Carbamazepine Pharmacology

Carbamazepine is one of the most widely used anticonvulsant drugs. Here, we review the must-know pharmacology that you need to know to master this drug if it gets asked during the NAPLEX exam.

Carbamazepine is a carboxamide anticonvulsant used to control and prevent seizures, a mood stabilizer, and an agent used in the treatment of neuropathic pain. It is used widely – as it has high efficacy, demonstrates fewer side effects in the long term, and is well tolerated by patients.

Indications of carbamazepine therefore include:

• Treatment of partial seizures and generalized tonic-clonic seizures
• Treatment of trigeminal neuralgia
• For the prophylaxis of bipolar disorder unresponsive to lithium
• Acute alcohol withdrawal (as an adjunct)
• Management of diabetic neuropathy

Side Effects

The most common side effect of carbamazepine is skin rash.

Other side effects include:

• Allergic reactions including hepatosplenomegaly, fever, lymphadenopathy. However, the incidence of serious hypersensitivity reactions is rare.
• Systemic lupus erythematosus (which can alleviate on discontinuation of the drug)
• Blood dyscrasias.
• Exacerbation or precipitation of seizures, particularly in patients exhibiting generalized atypical absence seizures.
• Toxicity of the central nervous system can cause double vision, headache, dizziness, drowsiness, ataxia, or confusion.
• Transient leucopenia.
• Hyponatremia – due to the potentiation of the antidiuretic hormone on the kidney which can, in turn, lead to confusion and decreased seizure control.
• Induction of hepatic CYP3A4 can lead to drug-drug interactions.

Mechanism of Action

Carbamazepine is a sodium channel blocker.

It works by stopping the build-up of electrical signals of the nerve cells in the brain. An increase in glutamate concentration can cause seizures. Carbamazepine also reduces the release of glutamate, hence lowering seizures.

Carbamazepine can increase dopamine turnover and increase GABA transmission, hence helping in the treatment of bipolar disorders, reducing both maniac and depressive symptoms.

Drug Interactions

Carbamazepine pharmacology is heavily influenced by its metabolism, and carbamazepine is itself metabolized by the liver. Therefore, its long-term use can cause induction of hepatic enzymes leading to drug interactions.

• The most common drug interaction of carbamazepine is with oral combined contraceptive pills. Therefore, the dose of estrogen should be increased to avoid contraceptive failure.

• Carbamazepine can accelerate the metabolism of warfarin and cyclosporin.

• Drugs like clarithromycin, erythromycin, and diltiazem can increase the serum concentration of carbamazepine. Therefore, loss of seizure control can occur. Healthcare providers may need to increase the dose of carbamazepine to prevent seizures.

• Carbamazepine can also interact with hydrocodone by reducing its blood levels, resulting in the medication becoming less effective in controlling pain. If you incorporate carbamazepine into hydrocodone therapy, the patient may experience withdrawal symptoms due to decreased blood concentration. And if they take both of them together, stopping carbamazepine therapy can cause an increase in hydrocodone blood levels, leading to an overdose. As a result, the dose of hydrocodone needs to be lowered if carbamazepine is stopped.

Dosing Information

Carbamazepine is used as a first-line treatment for generalized tonic-clonic seizures and a drug of choice for the treatment of simple and complex focal seizures. It can be used in combination with other antiepileptic drugs if they fail to control seizures alone.

In the initial stages, the patient should be prescribed the lowest possible and effective dose and should be titrated according to the patient’s response to the drug. The dose should be increased gradually thereafter until stabilization of the patient’s condition is reached.

For focal and secondary generalized tonic-clonic seizures or primary generalized tonic-clonic seizures:

In adults:

• By mouth, initially, 100–200 mg 1–2 times a day. The dose can be increased in increments of 100 to 200 mg every 2 weeks. The usual dose is 0.8 to 1.2 grams daily in divided doses. However, it can be increased up to 1.6 to 2 grams in divided doses if required.

• By rectum – up to a total of 1 gram daily in four divided doses for up to 7 days. It is given rectally when the patient is unable to take the drug via the oral route.

For trigeminal neuralgia:

In adults:

By mouth, initially 100mg 1 to 2 times a day. However, some patients may require higher doses. The dose can be increased up to 1.6 grams daily. The usual dose of carbamazepine for trigeminal neuralgia is 200 mg 3 to 4 times per day.

For prophylaxis of bipolar disorder not responding to lithium:

In adults:

By mouth, initially 400mg in divided doses. However, the dose can be increased until symptoms are controlled. The maximum dose that can be given is 1.6 grams in a day. The usual dose of carbamazepine for bipolar disorder prophylaxis is 400 to 600mg daily.

Adjunct in Alcohol Withdrawal:

For adults:

By mouth, begin with an initial dose of 800mg per day in divided doses. Then reduce up to 200 mg – given for 7 to 10 days, and taper off thereafter over a 5-day period.

Diabetic Neuropathy:

For adults:

By mouth, initiate with 100mg 1 to 2 times a day. It can be increased gradually according to response. However, the usual daily dose of carbamazepine for diabetic neuropathy is 200mg, given 3 to 4 times a day. It can be increased up to 1.6 grams per day if needed.

Focal and Generalized Tonic-Clonic Seizures:

In children aged 1 to 11 months:

By mouth, initially, as 5mg/kg, once daily given at night or 2.5mg/kg given twice a day.

It should be increased in the steps of 2.5 to 5mg/kg every 3 to 7 days as required. The maintenance dose is 5mg/kg 2 to 3 times a day that could be increased up to 20mg/kg daily.

In Children aged 12 to 17 years:

Initially, 100 to 200mg is given 1 to 2 times a day that can be increased up to 200 to 400 mg 2 to 3 times a day. The dose can be increased slowly up to 1.8g daily.

Brand Names

Common brand names of carbamazepine you may encounter include:

• Tegretol
• Tegretol-XR
• Epitol
• Carbatrol

Carbamazepine is available as 100mg, 200mg, and 300 mg oral capsules and extended-release preparations. It is also available as an oral suspension in the concentration of 100mg/5ml.

That completes our NAPLEX review of carbamazepine pharmacology! If you have found this helpful, check back to NAPLEX Study Guide soon for even more exclusive content to help you pass the NAPLEX exam.