Old Doc, New Drugs: Levetiracetam

This is a new series of written posts I am doing for the blog.  Basic concept:  I last studied pharmacology 20 years ago. In that time a heap of new drugs have appeared in the pharmacy… and I have been using a lot of them in my practice with little or no understanding of their mechanism, kinetics, side effects, interactions…or even spelling! While we are aware of many drugs in the market primarily due to their abuse which leads people looking for a Quick Drug Detoxification Treatment, the following are helpful medications I wanted to let you know about.Please feel free to join me on the Pharmacology Phun!

First medication on my hit list is…. LEVETIRACETAM or as it is more commonly called due to its uncertain pronunciation, Keppra.

Levetiracetam is the modern darling drug of Neurologists the world over.  It seems to be the best thing since… well, let’s face it most seizure medications are pretty ordinary things to prescribe to anyone for any period of time.  In the past 5 years, phenytoin has been slowly pushed out as the first line for acute seizure management and longer-term prophylaxis.  This does not make me sad as phenytoin is a pretty tricky drug to use.  It can be toxic if dosed wrong, has weird unpredictable kinetics and makes your patients unhappy due to longer-term use effects.

HISTORY:  Levetiracetam is related to a group of drugs called racetams which are based on pyrrolidone ring.  Molecules such as piracetam and oxiracetam are sold as “smart supplements” or nootropics – ie. agents that make you smarter.  There is not much evidence that they actually do this.

MECHANISM:  KEPPRA is the S-enantiomer of etiracetam.  The exact mechanism of action is unknown but it seems to inhibit presynaptic Ca-channels and vesicle proteins.  This seems to modulate neurotransmission… slow things down.

DOSING:  Keppra is simple to dose as it has pretty much 100% oral bioavailability – so you PO dose is the same as an IV dose.

Most adults are started on about 500mg bd and titrated up to effect.  Kids get 10mg/kg bid initially.

There does not seem to be much benefit in increasing past 3000 mg per day.

The initial IV dose to control seizures is about 20 mg.kg. (although 40/kg is used in some centres)   We can push a standard dose over about 5 – 10 minutes without all the concerns about arrhythmias that comes with phenytoin.  The successful control of seizures was a bit higher with Keppra (probably because you get the dose in quicker!)

METABOLISM:  Levetiracetam is safe to use in hepatic impairment and has no active metabolites making it predictable.

It is cleared by the kidneys – so dose adjustments are needed if you have a decreased GFR.

INTERACTIONS:  This is where Keppra is a winner – it has no known interactions or metabolites that mess with other common drugs.

ADVERSE EFFECTS:

• most patients will experience somnolence, some fogginess, and dyscoordination in the first few weeks of use.
• minor psychiatric symptoms: anxiety, agitation, emotional lability or depression occurs in 13%
• Major psych sxs including hallucinations, suicidal ideation or psychosis in 1%, tends to get better with cessation.
• using pyridoxine was shown to decrease neuropsych sxs in one trial
• Severe skin reactions eg. Stevens-Johnson syndrome / TEN occurs at about 1/3000 patients…. this is a similar rate to other common anti-epileptics

So it is hard to see why we would continue to use phenytoin if one works in a place where levetiracetam is available.  It seems simpler, effective and safer than our old standards.

OK.  That is it for the first “Old Doc, New Drugs” article.  Hope it was helpful.

Please comment below or let me know which drugs you are struggling to come to terms with and I will do the reading and get it up when I can!!

Casey