Lamictal Information
Lamictal (Lamotrigine) Indications And Usage
Adjunctive Therapy:
Monotherapy:
Safety and effectiveness of Lamictal (Lamotrigine) have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.
Lamictal (Lamotrigine) is indicated for the maintenance treatment of Bipolar I Disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in adults (≥18 years of age) treated for acute mood episodes with standard therapy. The effectiveness of Lamictal (Lamotrigine) in the acute treatment of mood episodes has not been established.
The effectiveness of Lamictal (Lamotrigine) as maintenance treatment was established in 2 placebo-controlled trials in patients with Bipolar I Disorder as defined by DSM-IV . The physician who elects to prescribe Lamictal (Lamotrigine) for periods extending beyond 16 weeks should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
Lamictal (Lamotrigine) Dosage And Administration
The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation of Lamictal (Lamotrigine) is exceeded and in patients with a history of allergy or rash to other AEDs.
Lamictal (Lamotrigine) Starter Kits and Lamictal (Lamotrigine) ODT Patient Titration Kits provide Lamictal (Lamotrigine) at doses consistent with the recommended titration schedule for the first 5 weeks of treatment, based upon concomitant medications, for patients with epilepsy (>12 years of age) and Bipolar I Disorder (≥18 years of age) and are intended to help reduce the potential for rash. The use of Lamictal (Lamotrigine) Starter Kits and Lamictal (Lamotrigine) ODT Patient Titration Kits is recommended for appropriate patients who are starting or restarting Lamictal (Lamotrigine) .
It is recommended that Lamictal (Lamotrigine) not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine, unless the potential benefits clearly outweigh the risks. If the decision is made to restart a patient who has discontinued lamotrigine, the need to restart with the initial dosing recommendations should be assessed. The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations. If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed. The half-life of lamotrigine is affected by other concomitant medications
Adjustments to the Maintenance Dose of Lamictal (Lamotrigine) In Women Taking Estrogen-Containing Oral Contraceptives:
Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy:
If a decision is made to discontinue therapy with Lamictal (Lamotrigine) , a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal
Discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation, should prolong the half-life of lamotrigine; discontinuing valproate should shorten the half-life of lamotrigine.
This section provides specific dosing recommendations for patients greater than 12 years of age and patients 2 to 12 years of age. Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AED or other concomitant medications (Table 1 for patients greater than 12 years of age and Table 2 for patients 2 to 12 years of age). A weight-based dosing guide for patients 2 to 12 years of age on concomitant valproate is provided in Table 3.
Patients Over 12 Years of Age:
a
[see Drug Interactions (7), Clinical Pharmacology (12.3)]
b
Patients 2 to 12 Years of Age:
Smaller starting doses and slower dose escalations than those used in clinical trials are recommended because of the suggestion that the risk of rash may be decreased by smaller starting doses and slower dose escalations. Therefore, maintenance doses will take longer to reach in clinical practice than in clinical trials. It may take several weeks to months to achieve an individualized maintenance dose. Maintenance doses in patients weighing less than 30 kg, regardless of age or concomitant AED, may need to be increased as much as 50%, based on clinical response.
Note: Only whole tablets should be used for dosing.
a
[see Drug Interactions (7), Clinical Pharmacology (12.3)].
b
The usual maintenance doses identified in Tables 1 and 2 are derived from dosing regimens employed in the placebo-controlled adjunctive studies in which the efficacy of Lamictal (Lamotrigine) was established. In patients receiving multidrug regimens employing carbamazepine, phenytoin, phenobarbital, or primidone , maintenance doses of adjunctive Lamictal (Lamotrigine) as high as 700 mg/day have been used. In patients receiving , maintenance doses of adjunctive Lamictal (Lamotrigine) as high as 200 mg/day have been used. The advantage of using doses above those recommended in Tables 1 through 4 has not been established in controlled trials.
The goal of the transition regimen is to effect the conversion to monotherapy with Lamictal (Lamotrigine) under conditions that ensure adequate seizure control while mitigating the risk of serious rash associated with the rapid titration of Lamictal (Lamotrigine) .
The recommended maintenance dose of Lamictal (Lamotrigine) as monotherapy is 500 mg/day given in 2 divided doses.
To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of Lamictal (Lamotrigine) should not be exceeded .
Conversion From Adjunctive Therapy With AEDs Other Than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy With Lamictal (Lamotrigine) :
The goal of maintenance treatment with Lamictal (Lamotrigine) is to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. The target dose of Lamictal (Lamotrigine) is 200 mg/day (100 mg/day in patients taking valproate, which decreases the apparent clearance of lamotrigine, and 400 mg/day in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that increase the apparent clearance of lamotrigine). In the clinical trials, doses up to 400 mg/day as monotherapy were evaluated; however, no additional benefit was seen at 400 mg/day compared with 200 mg/day. Accordingly, doses above 200 mg/day are not recommended. Treatment with Lamictal (Lamotrigine) is introduced, based on concurrent medications, according to the regimen outlined in Table 5. If other psychotropic medications are withdrawn following stabilization, the dose of Lamictal (Lamotrigine) should be adjusted. For patients discontinuing valproate, the dose of Lamictal (Lamotrigine) should be doubled over a 2-week period in equal weekly increments (see Table 6). For patients discontinuing carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation, the dose of Lamictal (Lamotrigine) should remain constant for the first week and then should be decreased by half over a 2-week period in equal weekly decrements (see Table 6). The dose of Lamictal (Lamotrigine) may then be further adjusted to the target dose (200 mg) as clinically indicated.
If other drugs are subsequently introduced, the dose of Lamictal (Lamotrigine) may need to be adjusted. In particular, the introduction of valproate requires reduction in the dose of Lamictal (Lamotrigine)
To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of Lamictal (Lamotrigine) should not be exceeded .
a
[see Drug Interactions (7), Clinical Pharmacology (12.3)]
b
a
[see Drug Interactions (7), Clinical Pharmacology (12.3)]
b
The benefit of continuing treatment in patients who had been stabilized in an 8- to 16-week open-label phase with Lamictal (Lamotrigine) was established in 2 randomized, placebo-controlled clinical maintenance trials . However, the optimal duration of treatment with Lamictal (Lamotrigine) has not been established. Thus, patients should be periodically reassessed to determine the need for maintenance treatment.
Lamictal (Lamotrigine) Chewable Dispersible Tablets may be swallowed whole, chewed, or dispersed in water or diluted fruit juice. If the tablets are chewed, consume a small amount of water or diluted fruit juice to aid in swallowing.
To disperse Lamictal (Lamotrigine) Chewable Dispersible Tablets, add the tablets to a small amount of liquid (1 teaspoon, or enough to cover the medication). Approximately 1 minute later, when the tablets are completely dispersed, swirl the solution and consume the entire quantity immediately.
Lamictal (Lamotrigine) ODT Orally Disintegrating Tablets should be placed onto the tongue and moved around in the mouth. The tablet will disintegrate rapidly, can be swallowed with or without water, and can be taken with or without food.
Lamictal (Lamotrigine) Dosage Forms And Strengths
25 mg, white, scored, shield-shaped tablets debossed with “Lamictal (Lamotrigine) ” and “25”
100 mg, peach, scored, shield-shaped tablets debossed with "Lamictal (Lamotrigine) " and "100"
150 mg, cream, scored, shield-shaped tablets debossed with "Lamictal (Lamotrigine) " and "150"
200 mg, blue, scored, shield-shaped tablets debossed with "Lamictal (Lamotrigine) " and "200"
2 mg, white to off-white, round tablets debossed with “LTG” over “2”
5 mg, white to off-white, caplet-shaped tablets debossed with “GX CL2”
25 mg, white, super elliptical-shaped tablets debossed with “GX CL5”
25 mg, white to off-white, round, flat-faced, radius edge, tablets debossed with “LMT” on one side and “25” on the other side.
50 mg, white to off-white, round, flat-faced, radius edge, tablets debossed with “LMT” on one side and “50” on the other side.
100 mg, white to off-white, round, flat-faced, radius edge, tablets debossed with “Lamictal (Lamotrigine) ” on one side and “100” on the other side.
200 mg, white to off-white, round, flat-faced, radius edge, tablets debossed with “Lamictal (Lamotrigine) ” on one side and “200” on the other side.
Lamictal (Lamotrigine) Contraindications
Lamictal (Lamotrigine) is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients .
Lamictal (Lamotrigine) Warnings And Precautions
Pediatric Population:
There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in pediatric patients. In pediatric patients who used valproate concomitantly, 1.2% (6 of 482) experienced a serious rash compared with 0.6% (6 of 952) patients not taking valproate.
Adult Population:
Among the rashes leading to hospitalization were Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, and a rash associated with a variable number of the following systemic manifestations: fever, lymphadenopathy, facial swelling, and hematologic and hepatologic abnormalities.
There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in adults. Specifically, of 584 patients administered Lamictal (Lamotrigine) with valproate in epilepsy clinical trials, 6 (1%) were hospitalized in association with rash; in contrast, 4 (0.16%) of 2,398 clinical trial patients and volunteers administered Lamictal (Lamotrigine) in the absence of valproate were hospitalized.
Patients With History of Allergy or Rash to Other AEDs:
Hypersensitivity reactions, some fatal or life-threatening, have also occurred. Some of these reactions have included clinical features of multiorgan failure/dysfunction, including hepatic abnormalities and evidence of disseminated intravascular coagulation. It is important to note that 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, the patient should be evaluated immediately. Lamictal (Lamotrigine) should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Prior to initiation of treatment with Lamictal (Lamotrigine) , the patient should be instructed that a rash or other signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy) may herald a serious medical event and that the patient should report any such occurrence to a physician immediately.
Multiorgan failure, which in some cases has been fatal or irreversible, has been observed in patients receiving Lamictal (Lamotrigine) . Fatalities associated with multiorgan failure and various degrees of hepatic failure have been reported in 2 of 3,796 adult patients and 4 of 2,435 pediatric patients who received Lamictal (Lamotrigine) in epilepsy clinical trials. No such fatalities have been reported in bipolar patients in clinical trials. Rare fatalities from multiorgan failure have also been reported in compassionate plea and postmarketing use. The majority of these deaths occurred in association with other serious medical events, including status epilepticus and overwhelming sepsis, and hantavirus, making it difficult to identify the initial cause.
Additionally, 3 patients (a 45-year-old woman, a 3.5-year-old boy, and an 11-year-old girl) developed multiorgan dysfunction and disseminated intravascular coagulation 9 to 14 days after Lamictal (Lamotrigine) was added to their AED regimens. Rash and elevated transaminases were also present in all patients and rhabdomyolysis was noted in 2 patients. Both pediatric patients were receiving concomitant therapy with valproate, while the adult patient was being treated with carbamazepine and clonazepam. All patients subsequently recovered with supportive care after treatment with Lamictal (Lamotrigine) was discontinued.
Antiepileptic drugs (AEDs), including Lamictal (Lamotrigine) , increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately 1 case of suicidal thinking or behavior for every 530 patients treated. There were 4 suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number of events is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanism of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed.
Table 7 shows absolute and relative risk by indication for all evaluated AEDs.
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Lamictal (Lamotrigine) or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Acute Treatment of Mood Episodes:
Clinical Worsening and Suicide Risk Associated With Bipolar Disorder:
In addition, patients with a history of suicidal behavior or thoughts, those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults are at an increased risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behavior especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
Prescriptions for Lamictal (Lamotrigine) should be written for the smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose. Overdoses have been reported for Lamictal (Lamotrigine) , some of which have been fatal
During the premarketing development of Lamictal (Lamotrigine) , 20 sudden and unexplained deaths were recorded among a cohort of 4,700 patients with epilepsy (5,747 patient-years of exposure).
Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at night. This represents an incidence of 0.0035 deaths per patient-year. Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with epilepsy not receiving Lamictal (Lamotrigine) (ranging from 0.0005 for the general population of patients with epilepsy, to 0.004 for a recently studied clinical trial population similar to that in the clinical development program for Lamictal (Lamotrigine) , to 0.005 for patients with refractory epilepsy). Consequently, whether these figures are reassuring or suggest concern depends on the comparability of the populations reported upon to the cohort receiving Lamictal (Lamotrigine) and the accuracy of the estimates provided. Probably most reassuring is the similarity of estimated SUDEP rates in patients receiving Lamictal (Lamotrigine) and those receiving other AEDs, chemically unrelated to each other, that underwent clinical testing in similar populations. Importantly, that drug is chemically unrelated to Lamictal (Lamotrigine) . This evidence suggests, although it certainly does not prove, that the high SUDEP rates reflect population rates, not a drug effect.
Because lamotrigine binds to melanin, it could accumulate in melanin-rich tissues over time. This raises the possibility that lamotrigine may cause toxicity in these tissues after extended use. Although ophthalmological testing was performed in one controlled clinical trial, the testing was inadequate to exclude subtle effects or injury occurring after long-term exposure. Moreover, the capacity of available tests to detect potentially adverse consequences, if any, of lamotrigine's binding to melanin is unknown .
Accordingly, although there are no specific recommendations for periodic ophthalmological monitoring, prescribers should be aware of the possibility of long-term ophthalmologic effects.
Lamictal (Lamotrigine) Adverse Reactions
The following adverse reactions are described in more detail in the section of the label:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Lamictal (Lamotrigine) has been evaluated for safety in patients with epilepsy and in patients with Bipolar I Disorder. Adverse reactions reported for each of these patient populations are provided below. Excluded are adverse reactions considered too general to be informative and those not reasonably attributable to the use of the drug.
Approximately 11% of the 3,378 adult patients who received Lamictal (Lamotrigine) as adjunctive therapy in premarketing clinical trials discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were rash (3.0%), dizziness (2.8%), and headache (2.5%).
In a dose-response study in adults, the rate of discontinuation of Lamictal (Lamotrigine) for dizziness, ataxia, diplopia, blurred vision, nausea, and vomiting was dose-related.
Monotherapy in Adults With Epilepsy:
Approximately 10% of the 420 adult patients who received Lamictal (Lamotrigine) as monotherapy in premarketing clinical trials discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were rash (4.5%), headache (3.1%), and asthenia (2.4%).
Adjunctive Therapy in Pediatric Patients With Epilepsy:
In 339 patients 2 to 16 years of age with partial seizures or generalized seizures of Lennox-Gastaut syndrome, 4.2% of patients on Lamictal (Lamotrigine) and 2.9% of patients on placebo discontinued due to adverse reactions. The most commonly reported adverse reaction that led to discontinuation of Lamictal (Lamotrigine) was rash.
Approximately 11.5% of the 1,081 pediatric patients 2 to 16 years of age who received Lamictal (Lamotrigine) as adjunctive therapy in premarketing clinical trials discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were rash (4.4%), reaction aggravated (1.7%), and ataxia (0.6%).
Controlled Adjunctive Clinical Studies in Adults With Epilepsy:
a
In a randomized, parallel study comparing placebo and 300 and 500 mg/day of Lamictal (Lamotrigine) , some of the more common drug-related adverse reactions were dose-related (see Table 9).
a
P
b
P
The overall adverse reaction profile for Lamictal (Lamotrigine) was similar between females and males, and was independent of age. Because the largest non-Caucasian racial subgroup was only 6% of patients exposed to Lamictal (Lamotrigine) in placebo-controlled trials, there are insufficient data to support a statement regarding the distribution of adverse reaction reports by race. Generally, females receiving either Lamictal (Lamotrigine) as adjunctive therapy or placebo were more likely to report adverse reactions than males. The only adverse reaction for which the reports on Lamictal (Lamotrigine) were greater than 10% more frequent in females than males (without a corresponding difference by gender on placebo) was dizziness (difference = 16.5%). There was little difference between females and males in the rates of discontinuation of Lamictal (Lamotrigine) for individual adverse reactions.
Controlled Monotherapy Trial in Adults With Partial Seizures:
a
b
c
Adverse reactions that occurred with a frequency of less than 5% and greater than 2% of patients receiving Lamictal (Lamotrigine) and numerically more frequent than placebo were:
Table 11 lists adverse reactions that occurred in at least 2% of 339 pediatric patients with partial seizures or generalized seizures of Lennox-Gastaut syndrome, who received Lamictal (Lamotrigine) up to 15 mg/kg/day or a maximum of 750 mg/day. Reported adverse reactions were classified using COSTART terminology.
Bipolar Disorder:
During the monotherapy phase of the double-blind, placebo-controlled trials of 18 months’ duration, 13% of 227 patients who received Lamictal (Lamotrigine) (100 to 400 mg/day), 16% of 190 patients who received placebo, and 23% of 166 patients who received lithium discontinued therapy because of an adverse reaction. The adverse reactions which most commonly led to discontinuation of Lamictal (Lamotrigine) were rash (3%) and mania/hypomania/mixed mood adverse reactions (2%). Approximately 16% of 2,401 patients who received Lamictal (Lamotrigine) (50 to 500 mg/day) for Bipolar Disorder in premarketing trials discontinued therapy because of an adverse reaction; most commonly due to rash (5%) and mania/hypomania/mixed mood adverse reactions (2%).
The overall adverse reaction profile for Lamictal (Lamotrigine) was similar between females and males, between elderly and nonelderly patients, and among racial groups.
a
b
[see Warnings and Precautions (5.1)].
These adverse reactions were usually mild to moderate in intensity. Other reactions that occurred in 5% or more patients but equally or more frequently in the placebo group included: dizziness, mania, headache, infection, influenza, pain, accidental injury, diarrhea, and dyspepsia.
Adverse reactions that occurred with a frequency of less than 5% and greater than 1% of patients receiving Lamictal (Lamotrigine) and numerically more frequent than placebo were:
During the double-blind, placebo-controlled clinical trials in Bipolar I Disorder in which patients were converted to monotherapy with Lamictal (Lamotrigine) (100 to 400 mg/day) from other psychotropic medications and followed for up to 18 months, the rates of manic or hypomanic or mixed mood episodes reported as adverse reactions were 5% for patients treated with Lamictal (Lamotrigine) (n = 227), 4% for patients treated with lithium (n = 166), and 7% for patients treated with placebo (n = 190). In all bipolar controlled trials combined, adverse reactions of mania (including hypomania and mixed mood episodes) were reported in 5% of patients treated with Lamictal (Lamotrigine) (n = 956), 3% of patients treated with lithium (n = 280), and 4% of patients treated with placebo (n = 803).
Lamictal (Lamotrigine) has been administered to 6,694 individuals for whom complete adverse reaction data was captured during all clinical trials, only some of which were placebo controlled. During these trials, all adverse reactions were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse reactions, similar types of adverse reactions were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. The frequencies presented represent the proportion of the 6,694 individuals exposed to Lamictal (Lamotrigine) who experienced an event of the type cited on at least one occasion while receiving Lamictal (Lamotrigine) . All reported adverse reactions are included except those already listed in the previous tables or elsewhere in the labeling, those too general to be informative, and those not reasonably associated with the use of the drug.
Adverse reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: adverse reactions are defined as those occurring in at least 1/100 patients; adverse reactions are those occurring in 1/100 to 1/1,000 patients; adverse reactions are those occurring in fewer than 1/1,000 patients.
The following adverse events (not listed above in clinical trials or other sections of the prescribing information) have been identified during postapproval use of Lamictal (Lamotrigine) . Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Lamictal (Lamotrigine) Drug Interactions
Significant drug interactions with lamotrigine are summarized in Table 13. Additional details of these drug interaction studies are provided in the Clinical Pharmacology section .
↓= Decreased (induces lamotrigine glucuronidation).
↑= Increased (inhibits lamotrigine glucuronidation).
? = Conflicting data.
Lamictal (Lamotrigine) Use In Specific Populations
Teratogenic Effects:
2
A behavioral teratology study was conducted in rats dosed during the period of organogenesis. At day 21 postpartum, offspring of dams receiving 5 mg/kg/day or higher displayed a significantly longer latent period for open field exploration and a lower frequency of rearing. In a swimming maze test performed on days 39 to 44 postpartum, time to completion was increased in offspring of dams receiving 25 mg/kg/day. These doses represent 0.1 and 0.5 times the clinical dose on a mg/m basis, respectively.
Lamotrigine did not affect fertility, teratogenesis, or postnatal development when rats were dosed prior to and during mating, and throughout gestation and lactation at doses equivalent to 0.4 times the highest usual human maintenance dose on a mg/m basis.
When pregnant rats were orally dosed at 0.1, 0.14, or 0.3 times the highest human maintenance dose (on a mg/m basis) during the latter part of gestation (days 15 to 20), maternal toxicity and fetal death were seen. In dams, food consumption and weight gain were reduced, and the gestation period was slightly prolonged (22.6 vs. 22.0 days in the control group). Stillborn pups were found in all 3 drug-treated groups with the highest number in the high-dose group. Postnatal death was also seen, but only in the 2 highest doses, and occurred between days 1 and 20. Some of these deaths appear to be drug-related and not secondary to the maternal toxicity. A no-observed-effect level (NOEL) could not be determined for this study.
Although lamotrigine was not found to be teratogenic in the above studies, lamotrigine decreases fetal folate concentrations in rats, an effect known to be associated with teratogenesis in animals and humans. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Exposure Registry:
Physicians are also encouraged to register patients in the Lamotrigine Pregnancy Registry; enrollment in this registry must be done prior to any prenatal diagnostic tests and . can obtain information by calling the Lamotrigine Pregnancy Registry at 1-800-336-2176 (toll-free).
Lamictal (Lamotrigine) is indicated for adjunctive therapy in patients ≥2 years of age for partial seizures, the generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures.
Safety and efficacy of Lamictal (Lamotrigine) , used as adjunctive treatment for partial seizures, were not demonstrated in a small randomized, double-blind, placebo-controlled, withdrawal study in very young pediatric patients (1 to 24 months). Lamictal (Lamotrigine) was associated with an increased risk for infectious adverse reactions (Lamictal (Lamotrigine) 37%, Placebo 5%), and respiratory adverse reactions (Lamictal (Lamotrigine) 26%, Placebo 5%). Infectious adverse reactions included bronchiolitis, bronchitis, ear infection, eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection. Respiratory adverse reactions included nasal congestion, cough, and apnea.
Safety and effectiveness in patients below the age of 18 years with Bipolar Disorder have not been established.
Lamotrigine is metabolized mainly by glucuronic acid conjugation, with the majority of the metabolites being recovered in the urine. In a small study comparing a single dose of lamotrigine in patients with varying degrees of renal impairment with healthy volunteers, the plasma half-life of lamotrigine was significantly longer in the patients with renal impairment .
Initial doses of Lamictal (Lamotrigine) should be based on patients' AED regimens; reduced maintenance doses may be effective for patients with significant renal impairment. Few patients with severe renal impairment have been evaluated during chronic treatment with Lamictal (Lamotrigine) . Because there is inadequate experience in this population, Lamictal (Lamotrigine) should be used with caution in these patients .
Lamictal (Lamotrigine) Description
Lamictal (Lamotrigine) (lamotrigine), an AED of the phenyltriazine class, is chemically unrelated to existing AEDs. Its chemical name is 3,5-diamino-6-(2,3-dichlorophenyl)--triazine, its molecular formula is CHNCl, and its molecular weight is 256.09. Lamotrigine is a white to pale cream-colored powder and has a pK of 5.7. Lamotrigine is very slightly soluble in water (0.17 mg/mL at 25°C) and slightly soluble in 0.1 M HCl (4.1 mg/mL at 25°C). The structural formula is:
Lamictal (Lamotrigine) Tablets are supplied for oral administration as 25 mg (white), 100 mg (peach), 150 mg (cream), and 200 mg (blue) tablets. Each tablet contains the labeled amount of lamotrigine and the following inactive ingredients: lactose; magnesium stearate; microcrystalline cellulose; povidone; sodium starch glycolate; FD&C Yellow No. 6 Lake (100 mg tablet only); ferric oxide, yellow (150 mg tablet only); and FD&C Blue No. 2 Lake (200 mg tablet only).
Lamictal (Lamotrigine) Chewable Dispersible Tablets are supplied for oral administration. The tablets contain 2 mg (white), 5 mg (white), or 25 mg (white) of lamotrigine and the following inactive ingredients: blackcurrant flavor, calcium carbonate, low-substituted hydroxypropylcellulose, magnesium aluminum silicate, magnesium stearate, povidone, saccharin sodium, and sodium starch glycolate.
Lamictal (Lamotrigine) ODT Orally Disintegrating Tablets are supplied for oral administration. The tablets contain 25 mg (white to off-white), 50 mg (white to off-white), 100 mg (white to off-white), or 200 mg (white to off-white) of lamotrigine and the following inactive ingredients: artificial cherry flavor, crospovidone, ethylcellulose, magnesium stearate, mannitol, polyethylene, and sucralose.
Lamictal (Lamotrigine) ODT Orally Disintegrating Tablets are formulated using technologies (Microcaps and AdvaTab) designed to mask the bitter taste of lamotrigine and achieve a rapid dissolution profile. Tablet characteristics including flavor, mouth-feel, after-taste, and ease of use were rated as favorable in a study of 108 healthy volunteers.
Lamictal (Lamotrigine) Clinical Pharmacology
The precise mechanism(s) by which lamotrigine exerts its anticonvulsant action are unknown. In animal models designed to detect anticonvulsant activity, lamotrigine was effective in preventing seizure spread in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests, and prevented seizures in the visually and electrically evoked after-discharge (EEAD) tests for antiepileptic activity. Lamotrigine also displayed inhibitory properties in the kindling model in rats both during kindling development and in the fully kindled state. The relevance of these models to human epilepsy, however, is not known.
One proposed mechanism of action of lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels. In vitro pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
Although the relevance for human use is unknown, the following data characterize the performance of lamotrigine in receptor binding assays. Lamotrigine had a weak inhibitory effect on the serotonin 5-HT receptor (IC = 18 µM). It does not exhibit high affinity binding (IC>100 µM) to the following neurotransmitter receptors: adenosine A and A; adrenergic α, α, and β; dopamine D and D; γ-aminobutyric acid (GABA) A and B; histamine H; kappa opioid; muscarinic acetylcholine; and serotonin 5-HT. Studies have failed to detect an effect of lamotrigine on dihydropyridine-sensitive calcium channels. It had weak effects at sigma opioid receptors (IC = 145 µM). Lamotrigine did not inhibit the uptake of norepinephrine, dopamine, or serotonin (IC>200 µM) when tested in rat synaptosomes and/or human platelets in vitro.
50
The mechanisms by which lamotrigine exerts its therapeutic action in Bipolar Disorder have not been established.
Melanin Binding:
The pharmacokinetics of lamotrigine have been studied in patients with epilepsy, healthy young and elderly volunteers, and volunteers with chronic renal failure. Lamotrigine pharmacokinetic parameters for adult and pediatric patients and healthy normal volunteers are summarized in Tables 14 and 16.
a
max
b
[see Drug Interactions (7)].
Lamotrigine is rapidly and completely absorbed after oral administration with negligible first-pass metabolism (absolute bioavailability is 98%). The bioavailability is not affected by food. Peak plasma concentrations occur anywhere from 1.4 to 4.8 hours following drug administration. The lamotrigine chewable/dispersible tablets were found to be equivalent, whether they were administered as dispersed in water, chewed and swallowed, or swallowed as whole, to the lamotrigine compressed tablets in terms of rate and extent of absorption. In terms of rate and extent of absorption, lamotrigine orally disintegrating tablets whether disintegrated in the mouth or swallowed whole with water were equivalent to the lamotrigine compressed tablets swallowed with water.
Dose Proportionality:
Metabolism:
14
Enzyme Induction:
Following multiple administrations (150 mg twice daily) to normal volunteers taking no other medications, lamotrigine induced its own metabolism, resulting in a 25% decrease in t and a 37% increase in Cl/F at steady state compared with values obtained in the same volunteers following a single dose. Evidence gathered from other sources suggests that self-induction by lamotrigine may not occur when lamotrigine is given as adjunctive therapy in patients receiving enzyme-inducing drugs such as carbamazepine, phenytoin, phenobarbital, primidone, or drugs such as rifampin that induce lamotrigine glucuronidation .
The net effects of drug interactions with Lamictal (Lamotrigine) are summarized in Tables 13 and 15, followed by details of the drug interaction studies below.
a
b
c
d
e
f
g
h
↔ = No significant effect.
? = Conflicting data.
Estrogen-Containing Oral Contraceptives:
max
Gradual transient increases in lamotrigine plasma levels (approximate 2-fold increase) occurred during the week of inactive hormone preparation (“pill-free” week) for women not also taking a drug that increased the clearance of lamotrigine (carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce lamotrigine glucuronidation ). The increase in lamotrigine plasma levels will be greater if the dose of Lamictal (Lamotrigine) is increased in the few days before or during the “pill-free” week. Increases in lamotrigine plasma levels could result in dose-dependent adverse reactions.
In the same study, coadministration of Lamictal (Lamotrigine) (300 mg/day) in 16 female volunteers did not affect the pharmacokinetics of the ethinylestradiol component of the oral contraceptive preparation. There were mean decreases in the AUC and Cof the levonorgestrel component of 19% and 12%, respectively. Measurement of serum progesterone indicated that there was no hormonal evidence of ovulation in any of the 16 volunteers, although measurement of serum FSH, LH, and estradiol indicated that there was some loss of suppression of the hypothalamic-pituitary-ovarian axis.
The effects of doses of Lamictal (Lamotrigine) other than 300 mg/day have not been systematically evaluated in controlled clinical trials.
The clinical significance of the observed hormonal changes on ovulatory activity is unknown. However, the possibility of decreased contraceptive efficacy in some patients cannot be excluded. Therefore, patients should be instructed to promptly report changes in their menstrual pattern (e.g., break-through bleeding).
Dosage adjustments may be necessary for women receiving estrogen-containing oral contraceptive preparations
Other Hormonal Contraceptives or Hormone Replacement Therapy:
Bupropion:
The addition of carbamazepine decreases lamotrigine steady-state concentrations by approximately 40%.
Felbamate:
Folate Inhibitors:
Gabapentin:
Levetiracetam:
Lithium:
Olanzapine:
In the same study, the AUC and C of lamotrigine were reduced on average by 24% and 20%, respectively, following the addition of olanzapine to lamotrigine in healthy male volunteers compared with those receiving lamotrigine alone. This reduction in lamotrigine plasma concentrations is not expected to be clinically relevant.
Oxcarbazepine:
max
In the same study, the AUC and C of lamotrigine were similar following the addition of oxcarbazepine (600 mg twice daily) to Lamictal (Lamotrigine) in healthy male volunteers compared with those receiving Lamictal (Lamotrigine) alone. Limited clinical data suggest a higher incidence of headache, dizziness, nausea, and somnolence with coadministration of lamotrigine and oxcarbazepine compared with lamotrigine alone or oxcarbazepine alone.
Phenobarbital, Primidone:
Phenytoin:
Pregabalin:
Rifampin:
Topiramate:
Valproate:
The addition of valproate increased lamotrigine steady-state concentrations in normal volunteers by slightly more than 2-fold. In one study, maximal inhibition of lamotrigine clearance was reached at valproate doses between 250 and 500 mg/day and did not increase as the valproate dose was further increased.
In a study of 18 patients with epilepsy, coadministration of zonisamide (200 to 400 mg/day) with lamotrigine (150 to 500 mg/day for 35 days) had no significant effect on the pharmacokinetics of lamotrigine.
Known Inducers or Inhibitors of Glucuronidation:
Results of in vitro experiments suggest that clearance of lamotrigine is unlikely to be reduced by concomitant administration of amitriptyline, clonazepam, clozapine, fluoxetine, haloperidol, lorazepam, phenelzine, risperidone, sertraline, or trazodone.
Results of in vitro experiments suggest that lamotrigine does not reduce the clearance of drugs eliminated predominantly by CYP2D6
Twelve volunteers with chronic renal failure (mean creatinine clearance: 13 mL/min; range: 6 to 23) and another 6 individuals undergoing hemodialysis were each given a single 100-mg dose of lamotrigine. The mean plasma half-lives determined in the study were 42.9 hours (chronic renal failure), 13.0 hours (during hemodialysis), and 57.4 hours (between hemodialysis) compared with 26.2 hours in healthy volunteers. On average, approximately 20% (range: 5.6 to 35.1) of the amount of lamotrigine present in the body was eliminated by hemodialysis during a 4-hour session
The pharmacokinetics of lamotrigine following a single 100-mg dose of lamotrigine were evaluated in 24 subjects with mild, moderate, and severe hepatic impairment (Child-Pugh Classification system) and compared with 12 subjects without hepatic impairment. The patients with severe hepatic impairment were without ascites (n = 2) or with ascites (n = 5). The mean apparent clearances of lamotrigine in patients with mild (n = 12), moderate (n = 5), severe without ascites (n = 2), and severe with ascites (n = 5) liver impairment were 0.30 ± 0.09, 0.24 ± 0.1, 0.21 ± 0.04, and 0.15 ± 0.09 mL/min/kg, respectively, as compared with 0.37 ± 0.1 mL/min/kg in the healthy controls. Mean half-lives of lamotrigine in patients with mild, moderate, severe without ascites, and severe with ascites hepatic impairment were 46 ± 20, 72 ± 44, 67 ± 11, and 100 ± 48 hours, respectively, as compared with 33 ± 7 hours in healthy controls .
The pharmacokinetics of lamotrigine following a single 2-mg/kg dose were evaluated in 2 studies of pediatric patients (n = 29 for patients 10 months to 5.9 years of age and n = 26 for patients 5 to 11 years of age). Forty-three patients received concomitant therapy with other AEDs and 12 patients received lamotrigine as monotherapy. Lamotrigine pharmacokinetic parameters for pediatric patients are summarized in Table 16.
Population pharmacokinetic analyses involving patients 2 to 18 years of age demonstrated that lamotrigine clearance was influenced predominantly by total body weight and concurrent AED therapy. The oral clearance of lamotrigine was higher, on a body weight basis, in pediatric patients than in adults. Weight-normalized lamotrigine clearance was higher in those subjects weighing less than 30 kg, compared with those weighing greater than 30 kg. Accordingly, patients weighing less than 30 kg may need an increase of as much as 50% in maintenance doses, based on clinical response, as compared with subjects weighing more than 30 kg being administered the same AEDs These analyses also revealed that, after accounting for body weight, lamotrigine clearance was not significantly influenced by age. Thus, the same weight-adjusted doses should be administered to children irrespective of differences in age. Concomitant AEDs which influence lamotrigine clearance in adults were found to have similar effects in children.
a
[see Drug Interactions (7)].
b
max
c
The clearance of lamotrigine is not affected by gender. However, during dose escalation of Lamictal (Lamotrigine) in one clinical trial in patients with epilepsy on a stable dose of valproate (n = 77), mean trough lamotrigine concentrations, unadjusted for weight, were 24% to 45% higher (0.3 to 1.7 mcg/mL) in females than in males.
The apparent oral clearance of lamotrigine was 25% lower in non-Caucasians than Caucasians.
Lamictal (Lamotrigine) Clinical Studies
Monotherapy With Lamictal (Lamotrigine) in Adults With Partial Seizures Already Receiving Treatment With Carbamazepine, Phenytoin, Phenobarbital, or Primidone as the Single AED
The effectiveness of monotherapy with Lamictal (Lamotrigine) was established in a multicenter, double-blind clinical trial enrolling 156 adult outpatients with partial seizures. The patients experienced at least 4 simple partial, complex partial, and/or secondarily generalized seizures during each of 2 consecutive 4-week periods while receiving carbamazepine or phenytoin monotherapy during baseline. Lamictal (Lamotrigine) (target dose of 500 mg/day) or valproate (1,000 mg/day) was added to either carbamazepine or phenytoin monotherapy over a 4-week period. Patients were then converted to monotherapy with Lamictal (Lamotrigine) or valproate during the next 4 weeks, then continued on monotherapy for an additional 12-week period.
Study endpoints were completion of all weeks of study treatment or meeting an escape criterion. Criteria for escape relative to baseline were: (1) doubling of average monthly seizure count, (2) doubling of highest consecutive 2-day seizure frequency, (3) emergence of a new seizure type (defined as a seizure that did not occur during the 8-week baseline) that is more severe than seizure types that occur during study treatment, or (4) clinically significant prolongation of generalized tonic-clonic (GTC) seizures. The primary efficacy variable was the proportion of patients in each treatment group who met escape criteria.
The percentages of patients who met escape criteria were 42% (32/76) in the group receiving Lamictal (Lamotrigine) and 69% (55/80) in the valproate group. The difference in the percentage of patients meeting escape criteria was statistically significant (p 0.0012) in favor of Lamictal (Lamotrigine) . No differences in efficacy based on age, sex, or race were detected.
Patients in the control group were intentionally treated with a relatively low dose of valproate; as such, the sole objective of this study was to demonstrate the effectiveness and safety of monotherapy with Lamictal (Lamotrigine) , and cannot be interpreted to imply the superiority of Lamictal (Lamotrigine) to an adequate dose of valproate.
Adjunctive Therapy With Lamictal (Lamotrigine) in Adults With Partial Seizures
The effectiveness of Lamictal (Lamotrigine) as adjunctive therapy (added to other AEDs) was established in 3 multicenter, placebo-controlled, double-blind clinical trials in 355 adults with refractory partial seizures. The patients had a history of at least 4 partial seizures per month in spite of receiving one or more AEDs at therapeutic concentrations and, in 2 of the studies, were observed on their established AED regimen during baselines that varied between 8 to 12 weeks. In the third, patients were not observed in a prospective baseline. In patients continuing to have at least 4 seizures per month during the baseline, Lamictal (Lamotrigine) or placebo was then added to the existing therapy. In all 3 studies, change from baseline in seizure frequency was the primary measure of effectiveness. The results given below are for all partial seizures in the intent-to-treat population (all patients who received at least one dose of treatment) in each study, unless otherwise indicated. The median seizure frequency at baseline was 3 per week while the mean at baseline was 6.6 per week for all patients enrolled in efficacy studies.
One study (n = 216) was a double-blind, placebo-controlled, parallel trial consisting of a 24-week treatment period. Patients could not be on more than 2 other anticonvulsants and valproate was not allowed. Patients were randomized to receive placebo, a target dose of 300 mg/day of Lamictal (Lamotrigine) , or a target dose of 500 mg/day of Lamictal (Lamotrigine) . The median reductions in the frequency of all partial seizures relative to baseline were 8% in patients receiving placebo, 20% in patients receiving 300 mg/day of Lamictal (Lamotrigine) , and 36% in patients receiving 500 mg/day of Lamictal (Lamotrigine) . The seizure frequency reduction was statistically significant in the 500-mg/day group compared with the placebo group, but not in the 300-mg/day group.
A second study (n = 98) was a double-blind, placebo-controlled, randomized, crossover trial consisting of two 14-week treatment periods (the last 2 weeks of which consisted of dose tapering) separated by a 4-week washout period. Patients could not be on more than 2 other anticonvulsants and valproate was not allowed. The target dose of Lamictal (Lamotrigine) was 400 mg/day. When the first 12 weeks of the treatment periods were analyzed, the median change in seizure frequency was a 25% reduction on Lamictal (Lamotrigine) compared with placebo (
The third study (n = 41) was a double-blind, placebo-controlled, crossover trial consisting of two 12-week treatment periods separated by a 4-week washout period. Patients could not be on more than 2 other anticonvulsants. Thirteen patients were on concomitant valproate; these patients received 150 mg/day of Lamictal (Lamotrigine) . The 28 other patients had a target dose of 300 mg/day of Lamictal (Lamotrigine) . The median change in seizure frequency was a 26% reduction on Lamictal (Lamotrigine) compared with placebo (
No differences in efficacy based on age, sex, or race, as measured by change in seizure frequency, were detected.
Adjunctive Therapy With Lamictal (Lamotrigine) in Pediatric Patients With Partial Seizures
The effectiveness of Lamictal (Lamotrigine) as adjunctive therapy in pediatric patients with partial seizures was established in a multicenter, double-blind, placebo-controlled trial in 199 patients 2 to 16 years of age (n = 98 on Lamictal (Lamotrigine) , n = 101 on placebo). Following an 8-week baseline phase, patients were randomized to 18 weeks of treatment with Lamictal (Lamotrigine) or placebo added to their current AED regimen of up to 2 drugs. Patients were dosed based on body weight and valproate use. Target doses were designed to approximate 5 mg/kg/day for patients taking valproate (maximum dose: 250 mg/day) and 15 mg/kg/day for the patients not taking valproate (maximum dose: 750 mg/day). The primary efficacy endpoint was percentage change from baseline in all partial seizures. For the intent-to-treat population, the median reduction of all partial seizures was 36% in patients treated with Lamictal (Lamotrigine) and 7% on placebo, a difference that was statistically significant (
The effectiveness of Lamictal (Lamotrigine) in the maintenance treatment of Bipolar I Disorder was established in 2 multicenter, double-blind, placebo-controlled studies in adult patients who met DSM-IV criteria for Bipolar I Disorder. Study 1 enrolled patients with a current or recent (within 60 days) depressive episode as defined by DSM-IV and Study 2 included patients with a current or recent (within 60 days) episode of mania or hypomania as defined by DSM-IV. Both studies included a cohort of patients (30% of 404 patients in Study 1 and 28% of 171 patients in Study 2) with rapid cycling Bipolar Disorder (4 to 6 episodes per year).
In both studies, patients were titrated to a target dose of 200 mg of Lamictal (Lamotrigine) , as add-on therapy or as monotherapy, with gradual withdrawal of any psychotropic medications during an 8- to 16-week open-label period. Overall 81% of 1,305 patients participating in the open-label period were receiving 1 or more other psychotropic medications, including benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics (including olanzapine), valproate, or lithium, during titration of Lamictal (Lamotrigine) . Patients with a CGI-severity score of 3 or less maintained for at least 4 continuous weeks, including at least the final week on monotherapy with Lamictal (Lamotrigine) , were randomized to a placebo-controlled, double-blind treatment period for up to 18 months. The primary endpoint was TIME (time to intervention for a mood episode or one that was emerging, time to discontinuation for either an adverse event that was judged to be related to Bipolar Disorder, or for lack of efficacy). The mood episode could be depression, mania, hypomania, or a mixed episode.
In Study 1, patients received double-blind monotherapy with Lamictal (Lamotrigine) 50 mg/day (n = 50), Lamictal (Lamotrigine) 200 mg/day (n = 124), Lamictal (Lamotrigine) 400 mg/day (n = 47), or placebo (n = 121). Lamictal (Lamotrigine) (200- and 400-mg/day treatment groups combined) was superior to placebo in delaying the time to occurrence of a mood episode. Separate analyses of the 200- and 400-mg/day dose groups revealed no added benefit from the higher dose.
In Study 2, patients received double-blind monotherapy with Lamictal (Lamotrigine) (100 to 400 mg/day, n = 59), or placebo (n = 70). Lamictal (Lamotrigine) was superior to placebo in delaying time to occurrence of a mood episode. The mean dose of Lamictal (Lamotrigine) was about 211 mg/day.
Although these studies were not designed to separately evaluate time to the occurrence of depression or mania, a combined analysis for the 2 studies revealed a statistically significant benefit for Lamictal (Lamotrigine) over placebo in delaying the time to occurrence of both depression and mania, although the finding was more robust for depression.
Lamictal (Lamotrigine) How Supplied/storage And Handling
100 mg, peach, scored, shield-shaped tablets debossed with "Lamictal (Lamotrigine) " and "100", bottles of 30 (NDC 21695-223-30) and 60 (NDC 21695-223-60).
150 mg, cream, scored, shield-shaped tablets debossed with "Lamictal (Lamotrigine) " and "150", bottles of 15 (NDC 21695-224-15).
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature] in a dry place and protect from light.
Lamictal (Lamotrigine) Patient Counseling Information
See Medication Guide that accompanies the product.
Patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy. Patients should be advised to notify their physicians if they intend to breastfeed or are breastfeeding an infant.
Patients should also be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334 .
Medication errors involving Lamictal (Lamotrigine) have occurred. In particular the names Lamictal (Lamotrigine) or lamotrigine can be confused with the names of other commonly used medications. Medication errors may also occur between the different formulations of Lamictal (Lamotrigine) . To reduce the potential of medication errors, write and say Lamictal (Lamotrigine) clearly. Depictions of the Lamictal (Lamotrigine) Tablets, Chewable Dispersible Tablets, and Orally Disintegrating Tablets can be found in the Medication Guide that accompanies the product to highlight the distinctive markings, colors, and shapes that serve to identify the different presentations of the drug and thus may help reduce the risk of medication errors. .
GlaxoSmithKline
Research Triangle Park, NC 27709
Lamictal (Lamotrigine) Tablets and Chewable Dispersible Tablets are manufactured by
DSM Pharmaceuticals, Inc., Greenville, NC 27834 or
GlaxoSmithKline, Research Triangle Park, NC 27709
Lamictal (Lamotrigine) Orally Disintegrating Tablets are manufactured by
Eurand, Inc., Vandalia, OH 45377
Lamictal (Lamotrigine) is a registered trademark of GlaxoSmithKline
Microcaps and AdvaTab are registered trademarks of Eurand, Inc.
©2009, GlaxoSmithKline. All rights reserved.
Lamictal (Lamotrigine)
Lamictal (Lamotrigine) Principal Display Panel
Lamictal (Lamotrigine) Principal Display Panel
