Lamictal XR

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Lamictal XR

Classes

Anticonvulsants, Miscellaneous
Mood Stabilizers

Administration

NOTE: Medication errors have been reported with lamotrigine starter kits. Mild to severe side effects, including Stevens-Johnson Syndrome have occurred. There are 3 different starter kits with titration schedules dependant on concurrent medications (see below). Patients must receive the correct kit to avoid over or under dosing.

A MedGuide is available that discusses the risk of suicidal thoughts and behaviors associated with the use of anticonvulsant medications.

Oral Administration

Lamotrigine may be administered without regard to meals.

Oral Solid Formulations

Orange starter kits: For patients NOT taking carbamazepine, phenytoin, phenobarbital, primidone, rifampin, or valproate.
Green starter kits: For patients taking carbamazepine, phenytoin, phenobarbital, primidone, or rifampin and NOT taking valproate.
Blue starter kits: For patients taking valproate.
Immediate-release tablets: Lamotrigine tablets should not be chewed, as the medication is very bitter.
Tablets for oral suspension: Lamotrigine may be swallowed whole, chewed, or mixed in water or in diluted fruit juice to aid swallowing. To mix the tablets in water or juice, add the tablets to a small amount of liquid (enough to cover the medication) in a glass or spoon. The tablets will dissolve in about 1 minute. Once dissolved, mix or swirl the liquid, and take the entire solution immediately. It is important to have the patient swallow all of the liquid used to prepare the dose. NOTE: The lowest available tablet strength is a 2 mg tablet for oral suspension, and all doses should be rounded to the nearest 2 mg dose. Only whole dispersible tablets should be administered; do not cut in half.
Orally disintegrating tablets: Lamotrigine tablets should be placed on tongue and moved around in the mouth to facilitate disintegration. The tablet will disintegrate rapidly and may be swallowed with or without water. When dispensing the blisterpack, advise patients to examine it prior to use and do not use if the blisters are torn, broken, or missing.
Extended-release tablets: Swallow lamotrigine tablets whole. Do not chew, crush, or divide.

Adverse Reactions

Severe

suicidal ideation / Delayed / 0.1-5.0
peptic ulcer / Delayed / 2.1-4.9
visual impairment / Early / 2.0-4.9
bronchospasm / Rapid / 2.0-2.0
hematemesis / Delayed / 0-0.1
uveitis / Delayed / 0-0.1
exfoliative dermatitis / Delayed / 0-0.1
toxic epidermal necrolysis / Delayed / 0-0.1
angioedema / Rapid / 0-0.1
erythema multiforme / Delayed / 0-0.1
Stevens-Johnson syndrome / Delayed / 0-0.1
renal failure (unspecified) / Delayed / 0-0.1
epididymitis / Delayed / 0-0.1
vasculitis / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
apnea / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
myocarditis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
red cell aplasia / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
aseptic meningitis / Delayed / Incidence not known
hemophagocytic lymphohistiocytosis / Delayed / Incidence not known

Moderate

blurred vision / Early / 4.0-25.0
ataxia / Delayed / 2.0-11.0
chest pain (unspecified) / Early / 5.0-5.0
constipation / Delayed / 2.0-5.0
contact dermatitis / Delayed / 2.1-5.0
depression / Delayed / 0.1-4.9
migraine / Early / 1.1-4.9
nystagmus / Delayed / 2.0-4.9
amnesia / Delayed / 1.1-4.9
hyperreflexia / Delayed / 2.1-4.9
peripheral edema / Delayed / 2.1-4.9
edema / Delayed / 1.1-4.9
dyspnea / Early / 2.1-4.9
vaginitis / Delayed / 4.0-4.0
hot flashes / Early / 0.1-2.0
lymphadenopathy / Delayed / 2.0-2.0
atopic dermatitis / Delayed / 2.0-2.0
hallucinations / Early / 0.1-1.0
aphasia / Delayed / 0.1-1.0
memory impairment / Delayed / 0.1-1.0
dyskinesia / Delayed / 0.1-1.0
hypertonia / Delayed / 0.1-1.0
akathisia / Delayed / 0.1-1.0
hostility / Early / 0.1-1.0
psychosis / Early / 0.1-1.0
dysarthria / Delayed / 0.1-1.0
euphoria / Early / 0.1-1.0
hypertension / Early / 0.1-1.0
palpitations / Early / 0.1-1.0
sinus tachycardia / Rapid / 0.1-1.0
peripheral vasodilation / Rapid / 0.1-1.0
orthostatic hypotension / Delayed / 0.1-1.0
myasthenia / Delayed / 0.1-1.0
dysphagia / Delayed / 0.1-1.0
elevated hepatic enzymes / Delayed / 0.1-1.0
gastritis / Delayed / 0.1-1.0
photophobia / Early / 0.1-1.0
conjunctivitis / Delayed / 0.1-1.0
leukopenia / Delayed / 0.1-1.0
impotence (erectile dysfunction) / Delayed / 0.1-1.0
urinary incontinence / Early / 0.1-1.0
hematuria / Delayed / 0.1-1.0
ejaculation dysfunction / Delayed / 0.1-1.0
neuritis / Delayed / 0-0.1
dystonic reaction / Delayed / 0-0.1
dysphoria / Early / 0-0.1
delirium / Early / 0-0.1
hyperalgesia / Delayed / 0-0.1
hyperesthesia / Delayed / 0-0.1
choreoathetosis / Delayed / 0-0.1
hypotonia / Delayed / 0-0.1
hepatitis / Delayed / 0-0.1
melena / Delayed / 0-0.1
colitis / Delayed / 0-0.1
stomatitis / Delayed / 0-0.1
glossitis / Early / 0-0.1
erythema / Early / 0-0.1
eosinophilia / Delayed / 0-0.1
anemia / Delayed / 0-0.1
lymphocytosis / Delayed / 0-0.1
thrombocytopenia / Delayed / 0-0.1
urinary retention / Early / 0-0.1
dysuria / Early / 0-0.1
cystitis / Delayed / 0-0.1
hyperbilirubinemia / Delayed / 0-0.1
hypothyroidism / Delayed / 0-0.1
hyperglycemia / Delayed / 0-0.1
goiter / Delayed / 0-0.1
mania / Early / 5.0
confusion / Early / 1.0
amblyopia / Delayed / 1.0
esophagitis / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
splenomegaly / Delayed / Incidence not known

Mild

diplopia / Early / 5.0-49.0
vomiting / Early / 5.0-20.0
drowsiness / Early / 5.0-17.0
fever / Early / 1.1-15.0
dizziness / Early / 5.0-14.0
pharyngitis / Delayed / 5.0-14.0
nausea / Early / 7.0-14.0
rash / Early / 7.0-14.0
diarrhea / Early / 5.0-11.0
tremor / Early / 4.0-10.0
abdominal pain / Early / 5.0-10.0
asthenia / Delayed / 2.1-8.0
fatigue / Early / 6.0-8.0
back pain / Delayed / 8.0-8.0
cough / Delayed / 5.0-7.0
dyspepsia / Early / 2.0-7.0
dysmenorrhea / Delayed / 5.0-7.0
xerostomia / Early / 2.0-6.0
weight loss / Delayed / 5.0-5.0
diaphoresis / Early / 2.1-4.9
libido increase / Delayed / 2.1-4.9
agitation / Early / 1.1-4.9
irritability / Delayed / 2.1-4.9
emotional lability / Early / 1.1-4.9
hypoesthesia / Delayed / 1.1-4.9
hyporeflexia / Delayed / 2.1-4.9
arthralgia / Delayed / 1.1-4.9
myalgia / Early / 1.1-4.9
epistaxis / Delayed / 2.0-4.9
sinusitis / Delayed / 1.1-4.9
flatulence / Early / 1.1-4.9
weight gain / Delayed / 1.1-4.9
anorexia / Delayed / 2.0-4.9
increased urinary frequency / Early / 1.1-4.9
xerosis / Delayed / 2.1-4.9
vertigo / Early / 2.0-3.0
amenorrhea / Delayed / 2.0-2.0
libido decrease / Delayed / 0.1-1.0
hyperkinesis / Delayed / 0.1-1.0
malaise / Early / 0.1-1.0
paranoia / Early / 0.1-1.0
flushing / Rapid / 0.1-1.0
syncope / Early / 0.1-1.0
yawning / Early / 0.1-1.0
eructation / Early / 0.1-1.0
hypersalivation / Early / 0.1-1.0
gingivitis / Delayed / 0.1-1.0
appetite stimulation / Delayed / 0.1-1.0
tinnitus / Delayed / 0.1-1.0
urticaria / Rapid / 0.1-1.0
ecchymosis / Delayed / 0.1-1.0
polyuria / Early / 0.1-1.0
menorrhagia / Delayed / 0.1-1.0
acne vulgaris / Delayed / 0.1-1.0
alopecia / Delayed / 0.1-1.0
hirsutism / Delayed / 0.1-1.0
skin discoloration / Delayed / 0.1-1.0
hiccups / Early / 0-0.1
hyperventilation / Early / 0-0.1
parosmia / Delayed / 0-0.1
ptosis / Delayed / 0-0.1
maculopapular rash / Early / 0-0.1
leukocytosis / Delayed / 0-0.1
petechiae / Delayed / 0-0.1
nocturia / Early / 0-0.1
urinary urgency / Early / 0-0.1
headache / Early / 5.0
paresthesias / Delayed / 1.0
insomnia / Early / 5.0
anxiety / Delayed / 3.0
rhinitis / Early / 5.0
influenza / Delayed / 3.0
infection / Delayed / 5.0
pruritus / Rapid / 2.0
nasal congestion / Early / Incidence not known

Boxed Warning

Hemophagocytic lymphohistiocytosis, history of angioedema, serious rash

Lamotrigine use is contraindicated in patients who have demonstrated hypersensitivity to lamotrigine (e.g., rash, history of angioedema, acute urticaria, extensive pruritus, mucosal ulceration) or other life-threatening hypersensitivity or serious immune-related events. Due to the potential for life-threatening serious rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis), discontinue lamotrigine if rash occurs at any time during treatment. It is important to note that discontinuation of lamotrigine may not prevent progression to a higher level of severity; therefore, monitor patients closely. Age is the only factor currently known to predict the occurrence or severity of a rash, with pediatric patients at increased risk. Other possible but unproven factors include concurrent use of valproate, exceeding the initial recommended dose, or exceeding the recommended dose titration. Almost all cases of life-threatening rash have occurred within the first 2 to 8 weeks of treatment. However, prolonged duration of therapy does not preclude the possibility of an association to the drug. Also, caution is advised when administering lamotrigine to patients with a history of rash or allergy to other anticonvulsants, since non-serious rashes have occurred 3 times more frequently in these patients during treatment with lamotrigine than in those without this history. Do not resume lamotrigine after prior discontinuation due to rash unless the benefits outweigh the risks. If the drug is reintroduced and it has been 5 half-lives or longer since the last dose, reinitiate using initial dosing recommendations. Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms (DRESS), have occurred. Some have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though a rash is not evident. If such signs or symptoms are present, evaluate the patient immediately. Discontinue lamotrigine if an alternative etiology for the signs or symptoms cannot be established. Lamotrigine may also cause hemophagocytic lymphohistiocytosis (HLH), which is a rare but serious uncontrolled immune system response that may result in hospitalization and death. Severe inflammation occurs throughout the body leading to severe problems with blood cells and organs throughout the body. HLH typically presents with a fever (more than 101 degrees F) and rash. Other signs and symptoms may include enlarged liver with pain, tenderness, or unusual swelling over the liver area in the upper right belly, swollen lymph nodes, yellow skin or eyes, unusual bleeding, hypertriglyceridemia, or nervous system problems (seizures, trouble walking, difficulty seeing, or other visual disturbances). A diagnosis may be established if 5 of the following symptoms from the HLH-2004 diagnostic criteria are present: fever or rash, enlarged spleen (splenomegaly), cytopenias, elevated concentrations of triglycerides or low blood concentrations of fibrinogen, high concentrations of blood ferritin, hemophagocytosis identified through bone marrow, spleen, or lymph node biopsy, decreased or absent natural killer cell activity, and elevated blood concentrations of CD25 showing prolonged immune cell activation. Evaluate patients who present with fever or rash promptly, as early recognition is necessary to improve outcomes and reduce mortality. HLH may be confused with other serious immune-system reactions such as DRESS.[28451] [63107]

Common Brand Names

Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR, Subvenite

Dea Class

Description

Oral antiepileptic drug (AED)
Used for adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures, and generalized seizures of Lennox-Gastaut syndrome; conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with certain other AEDs; and maintenance treatment of bipolar I disorder
Associated with life-threatening serious rashes and/or rash-related death, more frequently in pediatric patients

Dosage And Indications

For the treatment of partial seizures.

For the treatment of partial-onset seizures when converting to monotherapy from adjunctive therapy with carbamazepine, phenobarbital, phenytoin, or primidone. Oral dosage (immediate-release) Adults

50 mg PO once daily for 2 weeks, then 50 mg PO twice daily for 2 weeks, and then increase the dose by 100 mg/day every 1 to 2 weeks to a dose of 250 mg PO twice daily. After achieving a dose of lamotrigine 500 mg/day, withdraw the concomitant enzyme-inducing antiepileptic drug (AED) by 20% decrements weekly over a 4-week period. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The safety and effectiveness of immediate-release lamotrigine as initial monotherapy, for conversion to monotherapy from AEDs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate, or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs have not been established.

Adolescents 16 to 17 years

Oral dosage (extended-release) Adults

50 mg PO once daily for 2 weeks, then 100 mg PO once daily for 2 weeks, then 200 mg PO once daily for 1 week, then 300 mg PO once daily for 1 week, then 400 mg PO once daily for 1 week, and then 500 mg PO once daily. After achieving a dose of lamotrigine 500 mg/day, withdraw the concomitant enzyme-inducing antiepileptic drug (AED) by 20% decrements weekly over a 4-week period. At 2 weeks after completion of withdrawal of the enzyme-inducing AED, decrease the lamotrigine dose by no faster than 100 mg/day weekly to a dose of 250 to 300 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The safety and effectiveness of extended-release lamotrigine as initial monotherapy or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs have not been established.

Adolescents

For the treatment of partial-onset seizures when converting to monotherapy from adjunctive therapy with valproate. Oral dosage (immediate-release) Adults

25 mg PO every other day for 2 weeks, then 25 mg PO once daily for 2 weeks, and then increase the dose by 25 to 50 mg/day every 1 to 2 weeks to a dose of 200 mg/day in 1 or 2 divided doses. After achieving a dose of lamotrigine 200 mg/day, decrease the valproate dose by no more than 500 mg/day weekly to a dose of 500 mg/day; maintain for 1 week. Then, increase the lamotrigine dose to 300 mg/day in 1 or 2 divided doses and simultaneously decrease valproate to 250 mg/day; maintain for 1 week. Then, increase the lamotrigine dose by 100 mg/day weekly to a dose of 500 mg/day in 1 or 2 divided doses and discontinue valproate. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The safety and effectiveness of immediate-release lamotrigine as initial monotherapy, for conversion to monotherapy from AEDs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate, or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs have not been established.

Adolescents 16 to 17 years

Oral dosage (extended-release) Adults

25 mg PO every other day for 2 weeks, then 25 mg PO once daily for 2 weeks, then 50 mg PO once daily for 1 week, then 100 mg PO once daily for 1 week, and then 150 mg PO once daily. After achieving a dose of lamotrigine 150 mg/day, decrease the valproate dose by no more than 500 mg/day weekly to a dose of 500 mg/day; maintain for 1 week. Then, increase the lamotrigine dose to 200 mg/day and simultaneously decrease valproate to 250 mg/day; maintain for 1 week. Then, increase the lamotrigine dose to 250 or 300 mg/day and discontinue valproate. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The safety and effectiveness of extended-release lamotrigine as initial monotherapy or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs have not been established.

Adolescents

For the treatment of partial-onset seizures as adjunctive therapy with valproate. Oral dosage (immediate-release) Adults

25 mg PO every other day for 2 weeks, then 25 mg PO once daily for 2 weeks, and then increase the dose by 25 to 50 mg/day every 1 to 2 weeks to a dose of 100 to 200 mg/day in 2 divided doses with valproate alone and 100 to 400 mg/day in 2 divided doses with valproate and other drugs that induce glucuronidation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Adolescents

Children 2 to 12 years weighing 40 kg or more

0.15 mg/kg/day PO in 1 or 2 divided doses for 2 weeks, then 0.3 mg/kg/day PO in 1 or 2 divided doses for 2 weeks, and then increase the dose by 0.3 mg/kg/day every 1 to 2 weeks to a dose of 1 to 3 mg/kg/day in 1 or 2 divided doses with valproate alone and 1 to 5 mg/day in 1 or 2 divided doses with valproate and other anti-epileptic drugs. Max: 200 mg/day. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children 2 to 12 years weighing 34.1 to 40 kg

5 mg PO once daily for 2 weeks, then 10 mg PO once daily for 2 weeks, and then increase the dose by 0.3 mg/kg/day every 1 to 2 weeks to a dose of 1 to 3 mg/kg/day in 1 or 2 divided doses with valproate alone and 1 to 5 mg/day in 1 or 2 divided doses with valproate and other anti-epileptic drugs. Max: 200 mg/day. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children 2 to 12 years weighing 27.1 to 34 kg

4 mg PO once daily for 2 weeks, then 8 mg PO once daily for 2 weeks, and then increase the dose by 0.3 mg/kg/day every 1 to 2 weeks to a dose of 1 to 3 mg/kg/day in 1 or 2 divided doses with valproate alone and 1 to 5 mg/day in 1 or 2 divided doses with valproate and other anti-epileptic drugs. Max: 200 mg/day. The maintenance dose may need to be increased by as much as 50% in children weighing less than 30 kg based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children 2 to 12 years weighing 14.1 to 27 kg

2 mg PO once daily for 2 weeks, then 4 mg PO once daily for 2 weeks, and then increase the dose by 0.3 mg/kg/day every 1 to 2 weeks to a dose of 1 to 3 mg/kg/day in 1 or 2 divided doses with valproate alone and 1 to 5 mg/day in 1 or 2 divided doses with valproate and other anti-epileptic drugs. Max: 200 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children 2 to 12 years weighing 6.7 to 14 kg

2 mg PO every other day for 2 weeks, then 2 mg PO once daily for 2 weeks, and then increase the dose by 0.3 mg/kg/day every 1 to 2 weeks to a dose of 1 to 3 mg/kg/day in 1 or 2 divided doses with valproate alone and 1 to 5 mg/day in 1 or 2 divided doses with valproate and other anti-epileptic drugs. Max: 200 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (extended-release) Adults

25 mg PO every other day for 2 weeks, then 25 mg PO once daily for 2 weeks, then 50 mg PO once daily for 1 week, then 100 mg PO once daily for 1 week, then 150 mg PO once daily for 1 week, and then increase the dose by 100 mg/day weekly to a dose of 200 to 250 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Adolescents

For the treatment of partial-onset seizures when converting to monotherapy from adjunctive therapy with a single anti-epileptic drug other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate. Oral dosage (extended-release) Adults

25 mg PO once daily for 2 weeks, then 50 mg PO once daily for 2 weeks, then 100 mg PO once daily for 1 week, then 150 mg PO once daily, then 200 to 250 mg PO once daily, and then increase the dose by no more than 100 mg/day to a dose of 250 or 300 mg/day. After achieving a dose of lamotrigine 250 or 300 mg/day, withdraw the concomitant enzyme-inducing antiepileptic drug (AED) by 20% decrements weekly over a 4-week period. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The safety and effectiveness of extended-release lamotrigine as initial monotherapy or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs have not been established.

Adolescents 13 to 17 years

For the treatment of partial-onset seizures as adjunctive therapy with carbamazepine, phenobarbital, phenytoin, or primidone. Oral dosage (immediate-release) Adults

50 mg PO once daily for 2 weeks, then 50 mg PO twice daily for 2 weeks, and then increase the dose by 100 mg/day every 1 to 2 weeks to a dose of 300 to 500 mg/day in 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Adolescents

Children 2 to 12 years weighing 30 kg or more

0.3 mg/kg/dose PO twice daily for 2 weeks, then 0.6 mg/kg/dose PO twice daily for 2 weeks, and then increase the dose by 1.2 mg/kg/day every 1 to 2 weeks to a dose of 5 to 15 mg/kg/day in 2 divided doses. Max: 400 mg/day. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children 2 to 12 years weighing less than 30 kg

0.3 mg/kg/dose PO twice daily for 2 weeks, then 0.6 mg/kg/dose PO twice daily for 2 weeks, and then increase the dose by 1.2 mg/kg/day every 1 to 2 weeks to a dose of 5 to 15 mg/kg/day in 2 divided doses. Max: 400 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (extended-release) Adults

50 mg PO once daily for 2 weeks, then 100 mg PO once daily for 2 weeks, then 200 mg PO once daily for 1 week, then 300 mg PO once daily for 1 week, then 400 mg PO once daily for 1 week, and then increase the dose by 100 mg/day weekly to a dose of 400 to 600 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Adolescents

For the treatment of partial-onset seizures as adjunctive therapy with anti-epileptic drugs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate. Oral dosage (immediate-release) Adults

25 mg PO once daily for 2 weeks, then 50 mg PO once daily for 2 weeks, and then increase the dose by 50 mg/day every 1 to 2 weeks to a dose of 225 to 375 mg/day in 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Adolescents

Children 2 to 12 years weighing 30 kg or more

0.3 mg/kg/day PO in 1 or 2 divided doses for 2 weeks, then 0.3 mg/kg/dose PO twice daily for 2 weeks, then increase the dose by 0.6 mg/kg/day every 1 to 2 weeks to a dose of 4.5 to 7.5 mg/kg/day in 2 divided doses. Max: 300 mg/day. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children 2 to 12 years weighing less than 30 kg

0.3 mg/kg/day PO in 1 or 2 divided doses for 2 weeks, then 0.3 mg/kg/dose PO twice daily for 2 weeks, then increase the dose by 0.6 mg/kg/day every 1 to 2 weeks to a dose of 4.5 to 7.5 mg/kg/day in 2 divided doses. Max: 300 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (extended-release) Adults

25 mg PO once daily for 2 weeks, then 50 mg PO once daily for 2 weeks, then 100 mg PO once daily for 1 week, then 150 mg PO once daily for 1 week, then 200 mg PO once daily for 1 week, and then increase the dose by 100 mg/day weekly to a dose of 300 to 400 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Adolescents

For the treatment of primary generalized tonic-clonic seizures as adjunctive therapy.

For the treatment of primary generalized tonic-clonic seizures as adjunctive therapy with carbamazepine, phenobarbital, phenytoin, or primidone. Oral dosage (immediate-release) Adults

Adolescents

Children 2 to 12 years weighing 30 kg or more

Children 2 to 12 years weighing less than 30 kg

0.3 mg/kg/dose PO twice daily for 2 weeks, then 0.6 mg/kg/dose PO twice daily for 2 weeks, and then increase the dose by 1.2 mg/kg/day every 1 to 2 weeks to a dose of 5 to 15 mg/kg/day in 2 divided doses. Max: 400 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (extended-release) Adults

Adolescents

For the treatment of primary generalized tonic-clonic seizures as adjunctive therapy with valproate. Oral dosage (immediate-release) Adults

Adolescents

Children 2 to 12 years weighing 40 kg or more

Children 2 to 12 years weighing 34.1 to 40 kg

Children 2 to 12 years weighing 27.1 to 34 kg

Children 2 to 12 years weighing 14.1 to 27 kg

Children 2 to 12 years weighing 6.7 to 14 kg

Oral dosage (extended-release) Adults

Adolescents

For the treatment of primary generalized tonic-clonic seizures as adjunctive therapy with anti-epileptic drugs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate. Oral dosage (immediate-release) Adults

Adolescents

Children 2 to 12 years weighing 30 kg or more

Children 2 to 12 years weighing less than 30 kg

0.3 mg/kg/day PO in 1 or 2 divided doses for 2 weeks, then 0.3 mg/kg/dose PO twice daily for 2 weeks, then increase the dose by 0.6 mg/kg/day every 1 to 2 weeks to a dose of 4.5 to 7.5 mg/kg/day in 2 divided doses. Max: 300 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (extended-release) Adults

Adolescents

For the treatment of generalized seizures of Lennox-Gastaut syndrome as adjunctive therapy. For the treatment of generalized seizures of Lennox-Gastaut syndrome as adjunctive therapy with carbamazepine, phenobarbital, phenytoin, or primidone. Oral dosage (immediate-release) Adults

Adolescents

Children 2 to 12 years weighing 30 kg or more

Children 2 to 12 years weighing less than 30 kg

0.3 mg/kg/dose PO twice daily for 2 weeks, then 0.6 mg/kg/dose PO twice daily for 2 weeks, and then increase the dose by 1.2 mg/kg/day every 1 to 2 weeks to a dose of 5 to 15 mg/kg/day in 2 divided doses. Max: 400 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of generalized seizures of Lennox-Gastaut syndrome as adjunctive therapy with valproate. Oral dosage (immediate-release) Adults

Adolescents

Children 2 to 12 years weighing 40 kg or more

Children 2 to 12 years weighing 34.1 to 40 kg

Children 2 to 12 years weighing 27.1 to 34 kg

Children 2 to 12 years weighing 14.1 to 27 kg

Children 2 to 12 years weighing 6.7 to 14 kg

For the treatment of generalized seizures of Lennox-Gastaut syndrome as adjunctive therapy with anti-epileptic drugs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate. Oral dosage (immediate-release) Adults

Adolescents

Children 2 to 12 years weighing 30 kg or more

Children 2 to 12 years weighing less than 30 kg

0.3 mg/kg/day PO in 1 or 2 divided doses for 2 weeks, then 0.3 mg/kg/dose PO twice daily for 2 weeks, then increase the dose by 0.6 mg/kg/day every 1 to 2 weeks to a dose of 4.5 to 7.5 mg/kg/day in 2 divided doses. Max: 300 mg/day. The maintenance dose may need to be increased by as much as 50% based on clinical response. Round the dose down to the nearest whole tablet. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of bipolar disorder (bipolar I disorder) to delay the occurrence of mood episodes (i.e., depression, mania, hypomania, mixed episodes) in persons treated for acute mood episodes with standard therapy. For the treatment of bipolar disorder in persons not taking carbamazepine (or other enzyme-inducing drugs) or valproate. Oral dosage (immediate-release) Adults

25 mg PO once daily for 2 weeks, then 50 mg PO once daily for 2 weeks, then 100 mg PO once daily for 1 week, and then 200 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children† and Adolescents† 12 to 17 years

25 mg PO once daily for 2 weeks, then 50 mg/day PO in 1 or 2 divided doses for 2 weeks, then 100 mg/day PO in 1 or 2 divided doses, initially. May further increase the dose by 25 to 50 mg/week based on clinical response and tolerability. Max: 500 mg/day in 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children† 6 to 11 years

0.35 mg/kg/day PO in 2 divided doses for 2 weeks, then 0.7 mg/kg/day PO in 2 divided doses for 2 weeks, then 1.4 mg/kg/day PO in 2 divided doses for 2 weeks, initially. May further increase the dose by 1 mg/kg/day in 2 divided doses every week based on clinical response and tolerability. Usual dose: 5 to 15 mg/kg/day. Max: 400 mg/day in 2 divided doses. Round dose down to the nearest 5 mg. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of bipolar disorder in persons taking valproate. Oral dosage (immediate-release) Adults

25 mg PO every other day for 2 weeks, then 25 mg PO once daily for 2 weeks, than 50 mg PO once daily for 1 week, then 100 mg PO once daily. Upon discontinuation of valproate, increase the lamotrigine dose to 150 mg/day for 1 week, and then 200 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children† and Adolescents† 12 to 17 years

12.5 mg PO once daily for 2 weeks, initially. Increase the dose gradually based on clinical response and tolerability. Usual dose: 50 to 100 mg/day in 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of bipolar disorder in persons taking carbamazepine (or other enzyme-inducing drugs). Oral dosage (immediate-release) Adults

50 mg PO once daily for 2 weeks, then 50 mg PO twice daily for 2 weeks, then 100 mg PO twice daily for 1 week, then 150 mg PO twice daily for 1 week, then up to 200 mg PO twice daily. Upon discontinuation of carbamazepine (or other enzyme inducing drug), maintain lamotrigine 400 mg/day for 1 week, then decrease dose by 100 mg/day every week to a dose of 200 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of absence seizures†. Oral dosage (immediate-release) Children and Adolescents 3 to 13 years

0.25 mg/kg/dose PO twice daily for 2 weeks, then 0.5 mg/kg/day PO twice daily for 2 weeks, and then increase the dose by 1 mg/kg/day every 5 days until an effective dose is reached, side effects prohibit further titration, or to a maximum of 12 mg/kg/day. At 1 month, significantly more children were seizure free with valproic acid (52.6%) than lamotrigine (5.3%). There was no statistical difference by month 3 (63.1% vs. 36.8%). After 12 months, 68.4% and 52.6% of those receiving valproic acid and lamotrigine, respectively, were seizure free. Adverse effects (headache, skin rash, diplopia, nervousness, or increased appetite) were reported in 6 subjects receiving lamotrigine. The delayed response to lamotrigine may in part be due to the slow titration schedule. However, safety issues, such as the risk of a serious skin rash, must be taken into consideration when selecting a dosage titration. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For long-term prophylaxis of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)†. Oral dosage Adults

Limited case series and report suggest doses of 100 to 600 mg/day PO are effective in reducing or eliminating symptoms of SUNCT. Lamotrigine was initiated at 25 mg PO once daily and titrated every 4 to 5 days until patients experienced relief. While doses as high as 600 mg/day were allowed and required by some patients, most patients responded to doses of 100 mg to 400 mg/day. In a patient, a combination of carbamazepine and lamotrigine was required for cessation of SUNCT symptoms. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of trigeminal neuralgia†. Oral dosage (immediate-release) Adults

50 mg PO twice daily for 1 week, then 100 mg PO twice daily for 1 week, then 200 mg PO twice daily or alternatively, 25 mg PO once daily for 2 weeks, then 50 mg PO once daily for 2 weeks, then increase the dose by 50 mg/day every 2 weeks up to 200 mg PO twice daily. Max: 400 mg/day.

†Indicates off-label use

Dosing Considerations

Hepatic Impairment

Initial, escalation, and maintenance doses should generally be reduced by 25% in patients with moderate hepatic impairment or severe impairment without ascites, and by 50% in patients with severe hepatic impairment with ascites. Adjust doses as needed according to clinical response.

Renal Impairment

Dosage should be modified depending on clinical response and degree of renal impairment. A reduced maintenance dosage may be effective, but due to limited experience, no quantitative recommendations are available.

Intermittent hemodialysis
Hemodialysis lowers the apparent elimination half-life of lamotrigine by 70% to 80%. The half-life decreases from 43 to 57 hours in anuric subjects between dialysis treatments to 13 hours during dialysis treatments. Approximately 20% of lamotrigine present in the body is removed after a standard 4-hour dialysis session. No quantitative recommendations are available for adjustments.

Drug Interactions

Acetaminophen: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Aspirin: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Caffeine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Codeine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Dextromethorphan: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Diphenhydramine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Hydrocodone: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Ibuprofen: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Oxycodone: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Phenylephrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Acetaminophen; Pseudoephedrine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity, such as lamotrigine. Use with caution.
Alogliptin; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Alprazolam: (Moderate) Concomitant administration of alprazolam with CNS-depressant drugs, including anticonvulsants, can potentiate the CNS effects of either agent.
Apalutamide: (Moderate) Adjustments in lamotrigine escalation and maintenance dose regimens may be necessary with concomitant apalutamide use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and apalutamide induces glucuronidation.
Aripiprazole: (Minor) Coadministration of aripiprazole and lamotrigine may slightly decrease lamotrigine plasma concentrations; however, this interaction is not expected to be clinically meaningful. During clinical trials, lamotrigine exposure was reduced approximately 10% in patients (n = 18) on a stable regimen of lamotrigine 100 mg/day to 400 mg/day who received ariprazole 10 mg/day to 30 mg/day for 7 days, followed by 30 mg/day for an additional 7 days.
Atazanavir: (Major) Adjustments in lamotrigine maintenance dose regimens may be necessary with concomitant use of atazanavir boosted with ritonavir. No dose adjustments during dose escalation are necessary. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and atazanavir with ritonavir induces glucuronidation. Daily doses of atazanavir/ritonavir (300 mg/100 mg) in healthy volunteers reduced the AUC and Cmax of a single lamotrigine dose (100 mg) by approximately 32% and 6%, respectively. The lamotrigine half-life decreased by 27%. Concurrent use of lamotrigine and unboosted atazanavir is not expected to alter the plasma concentration of lamotrigine, and no dose adjustment of lamotrigine is necessary when administered without ritonavir.
Atazanavir; Cobicistat: (Major) Adjustments in lamotrigine maintenance dose regimens may be necessary with concomitant use of atazanavir boosted with ritonavir. No dose adjustments during dose escalation are necessary. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and atazanavir with ritonavir induces glucuronidation. Daily doses of atazanavir/ritonavir (300 mg/100 mg) in healthy volunteers reduced the AUC and Cmax of a single lamotrigine dose (100 mg) by approximately 32% and 6%, respectively. The lamotrigine half-life decreased by 27%. Concurrent use of lamotrigine and unboosted atazanavir is not expected to alter the plasma concentration of lamotrigine, and no dose adjustment of lamotrigine is necessary when administered without ritonavir.
Benzalkonium Chloride; Benzocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as benzocaine. Concomitant use of benzocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Benzocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as benzocaine. Concomitant use of benzocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Benzocaine; Butamben; Tetracaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as benzocaine. Concomitant use of benzocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Bupivacaine Liposomal: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as bupivacaine. Concomitant use of bupivacaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Bupivacaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as bupivacaine. Concomitant use of bupivacaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Bupivacaine; Epinephrine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as bupivacaine. Concomitant use of bupivacaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Bupivacaine; Lidocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as bupivacaine. Concomitant use of bupivacaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations. (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Bupivacaine; Meloxicam: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as bupivacaine. Concomitant use of bupivacaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Butalbital; Acetaminophen: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Butalbital; Acetaminophen; Caffeine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Canagliflozin; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Cannabidiol: (Moderate) Consider a dose reduction of lamotrigine, as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased lamotrigine exposure is possible. Lamotrigine is a UGT2B7 substrate. In vitro data predicts inhibition of UGT2B7 by cannabidiol potentially resulting in clinically significant interactions.
Carbamazepine: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant carbamazepine use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and carbamazepine induces glucuronidation. During concurrent use of lamotrigine with carbamazepine, lamotrigine steady-state concentration decreased by approximately 40%. Lamotrigine may increase the concentration of the 10, 11-epoxide metabolite of carbamazepine; small studies have demonstrated mixed results when evaluating carbamazepine-epoxide concentrations in the presence of lamotrigine. Limited data suggest that there is a higher incidence of dizziness, diplopia, ataxia, and blurred vision in patients receiving lamotrigine with carbamazepine than in patients receiving lamotrigine with other AEDs; the mechanism of the interaction is not known.
Cenobamate: (Major) Increase the dosage of lamotrigine as needed when coadministered with cenobamate due to the potential for reduced efficacy of lamotrigine. Coadministration of cenobamate and lamotrigine is expected to decrease lamotrigine concentrations by 21% to 52%.
Chloroprocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as chloroprocaine. Concomitant use of chloroprocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Cimetidine: (Minor) Coadministration of cimetidine and lamotrigine may decrease cimetidine clearance, resulting in increased plasma concentrations and the potential for cimetidine-related adverse events. Lamotrigine is an inhibitor of renal tubular secretion via organic cationic transporter 2 (OCT2) proteins, and cimetidine is excreted via this route.
Class IA Antiarrhythmics: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Class IB Antiarrhythmics: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Class IC Antiarrhythmics: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IC antiarrhythmics. Concomitant use of class IC antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Clozapine: (Major) One report has described an interaction between lamotrigine and clozapine. A 3-fold increase in clozapine concentrations occurred in a patient after lamotrigine was added to the drug regimen. The patient experienced drowsiness and dizziness that were clinically significant. Measurement of clozapine plasma concentrations during the time of the interaction and after lamotrigine was discontinued indicated a probable interaction, although the mechanism of the interaction is not certain. Clozapine may interact with anticonvulsants in several ways; therefore concurrent use of clozapine in patients on antiepileptic medications is not recommended if seizures are not controlled. Clozapine lowers the seizure threshold in a dose-dependent manner and thus may induce seizures. Dosage adjustments of clozapine should be cautious.
Cocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as cocaine. Concomitant use of cocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of lamotrigine. To minimize potential for interactions, consider administering oral anticonvulsants such as lamotrigine at least 1 hour before or at least 4 hours after colesevelam.
Conjugated Estrogens: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Conjugated Estrogens; Bazedoxifene: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Conjugated Estrogens; Medroxyprogesterone: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Dapagliflozin; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Desmopressin: (Major) Caution is recommended if a drug that may increase the risk of water intoxication with hyponatremia, such as lamotrigine, is administered with desmopressin acetate. Two children with diabetes insipidus had decreasing desmopressin requirements with lamotrigine initiation.
Desogestrel; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Dextromethorphan; Quinidine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Dienogest; Estradiol valerate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Diethylstilbestrol, DES: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Disopyramide: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Dofetilide: (Major) Coadministration of lamotrigine and dofetilide is not recommended. Coadministration may decrease dofetilide clearance, resulting in increased plasma concentrations and the potential for serious adverse events, including QT prolongation and cardiac arrhythmias. Lamotrigine is an inhibitor of renal tubular secretion via organic cationic transporter 2 (OCT2) proteins, and dofetilide is excreted via this route.
Drospirenone: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Drospirenone; Estetrol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Drospirenone; Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Drospirenone; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis. (Minor) L-methylfolate concentrations may be reduced when administered concomitantly with lamotrigine. Patients should be monitored closely for decreased efficacy of L-methylfolate if these agents are used together.
Elagolix; Estradiol; Norethindrone acetate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Empagliflozin; Linagliptin; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Empagliflozin; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Ertugliflozin; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Eslicarbazepine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as eslicarbazepine. Concomitant use of eslicarbazepine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Esterified Estrogens: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Esterified Estrogens; Methyltestosterone: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Estradiol; Levonorgestrel: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Estradiol; Norethindrone: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Estradiol; Norgestimate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Estradiol; Progesterone: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Estrogens: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Estropipate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been

observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced.
Ethinyl Estradiol; Norelgestromin: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Ethinyl Estradiol; Norethindrone Acetate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Ethinyl Estradiol; Norgestrel: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Etonogestrel: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Etonogestrel; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Flecainide: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IC antiarrhythmics. Concomitant use of class IC antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Fluorouracil, 5-FU: (Moderate) Lamotrigine inhibits dihydrofolate reductase. Caution should be exercised when administering fluorouracil, 5-FU, which may inhibit this enzyme.
Fosphenytoin: (Moderate) A lamotirigine dosage increase may be necessary during coadministration of fosphenytoin and lamotrigine. When phenytoin or fosphenytoin is added to lamotrigine therapy, phenytoin decreases the steady state concentrations of lamotrigine by approximately 40 percent. If enzyme inducing antiepileptic drugs are discontinued, lamotrigine doses may need to be adjusted downward. Phenytoin can decrease lamotrigine half-life, presumably through induction of the hepatic enzyme uridine diphosphate glucuronyltransferase (UGT).
Glipizide; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Glyburide; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Hydroxychloroquine: (Moderate) Monitor for seizures during concomitant use of hydroxychloroquine and lamotrigine. Hydroxychloroquine can lower the seizure threshold and the activity of antiepileptics may be impaired during concomitant use.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant rifampin use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and rifampin induces glucuronidation. During concurrent use of lamotrigine with rifampin in 10 volunteers, rifampin (600 mg/day for 5 days) decreased the AUC of lamotrigine (25 mg single dose) by approximately 40%.
Isoniazid, INH; Rifampin: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant rifampin use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and rifampin induces glucuronidation. During concurrent use of lamotrigine with rifampin in 10 volunteers, rifampin (600 mg/day for 5 days) decreased the AUC of lamotrigine (25 mg single dose) by approximately 40%.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., lamotrigine), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Leuprolide; Norethindrone: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Levomefolate: (Minor) L-methylfolate concentrations may be reduced when administered concomitantly with lamotrigine. Patients should be monitored closely for decreased efficacy of L-methylfolate if these agents are used together.
Levonorgestrel: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Levonorgestrel; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Lidocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lidocaine; Epinephrine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lidocaine; Prilocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations. (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as prilocaine. Concomitant use of prilocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Linagliptin; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Lopinavir; Ritonavir: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant lopinavir; ritonavir use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and lopinavir; ritonavir induces glucuronidation. During concurrent use of lamotrigine with lopinavir; ritonavir in 18 healthy subjects, induction of glucuronidation by lopinavir (400 mg twice daily); ritonavir (100 mg twice daily) decreased lamotrigine AUC, Cmax, and half-life by approximately 50% to 55.4%.
Maprotiline: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Medroxyprogesterone: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors. Some, but not all anticonvulsants, induce CYP3A4 and may increase the metabolism of mefloquine. Use of enzyme-inducing anticonvulsants can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria.
Mepivacaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as mepivacaine. Concomitant use of mepivacaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Metformin; Repaglinide: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Metformin; Rosiglitazone: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Metformin; Saxagliptin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Metformin; Sitagliptin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Methotrexate: (Moderate) Monitor for increased methotrexate-related adverse reactions during concomitant lamotrigine use. Concomitant use may have additive antifolate effects. Methotrexate inhibits dihydrofolate reductase, and lamotrigine is a weak inhibitor of dihydrofolate reductase.
Methsuximide: (Major) Methsuximide may reduce serum concentrations of lamotrigine by up to 70%. Conversely, if methsuximide is discontinued, lamotrigine doses may need to be adjusted downward. The mechanism by which this interaction occurs has not been established.
Mexiletine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
Nirmatrelvir; Ritonavir: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant lopinavir; ritonavir use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and lopinavir; ritonavir induces glucuronidation. During concurrent use of lamotrigine with lopinavir; ritonavir in 18 healthy subjects, induction of glucuronidation by lopinavir (400 mg twice daily); ritonavir (100 mg twice daily) decreased lamotrigine AUC, Cmax, and half-life by approximately 50% to 55.4%.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Norethindrone: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Norethindrone; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Norgestimate; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Norgestrel: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Oxcarbazepine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as oxcarbazepine. Concomitant use of oxcarbazepine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Phenobarbital: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant phenobarbital use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and phenobarbital induces glucuronidation. During concurrent use of lamotrigine with phenobarbital, lamotrigine steady-state concentration decreased by approximately 40%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant phenobarbital use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and phenobarbital induces glucuronidation. During concurrent use of lamotrigine with phenobarbital, lamotrigine steady-state concentration decreased by approximately 40%.
Phentermine; Topiramate: (Moderate) Monitor for loss of topiramate efficacy and/or an increase in topiramate-related adverse events during coadministration. Coadministration has resulted in both a 13% decrease and 15% increase in topiramate concentrations.
Phenytoin: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant phenytoin use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and phenytoin induces glucuronidation. During concurrent use of lamotrigine with phenytoin, lamotrigine steady-state concentration decreased by approximately 40%.
Pioglitazone; Metformin: (Moderate) Concomitant administration of metformin and lamotrigine may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 substrate; lamotrigine is an OCT2 inhibitor that may decrease metformin elimination by blocking renal tubular secretion.
Prilocaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as prilocaine. Concomitant use of prilocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Prilocaine; Epinephrine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as prilocaine. Concomitant use of prilocaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Primidone: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant primidone use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and primidone induces glucuronidation. During concurrent use of lamotrigine with primidone, lamotrigine steady-state concentration decreased by approximately 40%.
Procainamide: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Progesterone: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Progestins: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Propafenone: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IC antiarrhythmics. Concomitant use of class IC antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Pyrimethamine: (Moderate) Lamotrigine inhibits dihydrofolate reductase. Caution should be exercised when administering pyrimethamine, which also inhibits this enzyme.
Quinidine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Relugolix; Estradiol; Norethindrone acetate: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Rifampin: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant rifampin use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and rifampin induces glucuronidation. During concurrent use of lamotrigine with rifampin in 10 volunteers, rifampin (600 mg/day for 5 days) decreased the AUC of lamotrigine (25 mg single dose) by approximately 40%.
Ritonavir: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant lopinavir; ritonavir use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and lopinavir; ritonavir induces glucuronidation. During concurrent use of lamotrigine with lopinavir; ritonavir in 18 healthy subjects, induction of glucuronidation by lopinavir (400 mg twice daily); ritonavir (100 mg twice daily) decreased lamotrigine AUC, Cmax, and half-life by approximately 50% to 55.4%.
Rufinamide: (Moderate) Shortening of the QT interval has occurred during treatment with rufinamide. Therefore, caution is advisable during co-administration with other drugs associated with QT-shortening including lamotrigine. In addition, a population pharmacokinetic analysis showed a 7% to 13% decrease in lamotrigine concentrations and no effect on rufinamide concentrations during concurrent use.
Segesterone Acetate; Ethinyl Estradiol: (Major) A lamotrigine maintenance dose increase of up to 2-fold may be required during concomitant use of estrogen hormones. Increase the dose no more rapidly than 50 to 100 mg/day every week based on clinical response. Coadministration of an oral contraceptive containing 30 mcg of ethinyl estradiol has been observed to decrease the AUC and Cmax of lamotrigine by 52% and 39%, respectively. During the oral contraceptive pill-free week, trough lamotrigine concentrations have been observed to increase an average of 2-fold which may transiently increase the risk for lamotrigine-related adverse effects. If lamotrigine-related adverse effects consistently occur during the pill-free week, the overall lamotrigine maintenance dose may need to be reduced. (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis.
Tetracaine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as tetracaine. Concomitant use of tetracaine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Topiramate: (Moderate) Monitor for loss of topiramate efficacy and/or an increase in topiramate-related adverse events during coadministration. Coadministration has resulted in both a 13% decrease and 15% increase in topiramate concentrations.
Tramadol; Acetaminophen: (Moderate) Monitor patients for possible loss of lamotrigine efficacy and seizure activity during coadministration with acetaminophen. Acetaminophen may induce glucuronidation pathways involved in lamotrigine metabolism. During a study among 12 healthy volunteers, concomitant administration of acetaminophen 4 g/day with lamotrigine at steady-state increased the formation clearance of lamotrigine glucuronide conjugates by 45%, decreased lamotrigine AUC by 20%, and reduced lamotrigine trough concentrations by 25%.
Tricyclic antidepressants: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as tricyclic antidepressants. Concomitant use of tricyclic antidepressants with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Valproic Acid, Divalproex Sodium: (Major) Coadministration of valproic acid with lamotrigine can decrease the elimination of lamotrigine. Valproic acid more than doubles the elimination half-life of lamotrigine in both pediatric and adult patients. In a steady-state study involving 10 healthy volunteers, the elimination half-life of lamotrigine increased from 26 to 70 hours with valproate coadministration (a 165% increase). The decrease in apparent clearance of lamotrigine may occur via inhibition of lamotrigine metabolism through competition for liver glucuronidation sites. Serious skin reactions (such as Stevens-Johnson Syndrome and toxic epidermal necrolysis) have been reported with concomitant lamotrigine and valproate administration. In any patient receiving valproic acid, lamotrigine must be initiated at a reduced dosage that is less than half the dose used in patients not receiving valproic acid. In controlled clinical trials, lamotrigine had no appreciable effect on plasma valproic acid concentrations when added to existing valproic acid therapies. If valproic acid therapy is discontinued, lamotrigine doses may need to be adjusted upward. The inhibitory effects of valproic acid on lamotrigine elimination may offset the actions of other anticonvulsants with known hepatic enzyme-inducing properties on lamotrigine clearance.
Zonisamide: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as zonisamide. Concomitant use of zonisamide with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.

How Supplied

Lamictal CD/Lamotrigine Oral Tab Chew: 5mg, 25mg
Lamictal ODT/Lamotrigine Oral Tab Orally Dis: 25mg, 50mg, 100mg, 200mg, 25-50mg, 25-50-100mg, 50-100mg
Lamictal XR/Lamotrigine Oral Tab ER: 25mg, 50mg, 100mg, 200mg, 250mg, 300mg, 25-50mg, 25-50-100mg, 50-100-200mg
Lamictal/Lamotrigine/Subvenite Oral Tab: 25mg, 100mg, 150mg, 200mg, 25-100mg

Maximum Dosage

Adults

In seizure disorders, individualize to the patient's age, weight, indication, concurrent medication, and clinical response. In bipolar disorder, maximum monotherapy dosage is 200 mg/day PO; 100 mg/day PO if taking valproate; 400 mg/day PO if taking enzyme-inducing drugs.

Elderly

Adolescents

In seizure disorders, individualize to the patient's age, weight, indication, concurrent medication, and clinical response. Safe and effective use in bipolar disorder has not been established.

Children

>= 2 years: In seizure disorders, individualize to the patient's age, weight, indication, concurrent medication, and clinical response. Safe and effective use in bipolar disorder has not been established. Safe and effective use of extended-release formulation has not been established. Guidelines: Children receiving valproate: 200 mg/day PO as adjunct treatment. Children receiving enzyme-inducing AEDs (e.g., carbamazepine, phenobarbital, phenytoin, primidone) WITHOUT valproate: 400 mg/day PO as adjunct treatment. Children receiving AEDs OTHER than carbamazepine, phenobarbital, phenytoin, primidone, or valproate: 300 mg/day PO as adjunct treatment.
< 2 years: Safety and efficacy have not been established.

Mechanism Of Action

Mechanism of Action: The exact mechanism of anticonvulsant activity is not known, but studies suggest lamotrigine may stabilize neuronal membranes by acting at voltage-sensitive sodium channels. The blocking of sodium channels can decrease the presynaptic release of glutamate and aspartate, resulting in decreased seizure frequency. This mechanism is similar to that of carbamazepine and phenytoin. Lamotrigine appears to have little or no effect on the release of GABA, dopamine, acetylcholine, or norepinephrine. Lamotrigine is also a weak dihydrofolate reductase inhibitor in vitro and in animal studies. In clinical studies, however, no effect of lamotrigine on folate concentrations has been noted, although it is possible that folate concentrations may decrease during gestation.

Pharmacokinetics

Lamotrigine is administered orally as conventional tablets, chewable tablets, orally disintegrating tablets (ODT), and extended-release tablets. The volume of distribution is independent of dose and duration of therapy. Distribution into the CNS is not known. Extensive placental transfer appears to occur. In 9 women, the maternal plasma concentrations immediately after delivery were similar to concentrations found in the umbilical cords. Further, lamotrigine is distributed into breast milk. Two to three weeks after delivery, the median milk:maternal plasma concentration ratio was 0.61 (range, 0.47 to 0.77); the median plasma concentration in the neonates was approximately 30% (range, 23% to 50%) of the mother's plasma concentrations. Protein binding is 55% at plasma concentrations up to 10 mcg/ml.

Lamotrigine has a negligible first-pass effect, and undergoes glucuronidation in the liver. Carbamazepine, phenytoin, phenobarbital, and primidone can decrease lamotrigine half-life, presumably through induction of the hepatic enzyme uridine diphosphate glucuronyltransferase (UGT). Valproic acid decreases lamotrigine clearance and more than doubles elimination half-life, whether given with or without the other antiepileptic drugs. After multiple dosing in normal adult volunteers receiving no other medications, lamotrigine may induce its own metabolism which may decrease the half-life by 25% and increase plasma clearance by 37%. The mean plasma half-life in adults is approximately 24 hours (range 14-59 hours). Overall, 70% of a dose is excreted by the kidneys, 75% to 90% as metabolites. Less than 10% of a dose is eliminated unchanged by the kidney.

Affected cytochrome P450 isoenzymes and drug transporters: UGT1A4, UGT2B7, and OCT2
Lamotrigine is predominately metabolized by glucuronic acid conjugation; hence, drugs that are known to inhibit or induce glucuronidation may alter its clearance. Carbamazepine, phenytoin, phenobarbital, and primidone can decrease lamotrigine half-life, presumably through induction of the hepatic enzyme uridine diphosphate glucuronyltransferase (UGT). In addition, lamotrigine is an inhibitor of renal tubular secretion via organic cationic transporter 2 (OCT2) proteins at potentially clinically relevant concentrations, and may increase plasma concentrations of agents substantially excreted by this route.

Oral Route

After oral administration, lamotrigine is rapidly and almost completely absorbed (98%). The relative bioavailability of the extended-release tablets is about 21% lower than immediate-release lamotrigine in patients receiving enzyme-inducing AEDs. In some patients, a reduction in exposure of up to 70% has been observed when switching from the immediate-release to the extended-release formulation. Food does not affect extent of absorption, but it can slightly slow the rate of absorption. All of the immediate-release oral formulations have a similar rate and extent of absorption. Peak plasma concentrations occur 1.4 to 2.3 hours after an oral dose of immediate-release lamotrigine in normal adult volunteers or in adult patients receiving enzyme-inducing anticonvulsants and up to 4.8 hours after an oral dose in patients on concomitant valproic acid. A second peak may be seen 4 to 6 hours after administration; this may suggest entero-hepatic circulation. The median peak plasma concentration occurs 4 to 6 hours after the administration of the extended-release formulation in patients taking carbamazepine, phenytoin, phenobarbital, or primidone, 9 to 11 hours after administration in patients taking valproic acid, and 6 to 10 hours after administration in patients taking other AEDs. The therapeutic range of lamotrigine has not been established; however, plasma concentrations associated with adult doses of 300 to 500 mg/day ranged from 2 to 5 mcg/mL. Plasma concentrations after the administration of extended-release lamotrigine are characterized by lower peaks, longer time to peaks, and lower peak-to-trough fluctuations compared to immediate-release lamotrigine; however, there are not significant changes in trough plasma concentrations between the two formulations.

Pregnancy And Lactation

Pregnancy

Physiological changes during pregnancy may affect lamotrigine concentrations and/or therapeutic effect. There have been reports of decreased lamotrigine concentrations during pregnancy and restoration of prepartum concentrations after delivery. Dosage adjustments may be necessary to maintain clinical response. Data from several pregnancy registries and epidemiological studies of pregnant women have not detected an increased risk for major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared to the general population. After first-trimester maternal exposure to lamotrigine monotherapy, the International Lamotrigine Pregnancy Registry reported major congenital malformations in 2.2% (95% CI: 1.6%, 3.1%) of 1,558 infants, and the EURAP (an international registry focused outside of North America) reported major birth defects in 2.9% (95% CI: 2.3%, 3.7%) of 2,514 infants. The North American Antiepileptic Drug (NAAED) Pregnancy Registry reported major congenital malformations in 2% of 1,562 infants exposed to lamotrigine monotherapy during the first trimester. The NAAED Pregnancy Registry observed a 3-fold increased risk of isolated oral clefts among 2,200 infants exposed to lamotrigine early in pregnancy compared to unexposed healthy controls; the risk of oral clefts was 3.2 per 1,000 (95% CI: 1.4, 6.3). An increased risk of oral clefts has not been observed in other large international pregnancy registries. An adjusted odds ratio of 1.45 (95% CI: 0.8, 2.63) for isolated oral clefts with lamotrigine exposure was reported from a case-control study based on 21 congenital anomaly registries covering over 10 million births in Europe. Meta-analyses have not demonstrated any increased risk of fetal death, stillbirths, preterm births, small for gestational age, or neurodevelopmental delays in infants born to mothers with lamotrigine exposure.[28451] Use lamotrigine cautiously in patients with folate deficiency. In vitro data reveal that lamotrigine inhibits dihydrofolate reductase, and animal data show that lamotrigine decreased fetal, placental, and maternal folate concentrations. Significant reductions in folate concentrations are associated with teratogenesis (e.g., neural tube defects). Sufficient dietary supplementation with folic acid is recommended during pregnancy to maintain normal folate concentrations. Guidelines for the management of epilepsy during pregnancy make general recommendations to optimize treatment prior to conception, which include using monotherapy during pregnancy if possible, choosing the most effective AED for seizure type and syndrome, using the lowest effective dose, and supplementing the pregnant mother with folate.[28451] [48875] [63108] There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to lamotrigine; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.[28451]