Episode 2- Can we give levetiracetam as an IV push?


Episode Summary:

Join us this week as we discuss whether or not levetiracetam (Keppra) can be given as an undiluted push, straight out of the vial.

Show Notes:

Key Points:

Can we give levetiracetam as an IV push? Doses of:
– Up to 1500 mg –> safe to administer undiluted IV push over 5 minutes
– > 1500 mg – 3000 mg –> safe to administer diluted 1:1 in compatible solution (D5W, NS, LR) over 5 minutes
– > 3000 mg –> dilute in 100 mL compatible solution and administer over 15 minutes
ER-Rx Episode 2

References:

Brophy, G. M., et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012; 17 (1): 3-23

Moheet, A. M., et al. Standards for neurologic critical care units: a statement for healthcare Professionals from The Neurocritical Care Society. Neurocrit Care. 2018; 29 (2): 145-160

Keppra (levetiracetam) [prescribing information]. Columbus, OH: West-Ward Pharmaceuticals; 2017

Burakgazi E, et al. The safety and tolerability of different intravenous administrations of levetiracetam, bolus versus infusion, in intensive care unit patients. Clinical EEG and Neuroscience. 2014; 45 (2): 89–91

Wheless JW, et al. Rapid infusion of a loading dose of intravenous levetiracetam with minimal dilution: a safety study.  J Child Neurol. 2009; 24 (8): 946-951

Dalziel S, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019; 393: 2135–45

Transcript:

Hello and welcome to Episode 2 of ER- Rx. In this episode, we’re going to talk about whether or not we can safely give levetiracetam as an IV push versus as an IV piggyback. Now, picture this scenario. You’re working in the ER and a patient comes in in status epilepticus, and the provider wants to give a dose of IV levetiracetam as fast as possible. Per the Neurocritical Care Society, it is recommended that IV anti-epileptic drugs (AEDs) be available for administration within 15 minutes after a “STAT” order as a standard of care. Now, we all know as pharmacists that by the time a provider enters that order, the pharmacist verifies that order, and the other technician or the pharmacist in the IV room makes that order, it can be much greater than 15 minutes. That is why last year my site actually added levetiracetam into the Pyxis machines in the ER. This way, the ER pharmacists can compound a levetiracetam infusion at bedside during emergent situations. As a side note, levetiracetam is available as a 500 mg/ 5 mL vial, which currently must be compounded in 100 mLs of normal saline. This infusion is then given over 15 to 30 minutes as per the package insert.

However, several studies are starting to question this dogma. They have shown an equivalent safety profile in rapidly pushing levetiracetam undiluted versus giving it as an IV piggyback. For example, a retrospective study from Burakgazi, et al. compared IV piggyback versus IV push levetiracetam for doses up to 1500 milligrams and had no significant adverse drug events. Two prospective studies, one by Wheless, et al. and the other by Dalziel, et at, concluded that levetiracetam doses up to three grams, diluted 1:1 with normal saline and given over 5 to 6 minutes, were well-tolerated in both adults and pediatrics. To note, the ESETT trial used a 1:1 dilution, or 50 mg/mL, for a vial and gave it over 10 minutes using doses of up to 4500 milligrams. It is no surprise, therefore, that a recent poll sent out to the Neurocritical Care Society pharmacists showed that most centers are either allowing IV push of levetiracetam or are contemplating moving in that direction. Some sites use a maximum of 1000 to 1500 mg, given undiluted as an IV push, whereas others have no dose maximums.

So here’s my take on all of this and my current recommendations. In our ED, we allow IV push levetiracetam for doses up to and including 1500 mg undiluted. For doses greater than 1500 mg, up to a maximum of 3000 mg, we dilute this 1:1 with normal saline and administer it over five minutes. Now , if you do the math, if you have a dose of 3000 mg you will need 30 mLs of levetiracetam, and you will have to combine this 30 mLs with an additional 30 mLs of normal saline, all in a 60 mL syringe, and that can then be given over five minutes. I know that this can be kind of time consuming and maybe even confusing for some of the pharmacists, especially in a very hectic situation such as status epilepticus. Therefore, if you have doses that are 3000 milligrams, you can still consider diluting this as usual in 100 mLs of normal saline. However, you can give it much faster, for example, over five minutes instead of the 15 to 30 minutes that’s recommended in the package insert based on the previous studies. Finally, all doses greater than 3000 mg should be diluted in 100 mLs of normal saline and administered over 10 to 15 minutes. I would not personally recommend giving doses greater than 3000 mg as IV push undiluted drug until we have more data.

Thank you all so much for your time. Please remember to check out our show notes and don’t forget to subscribe to our podcast.







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