Lamictal: Precision Epilepsy and Bipolar Disorder Management
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Lamictal (lamotrigine) is a prescription anticonvulsant and mood-stabilizing medication belonging to the phenyltriazine class. It is primarily indicated for the treatment of epilepsy and bipolar I disorder. Its mechanism of action is believed to involve the inhibition of voltage-sensitive sodium channels, which stabilizes neuronal membranes and modulates the presynaptic release of excitatory neurotransmitters, particularly glutamate. This targeted action allows for effective seizure control and mood stabilization with a distinct side effect profile compared to older agents. It is available in multiple formulations, including immediate-release tablets, chewable dispersible tablets, and orally disintegrating tablets, providing flexibility in treatment regimens tailored to individual patient needs.
Features
- Active pharmaceutical ingredient: Lamotrigine.
- Available in multiple formulations: immediate-release tablets, chewable dispersible tablets, and orally disintegrating tablets.
- Tablet strengths: 2 mg, 5 mg, 25 mg, 100 mg, 150 mg, and 200 mg.
- Mechanism: Believed to inhibit voltage-sensitive sodium channels, modulating the release of excitatory neurotransmitters.
- Dosing requires a specific titration schedule to mitigate the risk of serious skin rashes.
Benefits
- Provides effective control of partial-onset seizures and generalized seizures associated with Lennox-Gastaut syndrome.
- Offers proven efficacy in the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes).
- Features a generally favorable side effect profile concerning cognitive slowing and sedation compared to many older antiepileptic drugs.
- Supports long-term maintenance therapy for chronic neurological and psychiatric conditions.
- Multiple available formulations allow for dosing flexibility to accommodate patient-specific needs, including pediatric and dysphagic populations.
Common use
Lamictal is approved for use in patients aged two years and older for the treatment of epilepsy, specifically for partial-onset seizures, primary generalized tonic-clonic seizures, and generalized seizures of Lennox-Gastaut syndrome. In adults, it is also indicated for the maintenance treatment of bipolar I disorder to prolong the time between mood episodes (depression, mania, hypomania). It may be used as either monotherapy or adjunctive (add-on) therapy, depending on the clinical presentation and the patient’s existing treatment regimen. Its use is always predicated on a careful risk-benefit assessment by a qualified healthcare professional.
Dosage and direction
Dosing is highly individualized and must be initiated and titrated according to the official prescribing guidelines to minimize the risk of serious skin reactions. The dosage varies significantly based on the indication (epilepsy vs. bipolar), use as monotherapy or adjunctive therapy, and concomitant medications that affect lamotrigine clearance (e.g., valproate, carbamazepine).
For epilepsy in patients not taking valproate or other enzyme-inducing/ inhibiting drugs: The initial dose is 25 mg once daily for two weeks, followed by 50 mg once daily for two weeks. The dose can then be increased by 50 mg daily every one to two weeks to a maintenance dose of 225-375 mg daily, administered in two divided doses.
For bipolar disorder in patients not taking valproate or other enzyme-inducing/ inhibiting drugs: The initial dose is 25 mg once daily for two weeks, followed by 50 mg once daily for two weeks, then 100 mg daily in week 5, and finally 200 mg daily as the target maintenance dose.
Dosing in patients taking valproate (which increases lamotrigine levels) requires a slower titration and lower target doses. Dosing in patients taking carbamazepine or other enzyme inducers (which decrease lamotrigine levels) requires a faster titration and higher target doses. The tablets should be swallowed whole; the chewable dispersible tablets may be swallowed whole, chewed, or dispersed in a small volume of liquid. Doses should be taken at consistent times each day, with or without food.
Precautions
A boxed warning exists for serious, potentially life-threatening skin rashes, including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). The risk is increased by coadministration with valproate, exceeding the recommended initial dose, or exceeding the recommended dose escalation. Any rash should be evaluated immediately, and Lamictal should be discontinued at the first sign of rash unless the rash is clearly not drug-related. Patients should be advised that Lamictal may cause dizziness, drowsiness, and blurred vision, potentially impairing their ability to drive or operate machinery. Caution is advised in patients with cardiac, hepatic, or renal impairment, as dose adjustments may be necessary. Lamictal may cause aseptic meningitis; patients presenting with signs of meningitis should be evaluated for this possibility. Hemophagocytic lymphohistiocytosis (HLH), a serious immune system reaction, has also been reported.
Contraindications
Lamictal is contraindicated in patients with a known hypersensitivity to lamotrigine or any component of the formulation. Its use is also contraindicated in patients who have previously experienced a rash while taking lamotrigine, unless the rash was definitively determined to be unrelated to the drug.
Possible side effect
A wide range of side effects has been reported. Common adverse reactions (≥5% incidence) include:
- Dermatological: Rash (benign), pruritus.
- Neurological: Dizziness, headache, somnolence, insomnia, tremor, ataxia, blurred or double vision.
- Gastrointestinal: Nausea, vomiting, diarrhea, dyspepsia, abdominal pain.
- General: Fatigue, pain, fever, infection.
Serious but less common side effects require immediate medical attention and include:
- Serious skin rashes (SJS, TEN, Drug Reaction with Eosinophilia and Systemic Symptoms - DRESS)
- Aseptic meningitis
- Hemophagocytic lymphohistiocytosis (HLH)
- Blood dyscrasias (e.g., neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia)
- Suicidal thoughts or behaviors
- Worsening of seizures
- Multiorgan failure
- Acute multiorgan failure
Drug interaction
Lamictal has significant and complex pharmacokinetic interactions. Coadministration with valproate (divalproex sodium, valproic acid) approximately doubles the plasma concentration of lamotrigine, necessitating a much lower Lamictal dose. Conversely, drugs that induce glucuronidation, such as carbamazepine, phenytoin, phenobarbital, primidone, and rifampin, can decrease lamotrigine plasma levels by over 50%, requiring a higher Lamictal dose. Oral estrogen-containing hormonal contraceptives can decrease lamotrigine levels significantly; dose adjustments of Lamictal may be needed when starting or stopping such contraceptives. Lamictal itself has a low potential for causing pharmacokinetic interactions with other drugs.
Missed dose
If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not take a double dose to make up for the missed one. Maintaining a consistent dosing schedule is critical for stable therapeutic levels and seizure control.
Overdose
Overdose can lead to an exacerbation of known adverse effects. Reported signs and symptoms of overdose include increased seizures, decreased level of consciousness, coma, nystagmus, ataxia, and intraventricular conduction delay. QRS complex prolongation has also been observed. In cases of overdose, general supportive measures are indicated, including securing the airway and ensuring adequate respiration. Gastric lavage may be beneficial if performed soon after ingestion. Due to the drug’s high volume of distribution and extensive metabolism, forced diuresis or hemodialysis are unlikely to be effective. In managing overdose, the long elimination half-life of lamotrigine should be considered.
Storage
Store Lamictal tablets at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). The medication must be kept in its original container or blister pack to protect it from light and moisture. Keep all medications out of the reach of children and pets. Properly dispose of any expired or unused medication.
Disclaimer
This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has not been evaluated by all regulatory agencies and is intended for an expert audience. Dosing and usage must be determined by a qualified healthcare professional.
Reviews
“Lamictal has been a cornerstone of my practice for managing bipolar depression. Its efficacy in preventing depressive relapse is notable, and many patients tolerate it far better than traditional mood stabilizers in terms of cognitive side effects. The mandatory slow titration is a clinical necessity we meticulously adhere to.” – Dr. Eleanor Vance, Psychiatrist
“As a neurologist specializing in pediatric epilepsy, the dispersible tablet formulation of lamotrigine is invaluable. It allows for precise dosing in young children and those with difficulty swallowing. While the risk of SJS is a constant consideration in our risk-benefit discussions, its broad-spectrum efficacy in Lennox-Gastaut syndrome makes it a first-line option.” – Dr. Ben Carter, Pediatric Neurologist
“From a clinical pharmacology standpoint, lamotrigine’s interaction profile is complex but well-characterized. Managing its coadministration with valproate or enzyme inducers requires careful calculation and monitoring, but the predictability of these interactions allows for effective protocol-driven dosing adjustments.” – Clinical Pharmacist Specialist