Lamotrigine

Increased risk of developing aseptic meningitis has been reported; symptoms (eg, headache, nuchal rigidity, fever, nausea/vomiting, rash, photophobia) have generally occurred within 1 to 45 days following therapy initiation. In some cases, new onset hepatic, renal and/or other organ involvement has also occurred with symptoms, possibly suggesting aseptic meningitis is associated with a hypersensitivity reaction (eg, anticonvulsant hypersensitivity syndrome). Symptoms of aseptic meningitis generally resolve following discontinuation. In some cases, re-exposure has resulted in a rapid return of symptoms (often more severe).

A spectrum of hematologic effects have been reported with use (eg, neutropenia, leukopenia, thrombocytopenia, pancytopenia, anemias, and rarely, aplastic anemia and pure red cell aplasia); patients with a previous history of adverse hematologic reaction to any drug may be at increased risk. Early detection of hematologic change is important; advise patients of early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy bruising, petechial or purpuric hemorrhage. May be associated with hypersensitivity syndrome.

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Serious skin rashes requiring hospitalization and discontinuation of treatment have been reported; incidence of serious rash is higher in pediatric patients than adults; risk may be increased by coadministration with valproic acid, higher than recommended initial doses, exceeding recommended initial dose titration, or exceeding the recommended dose escalation for lamotrigine. One rash-related death was reported in a pediatric patients taking lamotrigine immediate-release as adjunctive therapy. Nearly all cases of life-threatening rashes associated with lamotrigine have occurred within 2 to 8 weeks of treatment initiation; however, isolated cases may occur after prolonged treatment (eg, 6 months) or in patients without these risk factors; discontinue at first sign of rash and do not reinitiate therapy unless rash is clearly not drug related. Rare cases of toxic epidermal necrolysis and/or rash-related death have been reported. Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.

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; notify healthcare provider immediately if symptoms occur. Disease-related concerns:

Use with caution in patients with hepatic impairment; dosage adjustment may be required.

Use with caution in patients with renal impairment; dosage adjustment may be required. 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:

Children are at increased risk for developing serious skin rashes during therapy; lower starting doses and slower dose escalations may decrease the risk of rash. Dosage form specific issues:

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling. Other warnings/precautions:

Bipolar disorder use: Patients treated for bipolar disorder should be monitored closely for clinical worsening or suicidality; reassess patients to determine the need for maintenance treatment if on therapy >16 weeks. Prescriptions should be written for the smallest quantity consistent with good patient care. Treatment of acute manic or mixed episodes is not recommended; efficacy has not been established and slow titration limits use.

Medication errors have occurred; potential for medication errors with similar-sounding medications and between different lamotrigine formulations.

Binds to melanin and may accumulate in the eye and other melanin-rich tissues; the clinical significance of this is not known.

Epilepsy: Safety and efficacy have not been established for use as initial monotherapy, conversion to monotherapy from antiepileptic drugs (AED) other than carbamazepine, phenytoin, phenobarbital, primidone or valproic acid or conversion to monotherapy from two or more AEDs.

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. Taper over at least 2 weeks if possible.