Carbamazepine

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Carbamazepine
Name	Carbamazepine
Drug class	Anticonvulsant, mood stabilizer, sodium channel blocker
Daily dose	Depends on the specific condition; initial dose typically 100-200 mg twice a day for adults, slowly titrated up
Maximum dose	1200 mg/day for adults; doses should be individualized based on patient response
Metabolism	Hepatic (primarily by the CYP3A4 enzyme)
Half life	12-17 hours after several doses.
Indication	Epilepsy, trigeminal neuralgia, bipolar disorder
Contraindications	Hypersensitivity to carbamazepine or tricyclic antidepressants, history of bone marrow depression, MAO inhibitor use within the past 14 days, HLA genotype risk factor
Side effects	Dizziness, drowsiness, nausea, vomiting, blurred or double vision, unsteadiness, headache, dry mouth, constipation, skin rash
Interactions	Warfarin, phenytoin, valproic acid, phenobarbital, oral contraceptives, macrolide antibiotics, isoniazid, grapefruit juice, and many others
DrugBank ID	DB00564
NZ Formulary ID	2615 - Adults 2615 - Children

Carbamazepine is most commonly used in the treatment of epilepsy, bipolar affective disorder, and neuropathic pain especially trigeminal neuralgia.

Mechanism of Action

Carbamazepine modulates voltage-gated sodium channels (VGSC), inhibiting action potentials and reducing synaptic transmission. Similar to other anticonvulsants, carbamazepine is thought to bind to the alpha subunit of VGSC, specifically at a binding pocket formed by the external pore loop and the pore-lining part of domain IV. It is thought that carbamazepine maintains sodium channels in inactivated states, leading to fewer channels opening and thus inhibiting the generation of action potentials. Carbamazepine also binds to other voltage-gated ion channels, such as voltage-gated calcium channels.

Contraindications

Carbamazepine is contraindicated in patients with bone marrow depression or hypersensitivity to carbamazepine or tricyclic compounds like amitriptyline. Monoamine oxidase inhibitors should be discontinued for at least 14 days before administering carbamazepine.

Workup

Before prescription, first consider pharmacogenetic testing. Certain HLA genotypes give increased risk for Severe Cutaneous Adverse Reactions (an umbrella term that refers to Steven Johnson Syndrome, Toxic Epidermal Necrolysis, and Drug Reactions with Eosinophilia and Systemic Symptoms). If positive for either of the alleles then avoid the medication if at all possible.

• HLA-B*15:02: Han Chinese or Thai
• HLA-A*31:01: Japanese, Caucasian, indigenous populations of the Americas, Hispanic populations, southern Indian, Arabic descent

Also general baseline blood tests.

Initiation

It is vital to initiate the medication slowly. Generally use carbamazepine controlled release (CR). A typical regimen for trigeminal neuralgia is as follows:

• Initiation dose: 200mg nocte
• Titration 200mg every 3 days
• Dose range: 200-1200mg daily
• Frequency: 2 - 4 times a day. Twice daily usually best.

Most patients prefer a smaller dose in the morning and a larger dose in the evening to reduce the sedation effect.

Due to auto-induction of enzymes, a further increase in dose may be required at 6 to 8 weeks after initiating therapy to maintain serum levels. Note that the 200mg CR tablets can be halved and the CR effect is not lost.

Tapering is done by 200mg every 7 days.

Side Effects

Dizziness, drowsiness, fatigue, ataxia, diplopia, nausea, cognitive slowing, hyponatraemia leucopenia, thrombocytopenia, skin reactions, abnormal liver function tests

Monitoring

Monitor FBC, UEC, and LFTs in the first 1-2 months. Then monitor annually. Drug levels are not generally required unless there are side-effects, concern about compliance, or breakthrough seizures when used for epilepsy.

Also monitor for any mood changes.

Resources

Carbamazepine in neuromuscular disease - Dyong 2023.pdf - 1.23 MB (f)

Literature Review

Literature Review

Reviews from the last 7 years: review articles, free review articles, systematic reviews, meta-analyses, NCBI Bookshelf

Articles from all years: PubMed search, Google Scholar search.

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