levetiracetam (Keppra, Etiracetam, Spritam)
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Introduction
Tradename: Keppra.
Indications
- adjunctive agent for partial seizures
- adjunctive agent for generalized seizures[4]
- useful agent for Asians with HLA-B*1502 allele[5]
- effective for myoclonic seizures, myoclonic epilepsy[5]
- may improve cognition in Alzheimer's disease with epileptiform activity[10]
- bipolar disorder (unlabeled use)
- neuropathic pain (unlabeled use)
- may be preferred choice of anticonvulsant during pregnancy[7]
Contraindications
- avoid in patients with mood disorders[5]
* Pregnancy category: C
Dosage
- start 500 mg PO BID
- may increase every 3 days
- maximum 3000 mg/day
- pediatrics: start 10 mg/kg/day; maximum 30 mg/kg/day
Tabs:
- 250, 500, 750 (tablets may be crushed)
- Spritam (3D-printed) up to 1000 mg.tab[8]
* dosage adjustment in patients with severe liver failure[5]
Dosage adjustment in renal failure
- creatinine clearance 50-80 mL/min: 500-1000 mg BID
- creatinine clearance 30-50 mL/min: 250-750 mg BID
- creatinine clearance < 30 mL/min: 250-500 mg BID
- ESRD: 500-1000 mg/day, supplemental dose of 250-500 mg after dialysis
Pharmacokinetics
- bioavailability 100%, food may delay absorption
- peak effect 1 hour
- protein binding < 10%
- elimination 1/2life 608 hours
- excreted in urine 66% as unchanged drug
Adverse effects
- common (> 10%)
- behavioral symptoms (13% {adults}, 38% {children})
- somnolence (15-23%)
- headache (14%)
- vomiting (15%), anorexia (13%)
- weakness (9-15%)
- cough (2-11%)
- irritability
- depression
- sedation[5]
- less common (1-10%)
- uncommon (< 1%)
- alopecia, thrombocytopenia, pancytopenia
- 3-fold increased risk of suicide[6]
- well-tolerated in the elderly[5]
- in utero effect less than valproate[7]
- does not seem to affect language or developmental scores
- acute interstitial nephritis, acute renal failure[9]
- osteopenia & osteoporosis < carbamazepine, phenytoin, valproate[5]
- increased risk of Parkinson's disease (RR~1.8)[11]
Drug interactions
- few drug interactions[5]
- none with other anticonvulsants
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) anticonvulsants with statins
Mechanism of action
- inhibition of votage-dependent N-type Ca+2 channels
- inhibition of inhibitory GABA-ergic activity
- diminishes delayed rectifier K+ current
- binds synaptic proteins which modulate neurotransmitter release (SV2A)
More general terms
Additional terms
References
- ↑ Prescriber's Letter 7(5):28, May 2000
- ↑ Kaiser Permanente Northern California, Drug update, 9/2000
- ↑ Lexi-Comp, Drug Information 2005
- ↑ Jump up to: 4.0 4.1 Berkovic SF et al, Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology 2007, 69:1751 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17625106
- ↑ Jump up to: 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018.
- ↑ Jump up to: 6.0 6.1 Andersohn F et al, Use of antiepileptic drugs in epilepsy and the risk of self-harm or suicidal behavior Neurology 2010;75:335-340 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20660863 <Internet> http://www.neurology.org/cgi/content/abstract/75/4/335
- ↑ Jump up to: 7.0 7.1 7.2 Shallcross R et al In utero exposure to levetiracetam vs valproate. Development and language at 3 years of age. Neurology. Jan 8, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24401687 <Internet> http://www.neurology.org/content/early/2014/01/08/WNL.0000000000000030.short
Klein P, Mathews GC Antiepileptic drugs and neurocognitive development. Neurology. Jan 8, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24401684 <Internet> http://www.neurology.org/content/early/2014/01/08/WNL.0000000000000044.extract - ↑ Jump up to: 8.0 8.1 Aprecia News Release. Aug 3, 2015 FDA APPROVES THE FIRST 3D PRINTED DRUG PRODUCT Aprecia Introduces its First Product Using the ZipDose<TM> Formulation Platform for the Treatment of Epilepsy. https://www.aprecia.com/pdf/2015_08_03_Spritam_FDA_Approval_Press_Release.pdf
- ↑ Jump up to: 9.0 9.1 Lowes R New FDA Watch List Flags More Drugs Medscape Internal Medicine. July 3, 2017 http://www.medscape.com/viewarticle/882425
- ↑ Jump up to: 10.0 10.1 Vossel K, Ranasinghe KG, Beagle AJ et al Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity. A Randomized Clinical Trial. JAMA Neurol. Published online September 27, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34570177 https://jamanetwork.com/journals/jamaneurology/fullarticle/2784539
- ↑ Jump up to: 11.0 11.1 Kneisel K Epilepsy Drugs May Up Risk of Parkinson's. Strongest association seen for sodium valproate. MedPage Today December 27, 2022 https://www.medpagetoday.com/neurology/seizures/102398
Belete D, Jacobs BM, Simonet C et al Association Between Antiepileptic Drugs and Incident Parkinson Disease in the UK Biobank. JAMA Neurol. Published online December 27, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36574240 https://jamanetwork.com/journals/jamaneurology/fullarticle/2799620