Lamotrigine

10. OVERDOSAGE

10.1. Human Overdose Experience

Overdoses involving quantities up to 15 g have been reported for lamotrigine tablets, some of which have been fatal. Overdose has resulted in ataxia, nystagmus, increased seizures, decreased level of consciousness, coma, and intraventricular conduction delay.

10.2. Management of Overdose

11. DESCRIPTION

12. CLINICAL PHARMACOLOGY

12.1. Mechanism of Action

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-HT₃ receptor (IC₅₀ = 18 μM). It does not exhibit high affinity binding (IC₅₀>100 μM) to the following neurotransmitter receptors: adenosine A₁ and A₂; adrenergic α₁, α₂, and β; dopamine D₁ and D₂; γ-aminobutyric acid (GABA) A and B; histamine H₁; kappa opioid; muscarinic acetylcholine; and serotonin 5-HT₂. Studies have failed to detect an effect of lamotrigine on dihydropyridine-sensitive calcium channels. It had weak effects at sigma opioid receptors (IC₅₀ = 145 μM). Lamotrigine did not inhibit the uptake of norepinephrine, dopamine, or serotonin, (IC₅₀>200 μM) when tested in rat synaptosomes and/or human platelets in vitro.

Effect of Lamotrigine on N-Methyl d-Aspartate-Receptor Mediated Activity:
Lamotrigine did not inhibit N-methyl d-aspartate (NMDA)-induced depolarizations in rat cortical slices or NMDA-induced cyclic GMP formation in immature rat cerebellum, nor did lamotrigine displace compounds that are either competitive or noncompetitive ligands at this glutamate receptor complex (CNQX, CGS, TCHP). The IC₅₀ for lamotrigine effects on NMDA-induced currents (in the presence of 3 μM of glycine) in cultured hippocampal neurons exceeded 100 μM.

The mechanisms by which lamotrigine exerts its therapeutic action in Bipolar Disorder have not been established.

12.2. Pharmacodynamics

12.3. Pharmacokinetics

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 t½ 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 glucoronidation [see Drug Interactions (7)].

Elimination: The elimination half-life and apparent clearance of lamotrigine following administration of lamotrigine tablets to adult patients with epilepsy and healthy volunteers is summarized in Table 14. Half-life and apparent oral clearance vary depending on concomitant AEDs.

Drug Interactions: The apparent clearance of lamotrigine is affected by the coadministration of certain medications [see Warnings and Precautions (5.9, 5.13), Drug Interactions (7)].

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 glucorinidation [see Drug Interactions (7)]). The increase in lamotrigine plasma levels will be greater if the dose of lamotrigine tablets 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 lamotrigine tablets (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 C_max of 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 lamotrigine tablets 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 [see Dosage and Administration (2.1)].

Other Hormonal Contraceptives 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 in the presence of progestogens alone will likely not be needed. 

Zonisamide: 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) for 35 days had no significant effect on the pharmacokinetics of lamotrigine. 

Age: Pediatric Patients: 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.

13. NONCLINICAL TOXICOLOGY

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenicity was seen in 1 mouse study or 2 rat studies following oral administration of lamotrigine for up to 2 years at maximum tolerated doses (30 mg/kg per day for mice and 10 to 15 mg/kg per day for rats, doses that are equivalent to 90 mg/m² and 60 to 90 mg/m², respectively). Steady-state plasma concentrations ranged from 1 to 4 mcg/mL in the mouse study and 1 to 10 mcg/mL in the rat study. Plasma concentrations associated with the recommended human doses of 300 to 500 mg/day are generally in the range of 2 to 5 mcg/mL, but concentrations as high as 19 mcg/mL have been recorded.

Lamotrigine was not mutagenic in the presence or absence of metabolic activation when tested in 2 gene mutation assays (the Ames test and the in vitro mammalian mouse lymphoma assay). In 2 cytogenetic assays (the in vitro human lymphocyte assay and the in vivo rat bone marrow assay), lamotrigine did not increase the incidence of structural or numerical chromosomal abnormalities.

No evidence of impairment of fertility was detected in rats given oral doses of lamotrigine up to 2.4 times the highest usual human maintenance dose of 8.33 mg/kg per day or 0.4 times the human dose on a mg/m² basis. The effect of lamotrigine on human fertility is unknown.

14. CLINICAL STUDIES

14.1. Epilepsy

Monotherapy with Lamotrigine Tablets in Adults with Partial Seizures Already Receiving Treatment with Carbamazepine, Phenytoin, Phenobarbital, or Primidone as the Single AED: The effectiveness of monotherapy with lamotrigine tablets 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. Lamotrigine tablets (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 lamotrigine tablets 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 percentage of patients who met escape criteria were 42% (32/76) in the lamotrigine tablet group 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 lamotrigine tablet. 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 lamotrigine tablets, and cannot be interpreted to imply the superiority of lamotrigine tablet to an adequate dose of valproate.

Adjunctive Therapy with Lamotrigine Tablets in Adults with Partial Seizures: The effectiveness of lamotrigine tablets 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, lamotrigine tablets 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 lamotrigine tablets, or a target dose of 500 mg/day of lamotrigine tablets. 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 lamotrigine tablets, and 36% in patients receiving 500 mg/day of lamotrigine tablets. 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 lamotrigine tablets 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 lamotrigine tablets compared to placebo (p<0.001).

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 lamotrigine tablets. The 28 other patients had a target dose of 300 mg/day of lamotrigine tablets. The median change in seizure frequency was a 26% reduction on lamotrigine tablets compared with placebo (p<0.01).

No differences in efficacy based on age, sex, or race, as measured by change in seizure frequency, were detected.

Adjunctive Therapy with Lamotrigine Tablets in Pediatric Patients with Partial Seizures: The effectiveness of lamotrigine tablets as adjunctive therapy in pediatric patients with partial seizures was established in a multicenter, double-blind, placebo-controlled trial in 199 patients aged 2 to 16 years of age (n = 98 on lamotrigine tablets, n = 101 on placebo). Following an 8-week baseline phase, patients were randomized to 18 weeks of treatment with lamotrigine tablets 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 per day for patients taking valproate (maximum dose: 250 mg/day) and 15 mg/kg per day for the patients not taking valproate (maximum dose: 750 mg per 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 lamotrigine tablets and 7% on placebo, a difference that was statistically significant (p<0.01).

14.2. Bipolar Disorder

16. HOW SUPPLIED/STORAGE AND HANDLING

Lamotrigine Tablets, 25 mg

White to off-white, capsule shaped tablets, with break line on one side and debossed with “L121” on other side. They are supplied as follows: 

Lamotrigine Tablets, 100 mg

White to off-white, round tablets with break line on one side and debossed with “L122” on other side. They are supplied as follows:

Lamotrigine Tablets, 150 mg

White to off-white, round tablets with break line on one side and debossed with “L123” on other side. They are supplied as follows:

Lamotrigine Tablets, 200 mg

White to off-white, round tablets with break line on one side and debossed with “L124” on other side. They are supplied as follows:

Store at 20º-25°C (68º-77°F); excursion permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

17. PATIENT COUNSELING INFORMATION

17.1. Rash

17.2. Suicidal Thinking and Behavior

17.3. Worsening of Seizures

Patients should be advised to notify their physician if worsening of seizure control occurs.

17.4. CNS Adverse Effects

17.5. Blood Dyscrasias and/or Acute Multiorgan Failure

17.6. Pregnancy

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.

17.7. Oral Contraceptive Use

17.8. Discontinuing Lamotrigine Tablets

Patients should be advised to notify their physician if they stop taking lamotrigine tablets for any reason and not to resume lamotrigine tablets without consulting their physician.

17.9. Aseptic Meningitis

Patients should be advised that lamotrigine may cause aseptic meningitis. Patients should be advised to notify their physician immediately if they develop signs and symptoms of meningitis such as headache, fever, nausea, vomiting, stiff neck, rash, abnormal sensitivity to light, myalgia, chills, confusion, or drowsiness while taking lamotrigine.

17.10. Potential Medication Errors

MEDICATION GUIDE

LAMOTRIGINE TABLETS

Rx only

Read this Medication Guide before you start taking lamotrigine tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. If you have questions about lamotrigine tablets, ask your healthcare provider or pharmacist.

What is the most important information I should know about lamotrigine tablets?

• Lamotrigine tablets may cause a serious skin rash that may cause you to be hospitalized or to stop lamotrigine tablets; it may rarely cause death. 

• take lamotrigine tablets while taking valproate (DEPAKENE (valproic acid) or DEPAKOTE (divalproex sodium)).
• take a higher starting dose of lamotrigine tablets than your healthcare provider prescribed.
• increase your dose of lamotrigine tablets faster than prescribed.

Lamotrigine tablets can also cause other types of allergic reactions or serious problems which may affect organs and other parts of your body like the liver or blood cells. You may or may not have a rash with these types of reactions.

Call your healthcare provider right away if you have any of the following:

• a skin rash
• hives
• fever
• swollen lymph glands
• painful sores in the mouth or around your eyes
• swelling of your lips or tongue
• yellowing of your skin or eyes
• unusual bruising or bleeding
• severe fatigue or weakness
• severe muscle pain
• frequent infections

These symptoms may be the first signs of a serious reaction. A healthcare provider should examine you to decide if you should continue taking lamotrigine tablets.

2.     Like other antiepileptic drugs, lamotrigine tablets may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempt to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

Do not stop lamotrigine tablets without first talking to a healthcare provider.

• Stopping lamotrigine tablets suddenly can cause serious problems.
• Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions?

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.
• Call your healthcare provider between visits as needed, especially if you are worried about symptoms

3.   Lamotrigine tablets may rarely cause aseptic meningitis, a serious inflammation of the protective membrane that covers the brain and spinal cord.

• Headache
• Fever
• Nausea
• Vomiting
• Stiff neck
• Rash
• Unusual sensitivity to light
• Muscle pain
• Chills
• Confusion
• Drowsiness

Lamotrigine tabletscan have other serious side effects.

 

Taking the wrong medication can cause serious health problems. When your healthcare provider gives you a prescription for lamotrigine tablets:

• Make sure you can read it clearly.
• Talk to your pharmacist to check that you are given the correct medicine.
• Each time you fill your prescription, check the tablets you receive against the pictures of the tablet below.

What is lamotrigine tablet?

• together with other medicines to treat certain types of seizures (partial seizures, primary generalized tonic-clonic seizures, generalized seizures of Lennox-Gastaut syndrome) in people 2 years or older. 
• alone when changing from other medicines used to treat partial seizures in people 16 years or older.
• for the long-term treatment of Bipolar I Disorder to lengthen the time between mood episodes in people 18 years or older who have been treated for mood episodes with other medicine.

It is not known if lamotrigine tablet is safe or effective in children or teenagers under the age of 18 with mood disorders such as bipolar disorder or depression.

It is not known if lamotrigine tablet is safe or effective when used alone as the first treatment of seizures in adults.

Who should not take lamotrigine tablet ?

You should not take lamotrigine tablet if you have had an allergic reaction to lamotrigine or to any of the inactive ingredients in lamotrigine tablet. See the end of this leaflet for a complete list of ingredients in lamotrigine tablet.

What should I tell my healthcare provider before taking lamotrigine tablet?

Before taking lamotrigine tablet, tell your healthcare provider about all of your medical conditions, including if you:

• have had a rash or allergic reaction to another antiseizure medicine.
• have or have had depression, mood problems or suicidal thoughts or behavior.
• are taking oral contraceptives (birth control pills) or other female hormonal medicines. Do not start or stop taking birth control pills or other female hormonal medicine until you have talked with your healthcare provider. Tell your healthcare provider if you have any changes in your menstrual pattern such as breakthrough bleeding. Stopping or starting these medicines may cause side effects (such as dizziness, lack of coordination, or double vision) or lessen how well lamotrigine tablet works.
• are pregnant or plan to become pregnant. It is not known if lamotrigine tablet will harm your unborn baby. If you become pregnant while taking lamotrigine tablet, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy.
• are breastfeeding. Lamotrigine tablet can pass into your breast milk. You and your healthcare provider should decide if you should take lamotrigine tablet or breastfeed. Breastfeeding while taking lamotrigine tablet is not recommended.

Tell your healthcare provider about all the medicines you take or if you are planning to take a new medicine, including prescription and non-prescription medicines, vitamins, and herbal supplements. Using lamotrigine tablet with certain other medicines can affect each other, causing side effects.

How should I take lamotrigine tablet?

• Take lamotrigine tablet exactly as prescribed.
• Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.
• Do not stop taking lamotrigine tablet without talking to your healthcare provider. Stopping lamotrigine tablet suddenly may cause serious problems. For example, if you have epilepsy and you stop taking lamotrigine tablet suddenly, you may get seizures that do not stop. Talk with your healthcare provider about how to stop lamotrigine tablet slowly.
• If you miss a dose of lamotrigine tablet, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take two doses at the same time.
• You may not feel the full effect of lamotrigine tablet for several weeks.
• If you have epilepsy, tell your healthcare provider if your seizures get worse or if you have any new types of seizures.
• Swallow lamotrigine tablet whole.

What should I avoid while taking lamotrigine tablet ?

• Do not drive a car or operate complex, hazardous machinery until you know how lamotrigine tablet affects you.

What are possible side effects of lamotrigine tablet?

• See “What is the most important information I should know about lamotrigine tablet?”

Common side effects of lamotrigine tablet include:

• dizziness   
• tremor
• headache
• rash
• blurred or double vision
• fever
• lack of coordination
• abdominal pain
• sleepiness
• back pain
• nausea, vomiting
• tiredness
• insomnia
• dry mouth

Tell your healthcare provider about any side effect that bothers you or that does not go away.

These are not all the possible side effects of lamotrigine tablet. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store lamotrigine tablet ?

• Store lamotrigine tablet at 20º-25°C (68º-77°F); excursion permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
• Keep lamotrigine tablet and all medicines out of the reach of children.

General information about lamotrigine tablet

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lamotrigine tablet for a condition for which it was not prescribed. Do not give lamotrigine tablet to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about lamotrigine tablet. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about lamotrigine tablet that is written for healthcare professionals.

What are the ingredients in lamotrigine tablet ?

Lamotrigine tablets


This Medication Guide has been approved by the U.S. Food and Drug Administration.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Lamotrigine Lamotrigine TABLET Product Information Product Type Human prescription drug label Item Code (Source) NDC:16714-371 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LAMOTRIGINE LAMOTRIGINE 25 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate SODIUM STARCH GLYCOLATE TYPE A POTATO povidone MAGNESIUM STEARATE talc Product Characteristics Color Size Imprint Code Shape WHITE (White to off-White) 6 mm L121 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:16714-371-01 30 in 1 BOTTLE 2 NDC:16714-371-02 100 in 1 BOTTLE 3 NDC:16714-371-03 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090607 2011-01-25

Lamotrigine Lamotrigine TABLET Product Information Product Type Human prescription drug label Item Code (Source) NDC:16714-372 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LAMOTRIGINE LAMOTRIGINE 100 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate SODIUM STARCH GLYCOLATE TYPE A POTATO povidone MAGNESIUM STEARATE talc Product Characteristics Color Size Imprint Code Shape WHITE (White to off-White) 8 mm L122 ROUND Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:16714-372-01 30 in 1 BOTTLE 2 NDC:16714-372-02 100 in 1 BOTTLE 3 NDC:16714-372-03 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090607 2011-01-25

Lamotrigine Lamotrigine TABLET Product Information Product Type Human prescription drug label Item Code (Source) NDC:16714-373 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LAMOTRIGINE LAMOTRIGINE 150 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate SODIUM STARCH GLYCOLATE TYPE A POTATO povidone MAGNESIUM STEARATE talc Product Characteristics Color Size Imprint Code Shape WHITE (White to off-White) 9 mm L123 ROUND Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:16714-373-01 30 in 1 BOTTLE 2 NDC:16714-373-04 60 in 1 BOTTLE 3 NDC:16714-373-02 100 in 1 BOTTLE 4 NDC:16714-373-03 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090607 2011-01-25

Lamotrigine Lamotrigine TABLET Product Information Product Type Human prescription drug label Item Code (Source) NDC:16714-374 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LAMOTRIGINE LAMOTRIGINE 200 mg Inactive Ingredients Ingredient Name Strength lactose monohydrate SODIUM STARCH GLYCOLATE TYPE A POTATO povidone MAGNESIUM STEARATE talc Product Characteristics Color Size Imprint Code Shape WHITE (White to off-White) 10 mm L124 ROUND Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:16714-374-01 30 in 1 BOTTLE 2 NDC:16714-374-04 60 in 1 BOTTLE 3 NDC:16714-374-02 100 in 1 BOTTLE 4 NDC:16714-374-03 1000 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090607 2011-01-25