API: Carbamazepine

What Is Carbamazepine and How Does It Work?

Carbamazepine is a tricyclic carboxamide with anticonvulsant and analgesic properties. It is commonly used to treat epilepsy, neuropathic pain, and psychotic disorders. Its mechanism of action is believed to be similar to that of phenytoin, which has a similar three-dimensional structure and works as an anticonvulsant by binding to inactive sodium channels. This stops convulsions by preventing post-tetanic potentiation and polysynaptic reflexes.1 Carbamazepine also prevents epileptic seizures by working as GABA receptor agonist.2 The drug’s analgesic properties may be mediated by an ability to act as a serotonin releasing agent and a serotonin reuptake inhibitor.3

Approved Indications4:

  • Seizures: Carbamazepine is effective for treating generalized tonic-clonic seizures and partial seizures with complex symptomatology.
  • Neuropathic Pain: Carbamazepine can treat certain types of neuropathic pain, especially trigeminal neuralgia and diabetic neuropathy.
  • Psychotic Disorders: Carbamazepine can be used alone or in combination with other antipsychotic medications to treat schizophrenia and bipolar disorder. The drug may also be used to manage aggression and dyscontrol in patients with intermittent explosive disorder, conduct disorder, antisocial personality disorder, borderline personality disorder, and dementia.
  • Off-Label Uses: Carbamazepine has been used off-label for the treatment of alcohol withdrawal syndrome and tabes dorsalis. It has also been used to relieve pain and control paroxysmal symptoms of multiple sclerosis, paroxysmal kinesigenic choreoathetosis, Kluver-Bucy syndrome, post-hypoxic action myoclonus, and acute idiopathic polyneuritis. In children, it may help relieve pain from posttraumatic paresthesia, hemifacial spasm, and dystonia.

Side Effects and Drug Interactions:

Common side effects of carbamazepine include:

  • Nausea
  • Vomiting
  • Constipation
  • Drowsiness
  • Dizziness, loss of coordination, feeling unsteady
  • Dry mouth or swollen tongue

Patients should contact a doctor if they experience serious side effects, such as:

  • Bruising easily, purple or red pinpoint spots under the skin
  • Unusual bleeding from the nose, mouth, vagina, or rectum
  • Mouth sores
  • Slow, fast, or pounding heartbeat
  • Shortness of breath, feeling light-headed, fainting
  • Confusion, vision problems, or hallucinations
  • Dark-colored urine or change in the amount of urine
  • Clay-colored stools
  • Rapid weight gain or swelling
  • Severe rash, which may be a sign of a potentially fatal skin reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis

Anti-convulsant medications can trigger suicidal thoughts or actions. Patients experiencing depression or other severe mood changes should get help immediately. Patients should not stop taking carbamazepine abruptly, as it can increase the risk of seizures. Patients who are pregnant should not take carbamazepine, as it can cause developmental disorders and congenital malformations in the fetus. The drug also passes into breast milk, so patients who are nursing should talk to a doctor before taking carbamazepine.5

Medications that are CYP3A4 inhibitors inhibit carbamazepine, which leads to an increase in plasma levels of the carbamazepine. These drugs include aprepitant, azoles, cimetidine, ciprofloxacin, danazol, diltiazem, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, trazodone, olanzapine, loratadine, terfenadine, omeprazole, oxybutynin, dantrolene, isoniazid, niacinamide, nicotinamide, ibuprofen, propoxyphene, protease inhibitors, and verapamil. Grapefruit juice contains bergamottin, a compound that is also a CYP3A4 inhibitor, so it should be avoided by patients who are taking carbamazepine. Inhibitors of human microsomal epoxide hydrolase, including loxapine, quetiapine, and valproic acid, can also increase plasma levels of carbamazepine.

CYP3A4 inducers increase the rate of carbamazepine metabolism, which lowers its effectiveness. These drugs include cisplatin, doxorubicin HCl, felbamate, rifampin, phenobarbital, phenytoin, primidone, methsuximide, and theophylline.

Because carbamazepine is a CYP450 inducer, it can increase the metabolism of aripiprazole, tacrolimus, temsirolimus, lamotrigine, lapatinib, nefazodone, phenytoin, valproic acid, and warfarin, thereby dampening their effects. Carbamazepine also increases the clearance of many benzodiazepines. Women using hormonal birth control to avoid pregnancy may want to avoid carbamazepine because it can speed metabolism of the hormones in the drug and render it ineffective.6

Latest News and Research

Carbamazepine was discovered in Switzerland in 1953. It was first marketed in 1963 as a treatment for epilepsy and neuropathic pain. Doctors in Japan began studying the drug’s ability to treat schizophrenia and bipolar disorder in the 1970’s. Today, carbamazepine is the most commonly prescribed antiepileptic drug on the market.7 It is included on the WHO Model List of Essential Medications, a list of the drugs that are considered to be critical for a basic health system.

Recent studies have explored different ways of delivering carbamazepine. The drug is usually taken orally, but the FDA is currently reviewing an intravenous formulation that can be administered to control seizures when epileptic patients are temporarily unable to take the drug by mouth.8 Researchers have also examined the efficacy of controlled-release oral formulations that deliver carbamazepine over a longer period of time. There is no evidence that controlled-release formulations are more effective than immediate-release formulations, but they may reduce adverse side effects.9

Scientists are also studying the environmental impacts of carbamazepine. The drug has been detected in streams across the United States and it may harm aquatic ecosystems.10 It has also been found in wastewater effluent, which is sometimes included in “sludge” that is used irrigate food crops. Studies suggest that this may pose a risk to human health.11

Buying Guide

Many compound pharmacists prefer Phenytoin Sodium or Gabapentin, which also treat epilepsy and neuropathic pain. Please find more information about our Bulk APIs here.

Show 11 footnotes

  1. “Carbamazepine,” 2016, https://pubchem.ncbi.nlm.nih.gov/compound/carbamazepine#section=Top
  2. “Modulation of the gamma-aminobutyric acid type A receptor by the antiepileptic drugs carbamazepine and phenytoin,” June 1995, http://www.ncbi.nlm.nih.gov/pubmed/7603459
  3. “Effects of carbamazepine treatment on pain threshold values and brain serotonin levels in rats,” March 1997, http://www.ncbi.nlm.nih.gov/pubmed/9127433
  4. “Carbamazepine,” May 30, 2016, https://www.drugs.com/monograph/carbamazepine.html
  5. “Tegretol Side Effects Center,” April 24, 2015, http://www.rxlist.com/tegretol-side-effects-drug-center.htm
  6. “Tegretrol Drug Interactions,” September 15, 2015, http://www.rxlist.com/tegretol-drug/side-effects-interactions.htm
  7. “Carbamazepine,” 2014, http://www.ilae.org/visitors/Documents/Epi_poster27-36_PRESS8.pdf
  8. “FDA Accepts Resubmission of New Drug Application for IV Carbamazepine for Epilepsy,” April 25, 2016, http://www.managedcaremag.com/news/fda-accepts-resubmission-new-drug-application-iv-carbamazepine-epilepsy
  9. “Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy,” December 3, 2014, http://www.ncbi.nlm.nih.gov/pubmed/25470302
  10. “Widely used diabetes drug found in many Southeastern US streams,” June 13, 2016, https://www.statnews.com/pharmalot/2016/06/13/diabetes-metformin-contaminants/
  11. “Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation,” February 2015, https://www.ncbi.nlm.nih.gov/pubmed/25486094?dopt=Abstract