Unit Converter
Carbamazepine
(Antiepileptic Drug – TDM Marker – Sodium Channel Blocker)
Synonyms
- Carbamazepine
- CBZ
- Tegretol®
- Carbatrol®
- 5H-dibenz[b,f]azepine-5-carboxamide
Units of Measurement
- µmol/L
- mg/dL
- mg/100 mL
- mg%
- mg/L
- µg/mL
Description
Carbamazepine is a first-line antiepileptic drug (AED) used to treat:
- Focal (partial) seizures
- Generalized tonic–clonic seizures
- Trigeminal neuralgia
- Bipolar disorder (mania)
It stabilizes hyperactive nerve membranes by blocking voltage-gated sodium channels.
Because carbamazepine has:
- Narrow therapeutic range
- Auto-induction of metabolism
- High protein binding
- Significant drug interactions
Therapeutic Drug Monitoring (TDM) is essential.
Pharmacology
- Absorbed slowly; peak ~6 hours
- Strong hepatic metabolism (CYP3A4)
- Metabolite CBZ-10,11-epoxide active & sometimes toxic
- Auto-induction lowers drug levels over first 2-4 weeks
- Half-life:
- Initial: 25-65 hours
- Chronic therapy: 12-17 hours
- Initial: 25-65 hours
Clinical Significance
High Carbamazepine Levels (Toxicity)
Neurological
- Nystagmus
- Ataxia
- Diplopia
- Dizziness
- Confusion
- Coma (severe)
Hematologic
- Leukopenia
- Thrombocytopenia
- Aplastic anemia (rare, serious)
Metabolic
- Hyponatremia (SIADH)
- Elevated liver enzymes
Cardiac
- Conduction delays
- Arrhythmias
Low Carbamazepine Levels
Causes:
- Non-adherence
- Auto-induction phase
- Rapid metabolism
- Drug interactions (CYP3A4 inducers)
- Pregnancy (increased clearance)
Insufficient levels → uncontrolled seizures.
Reference Intervals
(Tietz 8E + AAN/AES Epilepsy Guidelines + Mayo + ARUP)
Therapeutic Range
- 4 – 12 µg/mL
- 17 – 51 µmol/L
- 4 – 12 mg/L
Toxic Level
- > 15 µg/mL
- Severe toxicity > 40 µg/mL
Critical Range
- > 20–25 µg/mL (requires urgent intervention)
Active Metabolite (CBZ-epoxide)
- Therapeutic: 0.4 – 4 µg/mL
Unit Meanings
| Unit | Meaning |
| µmol/L | micromole per liter |
| mg/dL | milligram per deciliter |
| mg/100 mL / mg% | milligram per 100 mL |
| mg/L | milligram per liter |
| µg/mL | microgram per milliliter |
Diagnostic Uses
1. Therapeutic Drug Monitoring
Ensure optimal seizure control with minimal toxicity.
2. Detecting Toxicity
Levels >15–20 µg/mL correlate with neurotoxicity.
3. Assessing Drug Interactions
CYP3A4 inducers lower levels:
- Phenytoin
- Phenobarbital
- Rifampin
Inhibitors raise levels:
- Macrolides
- Azoles
- Grapefruit juice
4. Monitoring Pregnancy
Carbamazepine clearance increases; levels drop → dose adjustment required.
5. Monitoring in Elderly
Altered protein binding → risk of toxicity.
6. Acute Overdose Evaluation
Analytical Notes
- Use trough level (right before next dose)
- Serum or plasma acceptable
- Hemolyzed samples acceptable (minimal effect)
- Monitoring required:
- Baseline + every 2 weeks during dose titration
- Every 6–12 months thereafter
- More frequently with interacting medications
- Baseline + every 2 weeks during dose titration
Clinical Pearls
- Carbamazepine induces its own metabolism → expect decrease in levels after 2–4 weeks.
- Hyponatremia is common, especially in elderly patients.
- Test HLA-B*1502 before initiating in Asian ancestry to prevent Stevens–Johnson syndrome.
- Consider measuring CBZ-epoxide in toxicity or poor response.
- Always check levels with any new medication for interactions.
Interesting Fact
Carbamazepine was initially developed as an antidepressant in the 1950s but became world-famous as an anticonvulsant and mood stabilizer due to its strong sodium-channel blockade.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Therapeutic Drug Monitoring.
- AAN/AES Epilepsy Guidelines - TDM in AEDs.
- IFCC TDM Standardization.
- Mayo Clinic Laboratories - Carbamazepine Level.
- ARUP Consult - Anticonvulsant Drug Monitoring.
- MedlinePlus / NIH - Carbamazepine Drug Monitoring.
- Clinical Pharmacology Texts - Sodium Channel Blockers.