FULL PRESCRIBING INFORMATION
WARNING: SERIOUS SKIN RASHES
Lamotrigine can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.8% (8 per 1,000) in pediatric patients (2 to 16 years of age) receiving Lamotrigine as adjunctive therapy for epilepsy and 0.3% (3 per 1,000) in adults on adjunctive therapy for epilepsy. In clinical trials of bipolar and other mood disorders, the rate of serious rash was 0.08% (0.8 per 1,000) in adult patients receiving Lamotrigine as initial monotherapy and 0.13% (1.3 per 1,000) in adult patients receiving Lamotrigine as adjunctive therapy. In a prospectively followed cohort of 1,983 pediatric patients (2 to 16 years of age) with epilepsy taking adjunctive Lamotrigine, there was 1 rash-related death. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.
Other than age, there are as yet no factors identified that are known to predict the risk of occurrence or the severity of rash caused by Lamotrigine. There are suggestions, yet to be proven, that the risk of rash may also be increased by (1) coadministration of Lamotrigine with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of Lamotrigine, or (3) exceeding the recommended dose escalation for Lamotrigine. However, cases have occurred in the absence of these factors.
Nearly all cases of life-threatening rashes caused by Lamotrigine have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., 6 months). Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash.
Although benign rashes are also caused by Lamotrigine, it is not possible to predict reliably which rashes will prove to be serious or life-threatening. Accordingly, Lamotrigine should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug-related. Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring [see Warnings and Precautions (5.1)].
Indications and Usage for Lamotrigine
Epilepsy
Adjunctive Therapy: Lamotrigine tablets (chewable, dispersible) are indicated as adjunctive therapy for the following seizure types in patients ≥ 2 years of age:
- partial seizures
- primary generalized tonic-clonic seizures
- generalized seizures of Lennox-Gastaut syndrome
Monotherapy: Lamotrigine tablets (chewable, dispersible) are indicated for conversion to monotherapy in adults (≥ 16 years of age) with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED).
Safety and effectiveness of Lamotrigine tablets (chewable, dispersible) 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.
Bipolar Disorder
Lamotrigine tablets (chewable, dispersible) are 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 Lamotrigine tablets (chewable, dispersible) in the acute treatment of mood episodes has not been established.
The effectiveness of Lamotrigine tablets (chewable, dispersible) as maintenance treatment was established in 2 placebo-controlled trials in patients with Bipolar I Disorder as defined by DSM-IV [see Clinical Studies (14.2)]. The physician who elects to prescribe Lamotrigine tablets (chewable, dispersible) for periods extending beyond 16 weeks should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
Lamotrigine Dosage and Administration
General Dosing Considerations
Rash: There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be increased by (1) coadministration of Lamotrigine tablets (chewable, dispersible) with valproate, (2) exceeding the recommended initial dose of Lamotrigine tablets (chewable, dispersible), or (3) exceeding the recommended dose escalation for Lamotrigine tablets (chewable, dispersible). However, cases have occurred in the absence of these factors [see Boxed Warning]. Therefore, it is important that the dosing recommendations be followed closely.
The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation of Lamotrigine tablets (chewable, dispersible) is exceeded and in patients with a history of allergy or rash to other AEDs.
It is recommended that Lamotrigine tablets (chewable, dispersible) 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 [see Clinical Pharmacology (12.3)].
Lamotrigine Added to Drugs Known to Induce or Inhibit Glucuronidation: Drugs other than those listed in the Clinical Pharmacology section [see Clinical Pharmacology (12.3)] have not been systematically evaluated in combination with Lamotrigine. Because Lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of Lamotrigine and doses of Lamotrigine tablets (chewable, dispersible) may require adjustment based on clinical response.
Target Plasma Levels for Patients With Epilepsy or Bipolar Disorder: A therapeutic plasma concentration range has not been established for Lamotrigine. Dosing of Lamotrigine tablets (chewable, dispersible) should be based on therapeutic response [see Clinical Pharmacology (12.3)].
Women Taking Estrogen-Containing Oral Contraceptives: Starting Lamotrigine Tablets (Chewable, Dispersible) in Women Taking Estrogen-Containing Oral Contraceptives: Although estrogen-containing oral contraceptives have been shown to increase the clearance of Lamotrigine [see Clinical Pharmacology (12.3)], no adjustments to the recommended dose-escalation guidelines for Lamotrigine tablets (chewable, dispersible) should be necessary solely based on the use of estrogen-containing oral contraceptives. Therefore, dose escalation should follow the recommended guidelines for initiating adjunctive therapy with Lamotrigine tablets (chewable, dispersible) based on the concomitant AED or other concomitant medications (see Table 1 or Table 5). See below for adjustments to maintenance doses of Lamotrigine tablets (chewable, dispersible) in women taking estrogen-containing oral contraceptives.
Adjustments to the Maintenance Dose of Lamotrigine Tablets (Chewable, Dispersible) in Women Taking Estrogen-Containing Oral Contraceptives:
(1) Taking Estrogen-Containing Oral Contraceptives: For women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce Lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of Lamotrigine tablets (chewable, dispersible) will in most cases need to be increased, by as much as 2 fold over the recommended target maintenance dose, in order to maintain a consistent Lamotrigine plasma level [see Clinical Pharmacology (12.3)].
(2) Starting Estrogen-Containing Oral Contraceptives: In women taking a stable dose of Lamotrigine tablets (chewable, dispersible) and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce Lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose will in most cases need to be increased by as much as 2 fold in order to maintain a consistent Lamotrigine plasma level. The dose increases should begin at the same time that the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week. Dose increases should not exceed the recommended rate (see Table 1 or Table 5) unless Lamotrigine plasma levels or clinical response support larger increases. Gradual transient increases in Lamotrigine plasma levels may occur during the week of inactive hormonal preparation (“pill-free” week), and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation. Increased Lamotrigine plasma levels could result in additional adverse reactions, such as dizziness, ataxia, and diplopia. If adverse reactions attributable to Lamotrigine tablets (chewable, dispersible) consistently occur during the “pill-free” week, dose adjustments to the overall maintenance dose may be necessary. Dose adjustments limited to the “pill-free” week are not recommended. For women taking Lamotrigine tablets (chewable, dispersible) in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce Lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of Lamotrigine tablets (chewable, dispersible) should be necessary.
(3) Stopping Estrogen-Containing Oral Contraceptives: For women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce Lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], the maintenance dose of Lamotrigine tablets (chewable, dispersible) will in most cases need to be decreased by as much as 50% in order to maintain a consistent Lamotrigine plasma level. The decrease in dose of Lamotrigine tablets (chewable, dispersible) should not exceed 25% of the total daily dose per week over a 2 week period, unless clinical response or Lamotrigine plasma levels indicate otherwise [see Clinical Pharmacology (12.3)]. For women taking Lamotrigine tablets (chewable, dispersible) in addition to carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin that induce Lamotrigine glucuronidation [see Drug Interactions (7), Clinical Pharmacology (12.3)], no adjustment to the dose of Lamotrigine tablets (chewable, dispersible) should be necessary.
Women and Other Hormonal Contraceptive Preparations or Hormone Replacement Therapy: The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of Lamotrigine has not been systematically evaluated. It has been reported that ethinylestradiol, not progestogens, increased the clearance of Lamotrigine up to 2 fold, and the progestin-only pills had no effect on Lamotrigine plasma levels. Therefore, adjustments to the dosage of Lamotrigine tablets (chewable, dispersible) in the presence of progestogens alone will likely not be needed.
Patients With Hepatic Impairment: Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study in 24 patients with mild, moderate, and severe liver impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)], the following general recommendations can be made. No dosage adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be adjusted according to clinical response.
Patients With Renal Impairment: Initial doses of Lamotrigine tablets (chewable, dispersible) should be based on patients' concomitant medications (see Tables 1 to 3 or Table 5); reduced maintenance doses may be effective for patients with significant renal impairment [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)]. Few patients with severe renal impairment have been evaluated during chronic treatment with Lamotrigine tablets (chewable, dispersible). Because there is inadequate experience in this population, Lamotrigine tablets (chewable, dispersible) should be used with caution in these patients.
Discontinuation Strategy: Epilepsy: For patients receiving Lamotrigine tablets (chewable, dispersible) in combination with other AEDs, a reevaluation of all AEDs in the regimen should be considered if a change in seizure control or an appearance or worsening of adverse reactions is observed.
If a decision is made to discontinue therapy with Lamotrigine tablets (chewable, dispersible), 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 [see Warnings and Precautions (5.10)].
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.
Bipolar Disorder: In the controlled clinical trials, there was no increase in the incidence, type, or severity of adverse reactions following abrupt termination of Lamotrigine tablets (chewable, dispersible). In clinical trials in patients with Bipolar Disorder, 2 patients experienced seizures shortly after abrupt withdrawal of Lamotrigine tablets (chewable, dispersible). However, there were confounding factors that may have contributed to the occurrence of seizures in these bipolar patients. Discontinuation of Lamotrigine tablets (chewable, dispersible) should involve a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) unless safety concerns require a more rapid withdrawal [see Warnings and Precautions (5.10)].
Epilepsy – Adjunctive Therapy
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: Recommended dosing guidelines are summarized in Table 1.
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For Patients TAKING Valproate* | For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,† or Valproate* | For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidone† and NOT TAKING Valproate* | |
| Weeks 1 and 2 | 25 mg every other day | 25 mg every day | 50 mg/day |
| Weeks 3 and 4 | 25 mg every day | 50 mg/day | 100 mg/day (in 2 divided doses) |
| Week 5 onwards to maintenance | Increase by 25 to 50 mg/day every 1 to 2 weeks | Increase by 50 mg/day every 1 to 2 weeks | Increase by 100 mg/day every 1 to 2 weeks |
| Usual Maintenance Dose | 100 to 200 mg/day with valproate alone 100 to 400 mg/day with valproate and other drugs that induceglucuronidation (in 1 or 2 divided doses) | 225 to 375 mg/day (in 2 divided doses) | 300 to 500 mg/day (in 2 divided doses) |
Patients 2 to 12 Years of Age: Recommended dosing guidelines are summarized in Table 2.
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.
The smallest available strength of Lamotrigine tablets (chewable, dispersible) is 2 mg, and only whole tablets should be administered. If the calculated dose cannot be achieved using whole tablets, the dose should be rounded down to the nearest whole tablet [see How Supplied/Storage and Handling (16) and Medication Guide].
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| For Patients TAKING Valproate* | For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,† or Valproate* | For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidone† and NOT TAKING Valproate* | |
| Weeks 1 and 2 | 0.15 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight based dosing guide) | 0.3 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet | 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet |
| Weeks 3 and 4 | 0.3 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight based dosing guide) | 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet | 1.2 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet |
| Week 5 onwards to maintenance | The dose should be increased every 1 to 2 weeks as follows: calculate 0.3 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose | The dose should be increased every 1 to 2 weeks as follows: calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose | The dose should be increased every 1 to 2 weeks as follows: calculate 1.2 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose |
| Usual Maintenance Dose | 1 to 5 mg/kg/day (maximum 200 mg/day in 1 or 2 divided doses) 1 to 3 mg/kg/day with valproate alone | 4.5 to 7.5 mg/kg/day (maximum 300 mg/day in 2 divided doses) | 5 to 15 mg/kg/day (maximum 400 mg/day in 2 divided doses) |
| Maintenance dose in patients less than 30 kg | May need to be increased by as much as 50%, based on clinical response | May need to be increased by as much as 50%, based on clinical response | May need to be increased by as much as 50%, based on clinical response |
Note: Only whole tablets should be used for dosing. | |||
| If the patient’s weight is | Give this daily dose, using the most appropriate combination of Lamotrigine tablets, 2 mg and 5 mg | ||
| Greater than | And less than | Weeks 1 and 2 | Weeks 3 and 4 |
| 6.7 kg | 14 kg | 2 mg every other day | 2 mg every day |
| 14.1 kg | 27 kg | 2 mg every day | 4 mg every day |
| 27.1 kg | 34 kg | 4 mg every day | 8 mg every day |
| 34.1 kg | 40 kg | 5 mg every day | 10 mg every day |
Usual Adjunctive Maintenance Dose for Epilepsy: 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 Lamotrigine tablets (chewable, dispersible) was established. In patients receiving multidrug regimens employing carbamazepine, phenytoin, phenobarbital, or primidone without valproate, maintenance doses of adjunctive Lamotrigine tablets (chewable, dispersible) as high as 700 mg/day have been used. In patients receiving valproate alone, maintenance doses of adjunctive Lamotrigine tablets (chewable, dispersible) 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.
Epilepsy – Conversion From Adjunctive Therapy to Monotherapy
The goal of the transition regimen is to effect the conversion to monotherapy with Lamotrigine tablets (chewable, dispersible) under conditions that ensure adequate seizure control while mitigating the risk of serious rash associated with the rapid titration of Lamotrigine tablets (chewable, dispersible).
The recommended maintenance dose of Lamotrigine tablets (chewable, dispersible) 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 Lamotrigine tablets (chewable, dispersible) should not be exceeded [see Boxed Warning].
Conversion From Adjunctive Therapy With Carbamazepine, Phenytoin, Phenobarbital, or Primidone to Monotherapy With Lamotrigine Tablets (Chewable, Dispersible): After achieving a dose of 500 mg/day of Lamotrigine tablets (chewable, dispersible) according to the guidelines in Table 1, the concomitant AED should be withdrawn by 20% decrements each week over a 4 week period. The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial.
Conversion From Adjunctive Therapy With Valproate to Monotherapy With Lamotrigine Tablets (Chewable, Dispersible): The conversion regimen involves 4 steps outlined in Table 4.
| Lamotrigine | Valproate | |
| Step 1 | Achieve a dose of 200 mg/day according to guidelines in Table 1 (if not already on 200 mg/day). | Maintain previous stable dose. |
| Step 2 | Maintain at 200 mg/day. | Decrease to 500 mg/day by decrements no greater than 500 mg/day/week and then maintain the dose of 500 mg/day for 1 week. |
| Step 3 | Increase to 300 mg/day and maintain for 1 week. | Simultaneously decrease to 250 mg/day and maintain for 1 week. |
| Step 4 | Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day. | Discontinue. |
Conversion From Adjunctive Therapy With AEDs Other Than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy With Lamotrigine Tablets (Chewable, Dispersible): No specific dosing guidelines can be provided for conversion to monotherapy with Lamotrigine tablets (chewable, dispersible) with AEDs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate.
Bipolar Disorder
The goal of maintenance treatment with Lamotrigine tablets (chewable, dispersible) 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 Lamotrigine tablets (chewable, dispersible) 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 [see Clinical Studies (14.2)]. Accordingly, doses above 200 mg/day are not recommended. Treatment with Lamotrigine tablets (chewable, dispersible) 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 Lamotrigine tablets (chewable, dispersible) should be adjusted. For patients discontinuing valproate, the dose of Lamotrigine tablets (chewable, dispersible) 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 Lamotrigine tablets (chewable, dispersible) 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 Lamotrigine tablets (chewable, dispersible) may then be further adjusted to the target dose (200 mg) as clinically indicated.
If other drugs are subsequently introduced, the dose of Lamotrigine tablets (chewable, dispersible) may need to be adjusted. In particular, the introduction of valproate requires reduction in the dose of Lamotrigine tablets (chewable, dispersible) [see Drug Interactions (7), Clinical Pharmacology (12.3)].
To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations of Lamotrigine tablets (chewable, dispersible) should not be exceeded [see Boxed Warning].
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| For Patients TAKING Valproate* | For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone,† or Valproate* | For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidone† and NOT TAKING Valproate* | |
| Weeks 1 and 2 | 25 mg every other day | 25 mg daily | 50 mg daily |
| Weeks 3 and 4 | 25 mg daily | 50 mg daily | 100 mg daily, in divided doses |
| Week 5 | 50 mg daily | 100 mg daily | 200 mg daily, in divided doses |
| Week 6 | 100 mg daily | 200 mg daily | 300 mg daily, in divided doses |
| Week 7 | 100 mg daily | 200 mg daily | up to 400 mg daily, in divided doses |
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Discontinuation of Psychotropic Drugs (excluding Carbamazepine, Phenytoin, Phenobarbital, Primidone,* or Valproate†) | After Discontinuation of Valproate† | After Discontinuation of Carbamazepine, Phenytoin, Phenobarbital, or Primidone* | |
| Current dose of Lamotrigine (mg/day) 100 | Current dose of Lamotrigine (mg/day) 400 | ||
| Week 1 | Maintain current dose of Lamotrigine | 150 | 400 |
| Week 2 | Maintain current dose of Lamotrigine | 200 | 300 |
| Week 3 onward | Maintain current dose of Lamotrigine | 200 | 200 |
The benefit of continuing treatment in patients who had been stabilized in an 8 to 16 week open-label phase with Lamotrigine tablets (chewable, dispersible) was established in 2 randomized, placebo-controlled clinical maintenance trials [see Clinical Studies (14.2)]. However, the optimal duration of treatment with Lamotrigine tablets (chewable, dispersible) has not been established. Thus, patients should be periodically reassessed to determine the need for maintenance treatment.
Administration of Lamotrigine Tablets (Chewable, Dispersible)
Lamotrigine tablets (chewable, dispersible) 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 Lamotrigine tablets (chewable, dispersible), 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. No attempt should be made to administer partial quantities of the dispersed tablets.
Dosage Forms and Strengths
Chewable Dispersible Tablets
5 mg – white to off-white, round tablets, debossed “93” on one side and “688” on the other.
25 mg – white to off-white, oval-shaped tablets, debossed “93” on one side and “132” on the other.
Potential Medication Errors
Patients should be strongly advised to visually inspect their tablets to verify that they are receiving Lamotrigine as well as the correct formulation of Lamotrigine each time they fill their prescription. Depictions of the Lamotrigine tablets (chewable, dispersible) can be found in the Medication Guide that accompanies the product.
Contraindications
Lamotrigine tablets (chewable, dispersible) are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients [see Boxed Warning, Warnings and Precautions (5.1), (5.2)].
Warnings and Precautions
Serious Skin Rashes [see Boxed Warning]
Pediatric Population: The incidence of serious rash associated with hospitalization and discontinuation of Lamotrigine in a prospectively followed cohort of pediatric patients (2 to 16 years of age) with epilepsy receiving adjunctive therapy was approximately 0.8% (16 of 1,983). When 14 of these cases were reviewed by 3 expert dermatologists, there was considerable disagreement as to their proper classification. To illustrate, one dermatologist considered none of the cases to be Stevens-Johnson syndrome; another assigned 7 of the 14 to this diagnosis. There was 1 rash-related death in this 1,983 patient cohort. Additionally, there have been rare cases of toxic epidermal necrolysis with and without permanent sequelae and/or death in U.S. and foreign postmarketing experience.
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: Serious rash associated with hospitalization and discontinuation of Lamotrigine occurred in 0.3% (11 of 3,348) of adult patients who received Lamotrigine in premarketing clinical trials of epilepsy. In the bipolar and other mood disorders clinical trials, the rate of serious rash was 0.08% (1 of 1,233) of adult patients who received Lamotrigine as initial monotherapy and 0.13% (2 of 1,538) of adult patients who received Lamotrigine as adjunctive therapy. No fatalities occurred among these individuals. However, in worldwide postmarketing experience, rare cases of rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate.
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 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 Lamotrigine in the absence of valproate were hospitalized.
Patients With History of Allergy or Rash to Other AEDs: The risk of nonserious rash may be increased when the recommended initial dose and/or the rate of dose escalation of Lamotrigine is exceeded and in patients with a history of allergy or rash to other AEDs.
Hypersensitivity Reactions
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. Lamotrigine should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Prior to initiation of treatment with 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.
Acute Multiorgan Failure
Multiorgan failure, which in some cases has been fatal or irreversible, has been observed in patients receiving 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 Lamotrigine in epilepsy clinical trials. No such fatalities have been reported i
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