Chapter 5: Carbamazepine

INTRODUCTION

Carbamazepine was first indicated and marketed for trigeminal neuralgia and was later found to be an effective antiepileptic.¹ Carbamazepine is a broad-spectrum antiepileptic drug (AED) and is indicated for partial seizures with complex symptomatology (psychomotor, temporal lobe), generalized tonic-clonic seizures (grand mal), and mixed seizure patterns.^2,3 Extended-release carbamazepine is also indicated alone or in combination with other antipsychotic agents for acute manic or mixed episodes associated with bipolar 1 disorder either as treatment or prevention.⁴ Carbamazepine may be used as an adjunct for the symptomatic management of the acute phase of schizophrenia in patients who are refractory to antipsychotics.⁴ Carbamazepine has also been used for the management of restless leg syndrome, peripheral neuropathy, diabetic peripheral neuropathy, and posttraumatic stress disorders.^3,4

THERAPEUTIC AND TOXIC PLASMA CONCENTRATIONS

The therapeutic serum level for carbamazepine is 4–12 mg/L. Central nervous system (CNS) adverse effects such as drowsiness, dizziness, and headaches, increase when levels are greater than 8 mg/L.⁵ Carbamazepine exhibits concentration related toxicity, serum levels of 11–15 mg/L are associated with somnolence, nystagmus, and ataxia; levels of 15–25 mg/L are associated with combativeness, hallucinations, and chorea; and levels greater than 25 mg/L are associated with seizures and coma. In order to minimize carbamazepine CNS adverse effects, clinicians may target a therapeutic serum level of 4–8 mg/L.⁶

ADVERSE EFFECTS

Carbamazepine causes gastrointestinal adverse effects such as nausea, vomiting, and anorexia.⁴ Carbamazepine has mild anticholinergic properties and occasionally can cause xerostomia.⁴ Carbamazepine may cause bradycardia in the elderly, and patients over 50 years of age should have a baseline electrocardiogram completed prior to use.^{8, 9, and 10} Conversely, in young patients, toxic carbamazepine levels will manifest with tachycardia.^{8, 9, and 10} Carbamazepine may cause osteoporosis and elevated alkaline phosphatases are common with its use.¹¹ Carbamazepine is hepatotoxic, and liver enzyme tests and liver function tests should be monitored at baseline and periodically.^3,4

Carbamazepine is known to cause blood dyscrasias including aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, anemias, and pancytopenia.⁴ A boxed warning for carbamazepine-induced aplastic anemia and agranulocytosis exists due to a risk five to eight times greater than in the general population. However, the risk of these reactions in the general population is low, approximately six patients per 1 million population per year for agranulocytosis and two patients per 1 million population per year for aplastic anemia.⁷ Carbamazepine should be discontinued when the white blood cell count is less than 2,500/mm³ or the absolute neutrophil count is less than 1,000/mm.^3,7 Most patients who develop leukopenia do not progress to aplastic anemia or agranulocytosis.

Carbamazepine has been known to cause the antiepileptic drug (AED) hypersensitivity syndrome and is contraindicated due to cross-reactivity with other aromatic anticonvulsant agents ...