What are the side effects of carbamazepine?

Side Effects of Carbamazepine

Carbamazepine commonly causes dizziness, drowsiness, and problems with walking and coordination, with 65% of patients experiencing at least one adverse event compared to 27% on placebo, though most side effects are dose-dependent and transient. 1, 2

Most Common Side Effects

The most frequently reported adverse effects include:

• Dizziness and drowsiness are the predominant side effects, occurring commonly during both initiation and long-term therapy 2, 3
• Problems with walking and coordination (ataxia/unsteadiness) affect a significant proportion of patients 2, 3
• Nausea and vomiting are common gastrointestinal complaints 2
• Diplopia (double vision) occurs in a dose-dependent manner during long-term use 3
• Loss of coordination and vertigo were the most commonly observed effects in pediatric patients, though almost always transient and dose-related 4

Serious and Life-Threatening Reactions

Severe Skin Reactions

• Stevens-Johnson syndrome and toxic epidermal necrolysis can occur, particularly in patients of Asian descent (especially Han Chinese population) 5, 2
• HLA-B*15:02 screening is mandatory before initiating treatment in Asian patients to reduce risk of these potentially fatal skin reactions 6, 5
• Anticonvulsant hypersensitivity syndrome presents with cutaneous rash, high fever, lymphadenopathy, eosinophilia, and elevated transaminases 7

Hematologic Complications

• Leukopenia occurs relatively commonly during treatment 3
• Aplastic anemia (27 cases) and agranulocytosis (10 cases) were reported out of more than 4 million patients treated between 1975-1986 4
• Thrombocytopenia can develop as part of hypersensitivity reactions 7
• Regular monitoring of complete blood count is essential throughout treatment 6

Hepatic and Metabolic Effects

• Hepatitis and liver problems can occur, presenting with jaundice, dark urine, right upper quadrant pain, easy bruising, loss of appetite, or nausea 2, 3
• Elevated transaminases may occur, requiring monitoring with liver function tests at baseline, monthly for 3 months, then every 3-6 months if stable 6
• Hyponatremia (low sodium) can develop during treatment 3
• Disturbances of vitamin D metabolism have been documented 3

Cardiovascular Effects

• Irregular heartbeat including fast, slow, or pounding heartbeat, with associated shortness of breath, lightheadedness, or fainting 2

Neurologic Toxicity

• Severe toxicity can cause cardiovascular instability, intractable seizures, and coma in cases of overdose or supratherapeutic dosing 8
• Focal neurological deficits mimicking cerebrovascular accidents can occur with acute toxicity 8
• Nystagmus, headache, and dizziness are common neurological manifestations 9

Psychiatric Effects

• Mental disorders including emotional instability, personality changes, delusions of reference and persecution, depressive state, and hyperventilation syndrome have been reported, though rare 9
• Suicidal thoughts or actions, depression, or mood problems can occur 2

Timing and Management Considerations

• Most side effects are transient and occur during early phases of treatment rather than during long-term use 3
• 30-50% of children and adults remain free of side effects in comparative studies 4
• Side effects are usually reversible with dosage adjustment or slower titration 4
• Taking carbamazepine at bedtime may minimize daytime side effects like dizziness 6
• Therapeutic blood levels should be maintained between 4-8 mcg/mL to optimize efficacy while minimizing dose-dependent toxicity 6

Critical Drug Interactions

• Carbamazepine significantly decreases levels of oral contraceptives, warfarin, and corticosteroids through hepatic enzyme induction 1, 6, 2
• Isoniazid can increase carbamazepine levels, potentially leading to toxicity 1, 6
• Phenytoin levels can increase when given concurrently 1
• Women using oral contraceptives should be advised of reduced effectiveness and consider alternative contraception 1, 2

Monitoring Requirements

• Baseline HLA-B*15:02 testing in Asian patients before initiation 6, 5
• Complete blood count and liver enzyme monitoring at regular intervals 6
• More frequent monitoring required in patients with preexisting liver disease or when hospitalized with complications 6
• Blood samples for carbamazepine levels should be drawn 4-6 days after dosing to avoid transient elevations 6

Special Populations

• Pregnancy: Carbamazepine may harm the unborn baby; comprehensive risk-benefit assessment required before conception, with consideration of discontinuation in mild cases 5, 2
• Breastfeeding: Carbamazepine passes into breast milk; patients should not both breastfeed and take carbamazepine 2
• Patients should avoid alcohol and CNS depressants as carbamazepine potentiates sedation and dizziness 2