Oxcarbazepine

Agranulocytosis, leukopenia, and pancytopenia have been reported with use (rare); discontinuation and conversion to alternate therapy may be required.

Long term use has been associated with decreased bone mineral density, osteopenia, osteoporosis, and fractures.

Use has been associated with CNS-related adverse events, most significant of these were cognitive symptoms including psychomotor slowing, difficulty with concentration, and speech or language problems, somnolence or fatigue, and coordination abnormalities, including ataxia and gait disturbances. Caution patients about performing tasks which require mental alertness (eg, operating machinery or driving).

Potentially serious, sometimes fatal, dermatologic reactions (eg, Stevens-Johnson, toxic epidermal necrolysis) have been reported in adults and children; the median time to onset was 19 days after treatment initiation. Monitor for signs and symptoms of skin reactions; discontinuation and conversion to alternate therapy may be required. Recurrence of serious skin reactions have been reported with oxcarbazepine rechallenge.

Hepatitis has been reported rarely (Hsu 2010). Promptly evaluate any symptoms of hepatic dysfunction (eg, anorexia, nausea/vomiting, right upper quadrant pain, pruritus) and discontinue therapy immediately if significant abnormalities are confirmed.

Rare cases of anaphylaxis and angioedema have been reported, even after initial dosing; permanently discontinue should symptoms occur. Use caution in patients with previous hypersensitivity to carbamazepine (cross-sensitivity occurs in 25% to 30% of patients). Potentially serious, sometimes fatal drug reaction with eosinophilia and systemic symptoms (DRESS) also known as multiorgan hypersensitivity reactions have also been reported in close association with initiation of oxcarbazepine; monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, cardiovascular, and/or hematologic organ systems; discontinuation and conversion to alternate therapy may be required.

Clinically significant hyponatremia (serum sodium • Hypothyroidism: Hypothyroidism has been reported; consider monitoring thyroid function, particularly in pediatric patients. Discontinuation of therapy has been associated with return of normal thyroxine levels.

Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; patients should be instructed to notify healthcare provider immediately if symptoms occur. Disease-related concerns:

Clinical trials excluded patients with significant cardiovascular disease or ECG abnormalities. Monitor body weight/fluid retention in patients with HF; evaluate serum sodium with worsening cardiac function or fluid retention.

Single-dose studies show that half-life of the primary active metabolite is prolonged 3- to 4-fold and AUC is doubled in patients with CrCl • Seizure disorder: Exacerbation of or new onset primary generalized seizures has been reported, particularly in children. In case of seizure aggravation, discontinue oxcarbazepine. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Consider screening patients of Asian descent for the variant human leukocyte antigen (HLA) allele B*1502 prior to initiating therapy. This genetic variant has been associated with a significantly increased risk of developing Stevens-Johnson syndrome and/or toxic epidermal necrolysis in patients receiving carbamazepine. Structural similarity of oxcarbazepine to carbamazepine, available clinical evidence, and data from nonclinical studies showing a direct interaction of oxcarbazepine with the HLA-B*1502 protein suggest patients receiving oxcarbazepine may also be at a similar risk. Consider avoiding use of oxcarbazepine in patients with a positive result. Screening is not recommending in low-risk populations or in current oxcarbazepine patients (risk usually during first few months of therapy). Other warnings/precautions:

Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.