Levetiracetam Phenobarbital

Phenobarbital Phenytoin Topiramate Valproate Oxcarbazepine Topiramate Second-line Clobazam6 Gabapentin Levetiracetam Phenytoin Tiagabine... 

Carbamazepine, phenytoin, phenobarbital, valproate, gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate, zonisamide... 

Levetiracetam Action on synaptic protein SV2A Well absorbed orally not bound to plasma proteins metabolized to 3 inactive metabolites ty2 6-11 h Generalized tonic-clonic seizures, partial seizures, generalized seizures Toxicity Nervousness, dizziness, depression, seizures Interactions Phenobarbital, phenytoin, carbamazepine, primidone... 

Partial seizures Carbamazepine Phenytoin Lamotrigine Valproic acid Oxcarbazepine Gabapentin Topiramate Levetiracetam Zonisamide Tiagabine Primidone, phenobarbital Felbamate... 

Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete. Phenobarbital, introduced in 1912, controlled patients resistant to bromides. The next success was the discovery in 1938 of phenytoin (a hydantoin) which is structurally related to the barbiturates. Since then many other drugs have been discovered, but phenytoin still remains a drug of choice in the treatment of major epilepsy. Over the past ten years there has been a dramatic increase in the number of new anticonvulsant drugs (vigabatrin, gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam), but none has been shown to be superior to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). 

There is some evidence that the enzyme-inducing antiepileptics (carbamazepine, phenobarbital, phenytoin and primidone) may modestly reduce levetiracetam levels, but this is not thought to be clinically relevant. Levetiracetam does not usually alter the levels of these antiepileptics. However, some studies have found modestly raised phenytoin levels, and cases of possible carbamazepine toxicity have also been reported. There appears to be no pharmacokinetic interaction between levetiracetam and gabapentin, lamotrigine, or valproate. 

In six neonates (body weight over 2000 g, gestational age over 30 weeks) in a prospective pilot study on the use of oral levetiracetam as monotherapy in the treatment of neonatal seizures the dose was increased by 10 mg/kg day over 3 days [206 ]. There were no clear adverse events during the study. There was mild sedation during titration in one neonate taking concomitant phenobarbital. 

Observational studies Phenobarbital has been compared with levetiracetam and lamotrigine in patients with seizures and Alzheimer s disease in a prospective, randomized, three-arm parallel-group, case-control study (see above under Lamotrigine). 

Nervous system The effects of phenobarbital (n=2 X levetiracetam ( =38), and lamotrigine ( =29) have been evaluated in patients with seizures and Alzheimer s disease in a prospective, randomized, three-arm parallel-group, case-control study with a 4-week dosage adjustment and a 12-month evaluation period [230 ]. The adverse reactions were somnolence (8%), dizziness (4%), headache (1 4%), and weakness (12%). Those who took phenobarbital had significantly worse cognitive performance. 

Cumbo E, ligori LD. Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer s disease. Epilepsy Behav 2010 17(4) 461-6. 

Her dose of phenobarbital was increased to 90 mg/day and she again became seizure-free. Lamotrigine had to be withdrawn because of a rash. Levetiracetam was started and at a dose of 500 mg bd the dose of phenobarbital was tapered again at a slower rate. However, she had complex partial seizures again when she was taking phenobarbital 30 mg/day and levetiracetam 750 mg bd. The dose of levetiracetam was increased to 1000 mg bd, but complex partial seizures continued while the dose of phenobarbital was being tapered and for 3 weeks after withdrawal. No further seizures occurred during the next 24 months. 

---