Carbamazepine
Carbamazepine is an anticonvulsant medication commonly used to treat epilepsy, as well as certain psychiatric conditions, such as bipolar disorder and trigeminal neuralgia. It is effective in controlling seizures and stabilizing mood in patients with bipolar disorder.
Trade Name
Carbamazepine is marketed under several brand names, including Tegretol, Carbatrol, and Equetro.
Chemical Properties
Chemical structure: Carbamazepine is a dibenzazepine derivative.
Molecular formula: C₁₅H₁₄N₂O
Molecular weight: 236.3 g/mol
Solubility: Carbamazepine is poorly soluble in water but is available in oral tablet, chewable tablet, and suspension forms.
Biochemical Properties
Mechanism of action: Carbamazepine works primarily by blocking voltage-gated sodium channels in neurons, stabilizing neuronal membranes, and reducing the excessive firing of neurons. This action prevents seizures and may also reduce symptoms in certain psychiatric conditions, such as mania in bipolar disorder.
Pharmacology
Administration: Carbamazepine is typically administered orally in tablet or liquid form, and is also available as an extended-release formulation for once-daily dosing.
Bioavailability: Carbamazepine is well absorbed after oral administration, with a bioavailability of approximately 80%. It undergoes extensive first-pass metabolism in the liver.
Metabolism: Carbamazepine is primarily metabolized by the liver through the cytochrome P450 enzyme system, mainly CYP3A4. It is also an inducer of this enzyme, which can affect the metabolism of other drugs.
Half-life: The half-life of carbamazepine is about 12–17 hours, but this can vary significantly with long-term use due to the drug’s induction of its own metabolism.
Clinical Indications
Epilepsy: It is effective in the treatment of focal (partial) and generalized tonic-clonic seizures. It can be used as monotherapy or in combination with other anticonvulsants. Bipolar disorder: Carbamazepine is used as a mood stabilizer in the treatment of manic episodes in patients with bipolar disorder.
Trigeminal neuralgia: Carbamazepine is a first-line treatment for trigeminal neuralgia, a condition characterized by severe, stabbing pain in the face.
Other uses: Carbamazepine is sometimes used off-label for conditions like neuropathic pain, restless leg syndrome, and certain psychiatric disorders, such as schizophrenia.
Side Effects
Dizziness and drowsiness: These effects are particularly noticeable when starting treatment or increasing the dose.
Gastrointestinal issues: Nausea, vomiting, and constipation are common, especially at higher doses.
Skin rash: A rash is a frequent side effect, and in some cases, it can develop into more severe reactions such as Stevens-Johnson syndrome, a potentially life-threatening skin condition.
Hyponatremia: Low sodium levels in the blood are a known side effect of carbamazepine and can lead to symptoms such as confusion, seizures, and weakness.
Blood dyscrasias: Carbamazepine can cause blood-related side effects, including leukopenia (low white blood cell count), thrombocytopenia (low platelet count), and anemia.
Ataxia and coordination problems: Difficulty with balance and coordination may occur, especially at higher doses. Cognitive effects: Some individuals may experience confusion, memory problems, or difficulty concentrating.
Hepatotoxicity: In rare cases, carbamazepine can cause liver damage, leading to jaundice or liver failure.
Monitoring and Considerations
Therapeutic drug monitoring: Due to the risk of toxicities and variable metabolism, carbamazepine levels should be monitored, especially during the initiation of therapy or when dosage adjustments are made. The target serum concentration is typically between 4-12 mcg/mL.
Dose adjustments: Carbamazepine is known to induce its own metabolism, which may lead to a reduction in drug levels over time. As a result, dosage adjustments may be required during long-term therapy.
Pregnancy: Carbamazepine is classified as a Category D drug during pregnancy, meaning it can cause harm to the fetus. It has been associated with neural tube defects and other congenital malformations. It should be used during pregnancy only if the benefits outweigh the risks, and alternative medications should be considered for women who are pregnant or planning to become pregnant.
Drug interactions: Carbamazepine is an enzyme inducer and can decrease the levels of other drugs that are metabolized by the cytochrome P450 system. It is important to monitor for interactions with drugs such as oral contraceptives, other anticonvulsants, and certain antibiotics.
Carbamazepine is a widely used anticonvulsant with a broad range of indications, including epilepsy, bipolar disorder, and trigeminal neuralgia. While it is effective for these conditions, its use requires careful monitoring due to its potential for side effects and drug interactions. Special caution is needed during pregnancy, and the drug's potential to induce liver enzymes means that interactions with other medications should be closely monitored.
