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Special Alerts
Antiepileptics: Increased Risk of Suicidal Behavior or Ideation - February, 2008
The U.S. Food and Drug Administration (FDA) is informing healthcare professionals of an increased risk of suicidality (suicidal behavior or ideation) observed from analysis of clinical studies using various antiepileptic medications compared to placebo. The analysis was performed on 199 placebo-controlled studies involving 43,892 patients (27,863 treated patients versus 16,029 placebo patients) aged ?5 years receiving one of the following 11 drugs: carbamazepine (Carbatrol®, Equetro™, Tegretol®, Tegretol® XR), felbamate (Felbatol®), gabapentin (Neurontin®), lamotrigine (Lamictal®), levetiracetam (Keppra®), oxcarbazepine (Trileptal®), pregabalin (Lyrica®), tiagabine (Gabitril®), topiramate (Topamax®), valproate (Depakote®, Depakote® ER, Depakene®, Depacon®), and zonisamide (Zonegran®). Studies examined medication efficacy in a variety of disorders, including epilepsy, psychiatric disorders (eg, depression, bipolar disorder), and other conditions (eg, migraine, neuropathic pain). According to the FDA, the results revealed a statistically significant increased risk of suicidality in 0.43% treated patients compared to 0.22% placebo patients, or an estimated 2.1 per 1000 (95% CI: 0.7, 4.2) more patients in the treated groups relative to placebo. This increased risk was reported anywhere from 1 week of therapy through 24 weeks. However, most trials were ?24 weeks duration and the risk of suicide extending beyond 24 weeks is currently unknown. The relative risk of suicidal behavior or ideation in the treated patients was higher for patients with epilepsy (RR=3.6) compared to patients treated for psychiatric (RR=1.6) or other conditions (RR=2.3). Overall, the incidence of suicidal behavior or ideation occurred consistently across all demographic subgroups and with each of the drugs studied. Of note, four patients receiving an antiepileptic committed suicide relative to none in the placebo groups.
Forthcoming product labeling changes are likely to extend to all antiepileptic drugs and not limited to the drugs used in the studies, pending discussions scheduled for the upcoming advisory committee meeting. Healthcare professionals and family members/caregivers are encouraged to monitor patients receiving any antiepileptic medication for signs/symptoms of suicidality (eg, anxiety, depression, behavior changes). Patients should not stop taking their antiepileptic therapy unless advised by a healthcare professional.
Additional information can be found at http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antiepileptic
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
LamoTRIgine may be confused with labetalol, Lamisil®, lamiVUDine, Lomotil®, ludiomil
Lamictal® may be confused with Lamisil®, Lomotil®, ludiomil
Pronunciation
(la MOE tri jeen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Adjunctive therapy in the treatment of generalized seizures of Lennox-Gastaut syndrome, primary generalized tonic-clonic seizures, and partial seizures in adults and children ?2 years of age; conversion to monotherapy in adults with partial seizures who are receiving treatment with valproic acid or a single enzyme-inducing antiepileptic drug (specifically carbamazepine, phenytoin, phenobarbital or primidone); maintenance treatment of bipolar I disorder
Pregnancy Risk Factor
C
Pregnancy Considerations
Lamotrigine has been found to decrease folate concentrations in animal studies. Teratogenic effects in animals were not observed. Lamotrigine crosses the human placenta and can be measured in the plasma of exposed newborns. Preliminary data from the North American Antiepileptic Drug Pregnancy Registry (NAAED) suggest an increased incidence of cleft lip and/or cleft palate following first trimester exposure. Healthcare providers may enroll patients in the Lamotrigine Pregnancy Registry by calling (800) 336-2176. Patients may enroll themselves in the NAAED registry by calling (888) 233-2334. Dose of lamotrigine may need adjustment during pregnancy to maintain clinical response; lamotrigine serum levels may decrease during pregnancy and return to prepartum levels following delivery. Monitor frequently during pregnancy, following delivery, and when adding or discontinuing combination hormonal contraceptives.
Lactation
Enters breast milk/not recommended (AAP rates “of concern”)
Breast-Feeding Considerations
Lamotrigine is found in breast milk. In one study, the relative dose to the infant was 9% (range 2% to 20%) of the weight-adjusted maternal dose. Lamotrigine was measurable in the plasma of nursing infants; adverse events were not observed.
Contraindications
Hypersensitivity to lamotrigine or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Skin rashes: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Blood dyscrasias: A spectrum of hematologic effects have been reported with use (eg, neutropenia, leukopenia, thrombocytopenia, pancytopenia, and anemias); patients with a previous history of adverse hematologic reaction to any drug may be at increased risk. Early detection of hematologic change is important; advise patients of early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy bruising, petechial or purpuric hemorrhage. May be associated with hypersensitivity syndrome.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Multiorgan hypersensitivity reactions: Potentially serious, sometimes fatal multiorgan hypersensitivity reactions have been reported with some antiepileptic drugs; monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems; gradual discontinuation and conversion to alternate therapy may be required.
• Skin rashes: [U.S. Boxed Warning]: Severe and potentially life-threatening skin rashes requiring hospitalization have been reported; risk may be increased by coadministration with valproic acid, higher than recommended starting doses, and rapid dose titration. The majority of cases occur in the first 8 weeks; however, isolated cases may occur after prolonged treatment; discontinue at first sign of rash unless rash is clearly not drug related.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with impaired cardiac function.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
• Hormonal contraceptives: May cause a decrease in lamotrigine levels requiring dose adjustment.
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Other warnings/precautions:
• Bipolar disorder use: Patients treated for bipolar disorder should be monitored closely for clinical worsening or suicidality; prescriptions should be written for the smallest quantity consistent with good patient care.
• Melanin binding: Binds to melanin and may accumulate in the eye and other melanin-rich tissues; the clinical significance of this is not known.
• Monotherapy: Safety and efficacy have not been established for use as initial monotherapy, conversion to monotherapy from antiepileptic drugs (AED) other than carbamazepine, phenytoin, phenobarbital, primidone or valproic acid or conversion to monotherapy from two or more AEDs.
• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Taper over at least 2 weeks if possible.
Adverse Reactions
Percentages reported in adults on monotherapy for epilepsy or bipolar disorder.
>10%: Gastrointestinal: Nausea (7% to 14%)
1% to 10%:
Cardiovascular: Chest pain (5%), peripheral edema (2% to 5%), edema (1% to 5%)
Central nervous system: Somnolence (9%), fatigue (8%), dizziness (7%), anxiety (5%), insomnia (5% to 10%), pain (5%), ataxia (2% to 5%), irritability (2% to 5%), suicidal ideation (2% to 5%), agitation (1% to 5%), amnesia (1% to 5%), depression (1% to 5%), dream abnormality (1% to 5%), emotional lability (1% to 5%), fever (1% to 5%), hypoesthesia (1% to 5%), migraine (1% to 5%), thought abnormality (1% to 5%), confusion (1%)
Dermatologic: Rash (nonserious: 7%), dermatitis (2% to 5%), dry skin (2% to 5%)
Endocrine & metabolic: Dysmenorrhea (5%), libido increased (2% to 5%)
Gastrointestinal: Vomiting (5% to 9%), dyspepsia (7%), abdominal pain (6%), xerostomia (2% to 6%), constipation (5%), weight loss (5%), anorexia (2% to 5%), peptic ulcer (2% to 5%), rectal hemorrhage (2% to 5%), flatulence (1% to 5%), weight gain (1% to 5%)
Genitourinary: Urinary frequency (1% to 5%)
Neuromuscular & skeletal: Back pain (8%), coordination abnormal (7%), weakness (2% to 5%), arthralgia (1% to 5%), myalgia (1% to 5%), neck pain (1% to 5%), paresthesia (1%)
Ocular: Nystagmus (2% to 5%), vision abnormal (2% to 5%), amblyopia (1%)
Respiratory: Rhinitis (7%), cough (5%), pharyngitis (5%), bronchitis (2% to 5%), dyspnea (2% to 5%), epistaxis (2% to 5%), sinusitis (1% to 5%)
Miscellaneous: Infection (5%), diaphoresis (2% to 5%), reflexes increased/decreased (2% to 5%), dyspraxia (1% to 5%)
<1%: Any indication (limited to important or life-threatening): Accommodation abnormality, acne, alcohol intolerance, allergic reaction, alopecia, anemia, angina, angioedema, aphasia, appetite increased, arthritis, atrial fibrillation, breast pain, bruising, cerebellar syndrome, cerebral sinus thrombosis, cerebrovascular accident, chills, choreoathetosis, CNS depression/stimulation, conjunctivitis, deafness, deep thrombophlebitis, delirium, delusions, dermatitis (exfoliative, fungal), dry eyes, dysphagia, dysphoria, dystonia, ear pain, ECG abnormality, ejaculation abnormal, eructation, euphoria, extrapyramidal syndrome, faintness, flushing, gastritis, gingivitis, goiter, halitosis, hallucinations, hematuria, hemiplegia, hemorrhage, hiccup, hirsutism, hot flashes, hyperalgesia, hyperglycemia, hypertension, hyperventilation, hypokinesia, hypothyroidism, hypotonia, impotence, kidney failure (acute), leg cramps, leukopenia, liver function tests abnormal, maculopapular rash, malaise, menorrhagia, MI, mouth ulceration, movement disorder, muscle spasm, myasthenia, neuralgia, neurosis, palpitation, paralysis, peripheral neuritis, photophobia, polyuria, postural hypotension, salivation increased, skin discoloration, Stevens-Johnson syndrome, suicide, syncope, tachycardia, taste loss/perversion, thrombocytopenia, tinnitus, tongue edema, twitching, urinary incontinence, urticaria, vasodilation, yawn
Also observed: Rash requiring hospitalization: Children <16 years 0.8% (epilepsy adjunctive therapy); Adults 0.3% (epilepsy adjunctive therapy), 0.13% (epilepsy monotherapy), 0.8% (bipolar disorder, monotherapy)
Postmarketing and/or case reports (any indication): Agranulocytosis, aplastic anemia, apnea, disseminated intravascular coagulation, esophagitis, hemolytic anemia, hypersensitivity reactions, lupus-like reaction, multiorgan failure, neutropenia, pancreatitis, pancytopenia, parkinsonian exacerbation, progressive immunosuppression, red cell aplasia, rhabdomyolysis, tic, toxic epidermal necrolysis, vasculitis
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Barbiturates: May increase the metabolism of LamoTRIgine. Risk D: Consider therapy modification
CarBAMazepine: LamoTRIgine may enhance the adverse/toxic effect of CarBAMazepine. CarBAMazepine may increase the metabolism of LamoTRIgine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Desmopressin: LamoTRIgine may enhance the adverse/toxic effect of Desmopressin. LamoTRIgine may enhance the therapeutic effect of Desmopressin. Risk C: Monitor therapy
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated in persons with a history of convulsions. If anticonvulsant is being used for another indication monitor response to treatment closely, as concurrent mefloquine may decrease response to treatment. Risk D: Consider therapy modification
OLANZapine: LamoTRIgine may enhance the sedative effect of OLANZapine. Risk C: Monitor therapy
Oral Contraceptive (Estrogens): May decrease the serum concentration of LamoTRIgine. Risk D: Consider therapy modification
Phenytoin: May increase the metabolism of LamoTRIgine. Risk D: Consider therapy modification
Primidone: May increase the metabolism of LamoTRIgine. Risk D: Consider therapy modification
Rifampin: May increase the metabolism of LamoTRIgine. Risk C: Monitor therapy
Ritonavir: May decrease the serum concentration of LamoTRIgine. Risk D: Consider therapy modification
Valproic Acid: May enhance the adverse/toxic effect of LamoTRIgine. Valproic Acid may increase the serum concentration of LamoTRIgine. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Has no effect on absorption.
Herb/Nutraceutical: Avoid evening primrose (seizure threshold decreased).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Mechanism of Action
A triazine derivative which inhibits release of glutamate (an excitatory amino acid) and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membranes. Lamotrigine has weak inhibitory effect on the 5-HT3 receptor; in vitro inhibits dihydrofolate reductase.
Pharmacodynamics/Kinetics
Absorption: Rapid and complete
Distribution: Vd: ~1 L/kg
Protein binding: 55%
Metabolism: Hepatic and renal; metabolized by glucuronic acid conjugation to inactive metabolites
Bioavailability: 98%
Half-life elimination: Adults: 25-33 hours
Concomitant valproic acid therapy: 59-70 hours
Concomitant phenytoin or carbamazepine therapy: 13-14 hours
Chronic renal failure: 43 hours
Hemodialysis: 13 hours during dialysis; 57 hours between dialysis
Hepatic impairment: 26-148 hours
Time to peak, plasma: 1-5 hours
Excretion: Urine (94%, ~90% as glucuronide conjugates and ~10% unchanged); feces (2%)
Dosage
Note: Only whole tablets should be used for dosing, round calculated dose down to the nearest whole tablet. Enzyme-inducing regimens specifically refer to those containing carbamazepine, phenytoin, phenobarbital, or primidone. Oral:
Children 2-12 years: Lennox-Gastaut (adjunctive), primary generalized tonic-clonic seizures (adjunctive), or partial seizures (adjunctive): Note: Children <30 kg will likely require maintenance doses to be increased as much as 50% based on clinical response regardless of regimen below:
Initial: 0.3 mg/kg/day in 1-2 divided doses for weeks 1 and 2, then increase to 0.6 mg/kg/day in 1-2 divided doses for weeks 3 and 4. Maintenance: Titrate dose to effect; after week 4, increase daily dose every 1-2 weeks by 0.6 mg/kg/day; usual maintenance: 4.5-7.5 mg/kg/day in 2 divided doses; maximum: 300 mg/day in 2 divided doses
Adjustment for AED regimens containing valproic acid (see "Note"): Initial: 0.15 mg/kg/day in 1-2 divided doses for weeks 1 and 2, then increase to 0.3 mg/kg/day in 1-2 divided doses for weeks 3 and 4. Maintenance: Titrate dose to effect; after week 4, increase daily dose every 1-2 weeks by 0.3 mg/kg/day; usual maintenance: 1-5 mg/kg/day in 2 divided doses; maximum: 200 mg/day in 1-2 divided doses
Note: For patients >6.7 kg and <14 kg, initial dosing should be 2 mg every other day for first 2 weeks, then increased to 2 mg daily for weeks 3-4. For patients taking lamotrigine with valproic acid alone, the usual maintenance dose is 1-3 mg/kg/day in 2 divided doses
Adjustment for enzyme-inducing AED regimens without valproic acid: Initial: 0.6 mg/kg/day in 2 divided doses for weeks 1 and 2, then increase to 1.2 mg/kg/day in 2 divided doses for weeks 3 and 4. Maintenance: Titrate dose to effect; after week 4, increase daily dose every 1-2 weeks by 1.2 mg/kg/day; usual maintenance: 5-15 mg/kg/day in 2 divided doses; maximum: 400 mg/day in 2 divided doses
Children >12 years: Lennox-Gastaut (adjunctive), primary generalized tonic-clonic seizures (adjunctive), or partial seizures (adjunctive): Refer to adult dosing.
Children ?16 years: Conversion from adjunctive therapy with valproic acid or a single enzyme-inducing AED regimen to monotherapy with lamotrigine: Refer to adult dosing.
Adults:
Lennox-Gastaut (adjunctive), primary generalized tonic-clonic seizures (adjunctive) or partial seizures (adjunctive): Initial: 25 mg/day for weeks 1 and 2, then increase to 50 mg/day for weeks 3 and 4. Maintenance: Titrate dose to effect; after week 4 increase daily dose every 1-2 weeks by 50 mg/day; usual maintenance: 225-375 mg/day in 2 divided doses
Adjustment for AED regimens containing valproic acid (see "Note"): Initial: 25 mg every other day for weeks 1 and 2, then increase to 25 mg every day for weeks 3 and 4. Maintenance: Titrate dose to effect; after week 4 increase daily dose every 1-2 weeks by 25-50 mg/day; usual maintenance: 100-400 mg/day in 1 or 2 divided doses
Note: For patients taking lamotrigine with valproic acid alone, the usual maintenance dose is 100-200 mg/day
Adjustment for enzyme-inducing AED regimens without valproic acid: Initial: 50 mg/day for weeks 1 and 2, then increase to 100 mg/day in 2 divided doses for weeks 3 and 4. Maintenance: titrate dose to effect; after week 4 increase daily dose every 1-2 weeks by 100 mg/day; usual maintenance: 300-500 mg/day in 2 divided doses. Doses as high as 700 mg/day have been used, though additional benefit has not been established.
Conversion to monotherapy with lamotrigine:
Conversion from adjunctive therapy with valproic acid: Initiate and titrate as per recommendations to a lamotrigine dose of 200 mg/day. Then taper valproic acid dose in decrements of not >500 mg/day at intervals of 1 week (or longer) to a valproic acid dosage of 500 mg/day; this dosage should be maintained for 1 week. The lamotrigine dosage should then be increased to 300 mg/day while valproic acid is decreased to 250 mg/day; this dosage should be maintained for 1 week. Valproic acid may then be discontinued, while the lamotrigine dose is increased by 100 mg/day at weekly intervals to achieve a lamotrigine maintenance dose of 500 mg/day.
Conversion from adjunctive therapy with carbamazepine, phenytoin, phenobarbital, or primidone: Initiate and titrate as per recommendations to a lamotrigine dose of 500 mg/day. Concomitant enzyme-inducing AED should then be withdrawn by 20% decrements each week over a 4-week period. Patients should be monitored for rash.
Conversion from adjunctive therapy with AED other than carbamazepine, phenytoin, phenobarbital, primidone or valproic acid: No specific guidelines available
Bipolar disorder:
Initial: 25 mg/day for weeks 1 and 2, then increase to 50 mg/day for weeks 3 and 4, then increase to 100 mg/day for week 5; maintenance: increase dose to 200 mg/day beginning week 6
Adjustment for regimens containing valproic acid: Initial: 25 mg every other day for weeks 1 and 2, then increase to 25 mg every day for weeks 3 and 4, then increase to 50 mg/day for week 5; maintenance: 100 mg/day beginning week 6
Adjustment for enzyme-inducing regimens without valproic acid: Initial: 50 mg/day for weeks 1 and 2, then increase to 100 mg/day in divided doses for weeks 3 and 4, then increase to 200 mg/day in divided doses for week 5, then increase to 300 mg/day in divided dose for week 6; maintenance: 400 mg/day in divided doses beginning week 7
Adjustment following discontinuation of psychotropic medication:
Discontinuing valproic acid with current dose of lamotrigine 100 mg/day: 150 mg/day for week 1, then increase to 200 mg/day beginning week 2
Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or rifampin with current dose of lamotrigine 400 mg/day: 400 mg/day for week 1, then decrease to 300 mg/day for week 2, then decrease to 200 mg/day beginning week 3
Discontinuing therapy: Children and Adults: Decrease dose by ~50% per week, over at least 2 weeks unless safety concerns require a more rapid withdrawal. Discontinuing carbamazepine, phenytoin, phenobarbital, or primidone should prolong the half-life of lamotrigine; discontinuing valproic acid should shorten the half-life of lamotrigine
Restarting therapy after discontinuation: If lamotrigine has been withheld for >5 half-lives, consider restarting according to initial dosing recommendations.
Dosage adjustment with combination hormonal contraceptives: Follow initial dosing guidelines, maintenance dose should be adjusted as follows: Patients taking carbamazepine, phenytoin, phenobarbital, primidone or rifampin: No dosing adjustment required
Patients not taking carbamazepine, phenytoin, phenobarbital, primidone or rifampin: Maintenance dose may need increased by twofold over target dose. If already taking a stable dose of lamotrigine and starting contraceptive, maintenance dose may need increased by twofold. Dose increases should start when contraceptive is started and titrated to clinical response increasing no more rapidly than 50-100 mg/day every week. Gradual increases of lamotrigine plasma levels may occur during the inactive “pill-free” week and will be greater when dose increases are made the week before. If increased adverse events consistently occur during “pill-free” week, overall dose adjustments may be required. When discontinuing combination hormonal contraceptive, dose of lamotrigine may need decreased by as much as 50%; do not decrease by more than 25% of total daily dose over a 2-week period unless clinical response or plasma levels indicate otherwise. Dose adjustments during “pill-free” week are not recommended.
Dosage adjustment in renal impairment: Decreased dosage may be effective in patients with significant renal impairment; use with caution
Dosage adjustment in hepatic impairment:
Moderate-to-severe impairment without ascites: Decrease initial, escalation, and maintenance doses by ~25%
Moderate-to-severe impairment with ascites: Decrease initial, escalation, and maintenance doses by ~50%
Administration: Oral
Doses should be rounded down to the nearest whole tablet. Dispersible tablets may be chewed, dispersed in water or diluted fruit juice, or swallowed whole. To disperse tablets, add to a small amount of liquid (just enough to cover tablet); let sit ~1 minute until dispersed; swirl solution and consume immediately. Do not administer partial amounts of liquid. If tablets are chewed, a small amount of water or diluted fruit juice should be used to aid in swallowing.
Monitoring Parameters
Seizure, frequency and duration, serum levels of concurrent anticonvulsants, hypersensitivity reactions, especially rash
Reference Range
A therapeutic serum concentration range has not been established for lamotrigine. Dosing should be based on therapeutic response. Lamotrigine plasma concentrations of 0.25-29.1 mcg/mL have been reported in the literature.
Dietary Considerations
Take without regard to meals; drug may cause GI upset.
Patient Education
Take exactly as directed; do not increase dose or frequency or discontinue without consulting prescriber. Only whole tablets should be used for dosing, rounded down to the nearest whole tablet. When having the prescription refilled, contact the prescriber if the medicine looks different or the label name has changed. While using this medication, do not use alcohol and other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience drowsiness, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or nausea, vomiting, loss of appetite, heartburn, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Women who start or stop oral contraceptives should notify their prescriber. Wear identification of epileptic status and medications. Report CNS changes, mentation changes, suicidal ideation, depression, or changes in cognition; persistent GI symptoms (cramping, constipation, vomiting, anorexia); swelling of face, lips, or tongue; easy bruising or bleeding (mouth, urine, stool); vision changes; worsening of seizure activity, or loss of seizure control. A skin rash may indicate a serious medical problem; contact prescriber immediately if rash noted. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Geriatric Considerations
No pharmacokinetic differences noted between young adults and the elderly. Use with caution in the elderly with significant renal decline.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause sedation
Mental Health: Effects on Psychiatric Treatment
Valproic acid decreases clearance of lamotrigine; carbamazepine may decrease effects of lamotrigine
Mental Health: Comment
Lamotrigine is useful for the maintenance treatment of bipolar disorder. Best efficacy appears to be in the prophylaxis of depressive episodes. This medication requires a slow titration process. If patient is receiving valproic acid and/or carbamazepine, a dosage adjustment is necessary (see Dosage).
Potentially life-threatening skin rashes have been reported. These appear to be more frequent in pediatric patients and is associated with high serum levels, use of higher than recommended starting dose, and rapid dose titration. The majority of cases occur within the first 8 weeks of treatment. The combination use with valproate may increase this risk. Discontinue if rash develops.
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor therapeutic effectiveness, laboratory values, and adverse reactions at beginning of therapy and periodically with long-term use. Monitor for skin rash. Discontinue at the first sign of rash, unless clearly not drug related. Taper dosage slowly when discontinuing. Observe and teach seizure/safety precautions. Use caution in writing and/or interpreting prescriptions/orders. Confusion between Lamictal® (lamotrigine) and Lamisil® (terbinafine) has occurred. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 25 mg, 100 mg, 150 mg, 200 mg
Lamictal®: 25 mg, 100 mg, 150 mg, 200 mg
Tablet, combination package [each unit-dose starter kit contains]:
Lamictal® (blue kit; for patients taking valproic acid):
Tablet: Lamotrigine 25 mg (35s)
Lamictal® (green kit; for patients taking carbamazepine, phenytoin, phenobarbital, primidone, or rifampin and not taking valproic acid):
Tablet: Lamotrigine 25 mg (84s)
Tablet: Lamotrigine 100 mg (14s)
Lamictal® (orange kit; for patients not taking carbamazepine, phenytoin, phenobarbital, primidone, rifampin, or valproic acid):
Tablet: Lamotrigine 25 mg (42s)
Tablet: Lamotrigine 100 mg (7s)
Tablet, dispersible/chewable: 5 mg, 25 mg
Lamictal®: 2 mg, 5 mg, 25 mg [black currant flavor]
Pricing: U.S. (www.drugstore.com)
Tablets (Lamictal)
25 mg (60): $244.97
100 mg (60): $279.97
150 mg (60): $301.54
200 mg (60): $332.06
Tablets (Lamotrigine)
25 mg (100): $385.97
100 mg (100): $400.00
150 mg (60): $296.82
200 mg (60): $323.14
Extemporaneously Prepared
A 1 mg/mL oral suspension may be compounded as follows: Crush one 100 mg tablet and reduce to a fine powder. Add small amount of Ora-Sweet® or Ora-Plus® and mix to uniform paste. Transfer to graduate and qs to 100 mL. Shake well before using and refrigerate. Suspension is stable for 91 days.
Nahata M, Morosco R, Hipple T. “Stability of Lamotrigine in Two Extemporaneously Prepared Oral Suspensions at 4 and 25°C,” Am J Health Syst Pharm, 1999, 56:240-2.
References
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Besag FM, Wallace SJ, Dulac O, et al, “Lamotrigine for the Treatment of Epilepsy in Childhood,” J Pediatr, 1995, 127(6):991-7.
Brodie MJ, “Lamotrigine,” Lancet, 1992, 339(8806):1397-400.
Burstein AH, “Lamotrigine,” Pharmacotherapy, 1995, 15(2):129-43.
Calabrese JR, Suppes T, Bowden CL, et al, “A Double-Blind, Placebo-Controlled, Prophylaxis Study of Lamotrigine in Rapid-Cycling Bipolar Disorder,” J Clin Psychiatry, 2000, 61(11):841-50.
de Haan GJ, Edelbroek P, Segers J, et al, “Gestation-Induced Changes in Lamotrigine Pharmacokinetics: A monotherapy Study,” Neurology, 2004, 63(3):571-3.
Dooley J, Camfield P, Gordon K, et al, “Lamotrigine-Induced Rash in Children,” Neurology, 1996, 46(1):240-2.
Fitton A, and Goa KL, “Lamotrigine: An Update of its Pharmacology and Therapeutic Use in Epilepsy,” Drugs, 1995, 50(4):691-713.
Garnett WR and Pellock JM, “Focus on Lamotrigine: A New Antiepileptic Drug for Patients With Partial Seizures,” Hosp Formul, 1994, 29:806-12.
Gilman JT, “Lamotrigine: An Antiepileptic Agent for the Treatment of Partial Seizures,” Ann Pharmacother, 1995, 29(2):144-51.
Goa KL, Ross SR, and Chrisp P, “Lamotrigine: A Review of Its Pharmacological Properties and Clinical Efficacy in Epilepsy,” Drugs, 1993, 46(1):152-76.
Harchelroad F, Lang D, and Valeriano J, “Lamotrigine Overdose,” Vet Hum Toxicol, 1994, 36:372.
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International Brand Names
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Last full review/revision September 2008
Content last modified September 2008
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