Lamotrigine

Lamotrigine Uses, Dosage, Side Effects, Food Interaction and all others data.

Lamotrigine controls epileptic seizures by inhibiting voltage-sensitive sodium channels, thereby stabilizes neuronal membranes and consequently inhibits presynaptic excitatory neurotransmitter (e.g., glutamate and aspartate) release.

Lamotrigine likely prevents seizures and prevents mood symptoms via stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate, which contribute to seizure activity.

A note on cardiovascular effects

The metabolite of lamotrigine, 2-N-methyl metabolite (formed by glucuronidation), is reported to cause dose-dependent prolongations of the PR interval, widening of the QRS complex, and at higher doses, complete AV block. Although this harmful metabolite is only found in trace amounts in humans, plasma concentrations may increase in conditions that cause decreased drug glucuronidation, such as liver disease.

Trade Name Lamotrigine
Availability Prescription only
Generic Lamotrigine
Lamotrigine Other Names Lamotrigina, Lamotrigine, Lamotriginum
Related Drugs Vraylar, gabapentin, fluoxetine, clonazepam, quetiapine, diazepam, Abilify, Prozac, pregabalin, Seroquel
Type Oral tablet, oral tablet, disintegrating, oral tablet, dispersible, oral tablet, extended release
Formula C9H7Cl2N5
Weight Average: 256.091
Monoisotopic: 255.007850663
Protein binding

The plasma protein binding of lamotrigine is estimated at 55%. This drug is not expected to undergo clinically significant interactions with other drugs via competition for protein binding sites due its lower protein binding.

Groups Approved, Investigational
Therapeutic Class Primary anti-epileptic drugs
Manufacturer Aurobindo Pharma - Milpharm Ltd,
Available Country United Kingdom, United States
Last Updated: September 19, 2023 at 7:00 am
Lamotrigine
Lamotrigine

Uses

Lamotrigine is an antiepileptic drug (AED) used for:

Epilepsy (adjunctive therapy in patients aged 2 years and older):

  • Partial: Onset seizures.
  • Primary generalized tonic: Clonic seizures.
  • Generalized seizures of Lennox: Gastaut syndrome.

Epilepsy (monotherapy in patients aged 16 years and older).Bipolar disorder in patients aged 18 years and older.

Lamotrigine is also used to associated treatment for these conditions: Bipolar 1 Disorder, Grand mal Generalized tonic-clonic seizure, Partial-Onset Seizures, Generalized seizure, Conversion to monotherapy

How Lamotrigine works

The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters.

Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states.

Lamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin 5-HT3 receptor. Lamotrigine also weakly binds to Adenosine A1/A2 receptors, α1/α2/β adrenergic receptors, dopamine D1/D2 receptors, GABA A/B receptors, histamine H1 receptors, κ-opioid receptor (KOR), mACh receptors and serotonin 5-HT2 receptors with an IC50>100 µM. Weak inhibitory effects were observed at sigma opioid receptors. An in vivo study revealed evidence that lamotrigine inhibits Cav2.3 (R-type) calcium currents, which may also contribute to its anticonvulsant effects.

Dosage

Lamotrigine dosage

Monotherapy of seizures (adult and child over 16 years): Initially 25 mg once daily for 14 days, then 50 mg once daily for further 14 days, then increased by maximum 50 mg/day every 7-14 days; usual maintenance dose 225-375 mg/day in 1-2 divided doses.

Adjunctive therapy of seizures with Valproate:

  • Adult and child over 12 years: Initially 25 mg on alternate days for 14 days, then 25 mg once daily for further 14 days, thereafter increased by maximum 25-50 mg/day every 7-14 days; usual maintenance, 100-200 mg/day in 1-2 divided doses.
  • Child 2-12 years: Initially 150 mcg/kg/day in 1-2 divided doses for 14 days (those weighing under 13 kg may receive 2 mg on alternate days for first 14 days), then 300 mcg/kg/day in 1-2 divided doses for further 14 days, thereafter increased by maximum 300 mcg/kg/day every 7-14 days; usual maintenance 1-3 mg/kg/day in 1-2 divided doses.

Adjunctive therapy of seizures (with enzyme inducing drugs e.g., Carbamazepine, Phenytoin, Phenobarbital, or Primidone) without Valproate:

  • Adult and child over 12 years: Initially 50 mg once daily for 14 days, then 50 mg twice daily for further 14 days, thereafter increased by maximum 100 mg/day in every 7-14 days; usual maintenance 300-500 mg daily in 2 divided doses.
  • Child 2-12 years: Initially 600 mcg/kg/day in 2 divided doses for 14 days, then 1.2 mg/kg/day in 2 divided doses for further 14 days, thereafter increased by maximum 1.2 mg/kg/day in every 7-14 days; usual maintenance 5-15 mg/kg/day in 2 divided doses (maximum 400 mg/day in 2 divided doses).

Monotherapy therapy of bipolar disorder (without enzyme inducing Drugs) without Valproate:

  • Adult over 18 years: Initially 25 mg once daily for 14 days, then 50 mg once daily for further 14 days, then 100 mg once daily for further 7 days; usual maintenance dose 200 mg once daily; maximum 200 mg daily.

Adjunctive therapy of bipolar disorder with valproate:

  • Adult over 18 years: Initially 25 mg on alternate days for 14 days, then 25 mg once daily for further 14 days, then 50 mg once daily for further 7 days; usual maintenance dose 100 mg daily; maximum 100 mg daily.

Adjunctive therapy of bipolar disorder (with enzyme inducing drugs with enzyme inducing drugs e.g., Carbamazepine, Phenytoin, Phenobarbital, or Primidone) without Valproate:

  • Adult over 18 years: Initially 50 mg once daily for 14 days, then 50 mg twice daily for further 14 days, then 100 mg twice daily for further 7 days, then 150 mg twice daily for further 7 days; usual maintenance 200 mg twice daily

Side Effects

Adult: Dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, and rash.

Children: Vomiting, diarrhea, infection, fever, abdominal pain, and tremor.

Toxicity

The oral LD50 in mouse and rat is 205 mg/kg and 245 mg/kg, respectively.

Fatal cases of overdose of up to 15g of lamotrigine have been reported. Overdose with lamotrigine has been manifested by ataxia, nystagmus, increased seizures, decreased level of consciousness, coma, and intraventricular conduction delay. Though no known antidote exists for lamotrigine, hospitalization and general supportive measures should be employed in the case of a suspected lamotrigine overdose. Gastric lavage and emesis may be warranted with simultaneous protection of the airway. It is uncertain at this time whether hemodialysis is an effective means of removing lamotrigine from the sytemic circulation.

Precaution

  • Discontinue at the first sign of rash.
  • Blood dyscrasias (e.g., neutropenia, thrombocytopenia, pancytopenia): May occur, either with or without an associated hypersensitivity syndrome. Monitor for signs of anemia, unexpected infection, or bleeding.
  • Suicidal behavior and ideation: Monitor for suicidal thoughts or behaviors.
  • Aseptic meningitis: Monitor for signs of meningitis.

Interaction

  • Valproate increases lamotrigine concentrations more than 2-fold.
  • Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by approximately 40%.
  • Estrogen-containing oral contraceptives decrease lamotrigine concentrations by approximately 50%.
  • Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure by approximately 50% and 32%, respectively.

Food Interaction

  • Take with or without food. The absorption is unaffected by food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Volume of Distribution

The mean apparent volume of distribution (Vd/F) of lamotrigine following oral administration ranges from 0.9 to 1.3 L/kg and is independent of dose administered. Lamotrigine accumulated in the kidney of the male rat, and likely behaves in a similar fashion in humans. Lamotrigine also binds to tissues containing melanin, such as the eyes and pigmented skin.

Elimination Route

Lamotrigine is rapidly and entirely absorbed with minimal first-pass metabolism effects, with a bioavailability estimated at 98%. Cmax is reached in the range of 1.4 to 4.8 hours post-dose, but this depends on the dose administered, concomitant medications, and epileptic status. The rate and extent of lamictal absorption is considered equivalent between the compressed tablet form taken with water to that of the chewable dispersible tablets, taken with or without water.

Half Life

The average elimination half-life of lamotrigine ranges from approximately 14-59 hours. The value is dependent on the dose administered, concomitant drug therapy, as well as disease status. One pharmacokinetic study revealed a half-life of 22.8 to 37.4 hours in healthy volunteers. It also reported that enzyme-inducing antiepileptic drugs such as pheobarbital, phenytoin, or carbamazepine decrease the half-life of lamotrigine. On the other hand, valproic acid increases the half-life of lamotrigine (in the range of 48-59 hours).

Clearance

The mean apparent plasma clearance (Cl/F) ranges from 0.18 to 1.21 mL/min/kg. The values vary depending on dosing regimen, concomitant antiepileptic medications, and disease state of the individual. In one study, healthy volunteers on lamictal monotherapy showed a clearance of about 0.44 mL/min/kg after a single dose.

Elimination Route

Lamotrigine is excreted in both the urine and feces. Following oral administration of 240 mg radiolabelled lamotrigine, about 94% of total drug and its metabolites administered is recovered in the urine and 2% is recovered in the feces. One pharmacokinetic study recovered 43 to 87% of a lamotrigine dose in the urine mainly as glucuronidated metabolites. 2-N-glucuronide is mainly excreted in the urine.

Pregnancy & Breastfeeding use

Pregnancy category C. Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: Lamotrigine is present in milk from lactating women taking Lamotrigine.

Contraindication

Hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients.

Special Warning

Hepatic impairment: Dosage adjustments required in patients with moderate and severe liver impairment.

Renal impairment: Reduced maintenance doses may be effective for patients with significant renal impairment.

Acute Overdose

Symptoms: Nystagmus and muscle hypertonicity, QRS interval prolongation, low-grade fever, erythema, and periorbital oedema, generalised tonic-clonic seizures, tremor, muscle weakness, ataxia, hypertonia. 

Management: Gastric lavage and activated charcoal.

Storage Condition

Store below 30°C. Protect from light and moisture. Keep out of the reach of children

Innovators Monograph

You find simplified version here Lamotrigine

Lamotrigine contains Lamotrigine see full prescribing information from innovator Lamotrigine Monograph, Lamotrigine MSDS, Lamotrigine FDA label

FAQ

What is Lamotrigine used for?

Lamotrigine is a medication used to treat epilepsy and in regards to mental health, help the recurrence of depressive manic episodes in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome.

How safe is Lamotrigine?

To date, there are no known problems associated with long term use of Lamotrigine. It is a safe and effective medication when used as directed.

How safe is Lamotrigine?

Lamotrigine work by decreasing the intensity of irregular electrical activity in the brain.

What are the common side effects of Lamotrigine?

Common side effects of Lamotrigine are include:

  • loss of balance or coordination
  • double vision
  • blurred vision
  • uncontrollable movements of the eyes
  • difficulty thinking or concentrating
  • difficulty speaking
  • headache
  • drowsiness
  • dizziness
  • diarrhea
  • constipation
  • loss of appetite
  • weight loss
  • heartburn
  • nausea
  • vomiting
  • dry mouth
  • stomach, back, or joint pain
  • missed or painful menstrual periods
  • swelling, itching, or irritation of the vagina
  • uncontrollable shaking of a part of the body

Is Lamotrigine safe during pregnancy?

Pregnancy registries have consistently demonstrated Lamotrigine to be among the safest medications for a developing fetus, both in terms of fetal malformations and postpartum cognitive development.

Is Lamotrigine safe during breastfeeding?

The results indicated that Lamotrigine is a safe anti-epileptic drug for breastfeeding women with rare and usually mild adverse effects among neonates exposed to high milk concentration of this Lamotrigine and its metabolites.

Can I drink alcohol with Lamotrigine?

Yes, you can drink alcohol with Lamotrigine. But it may make you feel sleepy or tired, and alcohol and hangovers can bring on seizures in some people with epilepsy. During the first few days of taking Lamotrigine, it's best to stop drinking alcohol until you see how the medicine affects you.

Can I drive after taking Lamotrigine ?

feeling drowsy, sleepy or dizzy as your body gets used to Lamotrigine, these side effects should wear off. Do not drive, ride a bike or operate machinery until you feel more alert.

When is best taken of Lamotrigine?

You can take it with or without food. If you take it twice a day, try to space your doses evenly through the day. For example, first thing in the morning and in the evening.

How often can I take Lamotrigine?

It's usual to take Lamotrigine once or twice a day.

Can I take Lamotrigine on an empty stomach?

Lamotrigine may be taken with or without food or on a full or empty stomach.

How long does Lamotrigine take to work?

It usually takes around 6 weeks for lamotrigine to work properly.

How long does Lamotrigine stay in my system?

Lamotrigine will be out of your system after your last dose in about 338.8 hours (approximately 14 days). After multiple dosing of lamotrigine the elimination half-life is noted to be between 11.6 to 61.6 hours.

Can I take Lamotrigine for a long time ?

Many people can take Lamotrigine safely for several months or years. But there are some side effects that might happen over a long time. Long-term treatment with Lamotrigine can cause osteoporosis and osteopenia, increasing your risk of breaking a bone.

What does Lamotrigine do to the brain?

Lamotrigine also binds and weakly inhibits several other signaling receptors in the brain, including those to which dopamine and serotonin normally bind.

Is Lamotrigine bad for my liver?

Lamotrigine is a widely used antiseizure medication that is a rare but well known cause of idiosyncratic liver injury, that can be severe and even fatal.

Does Lamotrigine shorten my life?

Lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression.

Can Lamotrigine damage my kidneys?

Talk to your doctor if you have any concerns. Lamotrigine may cause serious allergic reactions affecting multiple body organs (eg, liver or kidney).

Who should not take Lamotrigine?

You should not take Lamotrigine if you are allergic to it. Lamotrigine may cause a severe or life-threatening skin rash, especially in children and in people who take a very high starting dose.

Can I stop taking Lamotrigine?

Do not start or stop taking seizure Lamotrigine during pregnancy without your doctor's advice. Having a seizure during pregnancy could harm both mother and baby. Tell your doctor right away if you become pregnant.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time. Get your prescription refilled before you run out of medicine completely.

What happens if I overdose?

Seek emergency medical attention. Overdose symptoms may include blurred vision, problems with coordination, increased seizures, feeling light-headed, or fainting.

Will Lamotrigine affect my fertility?

Lamotrigine does not seem to affect sperm counts, motility, or sex hormones in men.

Can Lamotrigine affects my heart?

Lamotrigine can increase the risk of serious arrhythmias, which can be life-threatening, in patients with clinically important structural or functional heart disorders.

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*** Taking medicines without doctor's advice can cause long-term problems.
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