Indications
Pharmacology
Lamotrigine is a Triazine Derivative
- Inhibits Release of the Excitatory Amino Acid, Glutamate
- Inhibits Voltage-Sensitive Sodium Channels, Stabilizing Neuronal Membranes
- Weak Inhibitory Effect on the 5-HT3 Serotonin Receptor
Metabolism
- Hepatic and Renal
- Over 75% is Metabolized By Glucuronidation
Administration
Oral (PO)
- Dose: XXXX
Dose Adjustment
Hepatic Dose Adjustment
- Mild Hepatic Impairment
- Moderate-Severe Hepatic Impairment without Ascites: decrease initial, escalation, and maintenance doses by 25%
- nModerate-Severe Hepatic Impairment with Ascites: decrease initial, escalation, and maintenance doses by 50%
Renal Dose Adjustment
- None Specified in Manufacturer Instructions
- May Decrease Maintenance Dosage with Significant Renal Impairment
Use During Pregnancy (see Pregnancy)
- xxx
Use During Breast Feeding
- Concentrations of Antiseizure Medications Can Be Detected in Breastmilk of Females with Epilepsy and Plasma/Serum of Infants Exposed Via Breastmilk ((Seizure, 2022) [MEDLINE]
Adverse Effects
Allergic/Immunologic Adverse Effects
Angioedema (see Angioedema)
- Epidemiology
- Angioedema Occurs in <1% of Patients
Dermatologic Adverse Effects
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome) (see Drug Rash with Eosinophilia and Systemic Symptoms)
- Epidemiology
- Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome) Has Been Reported (Ann Pharmacother, 2010) [MEDLINE] (BMJ Case Rep, 2015) [MEDLINE] (BMJ Case Rep, 2019) [MEDLINE] (J Dermatol, 2019) [MEDLINE]
- Risk Factors for Lamotrigine-Induced Skin Eruptions
- Age <13 y/o
- Concurrent Therapy with Inhibitors of Lamotrigine Metabolism (Such as Valproate)
- Higher Initial Dose and/or Rapid Titration
- HLA Molecular Variants (Specific to Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in Select Populations)
- Prior Rash with Other Antiseizure Medications
- Uridine Diphosphate-Glucuronosyltransferase (UGT) Enzyme Polymorphisms
- May Contribute
- Clinical
- Onset of Lamotrigine-Induced Skin Eruptions Occurs Between 5 Days-8 Weeks After Initiation of Therapy (Int J Neuropsychopharmacol, 2009 [MEDLINE]
Rash
- Epidemiology
- Rash is Common
- Rash Occurs in Up to 10% of Cases
- Risk Factors for Lamotrigine-Induced Skin Eruptions
- Age <13 y/o
- Concurrent Therapy with Inhibitors of Lamotrigine Metabolism (Such as Valproate)
- Higher Initial Dose and/or Rapid Titration
- HLA Molecular Variants (Specific to Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in Select Populations)
- Prior Rash with Other Antiseizure Medications
- Uridine Diphosphate-Glucuronosyltransferase (UGT) Enzyme Polymorphisms
- May Contribute
- Rash is Common
- Clinical
- Onset of Lamotrigine-Induced Skin Eruptions Occurs Between 5 Days-8 Weeks After Initiation of Therapy (Int J Neuropsychopharmacol, 2009 [MEDLINE]
- Benign Morbilliform Rashes with/without Pruritus
Stevens-Johnson Syndrome (SJS) (see Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis)
- Epidemiology
- Cases of Stevens-Johnson Syndrome (SJS) Have Been Reported
- Risk Factors for Lamotrigine-Induced Skin Eruptions
- Age <13 y/o
- Concurrent Therapy with Inhibitors of Lamotrigine Metabolism (Such as Valproate)
- Higher Initial Dose and/or Rapid Titration
- HLA Molecular Variants (Specific to Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in Select Populations)
- Prior Rash with Other Antiseizure Medications
- Uridine Diphosphate-Glucuronosyltransferase (UGT) Enzyme Polymorphisms
- May Contribute
- Clinical
- Onset of Lamotrigine-Induced Skin Eruptions Occurs Between 5 Days-8 Weeks After Initiation of Therapy (Int J Neuropsychopharmacol, 2009 [MEDLINE]
Gastrointestinal/Hepatic Adverse Effects
Acute Pancreatitis (see Acute Pancreatitis)
- Epidemiology
- Acute Pancreatitis Has Been Reported When Lamotrigine is Used in Combination with Vigabatrin (see Vigabatrin) (Seizure, 1994) [MEDLINE]
Drug-Induced Liver Injury (DILI)/Drug-Induced Hepatotoxicity (see Drug-Induced Hepatotoxicity)
- Epidemiology
- Cases of Hepatotoxicity Have Been Reported (Am J Psychiatry, 2008) [MEDLINE]
- Clinical
- Hepatitis with Increased Liver Function Tests (LFT’s)
Nausea (see Nausea and Vomiting)
- Epidemiology
- Nausea Occurs in 7-14% of Patients
Hematologic Adverse Effects
Anemia (see Anemia)
- Epidemiology
- XXXX
Aplastic Anemia (see xxxx)
- Epidemiology
- XXXX
Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation)
- Epidemiology
- Disseminated Intravascular Coagulation (DIC) Has Been Reported in Children Receiving Lamotrigine and Valproic Acid (Neurology, 1997) [MEDLINE]
Hemophagocytic Lymphohistiocytosis (HLH) (see Hemophagocytic Lymphohistiocytosis)
- Epidemiology
- XXXX
- Physiology
- Unknown Mechanism (J Med Case Rep, 2019) [MEDLINE]
- Stimuli are Believed to Activate Circulating Macrophages, Which Phagocytose Blood Cells, Resulting in Excessive Release of Cytokines
- Unknown Mechanism (J Med Case Rep, 2019) [MEDLINE]
- Clinical (J Med Case Rep, 2019) [MEDLINE] (Neurology, 2019) [MEDLINE]
- Onset is Typically within the First Several Weeks (17-24 Days) After Starting Therapy
- Cytopenias
- Fever (see Fever)
- Hepatosplenomegaly (see Hepatomegaly and Splenomegaly)
- Organ Dysfunction
- Rash
Leukopenia/Neutropenia (see Leukopenia and Neutropenia)
- Epidemiology
- XXXX
Pancytopenia (see Pancytopenia)
- Epidemiology
- Cases Have Been Reported (J Formos Med Assoc, 2018) [MEDLINE]
Thrombocytopenia (see Thrombocytopenia)
- Epidemiology
- XXXX
Neurologic Adverse Effects
Aseptic Meningitis (see Meningitis)
- Epidemiology
- Does Not Appear to Be Dose-Related (Int Clin Psychopharmacol, 2009) [MEDLINE] (Neurology, 2012) [MEDLINE]
- Risk Factors
- Some Cases of Aseptic Meningitis are Associated with the Concurrent Development of Rash and Organ Dysfunction (Suggesting a Broader Hypersensitivity Reaction) (Neurology, 2012) [MEDLINE]
- Physiology
- Immunologic Mechanism
- Clinical
- Onset is Variable
- Occurs within 1-42 Days Following Initiation of Lamotrigine
- In 40% of Cases of Rechallenge, Recurrence Often Resulted in a More Rapid Onset (Neurology, 2012 [MEDLINE]
- Recurrence Has Been Reported to Occur as Rapidly as 30-60 min Following Re-Exposure (Epilepsia, 2005) [MEDLINE] (Epilepsia, 2009) [MEDLINE] (Int Clin Psychopharmacol, 2009) [MEDLINE]
- Signs of Meningeal Inflammation
- Fever (see Fever)
- Headache (see Headache)
- Nuchal Rigidity (see xxxx)
- Photophobia (see Photophobia)
- Onset is Variable
Central Nervous System Depression
- Epidemiology
- XXXX
- Clinical XXXX
Renal Adverse Effects
Hyponatremia (see Hyponatremia)
- Epidemiology
- Hyponatremia Has Been Identified in Post-Marketing Studies (Innov Clin Neurosci, 2019) [MEDLINE]
Rheumatologic Adverse Effects
Peripheral Edema (see Peripheral Edema)
- Epidemiology
- Peripheral Edema Occurs in 2-5% of Cases
Rhabdomyolysis (see Rhabdomyolysis)
- Epidemiology
- Rhabdomyolysis Has Been Identified in Post-Marketing Studies (Ann Gen Psychiatry, 2016) [MEDLINE]
Toxicologic Adverse Effects
Serotonin Syndrome (see Serotonin Syndrome)
- Epidemiology
- Serotonin Syndrome Has Been Reported When Used in Conjunction with Aripiprazole and Cocaine [MEDLINE]
Other Adverse Effects
Infection
- Epidemiology
- Infection Occurs in 5% of Cases
- Herpes Zoster Infection Occurs in <1% of Cases (see Varicella-Zoster Virus)
Lamotrigine Intoxication
Clinical Manifestations
Cardiovascular Manifestations
- Electrocardiographic (EKG) Changes (see Electrocardiogram)
- Clinical
- Left Bundle Branch Block (LBBB) (see Torsade)
- Widened QRS
- Clinical
Gastrointestinal Adverse Effects
- Nausea/Vomiting (see Nausea and Vomiting)
Neurologic Adverse Effects
- Central Nervous System Depression
- Obtundation/Coma (see Obtundation/Coma)
- Paradoxical Seizures (see Seizures)
Treatment
- Activated Charcoal (see Activated Charcoal): recommended due to the fact that lamotrigine undergoes enterohepatic circulation
- Benzodiazepines (see Benzodiazepines): recommended for seizures
- Sodium Bicarbonate (see Sodium Bicarbonate): recommended
- May Be Effective for QRS Prolongation
- 20% Lipid Emulsion
- Has Been Reported to Have Efficacy in Lamotrigine (Sodium Channel Blocker) Intoxication, Possibly Mediated via the Lipophilic Properties of Lamotrigine (J Emerg Med, 2012) [MEDLINE]
References
General
- Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. Drugs. 1993 Jul;46(1):152-76 [MEDLINE]
Administration
- Concentrations of antiseizure medications in breast milk of lactating women with epilepsy: a systematic review with qualitative synthesis. Seizure: J Epilepsy. Published online March 27, 2022. doi:10.1016/j.seizure.2022.03.017 [MEDLINE]
Adverse Effects
- Acute pancreatitis associated with dual vigabatrin and lamotrigine therapy. Seizure. 1994 Dec;3(4):319 [MEDLINE]
- Multiorgan dysfunction and disseminated intravascular coagulation in children receiving lamotrigine and valproic acid. Neurology. 1997;49(5):1442-1444. doi:10.1212/wnl.49.5.1442 [MEDLINE]
- Evaluation of lamotrigine toxicity reported to poison centers. Ann Pharmacother. 2004;38(11):1811-1815 [MEDLINE]
- Recurrent severe aseptic meningitis after exposure to lamotrigine in a patient with systemic lupus erythematosus. Epilepsia. 2005;46(2):327-328. doi:10.1111/j.0013-9580.2005.43304.x [MEDLINE]
- Acute hepatotoxicity associated with lamotrigine. Am J Psychiatry. 2008;165(4):539-540. doi:10.1176/appi.ajp.2007.07050728 [MEDLINE]
- Lamotrigine-induced aseptic meningitis: a case report. Int Clin Psychopharmacol. 2009;24(3):159-161. doi:10.1097/YIC.0b013e32832a8edc [MEDLINE]
- Recurrent lamotrigine-induced aseptic meningitis. Epilepsia. 2009;50(4):968-969. doi:10.1111/j.1528-1167.2008.01985.x [MEDLINE]
- Lamotrigine-induced aseptic meningitis: a case report. Int Clin Psychopharmacol. 2009;24(3):159-161. doi:10.1097/YIC.0b013e32832a8edc [MEDLINE]
- First report of lamotrigine-induced drug rash with eosinophilia and systemic symptoms syndrome with pancreatitis. Ann Pharmacother. 2010 Dec;44(12):1998-2000. doi: 10.1345/aph.1P350 [MEDLINE]
- Lamotrigine and aseptic meningitis. Neurology. 2012;78(12):921-927. doi:10.1212/WNL.0b013e31824c4634 [MEDLINE]
- Lamotrigine and aseptic meningitis. Neurology. 2012;78(12):921-927. doi:10.1212/WNL.0b013e31824c4634 [MEDLINE]
- Lipid emulsion as rescue therapy in lamotrigine overdose. J Emerg Med. 2012 Jan;42(1):48-51. doi: 10.1016/j.jemermed.2010.11.055 [MEDLINE]
- Serotonin Syndrome in the Setting of Lamotrigine, Aripiprazole, and Cocaine Use. Case Rep Med. 2015;2015:769531. doi: 10.1155/2015/769531 [MEDLINE]
- Lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS). BMJ Case Rep. 2015;2015:bcr2014209170. doi:10.1136/bcr-2014-209170 [MEDLINE]
- Rhabdomyolysis after lamotrigine overdose: a case report and review of the literature. Ann Gen Psychiatry. 2016;15:6. doi:10.1186/s12991-016-0093-3 [MEDLINE]
- Lamotrigine-induced pancytopenia in bipolar disorder. J Formos Med Assoc. 2018;117(12):1128-1129. doi:10.1016/j.jfma.2018.07.004 [MEDLINE]
- Drug reaction with eosinophilia and systemic symptoms syndrome in a patient taking lamotrigine. BMJ Case Rep. 2019;12(10):e229180. doi:10.1136/bcr-2019-229180 [MEDLINE]
- Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs. J Dermatol. 2019;46(3):226-233. doi:10.1111/1346-8138.14776 [MEDLINE]
- Lamotrigine-induced hemophagocytic lymphohistiocytosis with Takotsubo cardiomyopathy: a case report. J Med Case Rep. 2019;13(1):345. doi:10.1186/s13256-019-2295-1 [MEDLINE]
- Hemophagocytic lymphohistiocytosis associated with the use of lamotrigine. Neurology. 2019;92(21):e2401-e2405. doi:10.1212/WNL.0000000000007517 [MEDLINE]
- Severe lamotrigine-induced hyponatremia associated with takotsubo cardiomyopathy. Innov Clin Neurosci. 2019;16(7-08):32-34 [MEDLINE]