Carbamazepine
| Carbamazepine | |
|---|---|
| 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.[1]
- 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 initiation regimen is as follows:
- Week 1 ā 200 mg nocte
- Week 2 and 3 ā 200 mg bd
- Week 4 and 5 ā 300 mg mane, 200 mg nocte
- Week 6+ ā 300 mg bd
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.
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
References
- ā "Pharmacogenomics ā Helps Reduce Rash Decisions". www.medsafe.govt.nz (in English). Retrieved 2023-03-23.
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.
- TRIP Database: clinical publications about evidence-based medicine.
- Other Wikis: Radiopaedia, Wikipedia Search, Wikipedia I Feel Lucky, Orthobullets,
