Indicated for:

Adjunctive Therapy:

• LAMICTAL XR is indicated as adjunctive therapy for primary generalized tonic-clonic (PGTC) seizures and partial-onset seizures with or without secondary generalization in patients aged 13 years and older.

Monotherapy:

• LAMICTAL XR is indicated for conversion to monotherapy in patients aged 13 years and older with partial onset seizures who are receiving treatment with a single antiepileptic drug (AED).

Safety and effectiveness of LAMICTAL XR have not been established (1) as initial monotherapy or (2) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs.

There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be increased by (1) co-administration of LAMICTAL XR with valproate, (2) exceeding the recommended initial dose of LAMICTAL XR, or (3) exceeding the recommended dose escalation for LAMICTAL XR. However, cases have occurred in the absence of these factors.

LAMICTAL XR can cause serious rashes requiring hospitalization and discontinuation of treatment. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.

The risk of serious rash caused by treatment with LAMICTAL XR is not expected to differ from that with immediate-release lamotrigine. However, the relatively limited treatment experience with LAMICTAL XR makes it difficult to characterize the frequency and risk of serious rashes caused by treatment with LAMICTAL XR.

No dosage adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites.

If a decision is made to discontinue therapy with LAMICTAL XR, a step-wise reduction of dose over at least 2 weeks (approximately 50% per week) is recommended unless safety concerns require a more rapid withdrawal.As with other AEDs, LAMICTAL XR should not be abruptly discontinued. In patients with epilepsy there is a possibility of increasing seizure frequency.

Initial doses of LAMICTAL XR should be based on patients’ concomitant medications reduced maintenance doses may be effective for patients with significant renal impairment. Because there is inadequate experience in this population, LAMICTAL XR should be used with caution in these patients.

Hemophagocytic lymphohistiocytosis (HLH) has occurred in pediatric and adult patients taking LAMICTAL XR for various indications.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms (DRESS), have occurred with lamotrigine. Some have been fatal or life threatening.

There have been reports of blood dyscrasias with immediate-release lamotrigine that may or may not be associated with multiorgan hypersensitivity (also known as DRESS).These have included neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, and, rarely, aplastic anemia and pure red cell aplasia.

Treatment with LAMICTAL XR caused an increased incidence of subnormal (below the reference range) values in some hematology analytes (e.g., total white blood cells, monocytes). 

AEDs, including LAMICTAL XR, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Therapy with lamotrigine increases the risk of developing aseptic meningitis. Because of the potential for serious outcomes of untreated meningitis due to other causes, patients should also be evaluated for other causes of meningitis and treated as appropriate.

Because lamotrigine binds to melanin, it could accumulate in melanin-rich tissues over time. This raises the possibility that lamotrigine may cause toxicity in these tissues after extended use.

Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine. Drugs that induce glucuronidation include carbamazepine, phenytoin, phenobarbital, primidone, rifampin, estrogen containing oral contraceptives, and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir. Valproate inhibits glucuronidation.

Taking Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the maintenance dose of LAMICTAL XR will in most cases need to be increased by as much as 2-fold over the recommended target maintenance dose to maintain a consistent lamotrigine plasma level.

Starting Estrogen-Containing Oral Contraceptives: In women taking a stable dose of LAMICTAL XR and not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the maintenance dose will in most cases need to be increased by as much as 2-fold to maintain a consistent lamotrigine plasma level. The dose increases should begin at the same time that the oral contraceptive is introduced and continue, based on clinical response, no more rapidly than 50 to 100 mg/day every week. Gradual transient increases in lamotrigine plasma levels may occur during the week of inactive hormonal preparation (pill-free week), and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation.

Stopping Estrogen-Containing Oral Contraceptives: In women not taking carbamazepine, phenytoin, phenobarbital, primidone, or other drugs such as rifampin and the protease inhibitors lopinavir/ritonavir and atazanavir/ritonavir that induce lamotrigine glucuronidation, the maintenance dose of LAMICTAL XR will in most cases need to be decreased by as much as 50% in order to maintain a consistent lamotrigine plasma level. The decrease in dose of LAMICTAL XR should not exceed 25% of the total daily dose per week over a 2-week period, unless clinical response or lamotrigine plasma levels indicate otherwise.

Co-administration of LAMICTAL XR with OCT2 substrates with a narrow therapeutic index (e.g., dofetilide) is not recommended.

Lamotrigine has been reported to interfere with the assay used in some rapid urine drug screens, which can result in false-positive readings, particularly for phencyclidine (PCP). A more specific analytical method should be used to confirm a positive result.

Data from several prospective pregnancy exposure registries and epidemiological studies of pregnant women 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. In animal studies, administration of lamotrigine during pregnancy resulted in developmental toxicity (increased mortality, decreased body weight, increased structural variation, neurobehavioral abnormalities).

Lamotrigine is present in milk from lactating women taking LAMICTAL XR. Neonates and young infants are at risk for high serum levels because maternal serum and milk levels can rise to high levels postpartum if lamotrigine dosage has been increased during pregnancy but is not reduced after delivery to the pre-pregnancy dosage. Glucuronidation is required for drug clearance. Glucuronidation capacity is immature in the infant and this may also contribute to the level of lamotrigine exposure.

GoToSource

• Use in patients under 13 years of age. GoToSource

• Unipolar depression. GoToSource

• Schizoaffective disorder. GoToSource

• Borderline personality disorder. GoToSource

• Bipolar II disorder. GoToSource

• Hemiplegic migraine. GoToSource

• Neuropathic pain. GoToSource

• Trigeminal neuralgia. GoToSource

• SUNCT syndrome, cluster headaches, glossopharyngeal neuralgia, allodynia, neuralgia after nerve section, postherpetic neuralgia, HIV-associated neuropathy, spinal cord injury pain and neuralgia after nerve section. GoToSource

• Depersonalization disorder. GoToSource

• Myotonia. GoToSource

• Delirium tremens. GoToSource

• Ketamine use disorder. GoToSource

• Startle-induced seizures. GoToSource

• Panic disorder. GoToSource

• Pathological skin picking. GoToSource

• Aggression in female borderline patients. GoToSource

• Post-traumatic stress disorder. GoToSource

Stevens-johnson syndrome and toxic epidermal necrolysis (severe skin reaction). GoToSource

Multi-organ failure. GoToSource

Lymphadenopathy (enlargement of lymph nodes). GoToSource

Eosinophilia and systemic symptoms (severe drug reaction). GoToSource

Liver failure. GoToSource

Aseptic meningitis (inflammation of membrane covering brain and spinal cord). GoToSource

Sudden unexplained death in epilepsy. GoToSource

Hemophagocytic lymphohistiocytosis (immune system produces too many activated immune cells). GoToSource

Blood dyscrasias (blood disorder). GoToSource

Withdrawal seizures. GoToSource

Syndrome of inappropriate antidiuretic hormone secretion (body makes too much antidiuretic hormone). GoToSource

Tinnitus (noise or ringing in ears), phonophobia (fear of loud noises), sensorineural hearing loss, dizziness, ataxia (lack of muscle coordination), disequilibrium (loss of equilibrium or stability), nystagmus (rapid and repetitive eye movement) and delayed conduction within the cochlea, auditory nerve and brainstem auditory pathways and central and/or peripheral vestibular dysfunctions. GoToSource

Anticonvulsant hypersensitivity syndrome (potentially fatal drug reaction). GoToSource

Immunoglobulin A (IgA) deficiency (lack or low level of a protein that fights infection). GoToSource

Hyponatremia (low blood sodium level). GoToSource

Pneumonitis (inflammation of lung tissue). GoToSource

Lymphadenopathy (enlargement of lymph nodes). GoToSource

Disabling tremor. GoToSource

Anger and aggression. GoToSource

Exacerbation of atherosclerosis. GoToSource

Brugada type 1 pattern (abnormal heart rhythm). GoToSource

Generalized myoclonus (involuntary muscle jerk) and spasticity. GoToSource

Tachypnea (rapid breathing), tachycardia (rapid heart rate), hypertension (high blood pressure), QTc prolongation and altered mental status. GoToSource

Visual and auditory hallucinations. GoToSource

Alopecia (hair loss). GoToSource

Oral hairy leukoplakia (white or gray lesions in mouth). GoToSource

Myocarditis (inflammation of heart muscle). GoToSource

Dyspepsia (indigestion), insomnia and drug-induced lupus. GoToSource

Neuroleptic malignant syndrome (life-threatening drug reaction). GoToSource

Downbeat nystagmus (eyes drift upward). GoToSource

Seizure aggravation. GoToSource

Suicidal thoughts and behavior. GoToSource

Lawsuits filed for aseptic meningitis, stevens-johnson syndrome, toxic epidermal necrolysis, birth defects and suicide.