Felbamate adverse effects

In spite of the seriousness of the adverse effects, thousands of patients worldwide remain on the medication. Usual dosages are 2000-4000 mg/d in adults, and effective plasma levels range from 30 mcg/mL to 100 mcg/mL. In addition to its usefulness in partial seizures, felbamate has proved effective against the seizures that occur in Lennox-Gastaut syndrome. 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Nausea, vomiting, diarrhea, and changes in appetite can occur with all anticonvulsants, although they are usually transient and rarely require withdrawal. Felbamate and to a lesser extent valproate are the anticonvulsants that most often cause gastrointestinal adverse effects. 

Central nervous system adverse effects are common with felbamate, and consist mainly of insomnia, headache, impaired concentration, ataxia, dizziness, somnolence, behavioral disturbances, and mood changes. Movement disorders, psychosis, increased seizures, status epilepticus, and withdrawal seizures are less common (SEDA-19, 67) (SEDA-20, 61). The incidence of these effects is increased in the elderly, possibly owing to reduced drug clearance (4), whereas patients with mental retardation may be more prone to behavioral disorders (SEDA-19, 68). 

Felbamate has no clinically relevant effect on the pharmacokinetics of oxcarbazepine, but concurrent use appears to increase the incidence of adverse effects. 

Any changes in the pharmacokinetics of oxcarbazepine brought about by other antiepileptics seem to be of minimal clinical relevance. However, the clinical relevance of the increase in the active metabolite monohydroxyoxcarbazepine with lamotrigine requires further study. In addition, there is the theoretical risk that monohydroxyoxcarbazepine levels might rise to toxic levels if carbamazepine or phenytoin were withdrawn. For mention that there may be an increase in adverse effects if oxcarbazepine is used with felbamate, see Oxcarbazepine +Felbamate , p.545. 

An established interaction. If felbamate is added to established treatment with phenobarbital or primidone, particularly in patients already taking substmtial doses, monitor well for any evidence of increased adverse effects (drowsiness, lethargy, anorexia, ataxia) and reduce the dosages of the phenobarbital or primidone if necessary. 

None of the interactions between the benzodiazepines and antiepileptics described here appear to be of major clinical importance, with the possible exception of the interaction between clobazam and felbamate. If both drugs are given be aware that additive sedative or other adverse effects may occur. This may also be possible in some rare cases with chlordiazepoxide or clobazam and phenobarbital clonazepam and lamotrigine or primidone and clorazepate and primidone. 

Urinary tract Crystalluria has been reported in an 11-year-old child who had taken felbamate for several years [152" ]. The crystals were heterogeneous, with long thin needle-shaped crystals, hairy crystals, and large asymmetric needle-shaped crystals. The crystals had intense polarization and a strong tendency to aggregation. The crystals did not contain calcium and were composed of felbamate. This was therefore a between-the-eyes adverse effect of type la [153 ]. 

A double-blind, randomised study in 8 healthy subjects found that oxcarbazepine 300 to 600 mg every 12 hours, given with felbamate 600 to 1200 mg every 12 hours for 10 days had no effect on the plasma levels of the major aetive metabolite of oxcarbazepine (monohydroxyoxcar-bazepine). However, the levels of dihydroxyoxcarbazepine (a minor, inactive metabolite) were reduced, and the maximum serum levels of oxearbazepine were reduced, by about 20%. Although these changes were eonsidered to be elinically irrelevant, the incidence of some adverse ef-feets (dizziness, somnolence, nausea, diplopia) rose during concurrent use. ... 

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