Valproic acid with lamotrigine

Mueller TH, Beeber AR. Delirium from valproic acid with lamotrigine. Am J Psychiatry (2004) 161,1128-9. 

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... 

Epilepsy is a clinical disorder characterized by spontaneous, recurrent seizures arising from excessive electrical activity in certain parts of the brain [51]. Currently available drugs, such as phenytoin, carbamazepine, valproic acid, lamotrigine, and topiramate (for molecular structures see Fig. 6), provide symptomatic seizure suppression in only 60-70% of those receiving treatment [52-54]. These drugs are also associated with unwanted side... 

Studies suggest that as monotherapy for partial seizures, lamotrigine is as effective as carbamazepine and phenytoin lamotrigine may be better tolerated. Clinical data suggest that oxcarbazepine is as effective as phenytoin, valproic acid, and immediate-release carbamazepine, with perhaps fewer side effects. 

Absence seizures are best treated with ethosuximide, valproic acid, and perhaps lamotrigine. For a combination of absence and other generalized or partial seizures, valproic acid is preferred. If valproic acid is ineffective in treating a mixed seizure disorder that includes absence, ethosuximide should be used in combination with another AED. 

Other than age, no factors have been identified that are known to predict the risk of occurrence or the severity of rash associated with lamotrigine. It is suggested, yet to be proven, that the risk of rash may also be increased by 1) coadministration of lamotrigine with valproic acid (VPA), 2) exceeding the recommended initial dose of lamotrigine, or 3) exceeding the recommended dose escalation for lamotrigine. However, cases have been reported in the absence of these factors. 

II.e. 5.2. Interactions between first and second generation AEDs. Felbamate raises plasma concentrations of phenytoin, valproic acid and carbamazepine. Clearance of tiagabine, topiramate and zon-isamide is increased in the presence of an enzyme inducer. Vigabatrin reduces phenytoin concentrations after 4-5 weeks of comedication (via an unknown mechanism). For tiagabine, the elimination half-life may be reduced by 2-3 hours in the presence of an enzyme-induction AED. Lamotrigine elimination is slower if given with valproic acid. Topiramate reduces elimination of phenytoin. 

Low bone density leads to an increased risk of fractures. There was a 30% increased risk of non-seizure-related fractures in 348 non-institutionalized patients with epilepsy compared with a large control population (129). For non-seizure-related fractures the crude fracture rate was 1.6 fractures per 100 patient-years of observation a similar rate (1.4) has been found in men with epilepsy (122). In addition, in children with epilepsy, treatment with valproic acid and/or lamotrigine for more than... 

Pseudolymphoma and a condition resembling malignant lymphoma occur very rarely with phenytoin (SED-13, 142). There is no evidence of a significant increase in the incidence of other tumors. There have also been reports of pseudolymphoma with other antiepileptic drugs, including carbamazepine (147-149), lamotrigine (150), phenobarbital (151), and valproic acid (151). 

May TW, Rambeck B, Jurgens U. Influence of oxcarbaze-pine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication results of a retrospective study. Ther Drug Monit 1999 21(2) 175-81. 

In a study of 400 serum concentrations from 372 patients taking lamotrigine and valproic acid, lamotrigine was associated with a slight reduction in valproate serum concentrations (81). However, the size of the effect was probably of no clinical significance. 

Yalcin B, Karaduman A. Stevens-Johnson syndrome associated with concomitant use of lamotrigine and valproic acid. J Am Acad Dermatol 2000 43(5 Pt 2) 898-9. 

Morris RG, Black AB, Lam E, Westley IS. Clinical study of lamotrigine and valproic acid in patients with epilepsy using a drug interaction to advantage Ther Drug Monit 2000 22(6) 656-60. 

Clinically important, potentially hazardous interactions with carbamazepine, lamotrigine, phenobarbital, primidone, topiramate, valproic acid, vigabatrin... 

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