Lamictal XR

What is Lamictal XR?

Lamictal XR is a prescription medicine used together with other medicines to treat primary generalized tonic-clonic seizures and partial-onset seizures in people aged 13 years and older, alone when changing from 1 other medicine used to treat partial-onset seizures in people aged 13 years and older.

It is not known if Lamictal XR is safe or effective in children younger than 13 years. Other forms of Lamictal can be used in children aged 2 to 12 years.

It is not known if Lamictal XR is safe or effective when used alone as the first treatment of seizures.

Description

LAMICTAL XR (lamotrigine), an AED of the phenyltriazine class, is chemically unrelated to existing AEDs. Lamotrigine’s chemical name is 3,5-diamino-6-(2,3-dichlorophenyl)-as-triazine, its molecular formula is C9H7N5Cl2, and its molecular weight is 256.09. Lamotrigine is a white to pale cream-colored powder and has a pKa 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 XR extended-release tablets are supplied for oral administration as 25-mg (yellow with white center), 50-mg (green with white center), 100-mg (orange with white center), 200-mg (blue with white center), 250-mg (purple with white center), and 300-mg (gray with white center) tablets. Each tablet contains the labeled amount of lamotrigine and the following inactive ingredients: glycerol monostearate, hypromellose, lactose monohydrate; magnesium stearate; methacrylic acid copolymer dispersion, polyethylene glycol 400, polysorbate 80, silicon dioxide (25- and 50-mg tablets only), titanium dioxide, triethyl citrate, carmine (250-mg tablet only), iron oxide black (50-, 250-, and 300-mg tablets only), iron oxide yellow (25-, 50-, and 100-mg tablets only), iron oxide red (100-mg tablet only), FD&C Blue No. 2 Aluminum Lake (200- and 250-mg tablets only). Tablets are printed with edible black ink.

LAMICTAL XR extended-release tablets contain a modified-release eroding formulation as the core. The tablets are coated with a clear enteric coat and have an aperture drilled through the coats on both faces of the tablet (DiffCORE) to enable a controlled release of drug in the acidic environment of the stomach. The combination of this and the modified-release core are designed to control the dissolution rate of lamotrigine over a period of approximately 12 to 15 hours, leading to a gradual increase in serum lamotrigine levels.

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).

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.

What is the most important information I should know about Lamictal XR?

1. Lamictal XR 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 Lamictal XR, but is more likely to happen within the first 2 to 8 weeks of treatment. Children aged between 2 and 16 years have a higher chance of getting this serious skin rash while taking Lamictal XR. Lamictal XR is not approved for use in children younger than 13 years.
The risk of getting a serious skin rash is higher if you:

• take Lamictal XR while taking valproate [Depakene (valproic acid) or Depakote (divalproex sodium)].
• take a higher starting dose of Lamictal XR than your healthcare provider prescribed.
• increase your dose of Lamictal XR faster than prescribed.
  Call your healthcare provider right away if you have any of the following:
  • a skin rash
  • blistering or peeling of your skin
  • hives
  • painful sores in your mouth or around your eyesThese symptoms may be the first signs of a serious skin reaction. A healthcare provider should examine you to decide if you should continue taking Lamictal XR.

2. Other serious reactions, including serious blood problems or liver problems. Lamictal XR can also cause other types of allergic reactions or serious problems that may affect organs and other parts of your body like your 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 these symptoms:

• fever
• frequent infections
• severe muscle pain
• swelling of your face, eyes, lips, or tongue
• swollen lymph glands
• unusual bruising or bleeding
• weakness, fatigue
• yellowing of your skin or the white part of your eyes

3. Like other antiepileptic drugs, Lamictal XR 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 moodDo not stop Lamictal XR without first talking to a healthcare provider.
• Stopping Lamictal XR 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 in myself or a family member?
• 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.

4. Lamictal XR may cause aseptic meningitis, a serious inflammation of the protective membrane that covers the brain and spinal cord.

• Call your healthcare provider right away if you have any of the following symptoms:
  • headache
  • fever
  • nausea
  • vomiting
  • stiff neck
  • rash
  • unusual sensitivity to light
  • muscle pains
  • chills
  • confusion
  • drowsinessMeningitis has many causes other than Lamictal XR, which your doctor would check for if you developed meningitis while taking Lamictal XR.

Lamictal XR can cause other serious side effects. For more information ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effect that bothers you. Be sure to read the section below entitled “What are the possible side effects of Lamictal XR?”

People prescribed Lamictal XR have sometimes been given the wrong medicine because many medicines have names similar to Lamictal XR, so always check that you receive Lamictal XR.
Taking the wrong medication can cause serious health problems. When your healthcare provider gives you a prescription for Lamictal XR:

• 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 tablets below.

These pictures show the distinct wording, colors, and shapes of the tablets that help to identify the right strength of Lamictal XR. Immediately call your pharmacist if you receive a Lamictal XR tablet that does not look like one of the tablets shown below, as you may have received the wrong medication.

Lamictal XR (lamotrigine) extended-release tablets

25 mg, yellow with white center Imprinted with Lamictal XR 25	50 mg, green with white center Imprinted with Lamictal XR 50	100 mg, orange with white center Imprinted with Lamictal XR 100
200 mg, blue with white center Imprinted with Lamictal XR 200	250 mg, purple with white center Imprinted with Lamictal XR 250	300 mg, gray with white center Imprinted with Lamictal XR 300

Who should not take Lamictal XR?

Do not take Lamictal XR:

• if you have had an allergic reaction to lamotrigine or to any of the inactive ingredients in Lamictal XR. See the end of this leaflet for a complete list of ingredients in Lamictal XR.

What should I tell my healthcare provider before taking Lamictal XR?

Before taking Lamictal XR, tell your healthcare provider about all of your health 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.
• have had aseptic meningitis after taking Lamictal (lamotrigine) or Lamictal XR.
• 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 these medicines while you are taking Lamictal XR may cause side effects (such as dizziness, lack of coordination, or double vision). Starting these medicines may lessen how well Lamictal XR works.
• are pregnant or plan to become pregnant. It is not known if Lamictal XR may harm your unborn baby. If you become pregnant while taking Lamictal XR, 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. Lamictal XR passes into breast milk and may cause side effects in a breastfed baby. If you breastfeed while taking Lamictal XR, watch your baby closely for trouble breathing, episodes of temporarily stopping breathing, sleepiness, or poor sucking. Call your baby’s healthcare provider right away if you see any of these problems. Talk to your healthcare provider about the best way to feed your baby if you take Lamictal XR.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Lamictal XR and certain other medicines may interact with each other. This may cause serious side effects.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Lamictal XR?

• Take Lamictal XR 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 Lamictal XR without talking to your healthcare provider. Stopping Lamictal XR suddenly may cause serious problems. For example, if you have epilepsy and you stop taking Lamictal XR suddenly, you may have seizures that do not stop. Talk with your healthcare provider about how to stop Lamictal XR slowly.
• If you miss a dose of Lamictal XR, 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 2 doses at the same time.
• If you take too much Lamictal XR, call your healthcare provider or your local Poison Control Center or go to the nearest hospital emergency room right away.
• You may not feel the full effect of Lamictal XR 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.
• Lamictal XR can be taken with or without food.
• Do not chew, crush, or divide Lamictal XR.
• Swallow Lamictal XR tablets whole.
• If you have trouble swallowing Lamictal XR tablets, tell your healthcare provider because there may be another form of Lamictal you can take.
• If you receive Lamictal XR in a blister pack, examine the blister pack before use. Do not use if blisters are torn, broken, or missing.

What should I avoid while taking Lamictal XR?

Do not drive, operate machinery, or do other dangerous activities until you know how Lamictal XR affects you.

What are the possible side effects of Lamictal XR?

Lamictal XR can cause serious side effects.

See “What is the most important information I should know about Lamictal XR?”

Common side effects of Lamictal XR include:

• dizziness
• vomiting
• tremor
• trouble with balance and coordination
• double vision
• anxiety
• nausea

Other common side effects that have been reported with another form of Lamictal include headache, sleepiness, blurred vision, runny nose, and rash.

These are not all the possible side effects of Lamictal XR.

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

General information about the safe and effective use of Lamictal XR

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Lamictal XR for a condition for which it was not prescribed. Do not give Lamictal XR 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, Lamictal XR 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 Lamictal XR.

You can ask your healthcare provider or pharmacist for information about Lamictal XR that is written for health professionals.

How should I store Lamictal XR?

• Store Lamictal XR at room temperature between 59°F and 86°F (15°C and 30°C).

Keep Lamictal XR and all medicines out of the reach of children.

What are the ingredients in Lamictal XR?

Active ingredient: lamotrigine.

Inactive ingredients: glycerol monostearate, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid copolymer dispersion, polyethylene glycol 400, polysorbate 80, silicon dioxide (25- and 50-mg tablets only), titanium dioxide, triethyl citrate, carmine (250-mg tablet only), iron oxide black (50-, 250-, and 300-mg tablets only), iron oxide yellow (25-, 50-, and 100-mg tablets only), iron oxide red (100-mg tablet only), FD&C Blue No. 2 Aluminum Lake (200- and 250-mg tablets only). Tablets are printed with edible black ink.

Label

PRINCIPAL DISPLAY PANEL

• NDC 0173-0781-00
• LAMICTAL® XRTM
• (LAMOTRIGINE)
• EXTENDED- RELEASE TABLETS
• 250 mg
• Once A Day
• Rx only
• CAUTION: Verify Product Dispensed
• 30 tablets
• Dispense the accompanying Medication Guide to each patient.
• See prescribing information for dosage information.
• Do not use if printed safety seal under cap is broken or missing.
• Store at 25oC (77oF); excursions permitted to 15oC to 30oC (59oF to 86oF) [see USP Controlled Room Temperature].
• GlaxoSmithKline
• RTP, NC 27709
• Made in India
• Rev. 4/17
• 10000000146235

SRC: NLM .