carbamazepine

Mechanism of action

These drugs work by binding to and stabilizing the inactivated state of sodium channels in neurons, which reduces the excitability of the neuron and can lead to decreased activity in areas of the brain such as the thalamus and decreased synaptic transmission and summation of temporal stimulation. This can ultimately lead to decreased neuronal discharge, which can have therapeutic effects in certain conditions such as seizures, pain, and hypertension.

Spectrum

It is a medication that belongs to a class of drugs called anticonvulsants. It is primarily used to treat seizures and bipolar disorder. It is also used off-label for several other conditions, such as neuropathic pain, trigeminal neuralgia, and borderline personality disorder. It works by decreasing abnormal electrical activity in the brain. The therapeutic range for carbamazepine is 4-12 mcg/ml; levels above this may cause adverse effects such as drowsiness, ataxia, and diplopia.

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined:

>10%

Dizziness

Nausea

Ataxia

Drowsiness

Vomiting

1-10%

Dry mouth

Rare

Stevens-Johnson syndrome

Punctate cortical lens opacities

Myocardial infarction

Hepatic failure

Frequency undefined:

Pancytopenia

Eosinophilia

Porphyria

Congestive heart failure

Hypotension

Pancreatitis

Leukocytosis

Eosinophilia

Edema

Drowsiness

Tinnitus

Speech disturbances

Leg cramps

Fever and chills

Leukopenia

Black box warning

It is used to treat seizures and certain types of chronic pain. The FDA has issued a black box warning for carbamazepine due to an increased risk of severe skin reactions, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). These reactions can be fatal and occur anytime during treatment, including after the first dose.

Patients should be closely monitored for signs of skin reactions, and if any symptoms occur, the medication should be discontinued immediately. Additionally, before starting treatment with carbamazepine, patients should be screened for the HLA-B*15:02 allele, as it is associated with a higher risk of developing SJS or TEN

Contraindications

Documented hypersensitivity to the drug, history of bone marrow suppression, administration of MAO inhibitors within the last 14 days, coadministration with nefazodone, and coadministration with NNRTIs are all contraindicated. Additionally, patients with jaundice or hepatitis should not take carbamazepine, and it is especially not recommended during the first trimester of pregnancy due to the risk of fetal carbamazepine syndrome.

Caution

Cardiac disorders: These may cause cardiac conduction disturbances, so patients with a history of cardiac disorders should be closely monitored.

Liver dysfunction: It should be used with caution in patients with liver dysfunction, as it may cause liver damage.

Blood disorders: It may cause blood disorders, such as aplastic anemia, agranulocytosis, and thrombocytopenia. Regular blood tests are recommended for patients taking the drug.

Dizziness and drowsiness: It may cause dizziness and drowsiness, so patients should be advised to avoid activities that require mental alertness until they know how the drug affects them.

Hyponatremia: It may cause hyponatremia, a condition characterized by low sodium levels in the blood.

Interactions: It may interact with other medications, so you must inform your healthcare provider of all medications and supplements you are taking.

Withdrawal: Rapid withdrawal of carbamazepine may cause seizures; it should be tapered off gradually under the guidance of a healthcare professional.

Pregnancy and breast-feeding: It should be used with caution during pregnancy and breastfeeding, as it may cause congenital disabilities and may be excreted in breast milk.

Pregnancy consideration: It should be used with caution during pregnancy, as it may cause congenital disabilities.

Lactation: Excretion of the drug in human breast milk is known

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

It is an anticonvulsant and mood-stabilizing drug. The exact mechanism of action has yet to be fully understood, but it is thought to involve several mechanisms.

Sodium channel inhibition: It blocks voltage-dependent sodium channels, which reduces neuronal hyperexcitability and seizures.

Calcium channel inhibition: It also blocks voltage-dependent calcium channels, which can affect neurotransmitter release.

Glutamate inhibition: It may inhibit the release of the excitatory neurotransmitter glutamate, which can also reduce neuronal hyperexcitability.

Modulation of GABAergic neurotransmission: It can also increase the activity of the inhibitory neurotransmitter GABA, further reducing neuronal hyperexcitability.

Hormonal modulation: It may also affect the levels of certain hormones, such as cortisol and melatonin

Pharmacodynamics

It treats seizures and the symptoms of trigeminal neuralgia by inhibiting sodium channels. In bipolar disorder, carbamazepine has been found to decrease mania symptoms in a clinically significant manner, according to the Young Mania Rating Scale (YMRS). It has a narrow therapeutic index.

Pharmacokinetics

Absorption: It is well-absorbed from the gastrointestinal tract, with a bioavailability of 85% when given as an oral suspension. The peak serum time for immediate-release tablets is 4.5 hours; for extended-release tablets is 3-12 hours; and for oral suspension is 1.5 hours.

Distribution: It is highly protein-bound, with a protein binding of 75-90%. The volume of distribution is 1.5 L/kg in neonates, 1.9 L/kg in children, and 0.59-2 L/kg in adults.

Metabolism: It is metabolized in the liver by the cytochrome P450 enzyme system, primarily by the CYP3A4 and CYP2C19 isoenzymes. The primary active metabolite is carbamazepine-10,11-epoxide, which also contributes to its anticonvulsant effect.

Elimination/Excretion: The half-life of carbamazepine is 25-65 hours after initial dosing, but it decreases to 10-20 hours after autoinduction. The half-life for extended-release tablets is 35-40 hours. It is eliminated mainly through the urine (72%) and, to a lesser extent, through the feces (28%)

Administration

For Intravenous use only

It is available for intravenous use only; it should be diluted with 100 mL of a compatible diluent, such as 0.9% NaCl, lactated Ringer’s solution, or D5W. The measured dose should be transferred to a 100 mL bag of the compatible solution. The solution should be visually inspected for particulate matter, cloudiness, or discoloration before administration, and if any of these are present, the solution should be discarded and not used.

Oral administration

It should be taken with food to reduce the risk of stomach upset. Extended-release tablets should not be chewed, crushed, or cut, as this can affect the controlled release of the medication and lead to a higher risk of side effects. The extended-release tablets should be swallowed whole.

Storage

carbamazepine IV solutions before dilution should be stored at 20-25°C (68-77°F) with excursions permitted to 15-30°C (59-86°F). Once diluted, the solution should be used within a specific time frame depending on storage conditions:

• Controlled room temperature (20-25°C [68-77°F]): Maximum of 4 hours
• Refrigerated (2-8°C [36-46°F]): Maximum of 24 hours.

It is essential to follow these storage guidelines to ensure the stability and potency of the medication. Any solution that has been stored beyond the recommended time frame or has been frozen should be discarded and not used.

Patient information leaflet

Generic Name: carbamazepine

Pronounced: [ kar-ba-MAZ-e-peen ]

Why do we use carbamazepine?

It is a medication that is used to treat several conditions, including:

• Epilepsy is used to control seizures in people with certain types of epilepsy. It is often used as a first-line treatment for partial seizures, and it can also be used to treat tonic-clonic seizures.
• Bipolar disorder is used to treat acute mania and rapid cycling in people with bipolar disorder.
• Neuropathic pain is used to treat certain types of chronic pain, such as trigeminal neuralgia and diabetic neuropathy.
• Migraine prevention: It may prevent migraines in people who have not responded to other treatments.
• Substance withdrawal: It may help prevent seizures and other withdrawal symptoms in people withdrawing from alcohol or other sedative-hypnotics