Lamotrigine: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on March 31, 2023.

1. How it works

• Lamotrigine is used either alone or in combination with other anticonvulsants to treat epilepsy. It may also be used to stabilize mood in people with bipolar disorder.
• Experts are not sure exactly how lamotrigine works But some have suggested that it inhibits voltage-sensitive sodium channels, stabilizing nerve membranes and moderating the release of excitatory amino acids such as glutamate and aspartate.
• Lamotrigine belongs to the class of medicines known as triazine anticonvulsants.

2. Upsides

• May be used in combination with other anticonvulsants for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, and generalized seizures associated with Lennox-Gastaut syndrome. May be used as the sole treatment for partial-onset seizures.
• May be used as maintenance treatment and to stabilize mood and delay the occurrence of depression, mania, hypomania, or mixed episodes of bipolar I disorder.
• Blood levels of lamotrigine do not require monitoring.
• Structurally unrelated to other anticonvulsants.
• Available in immediate-release and extended-release tablets.
• Immediate-release preparations are available as chewable/dispersible tablets and orally disintegrating tablets.
• Immediate-release preparations may be used in adults and children over the age of 2 years with generalized seizures associated with Lennox-Gastaut syndrome.
• May be administered with or without food.
• May be administered as a single daily dose or in two divided doses.
• Generic lamotrigine is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Dizziness, coordination problems, sleepiness, headache, double or blurred vision, nausea, vomiting, and rash. The risk of side effects increases at higher dosages and with certain other medications such as carbamazepine.
• Rarely, life-threatening skin rashes that require hospitalization and discontinuation of lamotrigine treatment may occur. The risk is higher in younger children and possibly with higher lamotrigine dosages or co-administration with valproate. Most, but not all, cases occur within two to eight weeks of treatment initiation. Lamotrigine may also cause a benign, non-problematic rash, and distinguishing between different rashes caused by lamotrigine may be difficult. Seek urgent medical advice at the first sign of a rash with lamotrigine, unless the rash is not drug-related. Adhere to recommended dosing regimens. Discontinuation of lamotrigine at the first sign of a rash, unless the rash is known not to be drug-related.
• Multi-organ failure has been reported rarely with lamotrigine, usually in association with other serious medical events such as status epilepticus, sepsis, or hantavirus infection. Other serious side effects include blood dyscrasias, such as neutropenia, leukopenia, thrombocytopenia, and anemia.
• Lamotrigine should not be discontinued abruptly, particularly in those with seizure disorders. Taper slowly over at least 2 weeks unless more rapid discontinuation is warranted because of safety concerns. If lamotrigine is discontinued temporarily for longer than 5 half-lives (the half-life of lamotrigine is 25 hours (multiple dosing) to 33 hours (single dosing), then therapy should be resumed using the recommended initial dosing regimen.
• The initial and maintenance dosage of lamotrigine needs to be individualized depending on what other medications a person is taking. See the product information for the recommended dosing schedule. The dosage of lamotrigine will also need to be reduced by 25% in those with moderate to severe liver disease without ascites and by 50% in those with ascites. A reduced maintenance dosage may be appropriate in those with kidney disease, although the manufacturers make no specific recommendation. The lower end of the dosing range should be used for seniors.
• Rarely, hemophagocytic lymphohistiocytosis (a life-threatening immune system syndrome) or potentially fatal hypersensitivity reactions leading to organ failure may also occur. Seek medical advice with any sign of rash, fever, or swollen lymph nodes. The use of lamotrigine also increases the risk of aseptic meningitis.
• As with other anti-epileptics, lamotrigine may increase the risk of suicidal thoughts or behavior; monitor for worsening depression or mood changes.
• May interact with several drugs including other anticonvulsants (such as carbamazepine and phenytoin), estrogen-containing oral contraceptives, and some HIV antivirals.
• Rarely, has been associated with sudden unexplained death.
• Caution may be needed when used in people with renal or hepatic impairment and some other medical conditions.
• Extended-release tablets are not recommended for children or adolescents under the age of 13 years.
• Children weighing less than 30kg have a higher weight-normalized lamotrigine clearance than those weighing greater than 30kg.
• Lamotrigine has a Risk Evaluation and Mitigation Strategy (REMS); the aim is to inform patients about serious risks (such as suicidality) associated with lamotrigine. The REMS consists of a medication guide.
• Lamotrigine should not be used during pregnancy unless the benefits outweigh the risks. There is a possible association between lamotrigine exposure during the first trimester of pregnancy and a cleft palate or cleft lip. In animal studies, lamotrigine has decreased fetal folate concentrations which are associated with teratogenesis in animals and humans. Lamotrigine may interact with some hormonal contraceptives and a higher dosage of lamotrigine may be needed, depending on what other medications are also being taken. If a woman inadvertently becomes pregnant while taking lamotrigine then enroll her on the lamotrigine pregnancy registry at 800-336-2176. Lamotrigine is not recommended during breastfeeding.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Lamotrigine may be used to decrease the frequency and severity of seizures in some types of epilepsy and also to stabilize mood in bipolar disorder. Rarely, lamotrigine may cause a potentially fatal rash requiring immediate drug discontinuation.

5. Tips

• May be taken with or without food. If you develop a stomach upset after taking lamotrigine, taking it with food may help.
• Always read the medication guide given with your lamotrigine tablets. It explains the risks associated with lamotrigine use.
• Visually inspect your lamotrigine tablets to verify that they are indeed lamotrigine, as this drug has been associated with several dispensing errors, particularly with drugs that sound the same, such as Lamisil (an antifungal), Lomotil (an anti-diarrheal medication), and labetalol ( a heart medication). Always check with your pharmacist if you think you have the wrong medication.
• Chewable and dispersible tablets are available. Chew tablets with a small amount of water or juice to aid swallowing; dispersible tablets may be dispersed in either 5mL of water or diluted fruit juice; allow the tablet to disperse completely before taking. Do not attempt to administer partial quantities of the dispersed tablets. Swallow extended-release tablets whole; do not crush or chew.
• Take exactly as directed by your doctor. Do not stop taking lamotrigine suddenly without your doctor's advice because withdrawal seizures may occur. It may take several weeks before lamotrigine starts to have an effect. The dosage will need tapering off on discontinuation as directed by your doctor.
• May cause drowsiness and affect your ability to drive or operate machinery. Avoid alcohol, because alcohol may make these symptoms worse.
• Talk to your doctor if you develop any side effects, such as a low mood, a worsening of seizure control, enlarged liver or lymph nodes, unusual bleeding, yellowing of the skin and eyes, or visual disturbances.
• Seek urgent medical advice if you develop a severe rash or reaction after taking lamotrigine. Symptoms may include red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes. The risk of a severe skin reaction is greater in children aged 2 to 17 years; when taken in conjunction with valproate, with higher dosages of lamotrigine, or if the dosage of lamotrigine is increased too fast.
• The extended-release form of lamotrigine (Lamictal XR) should only be used in adults and children aged 13 years or older. The immediate-release form (Lamictal, Lamictal ODT) can be used in children aged 2 years or older as long as it is used in combination with other seizure medications. When used alone, this form can only be used in adults and teenagers over the age of 16.
• Use adequate contraception to ensure you do not become pregnant while taking lamotrigine. If you inadvertently become pregnant while taking lamotrigine then enroll on the North American Antiepileptic Drug (NAAED) pregnancy registry at 888-233-2334. Lamotrigine is not recommended during breastfeeding.

6. Response and effectiveness

• Lamotrigine is rapidly absorbed and peak levels are reached within 1.5 to 4.8 hours of administration.
• The effects of lamotrigine last for over 24 hours, and once-daily dosing is often prescribed. However, some doctors prefer to split the dose to decrease the risk of side effects such as drowsiness.

7. Interactions

Medicines that interact with lamotrigine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with lamotrigine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with lamotrigine include:

• estrogen-containing oral contraceptives
• anticonvulsants such as carbamazepine, oxcarbazepine, phenytoin, phenobarbital, phenytoin, primidone, topiramate, or valproic acid
• antipsychotics, such as aripiprazole or clozapine
• buprenorphine
• cannabis
• duloxetine
• folate inhibitors
• folic acid
• herbals such as gingko or kava
• HIV medications such as atazanavir, indinavir and ritonavir
• lithium
• medications that cause drowsiness, such as benzodiazepines, sedating antihistamines, and sleeping pills
• metformin
• opioid analgesics such as fentanyl, oxycodone, and morphine
• rifampin
• tramadol
• trazodone.

Alcohol may worsen the side effects of lamotrigine such as drowsiness, dizziness, and liver toxicity.

Note that this list is not all-inclusive and includes only common medications that may interact with lamotrigine. You should refer to the prescribing information for lamotrigine for a complete list of interactions

References

• Lamotrigine. Revised 03/2023. Advagen Pharma Limited https://www.drugs.com/pro/lamotrigine.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use lamotrigine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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