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Lamotrigine is a synthetic phenyltriazine with antiepileptic and pain-relieving medicine. সহজ বাংলা: ব্যথানাশক ওষুধ।" data-rx-term="analgesic" data-rx-definition="An analgesic is a pain-relieving medicine. সহজ বাংলা: ব্যথানাশক ওষুধ।">analgesic properties. Lamotrigine enhances the action of gamma-aminobutyric acid, an inhibitory neurotransmitter, which may result in a reduction of pain-related transmission of signals along nerve fibers. This agent may also inhibit voltage-gated sodium channels, suppress glutamate release, and inhibit serotonin reuptake. (NCI04)
Lamotrigine can be used to treat the following partial seizures, primary generalized tonic-clonic seizures, bipolar I disorder maintenance, and Lennox-Gastaut syndrome. Off-label uses include treatment of acute bipolar depression, fibromyalgia, schizophrenia, and unipolar depression. This activity covers lamotrigine, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, contraindications, monitoring, and highlights the interprofessional team’s role in the management of lamotrigine therapy.
Mechanism of Action
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.[L9404] An in vivo study revealed evidence that lamotrigine inhibits Cav2.3 (R-type) calcium currents, which may also contribute to its anticonvulsant effects.[A31737]
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The mechanism of action for lamotrigine is not entirely understood. It is a triazine, and research has shown that lamotrigine selectively binds sodium channels, stabilizing presynaptic neuronal membranes and inhibiting glutamate release. Researchers have not demonstrated that lamotrigine to have significant effects on other neurotransmitters such as serotonin, norepinephrine, or dopamine.[rx] There is a theory that lamotrigine may interact with voltage-activated calcium-gated channels, contributing to its broad range of activity. In vitro studies have also shown that lamotrigine inhibited dihydrofolate reductase, potentially contributing to concerns for its teratogenicity. Lamotrigine follows first-order kinetics with a half-life of 29 hours.
Indications of Lamotrigine
- Lamotrigine can be used to treat the following: partial seizures, primary generalized tonic-clonic seizures, bipolar depression, bipolar disorder type I maintenance), and Lennox-Gastaut syndrome.[rx][rx][rx]
- Off-Label uses include treatment of rapid-cycling bipolar depression, basilar pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।" data-rx-term="migraine" data-rx-definition="Migraine is a recurring headache disorder often with throbbing pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।">migraine, panic disorder, and binge eating disorder.
- Anticonvulsants; Calcium Channel Blockers; Excitatory Amino Acid Antagonists; Voltage-Gated Sodium Channel Blockers
- Bipolar 1 Disorder
- Grand mal Generalized tonic-clonic seizure
- Partial-Onset Seizures
- Generalized seizure
- Borderline Personality Disorder
- Bipolar Disorder
- Anxiety
- Cyclothymic Disorder
- Depression
- Epilepsy
- pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।" data-rx-term="migraine" data-rx-definition="Migraine is a recurring headache disorder often with throbbing pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।">Migraine Prevention
- Post Traumatic Stress Disorder
- Restless Legs Syndrome
- Schizoaffective Disorder
Lamotrigine is indicated as adjunctive therapy for the following seizure types in patients ≥2 years of age: partial seizures, primary generalized tonic-clonic seizures, and generalized seizures due to Lennox-Gastaut syndrome. It is also indicated for the process of conversion to drug monotherapy for those at least 16 years of age or older with partial seizures and currently are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED).[L9404] In addition to the above, lamotrigine is also indicated for the maintenance treatment of bipolar I disorder, delaying the time to mood episodes (which may include mania, hypomania, depression, mixed episodes) in adults at least 18 years or older, who have been treated for acute mood symptoms with standard therapy.[L9404] Limitations of use It is important to note that lamotrigine should not be used in the treatment of acute mood episodes, as efficacy has not been established in this context.
Contraindications of Lamotrigine
- Hypersensitivity to lamotrigine or its ingredients is the primary contraindication for the administration of lamotrigine.
- Evaluating gender, age, and contraceptive use are essential for the consideration of starting lamotrigine. While some studies in humans have not shown an increased risk for congenital malformations during lamotrigine therapy during pregnancy, animal studies have demonstrated that an increased risk exists. The drug is pregnancy risk factor C; animal studies have shown the risk for congenital malformations.
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Lamotrigine is present in breast milk and is detectable in the blood of breast-fed infants. Symptoms of lamotrigine in infants include poor feeding, drowsiness, rash, and apnea. These symptoms can improve with the discontinuation of lamotrigine.
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Consideration for other drugs’ effects on glucuronidation merit consideration, as glucuronic acid conjugation primarily metabolizes lamotrigine.
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Drugs that induce lamotrigine glucuronidation include carbamazepine, phenytoin, phenobarbital, rifampin, lopinavir/ritonavir, atazanavir/ritonavir, and primidone.
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Valproic acid inhibits lamotrigine glucouronidation.
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Concurrent use with central nervous system (CNS) depressants may increase the potency of CNS depression.
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Lamotrigine reportedly interferes with urine drug screening and can cause false-positive readings of phencyclidine
Dosage of Lamotrigine
- Lamotrigine is available as tablets, chewable tablets, and orally disintegrating tablets. It is available in formulations of 25 mg, 100 mg, 150 mg, and 200 mg tablets in a tablet form. A chewable, dispersible tablet form is available in formulations of 2 mg, 5 mg, and 25 mg dispersible tablets. The orally disintegrating tablets are available in formulations of 25 mg, 50 mg, 100 mg, and 200 mg. All formulations should be stored at room temperature and needs protection from light.
- Lamotrigine dosing requires alteration if given concurrently with carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, and atazanavir, ritonavir, and valproic acid.
- If it is necessary to discontinue lamotrigine, it should be done in a step-wise fashion over two weeks, if possible. There is a possibility of withdrawal seizures when discontinuing lamotrigine, which lessens if the drug is tapered rather than stopped quickly.
For Seizures
- If not used concurrently with carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, atazanavir, ritonavir, and valproic acid, dosing instructions are as follows. Initially, dosing is 25 mg given daily. At week three, the dose should increase to 50 mg daily. At week five, increase by an additional 50 mg each week or every other week. The typical maintenance ranges from 225 mg to 375 mg in two divided doses.
- If being used concurrently with valproic acid, dosing instructions are as follows. Initially, dosing is 25 mg given every other day. At week three, the dose should increase to 25 mg daily. At week 5, increase the dose by an additional 25 mg to 50 mg every week or every other week. Typical maintenance varies from 100 mg to 200 mg daily in one or two divided doses if given with valproic acid alone or 100 mg to 400 mg in one or two divided doses if given with other medications that induce glucuronidation.
- If used concurrently with carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, and atazanavir or ritonavir, dosing instructions are as follows. Initially, the dose is 50 mg given daily. At week three, the dose should increase to 100 mg daily in 2 divided doses. At week five, increase by an additional 100 mg every week or every other week. Typical maintenance ranges from 300 mg to 500 mg to two divided doses.
For Bipolar I
- Maintenance is from 200 mg to 400 mg, with additional consideration given to medication given concurrently with lamotrigine.
Side Effects of Lamotrigine
Other adverse effects include multi-organ sensitivity, blood dyscrasias, suicidal behavior/ideations, aseptic meningitis, status epilepticus, and sudden unexplained death in epilepsy.[rx][rx]
The Most Common
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Nausea, vomiting
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Chest pain, back pain
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Xerostomia
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Edema
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Dysmenorrhea
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Weight changes
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Constipation
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Abdominal pain
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Pain, weakness
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Insomnia, drowsiness
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Dizziness, ataxia, diplopia.
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pain in the head or upper neck. সহজ বাংলা: মাথাব্যথা।" data-rx-term="headache" data-rx-definition="Headache means pain in the head or upper neck. সহজ বাংলা: মাথাব্যথা।">Headache.
Common
- fast, slow, or pounding heartbeats or fluttering in your chest;
- chest pain, shortness of breath;
- fever, swollen glands, weakness, severe muscle pain;
- any skin rash, especially with blistering or peeling;
- painful sores in your mouth or around your eyes;
- headache, neck stiffness, increased sensitivity to light, nausea, vomiting, confusion, drowsiness;
- jaundice (yellowing of the skin or eyes); or
- pale skin, cold hand and feet, easy bruising, unusual bleeding.
Rare
- headache, dizziness;
- blurred vision,
- double vision;
- tremor,
- loss of coordination;
- dry mouth, nausea, vomiting,
- stomach pain,
- diarrhea;
- fever, sore throat,
- runny nose;
- drowsiness,
- tired feeling;
- back pain; or
- sleep problems (insomnia).
Lamotrigine can cause serious rashes requiring hospitalization and discontinuation of this medication. Rash severity varies but includes a risk for Stevens-Johnson syndrome. The incidence of Stevens-Johnson syndrome in the pediatric population is 0.3% to 0.8% and 0.03% to 0.08% in adult populations. The number of cases associated with toxic epidermal necrolysis is too low to report an estimated incidence. Nearly all cases of a rash occur 2 to 8 weeks after the initiation of lamotrigine. It should also bear mentioning that the discontinuation of lamotrigine may not prevent a rash from becoming life-threatening. Patient education should include continuous monitoring of the rash for improvement after the discontinuation of the medication.[rx][rx]United States Boxed Warning
Drug interactions of Lamotrigine
View interaction reports for lamotrigine and the medicines listed below.
- Abilify (aripiprazole)
- Adderall (amphetamine / dextroamphetamine)
- Adderall XR (amphetamine / dextroamphetamine)
- Cymbalta (duloxetine)
- Fish Oil (omega-3 polyunsaturated fatty acids)
- Klonopin (clonazepam)
- Latuda (lurasidone)
- Lexapro (escitalopram)
- Lithium Carbonate ER (lithium)
- Lyrica (pregabalin)
- Prozac (fluoxetine)
- Seroquel (quetiapine)
- Synthroid (levothyroxine)
- Vitamin B12 (cyanocobalamin)
- Vitamin C (ascorbic acid)
- Vitamin D3 (cholecalciferol)
- Vyvanse (lisdexamfetamine)
- Wellbutrin XL (bupropion)
- Xanax (alprazolam)
- Zoloft (sertraline)
The concomitant use of valproic acid and/or hepatic enzyme-inducing anticonvulsant drugs (e.g., phenobarbital, primidone, carbamazepine, phenytoin) can increase or decrease the metabolism and elimination of lamotrigine, requiring dosage adjustments to maintain efficacy and/or avoid toxicity. The addition of valproic acid to lamotrigine therapy reduces lamotrigine clearance and increases steady-state plasma lamotrigine concentrations by slightly more than 50% whether or not hepatic enzyme-inducing anticonvulsant drugs are given concomitantly. Conversely, steady-state plasma concentrations of lamotrigine are decreased by about 40% when phenobarbital, primidone, or carbamazepine is added to lamotrigine therapy and by about 45-54% when phenytoin is added to lamotrigine therapy; the magnitude of the effect with phenytoin is dependent on the total daily dosage of phenytoin (from 100-400 mg daily). Discontinuance of an enzyme-inducing anticonvulsant drug can be expected to increase, and discontinuance of valproic acid can be expected to decrease, the elimination half-life and plasma concentrations of lamotrigine. Although the manufacturers state that a therapeutic plasma concentration range has not been established for lamotrigine and that dosage should be based on the therapeutic response, the change in plasma lamotrigine concentrations resulting from the addition or discontinuance of enzyme-inducing anticonvulsant drugs or valproic acid should be considered when these drugs are added to or withdrawn from an existing anticonvulsant drug regimen that includes lamotrigine.
Pregnancy Category
- AU TGA pregnancy category D
- US FDA pregnancy category Not Assigned:
Pregnancy
The benefit should outweigh the risk. The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.
Several prospective pregnancy exposure registries and epidemiological studies have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population; animal studies have shown developmental toxicities at doses administered clinically.
Monitoring
The value of monitoring lamotrigine concentrations remains unestablished to date. Due to pharmacokinetics between lamotrigine and other drugs and their effect on lamotrigine concentration, clinical judgment must be exercised during concomitant use if there are concerns regarding lamotrigine levels. Dofetilide can have a severe interaction with lamotrigine, and the combination is strongly discouraged. Other drugs with potential serious interactions include valproic acid, rifampin, estrogen-containing contraceptives and estrogen replacement therapy medications, as well as certain barbiturates.
Labs should include pertinent serum levels of concurrent anticonvulsants and liver function testing, and renal function assessments. Clinical team staff should spend ample time educating patients on monitoring themselves for hypersensitivity, particularly rashes or other skin changes occurring near or on the mucosa. Patient education should also include discussing how to monitor for changes in seizures and their frequency and duration. Patients should also monitor for changes in suicidality, including suicidal thoughts and increased desire to commit suicide. Finally, patients should learn how to watch for signs/symptoms of aseptic meningitis.
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Lamotrigine [USAN:USP:INN:BAN]ChemIDplus Chemical Information Classification
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PubChem
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LamotrigineLamotrigineLamotrigineLamotrigineLamotrigineLamotrigineLamotrigine6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamineLamotrigineLamotrigine
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lamotrigine
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LamotrigineAnticonvulsantsSodium Channel BlockersCalcium Channel BlockersAntipsychotic Agents
