INDICATION AND USES:
LAMICTAL is indicated for:
- Epilepsy—adjunctive therapy in patients aged 2 years and older:
- partial-onset seizures. primary generalized tonic-clonic seizures.
- generalized seizures of Lennox-Gastaut syndrome. (1.1)
- Epilepsy—monotherapy in patients aged 16 years and older: Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug. (1.1)
- Bipolar disorder: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. (1.2)
Limitations of Use: Treatment of acute manic or mixed episodes is not recommended. Effectiveness of LAMICTAL in the acute treatment of mood episodes has not been established.
DOSAGE AND ADMINISTRATION
- Dosing is based on concomitant medications, indication, and patient age. (2.1, 2.2, 2.3, 2.4)
- To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded. LAMICTAL Starter Kits and LAMICTAL ODT Patient Titration Kits are available for the first 5 weeks of treatment. (2.1, 16)
- Do not restart LAMICTAL in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks. (2.1, 5.1)
- Adjustments to maintenance doses will be necessary in most patients starting or stopping estrogen-containing oral contraceptives. (2.1, 5.9)
- Discontinuation: Taper over a period of at least 2 weeks (approximately 50% dose reduction per week). (2.1, 5.10) Epilepsy:
- Adjunctive therapy—See Table 1 for patients older than 12 years and Tables 2 and 3 for patients aged 2 to 12 years. (2.2)
- Conversion to monotherapy—See Table 4. (2.3) Bipolar disorder: See Tables 5 and 6. (2.4)
SIDE EFFECTS:
Epilepsy: Most common adverse reactions (incidence ≥10%) in adults were dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, and rash. Additional adverse reactions (incidence ≥10%) reported in children included vomiting, infection, fever, accidental injury, diarrhea, abdominal pain, and tremor. (6.1)
Bipolar disorder: Most common adverse reactions (incidence >5%) in adults were nausea, insomnia, somnolence, back pain, fatigue, rash, rhinitis, abdominal pain, and xerostomia. (6.1)
CONTRAINDICATIONS:
Hypersensitivity to the drug or its ingredients. (Boxed Warning, 4)
WARNINGS AND PRECAUTIONS:
- Life-threatening serious rash and/or rash-related death: Discontinue at the first sign of rash, unless the rash is clearly not drug related. (Boxed Warning, 5.1)
- Hemophagocytic lymphohistiocytosis: Consider this diagnosis and evaluate patients immediately if they develop signs or symptoms of systemic inflammation. Discontinue LAMICTAL if an alternative etiology is not established. (5.2)
- Fatal or life-threatening hypersensitivity reaction: Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms, may be fatal or life threatening. Early signs may include rash, fever, and lymphadenopathy. These reactions may be associated with other organ involvement, such as hepatitis, hepatic failure, blood dyscrasias, or acute multiorgan failure. LAMICTAL should be discontinued if alternate etiology for this reaction is not found. (5.3)
- Cardiac rhythm and conduction abnormalities: Avoid LAMICTAL in patients with certain underlying cardiac disorders or arrhythmias. (5.4)
- Blood dyscrasias (e.g., neutropenia, thrombocytopenia, pancytopenia): May occur, either with or without an associated hypersensitivity syndrome. Monitor for signs of anemia, unexpected infection, or bleeding. (5.5)
- Suicidal behavior and ideation: Monitor for suicidal thoughts or behaviors. (5.6)
- Aseptic meningitis: Monitor for signs of meningitis. (5.7)
- Medication errors due to product name confusion: Strongly advise patients to visually inspect tablets to verify the received drug is correct. (5.8, 16, 17)
DRUG INTERACTIONS:
- Valproate increases lamotrigine concentrations more than 2-fold. (7, 12.3)
- Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by approximately 40%. (7, 12.3)
- Estrogen-containing oral contraceptives decrease lamotrigine concentrations by approximately 50%. (7, 12.3)
- Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure by approximately 50% and 32%, respectively. (7, 12.3)
- Coadministration with organic cationic transporter 2 substrates with narrow therapeutic index is not recommended (7, 12.3)
OVERDOSE:
Overdoses involving quantities up to 15 g have been reported for LAMICTAL, some of which have been fatal. Overdose has resulted in ataxia, nystagmus, seizures (including tonic-clonic seizures), decreased level of consciousness, coma, and intraventricular conduction delay.
Management of Overdose: There are no specific antidotes for lamotrigine. Following a suspected overdose, hospitalization of the patient is advised. General supportive care is indicated, including frequent monitoring of vital signs and close observation of the patient. If indicated, emesis should be induced; usual precautions should be taken to protect the airway. It should be kept in mind that immediate-release lamotrigine is rapidly absorbed [see Clinical Pharmacology (12.3)]. It is uncertain whether hemodialysis is an effective means of removing lamotrigine from the blood. In 6 renal failure patients, about 20% of the amount of lamotrigine in the body was removed by hemodialysis during a 4-hour session. A Poison Control Center should be contacted for information on the management of overdosage of LAMICTAL.
- Uses
-
INDICATION AND USES:
LAMICTAL is indicated for:
- Epilepsy—adjunctive therapy in patients aged 2 years and older:
- partial-onset seizures. primary generalized tonic-clonic seizures.
- generalized seizures of Lennox-Gastaut syndrome. (1.1)
- Epilepsy—monotherapy in patients aged 16 years and older: Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug. (1.1)
- Bipolar disorder: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. (1.2)
Limitations of Use: Treatment of acute manic or mixed episodes is not recommended. Effectiveness of LAMICTAL in the acute treatment of mood episodes has not been established.
DOSAGE AND ADMINISTRATION
- Dosing is based on concomitant medications, indication, and patient age. (2.1, 2.2, 2.3, 2.4)
- To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded. LAMICTAL Starter Kits and LAMICTAL ODT Patient Titration Kits are available for the first 5 weeks of treatment. (2.1, 16)
- Do not restart LAMICTAL in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks. (2.1, 5.1)
- Adjustments to maintenance doses will be necessary in most patients starting or stopping estrogen-containing oral contraceptives. (2.1, 5.9)
- Discontinuation: Taper over a period of at least 2 weeks (approximately 50% dose reduction per week). (2.1, 5.10) Epilepsy:
- Adjunctive therapy—See Table 1 for patients older than 12 years and Tables 2 and 3 for patients aged 2 to 12 years. (2.2)
- Conversion to monotherapy—See Table 4. (2.3) Bipolar disorder: See Tables 5 and 6. (2.4)
- Side Effects
-
SIDE EFFECTS:
Epilepsy: Most common adverse reactions (incidence ≥10%) in adults were dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, and rash. Additional adverse reactions (incidence ≥10%) reported in children included vomiting, infection, fever, accidental injury, diarrhea, abdominal pain, and tremor. (6.1)
Bipolar disorder: Most common adverse reactions (incidence >5%) in adults were nausea, insomnia, somnolence, back pain, fatigue, rash, rhinitis, abdominal pain, and xerostomia. (6.1)
- Precautions
-
CONTRAINDICATIONS:
Hypersensitivity to the drug or its ingredients. (Boxed Warning, 4)
WARNINGS AND PRECAUTIONS:
- Life-threatening serious rash and/or rash-related death: Discontinue at the first sign of rash, unless the rash is clearly not drug related. (Boxed Warning, 5.1)
- Hemophagocytic lymphohistiocytosis: Consider this diagnosis and evaluate patients immediately if they develop signs or symptoms of systemic inflammation. Discontinue LAMICTAL if an alternative etiology is not established. (5.2)
- Fatal or life-threatening hypersensitivity reaction: Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms, may be fatal or life threatening. Early signs may include rash, fever, and lymphadenopathy. These reactions may be associated with other organ involvement, such as hepatitis, hepatic failure, blood dyscrasias, or acute multiorgan failure. LAMICTAL should be discontinued if alternate etiology for this reaction is not found. (5.3)
- Cardiac rhythm and conduction abnormalities: Avoid LAMICTAL in patients with certain underlying cardiac disorders or arrhythmias. (5.4)
- Blood dyscrasias (e.g., neutropenia, thrombocytopenia, pancytopenia): May occur, either with or without an associated hypersensitivity syndrome. Monitor for signs of anemia, unexpected infection, or bleeding. (5.5)
- Suicidal behavior and ideation: Monitor for suicidal thoughts or behaviors. (5.6)
- Aseptic meningitis: Monitor for signs of meningitis. (5.7)
- Medication errors due to product name confusion: Strongly advise patients to visually inspect tablets to verify the received drug is correct. (5.8, 16, 17)
- Interactions
-
DRUG INTERACTIONS:
- Valproate increases lamotrigine concentrations more than 2-fold. (7, 12.3)
- Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by approximately 40%. (7, 12.3)
- Estrogen-containing oral contraceptives decrease lamotrigine concentrations by approximately 50%. (7, 12.3)
- Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure by approximately 50% and 32%, respectively. (7, 12.3)
- Coadministration with organic cationic transporter 2 substrates with narrow therapeutic index is not recommended (7, 12.3)
- Overdose
-
OVERDOSE:
Overdoses involving quantities up to 15 g have been reported for LAMICTAL, some of which have been fatal. Overdose has resulted in ataxia, nystagmus, seizures (including tonic-clonic seizures), decreased level of consciousness, coma, and intraventricular conduction delay.
Management of Overdose: There are no specific antidotes for lamotrigine. Following a suspected overdose, hospitalization of the patient is advised. General supportive care is indicated, including frequent monitoring of vital signs and close observation of the patient. If indicated, emesis should be induced; usual precautions should be taken to protect the airway. It should be kept in mind that immediate-release lamotrigine is rapidly absorbed [see Clinical Pharmacology (12.3)]. It is uncertain whether hemodialysis is an effective means of removing lamotrigine from the blood. In 6 renal failure patients, about 20% of the amount of lamotrigine in the body was removed by hemodialysis during a 4-hour session. A Poison Control Center should be contacted for information on the management of overdosage of LAMICTAL.