Levetiracetam+in+Hepatic+Dysfunction

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Levetiracetam+in+Hepatic+Dysfunction

  1. 1. Levetiracetam in Hepatic Dysfunction
  2. 2. Levetiracetam <ul><li>Is the S-enantiomer of etiracetam, </li></ul><ul><li>Approved for use as adjunctive therapy in adults with partial-onset seizures </li></ul>[email_address]
  3. 3. Epilepsy co-morbid with Hepatic Dysfunction and role of AEDs <ul><li>Patients with epilepsy may suffer from hepatic diseases that modify the metabolism of antiepileptic drugs </li></ul><ul><li>Seizures may occur in renal and hepatic disease, caused by the dysfunction itself, by its treatment, or by treatment of comorbidities </li></ul><ul><li>Loss of hepatocytes and disruption of liver blood flow alter the metabolism of AEDs </li></ul><ul><li>Some factors increases free AED levels:- </li></ul><ul><ul><li>Hypoalbuminemia, </li></ul></ul><ul><ul><li>Lower albumin binding affinity, and </li></ul></ul><ul><ul><li>impaired metabolism by cytochrome P450 (CYP450) and glucosyltranferase enzymes </li></ul></ul><ul><li>Low protein-bound AEDs with little liver metabolism, i.e., gabapentin, topiramate, vigabatrin, and Levetiracetam , are most suitable for treatment </li></ul>Reference: Glenda Lacerda et.al; Optimizing therapy of seizures in patients with renal or hepatic dysfunction; NEUROLOGY 2006;67(Suppl 4):S28–S33 [email_address]
  4. 4. Pharmacokinetics of Levetiracetam <ul><li>Major Route of excretion is urine (almost 95%) </li></ul><ul><li>Protein Binding: <10% (Not significant) </li></ul><ul><li>Less than 2% metabolism is by liver, so no dose adjustment required </li></ul><ul><li>In a study, it was found: </li></ul><ul><ul><li>Pharmacokinetics of Levetiracetam was not significantly different between healthy subjects and subjects in Child-Pugh classes A and B </li></ul></ul><ul><ul><li>In group with severe (class C) cirrhosis, the total clearance was reduced to 43% of that observed in healthy subject groups </li></ul></ul><ul><ul><li>Renal clearance was reduced in the Child-Pugh class C group to 34% of that in healthy group </li></ul></ul><ul><ul><li>No dose adjustment is necessary in patients with mild to moderate liver impairment . However, in those classified as Child-Pugh class C , careful monitoring and a dosage reduction of about 50% would be advisable </li></ul></ul>Reference: Brockmöller J; PK of levetiracetam in hepatically impaired subjects; Clin Pharmacol Ther. 2005 Jun; 77(6):529-41 [email_address]
  5. 5. Comparative study of pharmacokinetic parameters of Levetiracetam Reference: Brockmöller J; PK of levetiracetam in hepatically impaired subjects; Clin Pharmacol Ther. 2005 Jun; 77(6):529-41 [email_address]
  6. 6. Benefits of Using Levetiracetam <ul><li>Levetiracetam has no identified effect on CYP450 </li></ul><ul><li>NO DRUG – DRUG INTERACTION </li></ul><ul><li>Exhibits linear pharmacokinetics and steady-state is reached after 2 days of a twice-a-day administration </li></ul><ul><li>One report describes successful use of Levetiracetam as monotherapy after failure of Phenytoin in liver graft recipients </li></ul><ul><li>Levetiracetam does not induce hepatic metabolism </li></ul>Reference: Glenda Lacerda et.al; Optimizing therapy of seizures in patients with renal or hepatic dysfunction; NEUROLOGY 2006;67(Suppl 4):S28–S33 [email_address]
  7. 7. To sum up….. <ul><li>Levetiracetam is a preferred AED in cases of epilepsy co-morbid with liver dysfunction </li></ul><ul><li>No dose adjustment is necessary in patients with mild to moderate liver impairment </li></ul><ul><li>In those classified as Child-Pugh class C , careful monitoring and a dosage reduction of about 50% would be advisable </li></ul>[email_address]
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