Lamotrigine

Lamotrigine is used alone or with other medications to prevent or control seizures (epilepsy). It may also be used to help prevent the extreme mood swings of bipolar disorder in adults.

Lamotrigine is not approved for use in children younger than 2 years due to an increased risk of side effects (such as infections).

Lamotrigine is available under the following different brand names: Lamictal, Lamictal XR, and Lamictal ODT.

Adult and Pediatric Dosage Forms and Strengths

Tablet

• 25 mg
• 100 mg
• 150 mg
• 200 mg

Tablet, chewable

• 2 mg
• 5 mg
• 25 mg

Tablet, oral-disintegrating

• 25 mg
• 50 mg
• 100 mg
• 200 mg

Tablet, extended-release

• 25 mg
• 50 mg
• 100 mg
• 200 mg
• 250 mg
• 300 mg

Dosage Considerations – Should be Given as Follows:

Seizure Disorder

Adult, with enzyme-inducing anti-epileptic drugs (AEDs) but without valproic acid

• Initial: 50 mg orally once/day for 2 weeks, THEN
• 100 mg/day divided every 12 hours for 2 weeks
• At week 5 and beyond, may increase by 100 mg/day orally every 1-2 weeks to 300-500 mg/day orally divided every 12 hours
• Lamotrigine XR: Start 50 mg orally once/day (weeks 1 and 2), THEN 100 mg once/day (weeks 3 and 4), THEN increase by 100 mg/day orally once/week through week 7 (400 mg once/day); maintenance dose (week 8+): 400-600 mg orally once/day

Pediatric, with enzyme-inducing AED and no valproic acid (age 2-12 years)

• Initial: 0.6 mg/kg/day orally divided every 12 hours for 2 weeks, THEN
• 1.2 mg/kg/day orally divided every 12 hours for 2 weeks
• At 5 weeks increase by 1.2 mg/kg every 1-2 weeks to maintenance dose of 5-15 mg/kg/day orally divided every 12 hours
• Not to exceed 400 mg/day orally divided every 12 hours

Adult, with valproic acid

• Initial: 25 mg orally every other day for 2 weeks, THEN
• 25 mg orally once/day for 2 weeks
• At 5 weeks may increase by 25-50 mg/day every 1-2 weeks to 100-400 mg/day once/day or divided every 12 hours
• With valproate alone: 100-200 mg/day orally
• Lamotrigine XR: Start 25 mg orally every other day for 2 weeks, THEN 25 mg orally once/day for 2 weeks, THEN 50 mg orally once/day (week 5), 100 mg orally once/day (week 6), 150 mg orally once/day (week 7), to maintenance (200-250 mg orally once/day)

Pediatric, with valproic acid

• Age under 2 years: Safety and efficacy has not been established
• Age 2-12 years:
  • Initial: 0.15 mg/kg/day orally once/day or divided every 12 hours for 2 weeks, THEN
  • 0.3 mg/kg/day orally once/day or divided every 12 hours for 2 weeks
  • At 5 weeks increase by 0.3 mg/kg every 1-2 weeks to maintenance dose of 1-5 mg/kg/day orally once/day or divided every 12 hours; not to exceed 200 mg/day
  • Alternatively, 1-3 mg/kg/day orally with valproic acid only

• Age 2-12 years:

• Initial: 25 mg orally every other day for 2 weeks, THEN
• 25 mg orally once/day for 2 weeks
• At 5 weeks may increase by 25-50 mg/day every 1-2 weeks to 100-400 mg/day orally once/day or divided every 12 hours
• 100-200 mg/day orally with valproate alone
• Lamotrigine XR: Start 25 mg orally every other day for 2 weeks, THEN 25 mg orally once/day for 2 weeks, THEN 50 mg once/day (week 5), 100 mg once/day (week 6), 150 mg once/day (week 7); THEREAFTER 200-250 mg orally once/day

Adult, without enzyme-inducing AEDs or valproic acid

• Initial: 25 mg orally once/day for 2 weeks, THEN
• 50 mg/day orally for 2 weeks
• After 4 weeks may increase by 50 mg/day every 1-2 weeks to 225-375 mg/day divided every 12 hours
• Lamotrigine XR: Start 25 mg orally once/day for 2 weeks, THEN 50 mg orally once/day for 2 weeks, THEN 100 mg once/day (week 5), 150 mg once/day (week 6), 200 mg once/day (week 7), to maintenance (300-400 mg orally once/day)

Pediatric, without valproic acid or AED

• Age under 2 years: Safety and efficacy not established
• Age 2-12 years:
  • Initial: 0.3 mg/kg/day orally once/day or divided every 12 hours for 2 weeks, THEN
  • 0.6 mg/kg/day orally once/day or divided every 12 hours for 2 weeks, THEN
  • At 5 weeks increase by 0.6 mg/kg every 1-2 weeks to maintenance dose of 4.5-7.5 mg/kg/day orally once/day or divided every 12 hours; not to exceed 300 mg/day
• Age over 12 years:
  • Initial: 25 mg orally once/day for 2 weeks, THEN
  • 50 mg/day orally for 2 weeks
  • At 5 weeks may increase by 50 mg/day every 1-2 weeks to 225-375 mg/day orally divided every 12 hours
  • Lamotrigine XR: Start 25 mg orally once/day for 2 weeks, THEN 50 mg orally once/day for 2 weeks, THEN 100 mg once/day (week 5), 150 mg once/day (week 6), 200 mg once/day (week 7); THEREAFTER 300-400 mg orally once/day Partial-Onset Seizures (Conversion to Monotherapy)

Adult, taking valproic acid, conversion to immediate-release lamotrigine

• Initiate and titrate to lamotrigine dose of 200 mg/day, THEN
• Decrease valproic acid dose by 500 mg/day at intervals of 1 week or longer to valproic acid dose of 500 mg/day; maintain this dose for 1 week, THEN
• Increase lamotrigine dose to 300 mg while valproic acid is decreased to 250 mg/day; maintain this dose for 1 week, THEN
• Discontinue valproic acid
• Increase lamotrigine dose by 100 mg/day at weekly intervals to achieve a maintenance dose of 500 mg/day

Pediatric, taking valproic acid, conversion to immediate-release lamotrigine (age over 16 years)

• Initiate and titrate to lamotrigine dose of 200 mg/day, THEN
• Decrease valproic acid dose by 500 mg/day at intervals of 1 week or longer to valproic acid dose of 500 mg/day; maintain this dose for 1 week, THEN
• Increase lamotrigine dose to 300 mg while valproic acid is decreased to 250 mg/day; maintain this dose for 1 week, THEN
• Discontinue valproic acid
• Increase lamotrigine dose by 100 mg/day at weekly intervals to achieve a maintenance dose of 500 mg/day

Adult, taking valproic acid, conversion to extended-release lamotrigine

• Conversion to monotherapy for patients taking 1 anticonvulsant drug
• Weeks 1-2: 25 mg orally every other day
• Weeks 3-4: 25 mg orally once/day
• Week 5: 50 mg orally once/day
• Week 6: 100 mg orally once/day
• Weeks 7-10: 150 mg orally once/day; begin valproic acid withdrawal over 5-7 weeks to 500mg/day and maintain for 1 week
• Week 11: 200 mg orally once/day; decrease valproic acid dose to 250 mg/day for 1 week
• Weeks 12-23: 250-300 mg orally once/day; discontinue valproic acid

Pediatric, taking valproic acid, conversion to extended-release lamotrigine (age over 13 years)

• Conversion to monotherapy for patients taking 1 anticonvulsant drug
• Weeks 1-2: 25 mg orally every other day
• Weeks 3-4: 25 mg orally once/day
• Week 5: 50 mg orally once/day
• Week 6: 100 mg orally once/day; begin valproic acid withdrawal over 5-7 weeks
• Weeks 7-10: 150 mg orally once/day
• Week 11: 200 mg orally once/day
• Weeks 12-23: 250-300 mg orally once/day

Taking carbamazepine, phenytoin, phenobarbital, or primidone (conversion to immediate-release lamotrigine)

• Initiate and titrate to lamotrigine dose of 500 mg/day as per recommendations
• Decrease concomitant enzyme-inducing AED by 20% each week over a 4-week period and then withdraw

Taking neutral AED, conversion to extended-release lamotrigine

• Adult:
  • Conversion to monotherapy for patients taking 1 anticonvulsant drug
  • Weeks 1-2: 25 mg orally once/day
  • Weeks 3-4: 50 mg orally once/day
  • Week 5: 100 mg orally once/day
  • Week 6: 150-200 mg orally once/day
  • Weeks 7-23: 250-300 mg orally once/day; begin AED withdrawal over 5-week period by weekly 20% decreases in daily dose
  • Children over 16 years: Initiate and titrate to lamotrigine dose of 500 mg/day as per recommendations; decrease concomitant enzyme-inducing AED by 20% each week over a 4-week period and then withdraw

• Adult, conversion from immediate-release to extended-release lamotrigine
  • Dose of extended-release lamotrigine should equal the total daily dose of the immediate-release formulation
  • Adjust dose as needed within recommended dosing
• Pediatric, taking neutral AED, conversion to extended-release lamotrigine (age over 13 years)
  • Conversion to monotherapy for patients taking 1 anticonvulsant drug
  • Weeks 1-2: 25 mg orally once/day
  • Weeks 3-4: 50 mg orally once/day
  • Week 5: 100 mg orally once/day
  • Week 6: 150-200 mg orally once/day
  • Weeks 7-23: 250-300 mg orally once/day; begin AED withdrawal over 5-week period by weekly 20% decreases in daily dose

Bipolar Disorder

Indicated for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy

Efficacy and safety have not been established for treatment of acute manic or mixed episodes

Monotherapy or without enzyme inducers or valproic acid

• Initial: 25 mg orally once/day for 2 weeks, THEN
• 50 mg orally once/day for 2 weeks
• 100 mg orally once/day for 1 week
• Double dose once/week to maintenance at 200 mg/day orally

With AED regimen without valproic acid

• Initial: 50 mg orally once/day for 2 weeks, THEN
• 100 mg/day orally divided every 12 hours for 2 weeks
• Increase by 100 mg once/week to 400 mg/day orally divided every 12 hours

With valproic acid

• Initial: 25 mg orally every other day for 2 weeks, THEN
• 25 mg orally once/day for 2 weeks
• Double dose once/week to maintenance at 100 mg/day orally

Dosing Modifications

Renal impairment

• Use caution; may consider reduce the dose in significant renal impairment

Hepatic impairment

• Limited data, various recommendations
• Manufacturer: Decrease dose by 25% (moderate-severe without ascites) or by 50% (severe with ascites)
• Other (e.g., AHSP): Decrease dose by 50% (Child-Pugh class B) or by 75% (Child-Pugh class C)

Dosing Considerations, Pediatric

Approved indications

• Lamictal XR (over 13 years): Add-on therapy for primary generalized tonic-clonic seizures or partial seizures
• Lamictal XR (over 13 years): Partial seizures; conversion to monotherapy in patients over 13 years with partial seizures taking 1 AED; safety and efficacy has not been established as initial monotherapy or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs
• Lamictal tablets, chewable tablet, or ODT (over 2 years): Adjunctive treatment for partial seizures, primary generalized tonic-clonic seizures, generalized seizures of Lennox-Gastaut syndrome
• Lamictal tablets, chewable tablet, or ODT (over 16 years): Conversion to monotherapy in partial seizures
• Lamictal tablets, chewable tablet, or ODT (over 18 years): Bipolar I disorder

Common side effects of lamotrigine include:

• Dizziness
• Double vision
• Headache
• Problems with coordination
• Blurred vision
• Runny or stuffy nose
• Drowsiness
• Insomnia
• Fatigue
• Chest pain
• Swelling of extremities
• Suicidal ideation
• Dermatitis
• Dry skin
• Increased sex drive (libido)
• Rectal bleeding
• Weakness
• Agitation
• Slurred or slow speech
• Swelling (edema)
• Fever
• Migraine
• Abnormal thoughts
• Urinary frequency
• Shaking (tremors)
• Sleepiness
• Sleep problems (insomnia)
• Tired feeling
• Upset stomach
• Stomach pain
• Dry mouth
• Changes in menstrual periods
• Back pain
• Sore throat

Other side effects of lamotrigine include:

• Palpitations
• Anxiety
• Chills
• Depression
• Decreased memory
• Mood swings
• Incoordination
• Feeling unwell (malaise)
• Seizure exacerbation
• Spinning sensation (vertigo)
• Itching
• Rash
• Missed menstrual periods
• Hot flashes
• Abdominal pain
• Constipation
• Diarrhea
• Indigestion
• Nausea
• Vomiting
• Joint pain
• Neck pain
• Cough
• Flu syndrome
• Infection
• Vaginitis
• Repetitive, involuntary eye movements

Serious side effects of lamotrigine include:

• Rash
• Worsening depression or suicidal thoughts
• Flu-like symptoms such as body aches or swollen glands

Postmarketing side effects of lamotrigine reported include:

• Agranulocytosis, hemolytic anemia, lymphadenopathy not associated with hypersensitivity disorder
• Esophagitis
• Aseptic meningitis
• Pancreatitis
• Lupus-like reaction
• Vasculitis
• Apnea
• Muscle wasting (rhabdomyolysis) observed in patients experiencing hypersensitivity reactions
• Aggression
• Exacerbation of Parkinsonian symptoms in patients with pre-existing Parkinson's disease, tics
• Progressive immunosuppression

This is not a complete list of side effects and other serious side effects may occur. Call your doctor for information and medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

If your doctor has directed you to use this medication for your condition, your doctor or pharmacist may already be aware of any possible drug interactions or side effects and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any medicine before getting further information from your doctor, healthcare provider or pharmacist first.

• Lamotrigine has no known severe interactions with other drugs.
• Lamotrigine has no known serious interactions with other drugs.
• Lamotrigine has moderate interactions with at least 34 different drugs.
• Lamotrigine has mild interactions with at least 23 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Serious rashes requiring hospitalization (including Stevens-Johnson syndrome) and discontinuation of treatment have occurred in 0.3-0.8% of pediatric patients (aged 2-17 years) and in 0.08-0.3% of adult patients who have received the drug as adjunctive therapy for epilepsy with valproic acid.

The risk of serious rash caused by treatment with lamotrigine XR is not expected to differ from that with the immediate-release formulation; however, the relatively limited treatment experience with lamotrigine XR makes it difficult to characterize the frequency and risk of serious rashes caused by treatment with the drug; lamotrigine XR is not approved for patients younger than 13 years.

Almost all life-threatening rashes have occurred within 2- 8 weeks of lamotrigine therapy, but they have also occurred after prolonged treatment; duration cannot be relied on as a means to predict the potential risk heralded by the first appearance of a rash.

Although benign rashes also occur with lamotrigine, it is not possible to predict reliably which rashes will prove to be serious or life threatening. Thus, the drug should be discontinued at the first sign of rash unless the rash is clearly not drug related.

Discontinuation of treatment may not prevent a rash from becoming life threatening or permanently disabling or disfiguring.

This medication contains lamotrigine. Do not take Lamictal, Lamictal XR, and Lamictal ODT if you are allergic to lamotrigine or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity to any component of formulation

Effects of Drug Abuse

• No information available

Short-Term Effects

• May cause central nervous system (CNS) depression; use caution operating heavy machinery.
• See "What Are Side Effects Associated with Using Lamotrigine?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Lamotrigine?"

Cautions

• See FDA Warning on potential suicidal behavior.
• Clinical worsening, emergence of new symptoms, and suicidal ideation/behaviors may be associated with treatment of bipolar disorder; patients should be closely monitored, particularly early in treatment or during dosage changes.
• Use caution in renal impairment and hepatic impairment; dose adjustments may be necessary.
• Risk of serious rash; discontinue at first sign of rash.
• Rare cases of toxic epidermal necrolysis have been reported in worldwide postmarketing experience.
• May cause central nervous system (CNS) depression; use caution operating heavy machinery.
• Multi-organ hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported, with possible multi-organ failure.
• Round pediatric dose downward to nearest 5 mg.
• Do not withdraw abruptly.
• Need to modify dosage if adding or discontinuing hepatic enzyme-inducing anticonvulsant drugs or valproic acid.
• Increased risk of hematologic effects (e.g., neutropenia, anemia, leukopenia, thrombocytopenia, aplastic anemia) in patients with previous history of adverse hematologic reactions to any drug.
• Need to modify dosage if taking or stopping estrogen plus oral contraceptives.
• Risk of isolated oral clefts if used in early pregnancy.
• Aseptic meningitis cases reported; symptoms may include headache, fever, stiff neck, nausea, vomiting, rash, and sensitivity to light.
• May interfere with the assay used in some rapid urine drug screens, which can result in false-positive readings, particularly for phencyclidine (PCP); use a more specific analytical method to confirm a positive result.

Pregnancy and Lactation

• Use lamotrigine with caution during pregnancy if benefits outweigh risks. Animal studies show risk and human studies are not available or neither animal nor human studies were done.
• Lamotrigine is distributed into human breast milk; caution is advised if breastfeeding.
• Data from multiple small studies indicate that lamotrigine plasma levels in human milk-fed infants have been as high as 50% of the maternal serum levels. Neonates and young infants are at risk for high serum levels because maternal serum and milk levels can rise to high levels postpartum if lamotrigine dosage has been increased during pregnancy but not later reduced to the pre-pregnancy dosage.
• Exposure is further increased due to the immaturity of infants' glucuronidation capacity, needed for drug clearance; reported events include apnea, drowsiness, and poor sucking.
• Closely monitor infants and measure infant serum level for toxicity if concerns arise; discontinue with lamotrigine toxicity.