Lamotrigine toxicity

Kaufman KR, Gerner R. Lamotrigine toxicity secondary to sertraline. Seizure 1998 7 163-165. 

Sbei M, CampeUone TV. Stupor from lamotrigine toxicity. Epilepsia 2001 42(8) 1082-3. 

Lamotrigine Toxicity has been reported following the addition of sertraline. 

Lofton AL, Klein-Schwartz W. Evaluation of lamotrigine toxicity reported to poison centers. Aim Pharmacother 2004 38(11) 1811-5. 

Strimel WJ, Woodruff A, Cheung P, Kirmani BE, Stephen Huang SK. Brugada-like electrocardiographic pattern induced by lamotrigine toxicity. Clin Neu-ropharmacol 2010 33(5) 265-7. 

Close BR, Banks CJ. Seizures secondary to lamotrigine toxicity in a two-year-old. Ann Pharmacother 2010 44(6) 1112-5. 

When carbamazepine is administered with primidone, decreased primidone levels and higher carbamazepine serum levels may result. Cimetidine administered with carbamazepine may result in an increase in plasma levels of carbamazepine that can lead to toxicity. Blood levels of lamotrigine increase when the agent is administered with valproic acid, requiring a lower dosage of lamotrigine... 

Melanin-containing tissues Lamotrigine binds to melanin and may cause toxicity in... 

Carbamazepine Lamotrigine Increased concentrations of epoxide metabolite leading to toxicity... 

It is very important to choose medications with the least possibility of making an ill pediatric patient suffer additional morbidity from side effects to medication directed at mood or behavior. For these reasons, mood stabilizers such as lamotrigine (which carries with it the risk of a severely toxic rash) should be seen only as third- or fourth-line agents. 

Valproate may increase concentrations of phenobarbital, etho-suximide, and the active 10,11-epoxide metabolite of carba-mazepine, increasing the risk of toxicity. Valproate may also raise lamotrigine levels, increasing the risk of rash. 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

LAMOTRIGINE 1. CARBAMAZEPINE 2. OXCARBAZEPINE 1. Cases of t levels of an active metabolite of carbamazepine with toxicity 2. Case of toxicity with oxcarbazepine Uncertain Be aware watch for early features of toxicity of carbamazepine and oxcarbazepine... 

VALPROATE 1. BARBITURATES -phenobarbital, primidone 2. 7ETHOSUXIMIDE 3. LAMOTRIGINE t levels of these antiepileptics Uncertain Watch for early features of toxicity. Measure levels where possible... 

Phenobarbital Phenytoin Primidone Felbamate Lamotrigine Tiagabide Topiramate Valproate Zonisamide Clobazam Clonazepam Diazepam usually compensated by the effect of the added drug risk of toxicity when interfering drug is discontinued drug... 

Valproate Carbamazepine epoxide Diazepam Felbamate Lamotrigine Phenobarbital Risk of toxicity, particularly with phenobarbital including primidone-derived phenobarbital and lamotrigine Inhibition of metabolism of the affected drug. Valproate also displaces diazepam from protein binding sites, affecting relation between total diazepam concentration and effect... 

Valproate Lamotrigine Risk of toxicity therapeutic synergism possible Inhibition of lamotrigine metabolism and pharmacodynamic interaction... 

Sertraline Carbamazepine Diazepam Lamotrigine Phenytoin Risk of toxicity of the object drugs Inhibition of metabolism of the object drugs... 

Carbamazepine toxicity with lamotrigine pharmacokinetic or pharmacodynamic interaction Epilepsia... 

The postmortem blood concentration of carbamazepine has been reported in a case of suicide attributed to mixed drug toxicity with carbamazepine, lamotrigine, paroxetine, and thioridazine (86). It was 76 pmol/l. 

Liver toxicity from lamotrigine is extremely rare. Acute hepatic necrosis occurred in the context of a hypersensitivity reaction that also involved the skin (SEDA-20, 64). 

Published and unpublished cases of Stevens-Johnson syndrome (n = 43) and toxic epidermal necrolysis (n = 14) associated with lamotrigine have been reviewed (44). The patients with Stevens-Johnson syndrome were younger than those with toxic epidermal necrolysis (21 versus 31 years) the median time to onset for both reactions was 17 days the median dosage at onset (50 mg for Stevens-Johnson syndrome, 87.5 mg for toxic epidermal necrolysis) did not differ significantly. Valproate comedication was present in 74% and 64% of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis respectively. In three patients, toxic epidermal necrolysis occurred in the context of the anticonvulsant hypersensitivity syndrome. 

Stevens-Johnson syndrome, and 3 as suggestive of Stevens-Johnson syndrome two deaths were reported. Rashes associated with one or more symptoms of hypersensitivity reactions occurred in 19 children. Of 29 patients with Stevens-Johnson syndrome, toxic epidermal necrolysis, or hypersensitivity reactions, for whom precise details were available, 83% were taking lamotrigine with concomitant valproate and 85% were taking lamotrigine dosages higher than recommended. 

Although serious skin rashes have been reported with traditional anticonvulsants, the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis with these drugs appears to be lower than with lamotrigine. Data from the Saskatchewan Health Plan suggest that the risk of serious rashes is in the order of 0.9 1000 (1.4 1000 in children) for phenytoin, 0.6 1000 (1.4 1000 in children) for carbamaze-pine, and 0 1000 for valproate, but Stevens-Johnson syndrome constituted only a small minority of these cases (47). 

Co-administration of valproate is one of the most important risk factors for skin reactions to lamotrigine valproate co-medication was present in 74 and 64% of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis respectively (44). 

Froscher W, Keller F, Kraemer G, Vogt H. Serum level monitoring in assessing lamotrigine efficacy and toxicity. Epilepsia 1999 40(Suppl 2) 252. 

Kilpatrick ES, Forrest G, Brodie MJ. Concentration-effect and concentration-toxicity relations with lamotrigine a prospective study. Epilepsia 1996 37(6) 534-8. 

Dizziness, ataxia, diplopia, blurred vision, nausea, and vomiting are signs of toxicity that occur when the blood level exceeds 10 Ug/mL. A chromatographic method for analysis of lamotrigine has been reported. ... 

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