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Old doc, new drugs: Levetiracetam


Casey Parker


21/08/2018 2:51:45 PM

GP Dr Casey Parker writes for newsGP about how levetiracetam fares as an alternative to phenytoin.

News teaser
Dr Casey Parker says it can be easy for practitioners to to use new drugs without fully exploring their mechanisms, kinetics, side effects and interactions.

I last studied pharmacology 20 years ago. In that time, many new drugs have appeared in the pharmacy.
 
I have been using a lot of them in my practice without fully exploring their mechanisms, kinetics, side effects and interactions.
 
This is my attempt to rectify that situation.
 
What’s the story with levetiracetam?
The first medication on my hit list is levetiracetam (more commonly known by its brand name Keppra, due to the challenges of pronouncing the drug).
 
Levetiracetam is the 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 last five years, phenytoin has been slowly pushed out as the first-line treatment for acute seizure management and longer-term prophylaxis. This makes me happy, as phenytoin is a rather tricky drug to use. It can be toxic if dosed incorrectly, has weird unpredictable kinetics and can make your patients unhappy due to its longer-term use effects.
 
Let’s look at how levetiracetam fares as an alternative.
 
Family history
Levetiracetam is related to a group of drugs called racetams, which are based on the pyrrolidone ring.
 
Molecules such as piracetam and oxiracetam are sold as ‘smart supplements’ or nootropics, ie agents that supposedly make you smarter. There is not much evidence that they actually do anything of the sort.
 
Mechanism
Levetiracetam 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 and slow things down.
 
Dosing
Levetiracetam is simple to dose as it has almost 100% oral bioavailability, so your oral dose is the same as an intravenous (IV) dose.
 
Most adults are started on 500 mg twice a day (bd), orally and titrated up to effect. Kids initially get 10 mg/kg bd. 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 mg/kg is used in some centres. We can push a standard dose over about 5–10 minutes without the concern about arrhythmias that comes with phenytoin.
 
The successful control of seizures is a bit higher with levetiracetam (probably because you can 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 kidney function.
 
Interactions
This is where levetiracetam 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.
 
Anxiety, agitation, emotional lability or depression occurs in 13% of patients.
 
Around 1% get major psychological symptoms, including hallucinations, suicidal ideation or psychosis. This tends to get better with cessation.
 
Using pyridoxine was shown to decrease neuropsych symptoms in one paediatric trial
 
Severe skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN) occurs at about one in every 3000 patients. This is a similar rate to other common anti-epileptics.
 
In summary
It is hard to see why we would continue to use phenytoin if you work in a place in which levetiracetam is available. It seems simpler, more effective and safer than our old standards.
 
This article is adapted from Dr Casey Parker’s blog, Broome Docs.



drug mechanisms Keppra Levetiracetam medications





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