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Antiepileptic Drugs: Dose, Regime, Pharmocokinetics, Adverse Effects & Efficacy

 

Disclaimer

We make no claims for the accuracy of the information on this page, and will not be held legally responsible for its contents. Any discussion of specific antiepileptic medications does not constitute an endorsement of those agents or of the pharmaceutical companies which manufacture them.

Directory

• carbamazepine (Tegretol)
• clonazepam (Klonopin)
• ethosuximide (Zarontin)
• felbamate (Felbatol)
• fosphenytoin (Cerebyx)
• lamotrigine (Lamictal)
• levetiracetam (Keppra)
• oxcarbazepine (Trileptal)
• phenobarbital (Luminal)
• phenytoin (Dilantin)
• pregabalin (Lyrica)
• primidone (Mysoline)
• tiagabine (Gabitril)
• topiramate (Topamax)
• valproate, sodium divalproex (Depakene, Depakote)
• vigabatrin (Sabril)
• zonisamide (Zonegran)

 

• Cost Information

  

carbamazepine (Tegretol)

• Dose range
  • Adults: 600 to 2,000 mg per day
  • Children: 10 to 40 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response; initial doses are lower; pharmacokinetic interactions may affect dosage requirements.

 

• Regimen
  • Three to four times per day; two times per day for sustained release preparation, Tegretol XR

 

• Pharmocokinetics
  • Hepatic elimination by oxidation, aromatic hydroxylation, and N-glucuronidation
  • Half life 5-20 hours
  • Some clinically relevant pharmacokinetic drug interactions:
    • Carbamazepine induces the metabolism of cyclosporine A, tricyclic antidepressants, and warfarin (Coumadin)
    • Carbamazepine induces the metabolism of oral contraceptive agents, including ethinyl estradiol and levonorgestrel, with the potential for breakthrough bleeding and contraceptive failure
    • Carbamazepine levels are increased by the calcium-channel blockers verapamil and diltiazem, erythromycin and other macrolide antibiotics,isoniazid, cimetidine (Tagamet), and propoxyphene (Darvon).
    • Carbamazepine increases phenytoin metabolism to a variable degree
    • Carbamazepine increases primidone biotransformation to phenobarbital
    • Carbamazepine increases metabolism of valproate, ethosuximide, and lamotrigine Carbamazepine metabolism is increased by phenytoin, phenobarbital, primadone, and felbamate.
    • Felbamate increases carbamazepine epoxide levels
  • Comment: Steady-state values for the half life of carbamazepine are reached only after complete hepatic autoinduction, which occurs after approximately one month of carbamazepine administration.

 

• Adverse effects
  • Dose related: Double vision, Dizziness, Nausea, Headache
  • Idiosyncratic: Rash, Leucopenia
  • Comment: All antiepileptic drugs are potentially teratogenic. An increased incidence of neural tube defects has been shown to occur with carbamazepine.

 

• Efficacy:
  • Partial seizures
  • Secondarily generalized seizures

 

External Carbamazepine Link 1

External Carbamazepine Link 2

External Carbamazepine Link 3

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clonazepam (Klonopin)

• Dose range
  • Adults: 2-4 mg per day
  • Children: 0.1-0.3 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response; lower initial doses may reduce somnolence.

 

• Regimen
  • Two to three times per day

 

• Pharmacokinetics
  • Hepatic elimination by nitroreduction and acetylation
  • Half life 20-40 hours
  • Pharmacokinetic drug interactions are uncommon, but administration of hepatic enzyme inducing agents such as carbamazepine, phenobarbital and phenytoin may lower clonazpeam levels somewhat.

 

• Adverse effects
  • Dose related: Drowsiness, Ataxia, Irritability
  • Idiosyncratic: Rash, Leucopenia
  • Comment: All antiepileptic drugs are potentially teratogenic.

 

• Efficacy:
  • Myoclonic seizures
  • Absence seizures
  • Partial seizures
• Secondarily generalized seizures

 

External Clonazepam Link 1

External Clonazepam Link 2

 

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ethosuximide (Zarontin)

• Dose range
  • Adults: 500-1250 mg per day
  • Children: 10-60 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response.

 

• Regimen
  • Two to three times per day

 

• Pharmacokinetics
  • Elimination: Hepatic (80%) oxidation; Renal (20%)
  • Half life 30-60 hours
  • Ethosuximide is not protein bound
  • Some clinically relevant pharmacokinetic drug interactions:
    • Half life decreased by concomittant administration of hepatic enzyme inducing agents such as carbamazepine, phenytoin or phenobarbital
    • The half life of ethosuximide may be increased by valproate
    • Ethosuximide has little or no effect on the pharmacokinetics of other antiepileptic drugs

 

• Adverse effects
  • Dose related: Nausea, hiccups, anorexia
  • Idiosyncratic: Rash, SLE
  • Comment: All antiepileptic drugs are potentially teratogenic.

 

• Efficacy:
  • Absence seizures

     

  External Ethosuximide Link 1

   

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felbamate (Felbatol)

• Dose range
  • Adults: 2400-4600 mg per day
  • Children: 40-60 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response; initial doses are lower; pharmacokinetic interactions may affect dosage requirements.

 

• Regimen
  • Three times per day

 

• Pharmacokinetics
  • Elimination is both renal, and hepatic by hydroxylation and glucuronidation
  • Half life 15-20 hours
  • Some clinically significant pharmacokinetic drug interactions:
    • Felbamate increases phenytoin, phenobarbital and valproate levels
    • Felbamate decreases carbamazepine concentration but increases the concentration of carbamazepine epoxide
    • Felbamate levels are decreased by phenytoin, and carbamazepine, but valproate has little effect

     

• Adverse effects
  • Dose related: Anorexia, Weight loss, Headaches, Insomnia
  • Idiosyncratic: Aplastic Anemia, Liver failure
  • Comment: All antiepileptic drugs are potentially teratogenic.

   

• Efficacy:
  • Partial seizures
  • Secondarily generalized seizures
  • Generalized seizures
  • Absence seizures
  • Myoclonic seizures
  • Lennox-Gastaut syndrome

 

• Comment: Use of felbamate is restricted by an FDA advisory because of the risk of idiosyncratic side effects.

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fosphenytoin (Cerebyx)

This agent been approved for use in the United States. This is a phosphorylated prodrug of phentoin for intravenous and intramuscular injection. It is rapidly and completely converted to phenytoin by the body, but has significantly fewer IV injection site complications than older preparations of phenytoin (DIlantin) for intravenous injection. This is because fosphenytoin is water soluble, whereas phenytoin is provided in a solution of propylene glycol and water with a pH of 12.

Fosphenytoin is dispensed in units of mg phenytoin equivalents, with one mg phenytoin equivalent of fosphenytoin being equivalent to one mg of parenteral phenytoin. The maximum recommended intravenous infusion rate is 150 mg PE/min, with cardiac and blood pressure monitoring being required. This rate of infusion has been shown to be bioequivalent to a phenytoin infusion at a rate of 50 mg/min, that is, "therapeutic" levels of free phenytoin are achieved at approximately the same time after infusion of phenytoin at 50 mg/min and fosphenytoin at 150 mg PE/min.

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gabapentin (Neurontin)

• Dose range
  • Adults: 900-4800 mg per day
  • Children: 15-30 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response; lower initial doses may reduce ataxia or somnolence.

 

• Regimen
  • Three times per day

 

• Pharmacokinetics
• Renal elimination
• Half life 5-7 hours
• Gabapentin does not have significant pharmacokinetic drug interactions and is not significantly protein bound.

 

• Adverse effects
  • Dose related: Dizziness, Ataxia, Somnolence, Weight Gain
  • Idiosyncratic: Rash
  • Comment: All antiepileptic drugs are potentially teratogenic.

 

• Efficacy: Approved foruse as an add on treatment in adults for
  • Partial seizures
  • Secondarily generalized seizures

   

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lamotrigine (Lamictal)

• Possible mechanism of action:
  • Blockade of voltage sensitive sodium channels.

 

• Pharmacokinetics
  • Oral bioavailability: 98 %
  • Protein binding: 55 %
  • Elimination by hepatic N-glucuronidation
  • Half life ~26 hours
  • Some clinically relevant pharmacokinetic drug interactions:
    • Half-life prolonged by valproate
    • Half-life shortened by carbamazepine, phenytoin, phenobarbital, primidone

     

    • FDA Box Warning: Severe, potentially life-threatening rashes have been reported in association with the use of Lamictal. These reports, occurring in approximately one in every thousand adults, have included Stevens-Johnson syndrome (SJS), and rarely, toxic epidermal necrolysis (TEN). Rare deaths have been reported, but their numbers are too few to permit a a precise estimate of the rate.

 

The incidence of severe, potentially life-threatening rash in pediatric patients, however, is very much higher than that reported in adults using Lamictal; specifically, reports for clinical trials suggest as many as 1 in 50 to 1 in 100 pediatric patients develop a potentially life-threatening rash. It bears emphasis, accordingly, that Lamictal is not approved for use in patients below the age of 16. (see indications).

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

Nearly all cases of life-threatening rashes associated with lamictal have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have been reported after prolonged treatment (e.g., 6 months). Accordingly, duration of therapy cannot be relied upon as a means to predict the potential risk heralded by the first appearance of a rash.

Although benign rashes also occur with Lamictal, it is not possible to predict reliably which rashes will prove to be life-threatening. Accordingly, Lamictal should be discontinued at the first sign of rash, unless the rash is clearly not drug-related. Discontinuance of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.

• Efficacy: Approved for use in adults as add on treatment for
  • Partial seizures
  • Absences and atypical absences
  • Lennox-Gastaut syndrome Tonic and atonic seizures

 

• Side effects:
  • Dose Related: Diplopia, Somnolence, Dizziness, Ataxia, Insomnia
  • Idiosyncratic: Rash--The risk of rash is decreased by lower initial doses.
  • Comment: All antiepileptic drugs are potentially teratogenic.

   

• Dosage:
  • Adolescents and adults:
    • If added to valproate monotherapy: 25 mg daily for two weeks, then 50 mg daily for two weeks, then titrate up to 150 mg twice daily.
    • If added to carbamazepine, phenytoin,phenobarbital or primidone: Initial dose 50 mg twice daily, subsequent increases up to 100 - 200 mg twice daily.

     

  • Infants and children:
    • If added to valproate monotherapy: initial dose 0.5 mg/kg/day, final maintenance dose of 1 - 5 mg/kg/day.
    • If added to carbamazepine, phenytoin, phenobarbital, or primidone: initial doses 2 mg/kg/day, with subsequent increases to 5 - 15 mg/kg/day.

   

  • Comment: Optimal individual maintenance doses will be determined by clinical response.

 

External Lamotrigine Link (FDA)

External Lamotrigine Link

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levetiracetam (Keppra)

• Dose range
  • Adults: 1000-3000 mg/day
  • Children: dosage range not established

 

• Regimen
  • Twice a day

• Pharmacokinetics
  • Renal metabolism
  • Half-life: 7 hours
  • Drug interactions: None known.

• Adverse effects
  • Dose-related: Somnolence, weakness, headache, infection, behavioral difficulty
  • Idiosyncratic: none known

• Efficacy
  • Adjunctive therapy of partial and secondarily generalized seizures.

   

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oxcarbazepine (Trileptal)

• Dose range
  • Adults: 600-2400 mg per day
  • Children:10-30 mg / kg per day

 

• Regimen
  • Twice a day

 

• Pharmacokinetics

• Hepatic metabolism. hepatic metabolite MHD is largely responsible for anticonvulsant action
• Half-life 9 hours (MHD)
• Drug interactions:
  • Phenytoin levels increased by doses >1200 mg /d
  • MHD levels decreased by P450 inducers (phenytoin, carbamazepine, phenobarbital)
  • No auotinduction of MHD, unlike with carbamazepine.
  • Induces metabolism of oral contraceptives and may cause contraceptive failure
  • Induces metabolism of some dihydropyridine calcium-channel blockers

• Adverse effects
  • Dose-related: Dizziness, double vision, somnolence, fatigue, nausea
  • Idiosyncratic: Hyponatremia (higher than with carbamazepine), rash (about 35% of those with carbamazepine rash will get oxcarbazepine rash). No evidence of neutropenia seen with carbamazepine.
  • Comment: Overall is better tolerated than carbamazepine.

• Efficacy
  • Partial or secondarily gneralized seizures as adjunctive or monotherapy.

   

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phenobarbital (Luminal)

• Dose range
  • Adults: 30-180 mg per day
  • Children: 2-8 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response; initial doses are lower; pharmacokinetic interactions may affect dosage requirements.

 

• Regimen
  • Once per day

   

• Pharmacokinetics
  • Elimination is both renal, and hepatic by parahydroxylation and conjugation to glucuronic acid
  • Half life 65-110 hours
  • Some clinically relevant pharmacokinetic drug interactions:
    • Phenobarbital levels are significantly increased by valproate
    • Phenobarbital levels may be mildly increased by acetazolamide, phenylethylacetylurea and methsuximide
    • Phenobarbital lowers levels of valproate, and may cause mild lowering of carbamazepine levels
    • Interactions between phenobarbital and phenytoin are mild and inconsistent
    • Chloramphenicol elevates phenobarbital levels
    • Quinine and phenothiazines lower phenobarbital levels
    • Phenobarbital decreases levels of theophylline, chloramphenicol, doxicycline, warfarin (Coumadin), cimetidine, cyclosporine, digoxin, and chlorpropamizine
    • Phenobarbital increases metabolism of oral contraceptive agents potentially leading to breakthrough bleeding and contraceptive failure

     

• Adverse effects
  • Dose related: Somnolence, Hyperactivity, Depression
  • Idiosyncratic: Rash, SLE
  • Comment: All antiepileptic drugs are potentially teratogenic.

 

• Efficacy:
  • Partial seizures
• Secondarily generalized seizures
• Myoclonic seizures

 

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phenytoin (Dilantin)

• Dose range
  • Adults: 200-600 mg per day
  • Children: 5-10 mg/kg per day
  • Comment: The half life of phenytoin is concentration dependent due to nonlinear kinetics.
  • Comment: Optimal individual maintenance doses will be determined by clinical response; lower initial doses may reduce ataxia or somnolence; pharmacokinetic interactions may affect dosage requirements.

   

• Regimen
  • Once or twice per day

   

• Pharmacokinetics
  • Elimination is nearly entirely hepatic by oxidation, hydroxylation, and glucurinidation
  • Half life 10-60 hours
  • Some clinically relevant pharmacokinetic drug interactions:
    • Phenytoin levels are decreased by vigabatrin
    • Phenytoin levels may be decreased, increased or unchanged in an unpredictable fashion by phenobarbital or carbamazepine
    • Phenytoin decreases the levels of carbamazepine, lamotrigine, and valproate, and increases biotransformation of primidone to phenobarbital
    • Phenytoin increases metabolism of oral contraceptives and dexamethasone (Decadron)
    • Phenytoin decreases levels of theophylline, quinidine, cyclosporin, digitoxin, and chloramphenicol
    • Phenytoin has variable effects on warfarin (Coumadin)
    • Phenytoin levels are increased by amiodarone, diltiazam, isoniazid, sulfonamides, fluconazole, cimetidine, and phenylbutzone
    • Total phenytoin levels decreased, but free phenytoin levels may be increased by valproate, diazoxide and high doses of acetylsalicylic acid (Aspirin)

     

• Adverse effects
  • Dose related: Nystagmus, Ataxia, Gingival hyperplasia
  • Idiosyncratic: Rash, blood dyscrasia, dyskinesias
  • Comment: All antiepileptic drugs are potentially teratogenic.

 

• Efficacy:
  • Partial seizures
• Secondarily generalized seizures

 

External Phenytoin Link 1

External Phenytoin Link 2

 

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Pregabalin (Lyrica )

• Probable mechanism of action
  • blocks voltage-sensitive calcium channels in the CNS
  • reduces release of neurotransmitters
• Pharmacokinetics
  • Oral bioavailability: 90%+
  • Protein binding: None
  • Elimination: Renal o Half life: 6 hours
  • Drug-drug interactions: increased sedative effects with alchohol or benzodiazepine use. No reported interactions with OCPs or other AEDs.
  • Must adjust based on creatinine clearance in renal failure

    Creatinine Clearance (CLcr) (mL/min)	Total Pregabalin	Daily Dose	(mg/day)	Dose Regimen
    60 or greater	150	300	600	twice daily or three times daily
    30 to 60	75	150	300	twice daily or three times daily
    15 to 30	25 to 50	75	150	once daily or twice daily
    less than 15	25	25 to 50	75	once daily

    
    
  • Supplemental dose should be given immediately after 4 hour dialysis treatments

   

  Adjusted dose regimen based on Clcr	Supplementary dose
  25 milligrams (mg) once daily	one supplemental dose of 25 mg or 50 mg
  25 to 50 mg once daily	one supplemental dose of 50 mg or 75 mg
  75 mg once daily	one supplemental dose of 100 mg or 150 mg

  Efficacy: FDA approved as adjunctive treatment of partial seizures in adults

  Side Effects

  • dizziness (placebo-9%, 600 mg/d-43%)
  • somnolence (placebo-11%, 600mg/d-28%)
  • ataxia (placebo-3%, 600 mg/d-15%)
  • Blurred vision, tremor, incoordination, and dry mouth (5-10% above placebo)
  • Weight gain in 12.4% (placebo-0.5kg, 600 mg/d- 2.3kg)
  • Myoclonus
  • Effects are dose related
  • Teratogenicity unknown
    
  • Likely to be present in breastmilk, effects on infant unknown
    
    
    

  Dosage

  • Initial: no greater than 50 mg TID or 75 mg BID
  • Max: 600 mg/d divided BID or TID
  • Titrate according to individual tolerability and response

   

  Comment: also used for post-herpetic neuralgia and diabetic peripheral neuropathy

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primidone (Mysoline)

• Dose range
  • Adults: 500-1250 mg per day
  • Children: 5-20 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response; initial doses are lower; pharmacokinetic interactions may affect dosage requirements.

   

• Regimen
  • Three times per day

   

• Pharmacokinetics
  • Elimination by hepatic transformation by ring scission to phenylethylmalonamide (PEMA) and oxidation to phenobarbital; elimation is then primarily renal
  • Half life 8-15 hours
  • Some clinically relevant pharmacokinetic drug interactions:
    • Carbamazepine increases biotransformation to phenobarbital (minor)
    • Carbamazepine levels decreased by primadone
    • Phenytoin increase phenobarbital levels and decreases primadone levels
    • Phenytoin levels decreased by primadone
    • Valproate increases primadone and phenobarbital levels
    • Clonazpam increases primadone levels
    • Ethanol and isoniazid increase primadone levels
    • Primadone decreases warfarin (coumadin), cyclosporine, digitoxin, and theophylline

     

• Adverse effects
  • Dose related: Somnolence, Ataxia, Depression
  • Idiosyncratic: Rash, SLE
  • Comment: All antiepileptic drugs are potentially teratogenic.

 

• Efficacy:
  • Partial seizures
  • Secondarily generalized seizures
  • Myoclonic seizures

   

  External Primidone Link 1

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tiagabine (Gabatril)

This agent was approved for use in the United States on September 30, 1997 as an adjunctive therapy for adults and children over 12 with partial onset seizures.

• Possible Mechanism of Action

Tiagabine is believed to block reuptake of GABA into the presynaptic terminal by binding to recognition sites of the GABA uptake carrier, leading to accumulation of GABA in the synaptic cleft.

• Dose range
  • Suggested adult maintanance dose: 32 to 56 mg/day. Dosage titrations of 4-8 mg/day weekly are suggested by the manufacturer.
  • Comment: Optimal individual maintenance doses will be determined by clinical response; initial doses are lower; pharmacokinetic interactions may affect dosage requirements.

   

• Regimen
  • Three to four times per day

 

• Pharmacokinetics
  • Elimination is predominantly hepatic by thiophene ring oxidation and glucuronidation.
  • Half life approximately 7-9 hours.
  • Some clinically relevant pharmacokinetic drug interactions:
    • Tiagabine may slightly decrease valproate levels, but does not appear to affect levels of other antiepileptic drugs.
    • Tiagabine levels are significantly decreased by hepatic enzyme inducing antiepileptic drugs such as carbamazepine, phenytoin, phenobarbital and primidone.
    • Valproate significantly decreases binding of tiagabine, leading to increased levels of free tiagabine. The significance of this has not been demonstrated.

     

• Adverse effects
  • Common dose related: tremor, dizziness, nervousness, difficulty concentrating, sleepiness
  • Comment: All older antiepileptic drugs are potentially teratogenic. Specific data on risk of teratogenesis is unknown (Pregnancy category C).

 

• Efficacy
  • Tiagabine is approved for use for partial seizures.

   

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topiramate (Topamax)

This agent was approved for use in the United States on December 24, 1996 as an adjunctive therapy for adult patients with partial onset seizures.

• Possible Mechanism of Action
  • Several mechanisms may exist. The most likely mechanisms include enhancing the effect of GABA on Cl- currents at GABA-A receptors, by action at a site distinct from benzodiazepines and barbiturates, and blockade of voltage sensitive sodium channels.

 

• Dose range
  • Adults: 400 mg per day. An initiation schedule, where the medication dose is increased by 50 mg/day each week, is recommended to reduce adverse effects; slower rates of initiation are used by some physicians.
  • Comment: Optimal individual maintenance doses will be determined by clinical response; initial doses are lower; pharmacokinetic interactions may affect dosage requirements.

   

• Regimen
• Two times per day

• Pharmacokinetics
  • Elimination is primarily (approximately 70%) renal in patients not receiving hepatic enzyme inducing medications. A small proportion is metabolised by hydroxylation, hydrolysis and glucuronidation. 13-17% binding to plasma proteins occurs at typical concentrations. Hepatic elimination is significant in patients also taking carbamazepine, phenytoin, or barbiturates.
  • Half life approximately 21 hours.
  • Some clinically relevant pharmacokinetic drug interactions:
    • Topiramate may decrease valproate levels
    • Topiramate may increase phenytoin levels in some patients
    • Topiramate levels are decreased by carbamazepine, phenytoin and valproate

     

• Adverse effects
  • Common dose related: psychomotor slowing, fatigue, nausea, parasthesias, weight loss
  • In clinical trials of this agent, 1.5% of patients reported the occurrence of kidney stones.
  • Comment: All older antiepileptic drugs are potentially teratogenic. Because topiramate is a recently licensed agent, specific data on risk of teratogenesis is unknown (Pregnancy category C).

 

• Efficacy
  • Topiramate is approved for use for partial seizures. Clinical trials of its efficacy for other seizure syndromes, including primary general seizures and the Lennox-Gastaut syndrome are pending.

   

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valproate, sodium divalproex (Depakene, Depakote)

• Dose range
  • Adults: 750-4000 mg per day
  • Children: 15-70 mg/kg per day
  • Comment: Optimal individual maintenance doses will be determined by clinical response; initial doses are lower; pharmacokinetic interactions may affect dosage requirements.

   

• Regimen
  • Three to four times per day

 

• Pharmacokinetics
  • Elimination is almost entirely hepatic by several conjugation and oxidative reactions.
  • Half life 5-15 hours
  • Some clinically relevant pharmacokinetic drug interactions:
    • Valproate increases phenobarbital, lamotrigine, felbamate, and ethosuximide levels
    • Valproate decreases total phenytoin levels, but increases free phenytoin levels
    • When valproate is administered with primidone, both primidone and phenobarbital levels may increase
    • Valproate levels are decreased by carbamazepine, phenobarbital and phenytoin
    • Valproate levels are increased by felbamate
    • Valproate does not increase clearance of oral contraceptive agents

     

• Adverse effects
  • Dose related: Weight gain, Hair loss, Tremor
  • Idiosyncratic: Liver failure, Pancreatitiis, Thrombocytopenia
  • Comment: All antiepileptic drugs are potentially teratogenic. An increased incidence of neural tube defects has been shown to occur particularly with valproate.

   

• Efficacy:
  • Partial seizures
  • Secondarily generalized seizures
  • Generalized seizures
  • Absence seizures
  • Myoclonic seizures
  • Lennox-Gastaut syndrome

   

  External Valproate Link 1

  External Valproate Link 2

   

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vigabatrin (Sabril)

This agent is not currently approved for use in the United States. Information on this agent will be posted when this occurs.

External vigabatrin Link

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zonisamide (Zonegran )

• Dose range
  • Adults: 100 - 400 mg / day
  • Children: Dosage range not established

 

• Regimen
  • Once or twice a day

• Pharmacokinetics
  • Renal metabolism
  • Half-life 60-100 hours
  • Drug Interactions:
    • Half-life of zonisamide decreased to 26-46 hours by coadministration with phenytoin, carbamazepine, or valproate. Zonisamide does not affect the metabolism of these other drugs.

• Adverse effects
  • Dose Related: somnolence, difficulty concentrating, dizziness, anorexia, agitation/irritability
  • Idiosyncratic: renal stones
  • Comment: patients with sensitivity to sulfa drugs should avoid zonisamide

• Efficacy
  • Adjunctive therapy of partial and secondarily generalized seizures. May be useful in primarily generalized seizures as well.

   

   

  References:

  The most comprehensive reference on the properties of antiepileptic drugs is Antiepileptic Drugs, Fifth Edition Levy, R.H.; Mattson, R.H.; and Meldrum, B.S.; Raven Press, 1995. Some of the information on this page comes from this source

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Last updated: November 2007