lamotrigine

la-MOE-tri-jeen

Therapeutic Classification: anticonvulsants

REMS

Adjunct treatment of partial seizures in adults and children with epilepsy (immediate-release, extended-release, chewable, and orally disintegrating tablets).
Lennox-Gastaut syndrome (immediate-release, chewable, and orally disintegrating tablets only).
Adjunct treatment of primary generalized tonic-clonic seizures in adults and children (immediate-release, extended-release, chewable, and orally disintegrating tablets).
Conversion to monotherapy in adults with partial seizures receiving carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (immediate-release, extended-release, chewable, and orally disintegrating tablets only).
Maintenance treatment of bipolar disorder (immediate-release, chewable, and orally disintegrating tablets only).

Stabilizes neuronal membranes by inhibiting sodium transport.

Therapeutic effects:

Decreased incidence of seizures.
Delayed time to recurrence of mood episodes in bipolar disorder.

Absorption: 98% absorbed following oral administration.

Distribution: Highly bound to melanin-containing tissues (eyes, pigmented skin).

Metabolism/Excretion: Mostly metabolized by the liver via glucuronidation to inactive metabolites; 10% excreted unchanged by the kidneys.

Half-Life: Children taking enzyme-inducing anticonvulsants: 7–10 hr; Children taking enzyme inducers and valproic acid: 15–27 hr; Children taking valproic acid: 44–94 hr; Adults: 25.4 hr (during chronic therapy of lamotrigine alone).

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.4–4.8 hr; 4–10 hr (XR)	unknown

Contraindicated in:

Hypersensitivity;
Acute manic or mixed episodes;
Second- or third-degree heart block, ventricular arrhythmias, ischemic heart disease, HF, valvular heart disease, congenital heart disease, or Brugada syndrome.

Use Cautiously in:

All patients (may ↑ risk of suicidal thoughts/behaviors);
Renal impairment (lower maintenance doses may be required);
Hepatic impairment (lower maintenance doses may be required);
Prior history of rash to lamotrigine
;
OB: Exposure during 1st trimester may ↑ risk of cleft lip/palate;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children <13 yr (extended-release tablets) and <2 yr (immediate-release, chewable, and orally disintegrating tablets).

CV: arrhythmias, bradycardia, CARDIAC ARREST, heart block, QRS interval prolongation

Derm: photosensitivity, rash (higher incidence in children, patients taking valproic acid, high initial doses, or rapid dose ↑), DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: blurred vision, double vision, rhinitis

GI: nausea, vomiting, HEPATIC FAILURE

GU: vaginitis

Hemat: HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

MS: arthralgia

Neuro: ataxia, dizziness, headache, ASEPTIC MENINGITIS, behavior changes, depression, drowsiness, insomnia, SUICIDAL THOUGHTS, tremor

Drug-drug:

May ↑ levels of an active metabolite of carbamazepine.
Concurrent use with drugs that induce glucuronidation, including phenobarbital, phenytoin, primidone, carbamazepine, estrogen-containing oral contraceptives, rifampin, lopinavir/ritonavir, or atazanavir/ritonavir may ↓ levels and effectiveness; lamotrigine dose adjustments may be necessary when starting and stopping oral contraceptive or atazanavir/ritonavir therapy.
Concurrent use with drugs that inhibit glucuronidation, including valproic acid, may ↑ levels and incidence of rash; may also ↓ valproic acid levels (↓ lamotrigine dose by ≥50%).
Amiodarone, disopyramide, dronedarone, flecainide, lidocaine, mexiletine, procainamide, propafenone, or quinidine may ↑ risk of proarrhythmia; avoid concurrent use.

Epilepsy

In Combination With Other Antiepileptic Agents
PO (Adults and Children >12 yr; Immediate-Release, Chewable, or Orally Disintegrating Tablets): Patients taking anticonvulsant drugs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate: 25 mg once daily for 1st 2 wk, then 50 mg once daily for next 2 wk; then ↑ by 50 mg/day every 1–2 wk to maintenance dose of 225–375 mg/day (in 2 divided doses); Patients taking carbamazepine, phenobarbital, phenytoin, or primidone (and not valproate): 50 mg once daily for 1st 2 wk, then 50 mg twice daily for next 2 wk; then ↑ by 100 mg/day every 1–2 wk to maintenance dose of 300–500 mg/day (in 2 divided doses); Patients taking regimen containing valproate: 25 mg every other day for 1st 2 wk, then 25 mg once daily for next 2 wk; then ↑ by 25–50 mg/day every 1–2 wk to maintenance dose of 100–400 mg/day (in 1–2 divided doses) (maintenance dose of 100–200 mg/day if receiving valproate alone).
PO (Adults and Children ≥13 yr; Extended-Release Tablets): Patients taking anticonvulsant drugs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate: 25 mg once daily for 1st 2 wk, then 50 mg once daily for next 2 wk, then 100 mg once daily for 1 wk, then 150 mg once daily for 1 wk, then 200 mg once daily for 1 wk; then ↑ by 100 mg/day every wk to maintenance dose of 300–400 mg once daily; Patients taking carbamazepine, phenobarbital, phenytoin, or primidone (and not valproate): 50 mg once daily for 1st 2 wk, then 100 mg once daily for next 2 wk, then 200 mg once daily for 1 wk, then 300 mg once daily for 1 wk, then 400 mg once daily for 1 wk; then ↑ by 100 mg/day every wk to maintenance dose of 400–600 mg once daily; Patients taking regimen containing valproate: 25 mg every other day for 1st 2 wk, then 25 mg once daily for next 2 wk, then 50 mg once daily for 1 wk, then 100 mg once daily for 1 wk, then 150 mg once daily for 1 wk, then maintenance dose of 200–250 mg once daily.
PO (Children 2–12 yr; Immediate-Release, Chewable, or Orally Disintegrating Tablets): Patients taking anticonvulsant drugs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate : 0.3 mg/kg/day in 1–2 divided doses (rounded down to nearest whole tablet) for 1st 2 wk, then 0.6 mg/kg/day in 2 divided doses (rounded down to nearest whole tablet) for next 2 wk; then ↑ by 0.6 mg/kg/day (rounded down to nearest whole tablet) every 1–2 wk to maintenance dose of 4.5–7.5 mg/kg/day (not to exceed 300 mg/day in 2 divided doses); Patients taking carbamazepine, phenobarbital, phenytoin, or primidone (and not valproate): 0.6 mg/kg/day in 2 divided doses (rounded down to nearest whole tablet) for 1st 2 wk, then 1.2 mg/kg/day in 2 divided doses (rounded down to nearest whole tablet) for next 2 wk; then ↑ by 1.2 mg/kg/day (rounded down to nearest whole tablet) every 1–2 wk to maintenance dose of 5–15 mg/kg/day (not to exceed 400 mg/day in 2 divided doses). Patients taking regimen containing valproate: 0.15 mg/kg/day in 1–2 divided doses (rounded down to nearest whole tablet) for 1st 2 wk, then 0.3 mg/kg in 1–2 divided doses (rounded down to nearest whole tablet) for next 2 wk; then ↑ by 0.3 mg/kg/day (rounded down to nearest whole tablet) every 1–2 wk to maintenance dose of 1–5 mg/kg/day (not to exceed 200 mg/day in 1–2 divided doses) (maintenance dose of 1–3 mg/kg/day if receiving valproate alone).
Conversion to Monotherapy
PO (Adults and Children ≥16 yr; Immediate-Release, Chewable, or Orally Disintegrating Tablets): Patients taking carbamazepine, phenobarbital, phenytoin, or primidone (and not valproate): After achieving a dose of 500 mg/day (as per dosing guidelines above), ↓ dose of other antiepileptic by 20% weekly over 4 wk; Patients taking regimen containing valproate: After achieving a dose of 200 mg/day (as per dosing guidelines above), ↓ valproate dose by 500 mg/day on a weekly basis until a dose of 500 mg/day is achieved. Maintain the valproate dose of 500 mg/day and the lamotrigine dose of 500 mg/day for 1 wk. Then ↑ lamotrigine dose to 300 mg/day and ↓ valproate dose to 250 mg/day, and maintain these doses for 1 wk. Then discontinue valproate and ↑ lamotrigine dose by 100 mg/day every wk until maintenance dose of 500 mg/day is achieved.
PO (Adults and Children ≥13 yr; Extended-Release Tablets): Patients taking carbamazepine, phenobarbital, phenytoin, or primidone (and not valproate): After achieving a dose of 500 mg/day (as per dosing guidelines above), ↓ dose of other antiepileptic by 20% weekly over 4 wk. 2 wk later, ↓ dose of lamotrigine by 100 mg/day every wk to achieve maintenance dose of 250–300 mg/day; Patients taking regimen containing valproate: After achieving a dose of 150 mg/day (as per dosing guidelines above), ↓ valproate dose by 500 mg/day on a weekly basis until a dose of 500 mg/day is achieved. Maintain the valproate dose of 500 mg/day and the lamotrigine dose of 150 mg/day for 1 wk. Then ↑ lamotrigine dose to 200 mg/day and ↓ valproate dose to 250 mg/day, and maintain these doses for 1 wk. Then discontinue valproate and ↑ lamotrigine dose to 250–300 mg/day; Patients taking anticonvulsant drugs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate: After achieving a dose of 250–300 mg/day (as per dosing guidelines above), ↓ dose of other antiepileptic by 20% weekly over 4 wk.

Bipolar Disorder

Escalation Regimen
PO (Adults Immediate-Release, Chewable, or Orally Disintegrating Tablets): Patients not taking carbamazepine, phenobarbital, phenytoin, primidone, rifampin, or valproate: 25 mg once daily for 1st 2 wk, then 50 mg once daily for next 2 wk, then 100 mg once daily for 1 wk, then 200 mg once daily; Patients taking valproate: 25 mg every other day for first 2 wk, then 25 mg once daily for next 2 wk, then 50 mg once daily for 1 wk, then 100 mg once daily; Patients taking carbamazepine, phenobarbital, phenytoin, primidone, or rifampin (and not valproate) 50 mg once daily for 1st 2 wk, then 100 mg/day (in divided doses) for next 2 wk, then 200 mg/day (in divided doses) for one wk, then 300 mg/day (in divided doses) for 1 wk, then up to 400 mg/day (in divided doses).
Dosage Adjustment Following Discontinuation of Other Psychotropics
PO (Adults Immediate-Release, Chewable, or Orally Disintegrating Tablets): Following discontinuation of valproate (if current dose 100 mg/day):↑ to 150 mg/day for 1 wk, then 200 mg/day; Following discontinuation of carbamazepine, phenobarbital, phenytoin, primidone, or rifampin (if current dose 400 mg/day): 400 mg/day for 1 wk, then 300 mg/day for 1 wk, then 200 mg/day; Following discontinuation of other psychotropics: maintain previous dose.

(Generic available)

Immediate-release tablets: 25 mg; 100 mg; 150 mg; 200 mg
Extended-release tablets: 25 mg; 50 mg; 100 mg; 200 mg; 250 mg; 300 mg
Orally disintegrating tablets: 25 mg; 50 mg; 100 mg; 200 mg
Tablets for oral suspension berry flavor: 5 mg; 25 mg

Monitor closely for changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Monitor for severe cutaneous adverse reactions, including SJS and TEN. Frequently assess for progressive rash or symptoms such as fever, malaise, lymphadenopathy, joint/muscle pain, blisters, oral lesions, and conjunctivitis. Discontinue lamotrigine at the 1st sign of rash, as SJS/TEN may be life-threatening. Risk is highest within the first 2–8 wk. Risk factors include valproate coadministration, exceeding initial dose, or rapid titration. While benign rashes occur, severity is unpredictable; discontinue lamotrigine unless rash is clearly unrelated. Serious rashes, including fatal cases, are more common in pediatric patients.
Monitor for signs and symptoms of multiorgan hypersensitivity reactions: DRESS (rash, fever, lymphadenopathy). May be associated with other organ involvement (hepatitis, hepatic failure, blood dyscrasias, acute multiorgan failure). If cause cannot be determined, discontinue lamotrigine immediately.
Seizures: Assess location, duration, and characteristics of seizure activity. Institute seizure precautions as indicated.
Bipolar disorders: Assess mood, ideation, and behaviors frequently. Initiate suicide precautions if indicated.

Lab Test Considerations:

Lamotrigine plasma concentrations may be monitored periodically during therapy, especially in patients concurrently taking other anticonvulsants. Therapeutic plasma concentration range include: Seizures: 2.5–15 mcg/mL; Treatment-resistant depression: 3.25–15 mcg/mL.
May cause false-positive results for phencyclidine in some rapid urine drug screens. Use a more specific analytical method to confirm results.

Do not confuse lamotrigine with labetalol, lamivudine, levetiracetam, or levothyroxine. Do not confuse Lamictal with labetalol.
When converting from immediate-release to XR form, initial dose of XR should match the total daily dose of immediate-release lamotrigine; monitor closely and adjust as needed.
PO: May be administered without regard to meals. DNC: Swallow XR tablets whole; do not break, crush, or chew.
- Lamotrigine should be discontinued gradually over ≥2 wk, unless safety concerns require a more rapid withdrawal. Abrupt discontinuation may cause increase in seizure frequency.
May be swallowed whole, chewed, or dispersed in 5 mL of water or fruit juice. If dispersed, wait 1 min and swirl; then administer immediately. If chewed, follow with water or fruit juice to aid in swallowing. Only use whole tablets; do not attempt to administer partial quantities of dispersible tablets.
Orally Disintegrating Tablets: Place on the tongue and move around the mouth. Tablet will rapidly disintegrate; can be swallowed with or without water, and can be taken with or without food.

Explain the purpose and side effects of lamotrigine. Instruct patient to take as directed. Take missed doses as soon as possible unless almost time for next dose. Do not double doses. Do not discontinue abruptly; may cause increase in frequency of seizures. Instruct patient to read the Medication Guide before starting and with each Rx refill, changes may occur.
Advise patient to notify health care provider immediately if skin rash, fever, or swollen lymph glands occur or if frequency of seizures increases.
May cause dizziness, drowsiness, and blurred vision. Caution patient to avoid driving or activities requiring alertness until response to medication is known. Do not resume driving until physician gives clearance based on control of seizure disorder.
Caution patient to wear sunscreen and protective clothing to prevent photosensitivity reactions.
Advise patient and family to notify health care provider if thoughts about suicide or dying, attempts to commit suicide, new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme ↑ in activity and talking, or other unusual changes in behavior or mood occur or if symptoms of aseptic meningitis (headache, fever, nausea, vomiting, nuchal rigidity, rash, photophobia, myalgia, chills, altered consciousness, somnolence) or cardiac symptoms (fast, slow, or pounding heartbeat; heart skipping beats; shortness of breath; chest pain; feeling light-headed) occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Instruct patient to notify health care provider of medication regimen prior to treatment or surgery.
Medical ID describing disease process and medication regimen should be worn at all times in case of emergencies.
Advise patient to notify health care provider immediately if signs and symptoms of hemophagocytic lymphohistiocytosis (fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, ↑ serum ferritin, hypertriglyceridemia, liver function, coagulation abnormalities) occur. Symptoms usually occur between 8 and 24 days. May be fatal.
Rep: Advise women of reproductive potential to use a nonhormonal form of contraception while taking lamotrigine, avoid breastfeeding, and notify health care provider if pregnancy is planned or suspected. Encourage patients who become pregnant to enroll in the North American Antiepileptic Drug Pregnancy Registry. Must be done by patients themselves by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Enrollment in the registry must be done prior to any prenatal diagnostic tests and before fetal outcome is known.
Rep: Seizure Disorder Pregnancy Monitoring and Dosage Adjustments: Optimally establish a therapeutic baseline prior to pregnancy. Due to the possibility of ↑ lamotrigine clearance during pregnancy, monitor plasma concentrations approximately every 4 wk. If plasma concentration falls below an established therapeutic baseline, ↑ dose by 20– 25% and recheck plasma concentration after 4–5 wk. After Pregnancy: Measure plasma concentration within the 1st wk after birth. If there is no ↑ in plasma concentration, recheck after 1–2 wk. If plasma concentration is higher than therapeutic baseline, ↓ dose by 20–25%, and recheck plasma concentration every 1–2 wk until stable at therapeutic baseline. In patients who had ≥3–4 dose ↑ during pregnancy, ↓ dose by 20–25% on the 1st days after birth. Thereafter, if the plasma concentration is higher than the established therapeutic baseline, ↓ dose by 20–25%, and recheck plasma concentration every 1–2 wk until stable at baseline.

Decrease in the frequency of or cessation of seizures.
Delay in time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients with bipolar I disorder.

LaMICtal, LaMICtal ODT, LaMICtal XR, Subvenite

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Indications ⬆ ⬇

Action ⬆ ⬇

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Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

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Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

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US Brand Names ⬆