In general, anticonvulsants are:

  • Well absorbed orally
  • Highly protein bound
  • Hepatically metabolised by CYP450 enzymes, and induce their own metabolism (as well as that of other drugs)
  • Renally eliminated
  • Interact with each other
Property Phenytoin Sodium Valproate Carbamazepine Levetiracetam
Uses GTCS, partial seizures, trigeminal neuralgia, ventricular arrhythmias Partial seizures Antiepileptic, trigeminal neuralgia GTCS, partial seizures, myoclonic seizures, seizure prophylaxis
Presentation Capsules, syrup, solution. IV formulation incompatible with dextrose. Tablets, syrup, solution Tablets, suppositories, syrup Tablets, oral liquid, IV liquid
Route of Administration PO, IV, IM PO, IV PO PO, IV (over 15 minutes)
Dosing load, aiming plasma levels 300-1250mg BD 50-800mg BD Typically 1g loading, then 500mg BD increasing up to 1.5g BD. Dose adjusted in renal impairment.
Mechanism of Action Stabilises Na+ channels in their inactive state, inhibiting generation of further action potentials. Stabilises Na+ channels in their inactive state and potentiates GABA Stabilises Na+ channels in their inactive state and potentiates GABA Unknown, but different to other antiepileptics and may be related to inhibition of N-type Ca2+ currents
Absorption Slow PO absorption. PO bioavailability 90% PO bioavailability 100% 95% PO bioavailability Near 100% PO bioavailability
Distribution Highly protein bound Highly protein bound Highly protein bound Nil significant protein binding, VD
Metabolism Hepatic hydroxylation with highly individual variation in dosing. Obeys first-order kinetics in the therapeutic range, and zero-order kinetics just above the therapeutic range. Metabolised by CYP450. Induces warfarin, benzodiazepines, OCP metabolism. Inhibited by metronidazole, chloramphenicol, isoniazid. Genetic polymorphism results in reduced metabolism in 5-15% of patients. Hepatic to inactive and active metabolites Hepatic Hepatic hydrolysis to inactive metabolites
Elimination Renal elimination of inactive metabolites and active drug Renal elimination of metabolites and active drug Renal elimination Renal of active drug (major route) and metabolite (minor route)
CVS ↓ BP, heart block, and asystole with rapid administration, antiarrhythmic properties Antiarrhythmic
CNS ↑ Seizure threshold, paraesthesia, ataxia, nystagmus, slurred speech, tremor, vertigo. ↑ Seizure threshold ↑ Seizure threshold ↑ Seizure threshold, anxiolytic. Minimal ↓ in seizure threshold on cessation.
Renal Water retention from ADH-like effects Rarely precipitates AKI
GIT Hepatotoxicity (idiosyncratic). Nausea and vomiting. Hepatotoxicity.
Haeme Aplastic anaemia and other blood dyscrasias Thrombocytopenia, leukopenia (requires regular testing) Thrombocytopenia
Immune Rash SJS
Metabolic Hyperammonaemia
Other Requires monitoring due to narrow therapeutic window and significant pharmacokinetic variation.
Gum hyperplasia.
May precipitate porphyria.
Reduces efficacy of aminosteroids.


  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
  3. CICM March/May 2010
  4. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
  5. Levetiracetam - Drug Information. FDA. 2009.
Last updated 2020-11-10

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