LAMOTRIGINE

brands

Class

• Neuroscience-based Nomenclature: glutamate, voltage-gated sodium channel blocker (Glu-CB)
• Anticonvulsant, mood stabilizer, voltage- sensitive sodium channel antagonist

LAMOTRIGINE commonly prescribed for

(Bold for FDA approved)

How LAMOTRIGINE works

• Acts as a use-dependent blocker of voltagesensitive sodium channels

• Interacts with the open-channel conformation of voltage-sensitive sodium channels

• Interacts at a specific site of the alpha poreforming subunit of voltage-sensitive sodium channels

• Inhibits release of glutamate and aspartate

How long until LAMOTRIGINE works

• May take several weeks to improve bipolar depression

• May take several weeks to months to optimize an effect on mood stabilization

• Can reduce seizures by 2 weeks, but may take several weeks to months to reduce seizures

Notable Side Effects

• Benign rash (approximately 10%)

• Dose-dependent: blurred or double vision, dizziness, ataxia

• Sedation, headache, tremor, insomnia, poor coordination, fatigue

• Nausea (dose-dependent), vomiting, dyspepsia, rhinitis

• Additional effects in pediatric patients with epilepsy: infection, pharyngitis, asthenia

Life Threatening Side Effects

• Rare serious rash (risk may be greater in pediatric patients but still rare)

• Rare multi-organ failure associated with Stevens–Johnson syndrome, toxic epidermal necrolysis, or drug hypersensitivity syndrome

• Rare blood dyscrasias

• Rare aseptic meningitis

• Rare hemophagocytic lymphohistiocytosis

• Rare sudden unexplained deaths have occurred in epilepsy (unknown if related to lamotrigine use)

• Withdrawal seizures upon abrupt withdrawal

• Rare activation of suicidal ideation and behavior (suicidality)

weight gain

unusual

sedation

unusual

What to do about LAMOTRIGINE side effects

• Wait

• Take at night to reduce daytime sedation

• Divide dosing to twice daily

• If patient develops signs of a rash with benign characteristics (i.e., a rash that peaks within days, settles in 10–14 days, is spotty, nonconfluent, nontender, has no systemic features, and laboratory tests are normal):

• Reduce lamotrigine dose or stop dosage increase

• Warn patient to stop drug and contact physician if rash worsens or new symptoms emerge

• Prescribe antihistamine and/or topical corticosteroid for pruritis

• Monitor patient closely

• If patient develops signs of a rash with serious characteristics (i.e., a rash that is confluent and widespread, or purpuric or tender; with any prominent involvement of neck or upper trunk; any involvement of eyes, lips, mouth, etc.; any associated fever, malaise, pharyngitis, anorexia, or lymphadenopathy; abnormal laboratory tests for complete blood count, liver function, urea, creatinine):

• Stop lamotrigine (and valproate if administered)

• Monitor and investigate organ involvement (hepatic, renal, hematologic)

• Patient may require hospitalization

• Monitor patient very closely

usual dosage range

• Monotherapy for bipolar disorder: 100–200 mg/day

• Adjunctive treatment for bipolar disorder: 100 mg/day in combination with valproate; 400 mg/day in combination with enzymeinducing antiepileptic drugs such as carbamazepine, phenobarbital, phenytoin, and primidone

• Monotherapy for seizures in patients over age 12: 300–500 mg/day in 2 doses

• Adjunctive treatment for seizures in patients over age 12: 100–400 mg/day for regimens containing valproate; 100–200 mg/day for valproate alone; 300–500 mg/day in 2 doses for regimens not containing valproate

• Patients ages 2–12 with epilepsy are dosed based on body weight and concomitant medications

Dosage Forms

• Tablet 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg

• Chewable tablet 2 mg, 5 mg, 25 mg

• Orally disintegrating tablet 25 mg, 50 mg, 100 mg, 200 mg

• Extended-release tablet 25 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg

long term use

• Safe

habit forming

• No

Renal Impairment

• Lamotrigine is renally excreted, so the maintenance dose may need to be lowered

• Can be removed by hemodialysis; patients receiving hemodialysis may require supplemental doses of lamotrigine

Hepatic Impairment

• Dose adjustment not necessary in mild impairment

• Initial, escalation, and maintenance doses should be reduced by 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites

Cardiac Impairment

• Clinical experience is limited

• Drug should be used with caution

• In vitro data show that lamotrigine exhibits Class 1B antiarrhythmic activity at therapeutically relevant concentrations, prompting the FDA to warn against its use in patients with cardiac conduction disorders, ventricular arrhythmias, or cardiac disease or abnormality

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more susceptible to adverse effects

Children and Adolescents

• Ages 2 and older: approved as add-on for Lennox–Gastaut syndrome

• Ages 2 and older: approved as add-on for partial seizures

• No other use of lamotrigine is approved for patients under 16 years of age

• Risk of rash is increased in pediatric patients, especially in children under 12 and in children taking valproate

• When lamotrigine is added to treatment that includes valproate (ages 2–12): for the first 2 weeks administer 0.15 mg/kg per day in 1–2 doses rounded down to the nearest whole tablet; at week 3 increase to 0.3 mg/kg per day in 1–2 doses rounded down to the nearest whole tablet; every 1–2 weeks can increase by 0.3 mg/kg per day rounded down to the nearest whole tablet; usual maintenance dose 1–5 mg/kg per day in 1–2 doses (maximum generally 200 mg/ day) or 1–3 mg/kg per day in 1–2 doses if lamotrigine is added to valproate alone

• When lamotrigine is added to treatment with carbamazepine, phenytoin, phenobarbital, or primidone (without valproate) (ages 2–12): for the first 2 weeks administer 0.6 mg/kg per day in 2 doses rounded down to the nearest whole tablet; at week 3 increase to 1.2 mg/kg per day in 2 doses rounded down to the nearest whole tablet; every 1–2 weeks can increase by 1.2 mg/kg per day rounded down to the nearest whole tablet; usual maintenance dose 5–15 mg/kg per day in 2 doses (maximum dose generally 400 mg per day)

• Clearance of lamotrigine may be influenced by weight, such that patients weighing less than 30 kg may require an increase of up to 50% for maintenance doses

Pregnancy

• Controlled studies have not been conducted in pregnant women

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• Pregnancy registry data show increased risk of isolated cleft palate or cleft lip deformity with first-trimester exposure

• If treatment with lamotrigine is continued, plasma concentrations of lamotrigine may be reduced during pregnancy, possibly requiring increased doses with dose reduction following delivery

• Taper drug if discontinuing

• Seizures, even mild seizures, may cause harm to the embryo/fetus

• Recurrent bipolar illness during pregnancy can be quite disruptive

• For bipolar patients, lamotrigine should generally be discontinued before anticipated pregnancies

• For bipolar patients in whom treatment is discontinued, given the risk of relapse in the postpartum period, lamotrigine should generally be restarted immediately after delivery

• Atypical antipsychotics may be preferable to lithium or anticonvulsants such as lamotrigine if treatment of bipolar disorder is required during pregnancy, but lamotrigine may be preferable to other anticonvulsants such as valproate if anticonvulsant treatment is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

• Some drug is found in mother’s breast milk

• Generally recommended either to discontinue drug or formula feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects

• If infant shows signs of irritability or sedation, drug may need to be discontinued

• Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

• Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be preferable to lithium or lamotrigine during the postpartum period when breast feeding