LAMOTRIGINE - lamotrigine tablet
Aurobindo Pharma Limited
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use lamotrigine tablets safely and effectively. See full prescribing information for lamotrigine tablets USP.
Lamotrigine Tablets USP Initial U.S. Approval: 1994 WARNING: SERIOUS SKIN RASHES See full prescribing information for complete boxed warning. Cases of life-threatening serious rashes, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and/or rash-related death, have been caused by lamotrigine. The rate of serious rash is greater in pediatric patients than in adults. Additional factors that may increase the risk of rash include (5.1):
Benign rashes are also caused by lamotrigine; however, it is not possible to predict which rashes will prove to be serious or life threatening. Lamotrigine should be discontinued at the first sign of rash, unless the rash is clearly not drug related. (5.1) RECENT MAJOR CHANGES
Warnings and Precautions, Multiorgan Hypersensitivity Reactions and Organ Failure (5.2) August 2011
INDICATIONS AND USAGELamotrigine tablets USP are an antiepileptic drug (AED) indicated for: Epilepsy—adjunctive therapy in patients ≥2 years of age: (1.1)
Epilepsy—monotherapy in patients ≥16 years of age: conversion to monotherapy in patients with partial seizures who are receiving treatment with carbamazepine, phenobarbital, phenytoin, primidone, or valproate as the single AED. (1.1) Bipolar Disorder in patients ≥18 years of age: maintenance treatment of Bipolar I Disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. (1.2) DOSAGE AND ADMINISTRATION
Epilepsy
Bipolar Disorder: See Tables 5 and 6. (2.4) CONTRAINDICATIONSWARNINGS AND PRECAUTIONS
ADVERSE REACTIONS
To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: 9/2012 |
This section provides specific dosing recommendations for patients greater than 12 years of age and patients 2 to 12 years of age. Within each of these age-groups, specific dosing recommendations are provided depending upon concomitant AED or other concomitant medications (Table 1 for patients greater than 12 years of age and Table 2 for patients 2 to 12 years of age). A weight-based dosing guide for patients 2 to 12 years of age on concomitant valproate is provided in Table 3.
* Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. † These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect. |
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| For Patients TAKING Valproate* | For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone†, or Valproate* | For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidone† and NOT TAKING Valproate* |
Weeks 1 and 2 | 25 mg every other day | 25 mg every day | 50 mg/day |
Weeks 3 and 4 | 25 mg every day | 50 mg/day | 100 mg/day (in 2 divided doses) |
Week 5 onwards to maintenance | Increase by 25 to 50 mg/day every 1 to 2 weeks | Increase by 50 mg/day every 1 to 2 weeks | Increase by 100 mg/day every 1 to 2 weeks. |
Usual Maintenance Dose | 100 to 200 mg/day with valproate alone 100 to 400 mg/day with valproate and other drugs that induce glucuronidation (in 1 or 2 divided doses) | 225 to 375 mg/day (in 2 divided doses) | 300 to 500 mg/day (in 2 divided doses) |
Patients 2 to 12 Years of Age: Recommended dosing guidelines are summarized in Table 2.
Note: Only whole tablets should be used for dosing. * Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. † These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect. |
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| For Patients TAKING Valproate* | For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone†, or Valproate* | For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, or Primidone† and NOT TAKING Valproate* |
Weeks 1 and 2 | 0.15 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight based dosing guide) | 0.3 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet | 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet |
Weeks 3 and 4 | 0.3 mg/kg/day in 1 or 2 divided doses, rounded down to the nearest whole tablet (see Table 3 for weight based dosing guide) | 0.6 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet | 1.2 mg/kg/day in 2 divided doses, rounded down to the nearest whole tablet |
Week 5 onwards to maintenance | The dose should be increased every 1 to 2 weeks as follows: calculate 0.3 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose | The dose should be increased every 1 to 2 weeks as follows: calculate 0.6 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose | The dose should be increased every 1 to 2 weeks as follows: calculate 1.2 mg/kg/day, round this amount down to the nearest whole tablet, and add this amount to the previously administered daily dose |
Usual Maintenance Dose | 1 to 5 mg/kg/day (maximum 200 mg/day in 1 or 2 divided doses) 1 to 3 mg/kg/day with valproate alone | 4.5 to 7.5 mg/kg/day (maximum 300 mg/day in 2 divided doses) | 5 to 15 mg/kg/day (maximum 400 mg/day in 2 divided doses) |
Maintenance dose in patients less than 30 kg | May need to be increased by as much as 50%, based on clinical response | May need to be increased by as much as 50%, based on clinical response | May need to be increased by as much as 50%, based on clinical response |
If the patient’s weight is | Give this daily dose, using the most appropriate combination of lamotrigine 2 mg and 5 mg tablets |
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Greater than | And less than | Weeks 1 and 2 | Weeks 3 and 4 |
6.7 kg | 14 kg | 2 mg every other day | 2 mg every day |
14.1 kg | 27 kg | 2 mg every day | 4 mg every day |
27.1 kg | 34 kg | 4 mg every day | 8 mg every day |
34.1 kg | 40 kg | 5 mg every day | 10 mg every day |
| Lamotrigine Tablets | Valproate |
Step 1 | Achieve a dose of 200 mg/day according to guidelines in Table 1 (if not already on 200 mg/day). | Maintain previous stable dose. |
Step 2 | Maintain at 200 mg/day. | Decrease to 500 mg/day by decrements no greater than 500 mg/day/week and then maintain the dose of 500 mg/day for 1 week. |
Step 3 | Increase to 300 mg/day and maintain for 1 week. | Simultaneously decrease to 250 mg/day and maintain for 1 week. |
Step 4 | Increase by 100 mg/day every week to achieve maintenance dose of 500 mg/day. | Discontinue. |
Conversion From Adjunctive Therapy With Antiepileptic Drugs Other Than Carbamazepine, Phenytoin, Phenobarbital, Primidone, or Valproate to Monotherapy With Lamotrigine Tablets: No specific dosing guidelines can be provided for conversion to monotherapy with lamotrigine tablets with AEDs other than carbamazepine, phenobarbital, phenytoin, primidone, or valproate.
‡ Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. † These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect. |
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| For Patients TAKING Valproate‡ | For Patients NOT TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone†, or Valproate‡ | For Patients TAKING Carbamazepine, Phenytoin, Phenobarbital, Primidone†, and NOT TAKING Valproate‡ |
Weeks 1 and 2 | 25 mg every other day | 25 mg daily | 50 mg daily |
Weeks 3 and 4 | 25 mg daily | 50 mg daily | 100 mg daily, in divided doses |
Week 5 | 50 mg daily | 100 mg daily | 200 mg daily, in divided doses |
Week 6 | 100 mg daily | 200 mg daily | 300 mg daily, in divided doses |
Week 7 | 100 mg daily | 200 mg daily | up to 400 mg daily, in divided doses |
‡ Valproate has been shown to inhibit glucuronidation and decrease the apparent clearance of lamotrigine [see Drug Interactions (7), Clinical Pharmacology (12.3)]. † These drugs induce lamotrigine glucuronidation and increase clearance [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Other drugs that have similar effects include estrogen-containing oral contraceptives [see Drug Interactions (7), Clinical Pharmacology (12.3)]. Dosing recommendations for oral contraceptives can be found in General Dosing Considerations [see Dosage and Administration (2.1)]. Patients on rifampin, or other drugs that induce lamotrigine glucuronidation and increase clearance, should follow the same dosing titration/maintenance regimen as that used with anticonvulsants that have this effect. |
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| Discontinuation of Psychotropic Drugs (excluding Carbamazepine, Phenytoin, Phenobarbital, Primidone†, or Valproate‡) | After Discontinuation of Valproate‡ | After Discontinuation of Carbamazepine, Phenytoin, Phenobarbital, or Primidone† |
Current dose of lamotrigine tablets (mg/day) 100 | Current dose of lamotrigine tablets (mg/day) 400 |
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Week 1 | Maintain current dose of lamotrigine tablets | 150 | 400 |
Week 2 | Maintain current dose of lamotrigine tablets | 200 | 300 |
Week 3 onward | Maintain current dose of lamotrigine tablets | 200 | 200 |
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. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved.
Fatalities associated with acute multiorgan failure and various degrees of hepatic failure have been reported in 2 of 3,796 adult patients and 4 of 2,435 pediatric patients who received lamotrigine in epilepsy clinical trials. Rare fatalities from multiorgan failure have also been reported in postmarketing use.
Isolated liver failure without rash or involvement of other organs has also been reported with lamotrigine.
It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though a rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Lamotrigine should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Prior to initiation of treatment with lamotrigine, the patient should be instructed that a rash or other signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy) may herald a serious medical event and that the patient should report any such occurrence to a physician immediately.
Indication | Placebo Patients With Events Per 1,000 Patients | Drug Patients With Events Per 1,000 Patients | Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients | Risk Difference: Additional Drug Patients With Events Per 1,000 Patients |
Epilepsy | 1 | 3.4 | 3.5 | 2.4 |
Psychiatric | 5.7 | 8.5 | 1.5 | 2.9 |
Other | 1 | 1.8 | 1.9 | 0.9 |
Total | 2.4 | 4.3 | 1.8 | 1.9 |
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.
Postmarketing cases of aseptic meningitis have been reported in pediatric and adult patients taking lamotrigine for various indications. Symptoms upon presentation have included headache, fever, nausea, vomiting, and nuchal rigidity. Rash, photophobia, myalgia, chills, altered consciousness, and somnolence were also noted in some cases. Symptoms have been reported to occur within 1 day to one and a half months following the initiation of treatment. In most cases, symptoms were reported to resolve after discontinuation of lamotrigine. Reexposure resulted in a rapid return of symptoms (from within 30 minutes to 1 day following reinitiation of treatment) that were frequently more severe. Some of the patients treated with lamotrigine who developed aseptic meningitis had underlying diagnoses of systemic lupus erythematosus or other autoimmune diseases.
Cerebrospinal fluid (CSF) analyzed at the time of clinical presentation in reported cases was characterized by a mild to moderate pleocytosis, normal glucose levels, and mild to moderate increase in protein. CSF white blood cell count differentials showed a predominance of neutrophils in a majority of the cases, although a predominance of lymphocytes was reported in approximately one third of the cases. Some patients also had new onset of signs and symptoms of involvement of other organs (predominantly hepatic and renal involvement), which may suggest that in these cases the aseptic meningitis observed was part of a hypersensitivity reaction [see Warnings and Precautions (5.2)].
* Patients in these adjunctive studies were receiving 1 to 3 of the following concomitant AEDs (carbamazepine, phenytoin, phenobarbital, or primidone) in addition to lamotrigine or placebo. Patients may have reported multiple adverse reactions during the study or at discontinuation; thus, patients may be included in more than one category. |
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Body System/ Adverse Reaction | Percent of Patients Receiving Adjunctive Lamotrigine (n = 711) | Percent of Patients Receiving Adjunctive Placebo (n = 419) |
Body as a whole | | |
Headache | 29 | 19 |
Flu syndrome | 7 | 6 |
Fever | 6 | 4 |
Abdominal pain | 5 | 4 |
Neck pain | 2 | 1 |
Reaction aggravated (seizure exacerbation) | 2 | 1 |
Digestive | | |
Nausea | 19 | 10 |
Vomiting | 9 | 4 |
Diarrhea | 6 | 4 |
Dyspepsia | 5 | 2 |
Constipation | 4 | 3 |
Anorexia | 2 | 1 |
Musculoskeletal | | |
Arthralgia | 2 | 0 |
Nervous | | |
Dizziness | 38 | 13 |
Ataxia | 22 | 6 |
Somnolence | 14 | 7 |
Incoordination | 6 | 2 |
Insomnia | 6 | 2 |
Tremor | 4 | 1 |
Depression | 4 | 3 |
Anxiety | 4 | 3 |
Convulsion | 3 | 1 |
Irritability | 3 | 2 |
Speech disorder | 3 | 0 |
Concentration disturbance | 2 | 1 |
Respiratory | | |
Rhinitis | 14 | 9 |
Pharyngitis | 10 | 9 |
Cough increased | 8 | 6 |
Skin and appendages | | |
Rash | 10 | 5 |
Pruritus | 3 | 2 |
Special senses | | |
Diplopia | 28 | 7 |
Blurred vision | 16 | 5 |
Vision abnormality | 3 | 1 |
Urogenital | | |
Female patients only | (n = 365) | (n = 207) |
Dysmenorrhea | 7 | 6 |
Vaginitis | 4 | 1 |
Amenorrhea | 2 | 1 |
* Significantly greater than placebo group (p<0.05). † Significantly greater than group receiving lamotrigine 300 mg (p<0.05). |
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Adverse Reaction
| Percent of Patients Experiencing Adverse Reactions |
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Placebo (n = 73) | Lamotrigine 300 mg (n = 71) | Lamotrigine 500 mg (n = 72) |
|
Ataxia | 10 | 10 | 28*†
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Blurred vision | 10 | 11 | 25*†
|
Diplopia | 8 | 24*
| 49*†
|
Dizziness | 27 | 31 | 54*†
|
Nausea | 11 | 18 | 25*
|
Vomiting | 4 | 11 | 18*
|
* Patients in these studies were converted to lamotrigine or valproate monotherapy from adjunctive therapy with carbamazepine or phenytoin. Patients may have reported multiple adverse reactions during the study; thus, patients may be included in more than one category. † Up to 500 mg/day. ‡ 1,000 mg/day. |
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Body System/ Adverse Reaction | Percent of Patients Receiving Lamotrigine as Monotherapy† (n = 43) | Percent of Patients Receiving Low-Dose Valproate‡ Monotherapy (n = 44) |
Body as a whole | | |
Pain | 5 | 0 |
Infection | 5 | 2 |
Chest pain | 5 | 2 |
Digestive | | |
Vomiting | 9 | 0 |
Dyspepsia | 7 | 2 |
Nausea | 7 | 2 |
Metabolic and nutritional | | |
Weight decrease | 5 | 2 |
Nervous | | |
Coordination abnormality | 7 | 0 |
Dizziness | 7 | 0 |
Anxiety | 5 | 0 |
Insomnia | 5 | 2 |
Respiratory | | |
Rhinitis | 7 | 2 |
Urogenital (female patients only) | (n = 21) | (n = 28) |
Dysmenorrhea | 5 | 0 |
Body System/ Adverse Reaction | Percent of Patients Receiving Lamotrigine (n = 168) | Percent of Patients Receiving Placebo (n = 171) |
Body as a whole | | |
Infection | 20 | 17 |
Fever | 15 | 14 |
Accidental injury | 14 | 12 |
Abdominal pain | 10 | 5 |
Asthenia | 8 | 4 |
Flu syndrome | 7 | 6 |
Pain | 5 | 4 |
Facial edema | 2 | 1 |
Photosensitivity | 2 | 0 |
Cardiovascular | | |
Hemorrhage | 2 | 1 |
Digestive | | |
Vomiting | 20 | 16 |
Diarrhea | 11 | 9 |
Nausea | 10 | 2 |
Constipation | 4 | 2 |
Dyspepsia | 2 | 1 |
Hemic and lymphatic | | |
Lymphadenopathy | 2 | 1 |
Metabolic and nutritional | | |
Edema | 2 | 0 |
Nervous system | | |
Somnolence | 17 | 15 |
Dizziness | 14 | 4 |
Ataxia | 11 | 3 |
Tremor | 10 | 1 |
Emotional lability | 4 | 2 |
Gait abnormality | 4 | 2 |
Thinking abnormality | 3 | 2 |
Convulsions | 2 | 1 |
Nervousness | 2 | 1 |
Vertigo | 2 | 1 |
Respiratory | | |
Pharyngitis | 14 | 11 |
Bronchitis | 7 | 5 |
Increased cough | 7 | 6 |
Sinusitis | 2 | 1 |
Bronchospasm | 2 | 1 |
Skin | | |
Rash | 14 | 12 |
Eczema | 2 | 1 |
Pruritus | 2 | 1 |
Special senses | | |
Diplopia | 5 | 1 |
Blurred vision | 4 | 1 |
Visual abnormality | 2 | 0 |
Urogenital Male and female patients | | |
Urinary tract infection | 3 | 0 |
* Patients in these studies were converted to lamotrigine (100 to 400 mg/day) or placebo monotherapy from add-on therapy with other psychotropic medications. Patients may have reported multiple adverse reactions during the study; thus, patients may be included in more than one category. † In the overall bipolar and other mood disorders clinical trials, the rate of serious rash was 0.08% (1 of 1,233) of adult patients who received lamotrigine as initial monotherapy and 0.13% (2 of 1,538) of adult patients who received lamotrigine as adjunctive therapy [see Warnings and Precautions (5.1)]. |
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Body System/ Adverse Reaction | Percent of Patients Receiving Lamotrigine (n = 227) | Percent of Patients Receiving Placebo (n = 190) |
General | | |
Back pain | 8 | 6 |
Fatigue | 8 | 5 |
Abdominal pain | 6 | 3 |
Digestive | | |
Nausea | 14 | 11 |
Constipation | 5 | 2 |
Vomiting | 5 | 2 |
Nervous System | | |
Insomnia | 10 | 6 |
Somnolence | 9 | 7 |
Xerostomia (dry mouth) | 6 | 4 |
Respiratory | | |
Rhinitis | 7 | 4 |
Exacerbation of cough | 5 | 3 |
Pharyngitis | 5 | 4 |
Skin | | |
Rash (nonserious)†
| 7 | 5 |
↓ = Decreased (induces lamotrigine gluronidation). ↑ = Increased (inhibits lamotrigine glucuronidation). ? = Conflicting data. |
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Concomitant Drug | Effect on Concentration of Lamotrigine or Concomitant Drug | Clinical Comment |
Estrogen-containing oral contraceptive preparations containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel | ↓ lamotrigine ↓ levonorgestrel | Decreased lamotrigine levels approximately 50%. Decrease in levonorgestrel component by 19%. |
Carbamazepine (CBZ) and CBZ epoxide | ↓ lamotrigine ? CBZ epoxide | Addition of carbamazepine decreases lamotrigine concentration approximately 40%. May increase CBZ epoxide levels |
Phenobarbital/Primidone | ↓ lamotrigine | Decreased lamotrigine concentration approximately 40%. |
Phenytoin (PHT) | ↓ lamotrigine | Decreased lamotrigine concentration approximately 40%. |
Rifampin | ↓ lamotrigine | Decreased lamotrigine AUC approximately 40%. |
Valproate | ↑ lamotrigine ? valproate | Increased lamotrigine concentrations slightly more than 2-fold. Decreased valproate concentrations an average of 25% over a 3-week period then stabilized in healthy volunteers; no change in controlled clinical trials in epilepsy patients. |
Lamotrigine is present in milk from lactating women taking lamotrigine. Data from multiple small studies indicate that lamotrigine plasma levels in human milk-fed infants have been reported to be as high as 50% of the maternal serum levels. 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 not later reduced to the pre-pregnancy dosage. Lamotrigine exposure is further increased due to the immaturity of the infant glucuronidation capacity needed for drug clearance. Events including apnea, drowsiness, and poor sucking have been reported in infants who have been human milk-fed by mothers using lamotrigine; whether or not these events were caused by lamotrigine is unknown. Human milk-fed infants should be closely monitored for adverse events resulting from lamotrigine. Measurement of infant serum levels should be performed to rule out toxicity if concerns arise. Human milk-feeding should be discontinued in infants with lamotrigine toxicity. Caution should be exercised when lamotrigine is administered to a nursing woman.
* The majority of parameter means determined in each study had coefficients of variation between 20% and 40% for half-life and Cl/F and between 30% and 70% for Tmax. The overall mean values were calculated from individual study means that were weighted based on the number of volunteers/patients in each study. The numbers in parentheses below each parameter mean represent the range of individual volunteer/patient values across studies. † Carbamazepine, phenobarbital, phenytoin, and primidone have been shown to increase the apparent clearance of lamotrigine. Estrogen-containing oral contraceptives and other drugs such as rifampin that induce lamotrigine glucuronidation have also been shown to increase the apparent clearance of lamotrigine [see Drug Interactions (7)]. |
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Adult Study Population | Number of Subjects | Tmax: Time of Maximum Plasma Concentration (hr) | t½: Elimination Half-life (hr) | Cl/F: Apparent Plasma Clearance (mL/min/kg) |
Healthy volunteers taking no
other medications: | | | | |
Single-dose lamotrigine | 179 | 2.2 (0.25-12) | 32.8 (14-103) | 0.44 (0.12-1.1) |
Multiple-dose lamotrigine | 36 | 1.7 (0.5-4) | 25.4 (11.6-61.6) | 0.58 (0.24-1.15) |
Healthy volunteers taking
valproate: | | | | |
Single-dose lamotrigine | 6 | 1.8 (1-4) | 48.3 (31.5-88.6) | 0.3 (0.14-0.42) |
Multiple-dose lamotrigine | 18 | 1.9 (0.5-3.5) | 70.3 (41.9-113.5) | 0.18 (0.12-0.33) |
Patients with epilepsy taking
valproate only: | | | | |
Single-dose lamotrigine | 4 | 4.8 (1.8-8.4) | 58.8 (30.5-88.8) | 0.28 (0.16-0.4) |
Patients with epilepsy taking
carbamazepine, phenytoin, phenobarbital, or primidone† plus valproate: | | | | |
Single-dose lamotrigine | 25 | 3.8 (1-10) | 27.2 (11.2-51.6) | 0.53 (0.27-1.04) |
Patients with epilepsy taking
carbamazepine, phenytoin, phenobarbital, or primidone: † | | | | |
Single-dose lamotrigine | 24 | 2.3 (0.5-5) | 14.4 (6.4-30.4) | 1.1 (0.51-2.22) |
Multiple-dose lamotrigine | 17 | 2 (0.75-5.93) | 12.6 (7.5-23.1) | 1.21 (0.66-1.82) |
* From adjunctive clinical trials and volunteer studies. † Net effects were estimated by comparing the mean clearance values obtained in adjunctive clinical trials and volunteer studies. ‡ The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of lamotrigine has not been systematically evaluated in clinical trials, although the effect may be similar to that seen with the ethinylestradiol/levonorgestrel combinations. § Modest decrease in levonorgestrel. ¦ Not administered, but an active metabolite of carbamazepine. ¶ Slight decrease, not expected to be clinically relevant. # Not administered, but an active metabolite of oxcarbazepine. ** Slight increase, not expected to be clinically relevant. = No significant effect. ? = Conflicting data. |
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Drug | Drug Plasma Concentration With Adjunctive Lamotrigine* | Lamotrigine Plasma Concentration With Adjunctive Drugs† |
Oral contraceptives (e.g., ethinylestradiol/levonorgestrel)‡ | ↔§ | ↓ |
Bupropion | Not assessed | ↔ |
Carbamazepine (CBZ) | ↔ | ↓ |
CBZ epoxide¦
| ? | |
Felbamate | Not assessed | ↔ |
Gabapentin | Not assessed | ↔ |
Levetiracetam | ↔ | ↔ |
Lithium | ↔ | Not assessed |
Olanzapine | ↔ | ↔¶
|
Oxcarbazepine | ↔ | ↔ |
10-monohydroxy oxcarbazepine metabolite# | ↔ | |
Phenobarbital/primidone | ↔ | ↓ |
Phenytoin (PHT) | ↔ | ↓ |
Pregabalin | ↔ | ↔ |
Rifampin | Not assessed | ↓ |
Topiramate | ↔** | ↔ |
Valproate | ↓ | ↑ |
Valproate + PHT and/or CBZ | Not assessed | ↔ |
Zonisamide | Not assessed | ↔ |
* Carbamazepine, phenobarbital, phenytoin, and primidone have been shown to increase the apparent clearance of lamotrigine. Estrogen-containing oral contraceptives and rifampin have also been shown to increase the apparent clearance of lamotrigine [see Drug Interactions (7)]. † Two subjects were included in the calculation for mean Tmax. ‡ Parameter not estimated. |
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Pediatric Study Population | Number of Subjects | Tmax
(hr) | t½
(hr) | Cl/F (mL/min/kg) |
Ages 10 months to 5.3 years
Patients taking carbamazepine, phenytoin, phenobarbital, or primidone* | 10 | 3 (1-5.9) | 7.7 (5.7-11.4) | 3.62 (2.44-5.28) |
Patients taking AEDs with no known effect on the apparent clearance of lamotrigine | 7 | 5.2 (2.9-6.1) | 19 (12.9-27.1) | 1.2 (0.75-2.42) |
Patients taking valproate only | 8 | 2.9 (1-6) | 44.9 (29.5-52.5) | 0.47 (0.23-0.77) |
Ages 5 to 11 years Patients taking carbamazepine, phenytoin, phenobarbital, or primidone* | 7 | 1.6 (1-3) | 7 (3.8-9.8) | 2.54 (1.35-5.58) |
Patients taking carbamazepine, phenytoin, phenobarbital, or primidone* plus valproate | 8 | 3.3 (1-6.4) | 19.1 (7-31.2) | 0.89 (0.39-1.93) |
Patients taking valproate only†
| 3 | 4.5 (3-6) | 65.8 (50.7-73.7) | 0.24 (0.21-0.26) |
Ages 13 to 18 years Patients taking carbamazepine, phenytoin, phenobarbital, or primidone* | 11 | ‡ | ‡ | 1.3 |
Patients taking carbamazepine, phenytoin, phenobarbital, or primidone* plus valproate | 8 | ‡ | ‡ | 0.5 |
Patients taking valproate only | 4 | ‡ | ‡ | 0.3 |
Tell your healthcare provider about all the medicines you take or if you are planning to take a new medicine, including prescription and non-prescription medicines, vitamins, and herbal supplements. Using lamotrigine tablets with certain other medicines can affect each other, causing side effects.
For more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876.
LAMOTRIGINE
lamotrigine tablet |
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LAMOTRIGINE
lamotrigine tablet |
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LAMOTRIGINE
lamotrigine tablet |
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LAMOTRIGINE
lamotrigine tablet |
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Labeler - Aurobindo Pharma Limited (650082092) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Aurobindo Pharma Limited | 918917642 | ANALYSIS(65862-227, 65862-228, 65862-229, 65862-230), MANUFACTURE(65862-227, 65862-228, 65862-229, 65862-230) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Aurobindo Pharma Limited | 918917626 | API MANUFACTURE(65862-227, 65862-228, 65862-229, 65862-230) |