy treatment that the correct dose is maintained to achieve adequate seizure control. Treatment typically starts at a low dose that is gradually increased (titrated up) over several weeks until an effective maintenance dose is reached.
Adults
Standard adult dosing
- Starting dose: 100–200 mg once or twice daily
- Dose titration: Increase by 100–200 mg every 1–2 weeks
- Maintenance dose: 800–1200 mg per day, divided into 2–3 doses
- Maximum dose: Up to 1600–2000 mg per day in some cases (under specialist supervision)
Children
Pediatric dosing (from 4 weeks of age)
- Dose range: 10–20 mg per kg body weight per day
- Divided into: 2–3 doses throughout the day
- Titration: Start low and increase gradually as directed by the pediatric neurologist
- Oral suspension: Available as 20 mg/ml suspension for children who cannot swallow tablets
Elderly
Older adults may be more sensitive to the effects of carbamazepine, particularly its sedative and cardiovascular effects. Lower starting doses and more cautious dose titration are generally recommended. Elderly patients are also more susceptible to hyponatremia (low sodium levels) and should have their sodium levels monitored regularly.
| Patient Group | Starting Dose | Maintenance Dose | Frequency |
|---|---|---|---|
| Adults | 100–200 mg/day | 800–1200 mg/day | 2–3 times daily |
| Children | 5 mg/kg/day | 10–20 mg/kg/day | 2–3 times daily |
| Elderly | 100 mg/day | 400–800 mg/day | 2–3 times daily |
| Trigeminal neuralgia | 100–200 mg/day | 200–1200 mg/day | 2–3 times daily |
How to take carbamazepine
Take carbamazepine during or after a meal with some liquid. This improves absorption and reduces stomach upset. For extended-release tablets, swallow them whole — do not crush or chew them. The oral suspension should be shaken well before each use.
Missed dose
If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten dose. Missing doses of antiepileptic medication can increase the risk of breakthrough seizures.
Overdose
If you have taken too much carbamazepine or if a child has accidentally ingested the medication, contact emergency services or your local poison control center immediately. Symptoms of overdose may include severe drowsiness, loss of consciousness, seizures, breathing difficulties, rapid heartbeat, and dangerously low blood pressure. There is no specific antidote; treatment is supportive.
What Are the Side Effects of Carbamazepine?
The most common side effects of carbamazepine include dizziness, drowsiness, unsteadiness (ataxia), nausea, vomiting, and elevated liver enzymes. Serious but rare side effects include Stevens-Johnson syndrome, agranulocytosis, aplastic anemia, and severe liver damage. Most common side effects improve over time.
Like all medicines, carbamazepine can cause side effects, although not everyone experiences them. Many side effects are dose-related and are more common at the beginning of treatment or after dose increases. They often improve as your body adjusts to the medication. Your doctor may adjust your dose to minimize side effects while maintaining effective seizure control.
Very Common
- Difficulty coordinating movements (ataxia)
- Dizziness
- Drowsiness and fatigue
- Nausea and vomiting
- Elevated liver enzyme values
Common
- Changes in white blood cell counts
- Fluid retention and reduced appetite
- Double vision and difficulty focusing
- Dry mouth
- Hives (urticaria) and skin rash
- Elevated alkaline phosphatase
Uncommon
- Headache
- Involuntary movements (tremors, twitching)
- Nystagmus (involuntary eye movements)
- Diarrhea or constipation
Rare to Very Rare
- Agranulocytosis — dangerous decrease in white blood cells that weakens immune defense
- Aplastic anemia — bone marrow failure
- Stevens-Johnson syndrome / Toxic epidermal necrolysis — severe, potentially fatal skin reactions
- Severe liver damage including jaundice
- Angioedema — swelling of face, tongue, or throat
- Pancreatitis — severe upper abdominal pain
- DRESS syndrome — allergic reaction with rash, fever, and abnormal blood values
- Hyponatremia (low blood sodium)
- Cardiac arrhythmias and heart conduction disturbances
- Hallucinations, depression, aggression, confusion
- Kidney function impairment
- Aseptic meningitis
- Bone density loss with long-term use (osteoporosis)
- Male infertility
- Increased prolactin levels
- Skin rash with blistering, peeling, or sores in the mouth/eyes/genitals
- Fever with severely worsened general condition or sore throat
- Swelling of face, lips, tongue, or throat with breathing difficulties
- Yellowing of the skin or eyes (jaundice)
- Unusual bruising or bleeding, unexplained infections
- Severe abdominal pain with vomiting
- Irregular heartbeat or chest pain
- Confusion, severe drowsiness, or loss of consciousness
Carbamazepine may cause dry mouth, which increases the risk of dental problems. Maintain thorough oral hygiene during treatment, including brushing with fluoride toothpaste twice daily.
Long-term use of carbamazepine has been associated with decreased bone density and an increased risk of fractures. Inform your doctor if you are taking carbamazepine long-term, have known osteoporosis, or are taking corticosteroids, as you may need bone density monitoring and supplementation.
How Should You Store Carbamazepine?
Store carbamazepine in its original packaging, protected from light, at room temperature. Keep out of reach and sight of children. Do not use after the expiration date printed on the package. Return unused medication to your pharmacy for safe disposal.
Proper storage of carbamazepine helps ensure the medication remains effective and safe throughout its shelf life:
- Store in original packaging: This protects the medication from light, which can degrade the active ingredient
- Room temperature: Store at normal room temperature unless otherwise instructed on the packaging
- Keep away from children: Store out of the sight and reach of children at all times
- Check expiration dates: Do not use carbamazepine after the expiration date printed on the package (the expiration date refers to the last day of the stated month)
- Oral suspension: Once opened, follow any specific storage instructions provided with the product. Shake well before each use
Do not dispose of medications in wastewater or household waste. Return unused or expired medications to your pharmacy for environmentally safe disposal.
What Does Carbamazepine Contain?
The active ingredient is carbamazepine. Inactive ingredients vary by formulation but may include microcrystalline cellulose, carmellose sodium, propylene glycol, sorbitol, and various preservatives. The oral suspension contains 20 mg/ml of carbamazepine.
Carbamazepine is available in several formulations, each containing different inactive ingredients (excipients):
Active ingredient
All formulations contain carbamazepine as the active pharmaceutical ingredient. The oral suspension contains 20 mg of carbamazepine per milliliter (20 mg/ml).
Inactive ingredients (oral suspension)
The oral suspension formulation typically contains the following excipients:
- Microcrystalline cellulose
- Carmellose sodium
- Flavoring agents
- Methyl parahydroxybenzoate (E 218) and propyl parahydroxybenzoate (E 216) — preservatives that may cause allergic reactions
- Macrogol stearate
- Propylene glycol (E 1520)
- Saccharin sodium
- Sorbic acid (preservative)
- Liquid sorbitol (E 420) — a source of fructose
- Hydroxyethylcellulose
- Purified water
Propylene glycol: Neonates under 4 weeks may lack the ability to metabolize propylene glycol, which can lead to serious side effects. Sorbitol: This medication contains sorbitol, a source of fructose. Contact your doctor before use if you have been diagnosed with hereditary fructose intolerance. Parahydroxybenzoates: These preservatives may cause allergic reactions (possibly delayed). Sodium: This medication contains less than 1 mmol (23 mg) sodium per ml, meaning it is essentially sodium-free.
Frequently Asked Questions About Carbamazepine
Medical References and Sources
This article is based on current medical research and international guidelines. All claims are supported by scientific evidence from peer-reviewed sources.
- European Medicines Agency (EMA). "Summary of Product Characteristics: Carbamazepine." Official European regulatory information for carbamazepine prescribing.
- U.S. Food and Drug Administration (FDA). "Tegretol (carbamazepine) Prescribing Information." Full prescribing information including boxed warning on serious dermatologic reactions and HLA-B*1502 testing.
- National Institute for Health and Care Excellence (NICE) (2022). "Epilepsies in children, young people and adults. NICE guideline NG217." Evidence-based UK guideline for epilepsy diagnosis and management, including carbamazepine as first-line for focal epilepsy.
- World Health Organization (WHO) (2023). "WHO Model List of Essential Medicines, 23rd edition." WHO Essential Medicines Carbamazepine included as essential antiepileptic medication.
- British National Formulary (BNF). "Carbamazepine monograph." Comprehensive drug information including dosing, interactions, and contraindications.
- Marson AG, et al. (2021). "The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy." The Lancet. 397(10282):1375-1386. Major randomized controlled trial informing first-line treatment choices for epilepsy.
- Chen P, et al. (2011). "Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan." New England Journal of Medicine. 364(12):1126-1133. Landmark study demonstrating the association between HLA-B*1502 and carbamazepine-induced SJS/TEN.
- International League Against Epilepsy (ILAE) (2022). "Updated evidence review of antiseizure medicine efficacy and effectiveness as initial monotherapy." Epilepsia. 63(8):1957-1975. Systematic review confirming carbamazepine as first-line option for focal epilepsy.
Evidence grading: This article uses the GRADE framework (Grading of Recommendations Assessment, Development and Evaluation) for evidence-based medicine. Evidence level 1A represents the highest quality of evidence, based on systematic reviews of randomized controlled trials.
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