The effectiveness of lamotrigine in the maintenance treatment of bipolar I disorder was established in 2 multicenter, double-blind, placebo-controlled trials in adult patients (aged 18 to 82 years) who met DSM-IV criteria for bipolar I disorder. Trial 1 enrolled patients with a current or recent (within 60 days) depressive episode as defined by DSM-IV and Trial 2 included patients with a current or recent (within 60 days) episode of mania or hypomania as defined by DSM-IV. Both trials included a cohort of patients (30% of 404 subjects in Trial 1 and 28% of 171 patients in Trial 2) with rapid cycling bipolar disorder (4 to 6 episodes per year).
In both trials, patients were titrated to a target dose of 200 mg of 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 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 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 Trial 1, patients received double-blind monotherapy with lamotrigine 50 mg/day (n = 50), lamotrigine 200 mg/day (n = 124), lamotrigine 400 mg/day (n = 47), or placebo (n = 121). Lamotrigine (200 and 400 mg/day treatment groups combined) was superior to placebo in delaying the time to occurrence of a mood episode (Figure 1). Separate analyses of the 200 and 400 mg/day dose groups revealed no added benefit from the higher dose.
In Trial 2, patients received double-blind monotherapy with lamotrigine (100 to 400 mg/day, n = 59), or placebo (n = 70). Lamotrigine was superior to placebo in delaying time to occurrence of a mood episode (Figure 2). The mean dose of lamotrigine was about 211 mg/day.
Although these trials were not designed to separately evaluate time to the occurrence of depression or mania, a combined analysis for the 2 trials revealed a statistically significant benefit for lamotrigine over placebo in delaying the time to occurrence of both depression and mania, although the finding was more robust for depression.
Figure 1: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Mood Episode (Trial 1)
Lamotrigine Tablets USP, 25 mg are white to off-white, round, flat, beveled-edged tablets with bisect on one side; one side of the bisect is debossed with logo of “ZC” and other side is debossed with “79” and other side is plain and are supplied as follows:
NDC 82009-131-10 in bottles of 1000 tablets
Lamotrigine Tablets USP, 100 mg are white to off-white, round, flat, beveled-edged tablets with bisect on one side; one side of the bisect is debossed with logo of “ZC” and other side is debossed with “80”and other side is plain and are supplied as follows:
NDC 82009-132-10 in bottles of 1000 tablets
Lamotrigine Tablets USP, 150 mg are white to off-white, round, flat, beveled-edged tablets with bisect on one side; one side of the bisect is debossed with logo of “ZC” and other side is debossed with “81” and other side is plain and are supplied as follows:
NDC 82009-133-05 in bottles of 500 tablets
Lamotrigine Tablets USP, 200 mg are white to off-white, round, flat, beveled-edged tablets with bisect on one side; one side of the bisect is debossed with logo of “ZC” and other side is debossed with “82” and other side is plain and are supplied as follows:
NDC 82009-134-05 in bottles of 500 tablets
Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature] in a dry place.
Dispense in a tight, light-resistant container as defined in the USP.
Prior to initiation of treatment with lamotrigine, inform patients that a rash or other signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy) may herald a serious medical event and instruct them to report any such occurrence to their healthcare providers immediately.
Prior to initiation of treatment with lamotrigine, inform patients that excessive immune activation may occur with lamotrigine and that they should report signs or symptoms such as fever, rash, or lymphadenopathy to a healthcare provider immediately.
Multiorgan Hypersensitivity Reactions, Blood Dyscrasias, and Organ Failure
Inform patients that multiorgan hypersensitivity reactions and acute multiorgan failure may occur with lamotrigine. Isolated organ failure or isolated blood dyscrasias without evidence of multiorgan hypersensitivity may also occur. Instruct patients to contact their healthcare providers immediately if they experience any signs or symptoms of these conditions [see Warnings and Precautions (5.3, 5.5)].
Cardiac Rhythm and Conduction Abnormalities
Inform patients that, due to its mechanism of action, lamotrigine could lead to irregular or slowed heart rhythm. This risk is increased in patients with underlying cardiac disease or heart conduction problems or who are taking other medications that affect heart conduction. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away. Patients who develop syncope should lie down with raised legs and contact their healthcare provider [see Warnings and Precautions (5.4)].
Suicidal Thinking and Behavior
Inform patients, their caregivers, and families that AEDs, including lamotrigine, may increase the risk of suicidal thoughts and behavior. Instruct them to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior or thoughts about self-harm. Instruct them to immediately report behaviors of concern to their healthcare providers.
Worsening of Seizures
Instruct patients to notify their healthcare providers if worsening of seizure control occurs.
Central Nervous System Adverse Effects
Inform patients that lamotrigine may cause dizziness, somnolence, and other symptoms and signs of central nervous system depression. Accordingly, instruct them neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on lamotrigine to gauge whether or not it adversely affects their mental and/or motor performance.
Pregnancy and Nursing
Instruct patients to notify their healthcare providers if they become pregnant or intend to become pregnant during therapy and if they intend to breastfeed or are breast-feeding an infant.
Encourage patients 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 [see Use in Specific Populations (8.1)] .
Inform patients who intend to breastfeed that lamotrigine is present in breast milk and advise them to monitor their child for potential adverse effects of this drug. Discuss the benefits and risks of continuing breast-feeding.
Oral Contraceptive Use
Instruct women to notify their healthcare providers if they plan to start or stop use of oral contraceptives or other female hormonal preparations. Starting estrogen-containing oral contraceptives may significantly decrease lamotrigine plasma levels and stopping estrogen-containing oral contraceptives (including the pill-free week) may significantly increase lamotrigine plasma levels [see Warnings and Precautions (5.9), Clinical Pharmacology (12.3)]. Also instruct women to promptly notify their healthcare providers if they experience adverse reactions or changes in menstrual pattern (e.g., break-through bleeding) while receiving lamotrigine in combination with these medications.
Instruct patients to notify their healthcare providers if they stop taking lamotrigine for any reason and not to resume lamotrigine without consulting their healthcare providers.
Inform patients that lamotrigine may cause aseptic meningitis. Instruct them to notify their healthcare providers 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.
Potential Medication Errors
To avoid a medication error of using the wrong drug or formulation, strongly advise patients to visually inspect their tablets to verify that they are lamotrigine, as well as the correct formulation of lamotrigine, each time they fill their prescription [see Dosage Forms and Strengths (3.1, 3.2), How Supplied/Storage and Handling (16)]. Refer the patient to the Medication Guide that provides depictions of the lamotrigine tablets.
Medication Guide available at www.quallentpharmaceuticals.com or call 1-877-605-7243.
Zydus Lifesciences Ltd.
Quallent Pharmaceuticals Health LLC
Grand Cayman, Cayman islands
|MEDICATION GUIDE Lamotrigine (la moe′ tri jeen) Tablets, USP|
| What is the most important information I should know about Lamotrigine? 1. Lamotrigine may cause a serious skin rash that may cause you to be hospitalized or even cause death. There is no way to tell if a mild rash will become more serious. A serious skin rash can happen at any time during your treatment with lamotrigine, but is more likely to happen within the first 2 to 8 weeks of treatment. Children and teenagers aged between 2 and 17 years have a higher chance of getting this serious skin rash while taking lamotrigine. The risk of getting a serious skin rash is higher if you: |
|25 mg, white to off-white||50 mg, white to off-white||100 mg, white to off-white||150 mg, white to off-white||200 mg, white to off-white||250 mg, white to-off white|
|One side of the bisect is debossed with “ZC” and other side is debossed with “79”||One side of the bisect is debossed with “ZC” and other side is debossed with “90”||One side of the bisect is debossed with “ZC” and other side is debossed with “80”||One side of the bisect is debossed with “ZC” and other side is debossed with “81”||One side of the bisect is debossed with “ZC” and other side is debossed with “82”||One side of the bisect is debossed with “ZC” and other side is debossed with “91”|
| What is lamotrigine? |
| Do not take lamotrigine: |
| Before taking lamotrigine, tell your healthcare provider about all of your health conditions, including if you: |
| How should I take lamotrigine? |
|What should I avoid while taking lamotrigine? Do not drive, operate machinery, or do other dangerous activities until you know how lamotrigine affects you.|
|What are the possible side effects of lamotrigine? Lamotrigine can cause serious side effects. See “ What is the most important information I should know about lamotrigine? ” Common side effects of lamotrigine include:|
|These are not all the possible side effects of lamotrigine. 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? |
|General information about the safe and effective use of lamotrigine Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lamotrigine for a condition for which it was not prescribed. Do not give lamotrigine to other people, even if they have the same symptoms that you have. It may harm them. If you take a urine drug screening test, lamotrigine may make the test result positive for another drug. If you require a urine drug screening test, tell the healthcare professional administering the test that you are taking lamotrigine. You can ask your healthcare provider or pharmacist for information about lamotrigine that is written for health professionals. Please address medical inquiries to https://www.quallentpharmaceuticals.com at 1-877-605-7243.|
|What are the ingredients in Lamotrigine? Lamotrigine Tablets Active ingredient: lamotrigine, USP. Inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and sodium starch glycolate. Medication Guide available at https://www.quallentpharmaceuticals.com at 1-877-605-7243. This Medication Guide has been approved by the U.S. Food and Drug Administration. DEPAKENE and DEPAKOTE are registered trademarks of Abbott Laboratories.|
|Manufactured by: Zydus Lifesciences Ltd. India Manufactured for: Quallent Pharmaceuticals Health LLC Grand Cayman, Cayman islands|
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