Bedside Snapshot
- Use It For
- Benzodiazepine-refractory status epilepticus (second-line); IV seizure therapy when oral is not possible; neonatal seizures after phenobarbital fails (specialist use)
- Adult Dose
- Status epilepticus: 60 mg/kg IV over 10 min (max 4,500 mg). Differs from FDA label: label is 15 min at no more than 15 mg/mL; trials used 10 min (ESETT) or 5 min
- Maintenance: 500–1,500 mg IV/PO every 12 hr
- Pediatric Dose
- Age 2 yr and over: 60 mg/kg IV/IO over 10 min (max 4,500 mg). Age 3 months to under 2 yr: 40 mg/kg IV/IO over 5 min (max 2,500 mg). Under 3 months: specialist use
- Onset / Duration
- IV: peak at end of infusion; median about 10 min to seizure stop in a small ESETT subset (n=14) / about 12 hr; PO: peak about 1 hr / about 12 hr
- Do Not Give / Hold If
- Known hypersensitivity to levetiracetam (including anaphylaxis or angioedema). Stop for any rash unless clearly unrelated. Reduce maintenance doses when CrCl is below 80 mL/min/1.73 m²
- Watch For
- Somnolence and airway loss after benzodiazepines (SpO₂, EtCO₂); agitation, psychosis or suicidal thoughts; rash or fever (SJS/TEN, DRESS); diastolic BP in children under 4 yr
- Reversal / Rescue
- No antidote: supportive care; hemodialysis removes about 50% in 4 hr. Seizures continue: valproate or fosphenytoin, then a midazolam or propofol infusion
- Must Remember
- Load fully: 60 mg/kg up to 4,500 mg. Vials hold 500 mg/5 mL: a 4,500 mg load is 45 mL of concentrate (9 vials), diluted before use. Keppra is confused with Keflex.
Indications
Emergency & Prehospital
- Benzodiazepine-refractory convulsive status epilepticus: the second-line drug, used once an adequate dose of lorazepam, midazolam or diazepam has failed. Levetiracetam, fosphenytoin and valproate perform about the same. Each one stops seizures in about half of patients (ESETT trial; ACEP 2024 Level A) (off-label)
ED / ICU / Transport
- Seizures when oral therapy is temporarily not feasible: Patients on oral levetiracetam get IV at the same daily dose (labeled use of the injection)
- Neonatal seizures not controlled by phenobarbital: one of the second-line options in the ILAE 2023 neonatal guideline. With cardiac disease it may be the preferred one (off-label)
- Seizures after cardiac arrest: The 2025 AHA Guidelines for CPR and ECC, Part 11, recommend treating clinically apparent seizures. The same antiseizure drugs used for other causes may be considered (class 2b). The guideline does not name levetiracetam. Treating EEG-only seizures is reasonable. Get an EEG promptly in patients who do not follow commands or who have myoclonus. Routine prophylaxis, and treating myoclonus with no EEG correlate, are not recommended (off-label)
- Early seizure prophylaxis after severe traumatic brain injury: per neurosurgical protocol (off-label).
Other Uses
- Partial-onset (focal) seizures: monotherapy or adjunct, age 1 month and older (labeled)
- Myoclonic seizures in juvenile myoclonic epilepsy: adjunct, age 12 years and older (labeled)
- Primary generalized tonic-clonic seizures: adjunct, age 6 years and older with idiopathic generalized epilepsy (labeled)
Dosing & Administration
These house doses follow the ESETT, EcLiPSE and ConSEPT trials and the AES 2016 ladder. For status epilepticus, the FDA label is different.
Available Forms
- Injection concentrate (Keppra, generics): 100 mg/mL in 5 mL (500 mg) single-dose vials; dilute before use. It is the form you will see most in the ED, ICU and transport.
- Premixed bags (levetiracetam in sodium chloride): 500 mg/100 mL (5 mg/mL), 1,000 mg/100 mL (10 mg/mL) and 1,500 mg/100 mL (15 mg/mL), single-dose. The label covers patients 16 yr and older only. For weight-based pediatric doses, draw up from the 100 mg/mL vial.
- Tablets: 250 mg, 500 mg, 750 mg and 1,000 mg (immediate release); Keppra XR is the once-daily version for outpatients.
- Oral solution: 100 mg/mL, for children and feeding tubes.
Adult Dosing
| Indication | Dose & Route | Repeat / Max | Notes |
|---|---|---|---|
| Status epilepticus, benzodiazepine-refractory (second-line) | 60 mg/kg IV over 10 min | Max 4,500 mg single load | After an adequate benzodiazepine dose. Actual weight; cap reached at 75 kg. Seizing 20 min after the load starts (40 min of seizure): different second-line drug or anesthetic infusion (below). |
| Maintenance after a load (ICU) | 500–1,500 mg IV/PO every 12 hr | Label max 3,000 mg/day; refractory status epilepticus up to 1,500 mg every 8 hr (off-label) | Adjust for renal function. |
| Partial-onset or generalized tonic-clonic seizures (labeled) | 500 mg IV/PO every 12 hr; increase by 500 mg per dose every 2 weeks | Max 1,500 mg every 12 hr (3,000 mg/day) | Target 1,500 mg every 12 hr for myoclonic (labeled from 12 yr) and generalized tonic-clonic seizures. |
| Replacing oral levetiracetam (NPO) | Same total daily dose and frequency IV | Same daily total; no conversion factor | IV (15-min infusion) and oral doses are bioequivalent. No study experience with IV use longer than 4 days; switch to oral when feasible. |
For renal dose reductions and dosing weight, see Special Populations.
Pediatric Dosing
| Indication | Dose (per kg) & Route | Max Single / Max Total | Notes |
|---|---|---|---|
| Status epilepticus, age 2 yr and older (ESETT regimen) | 60 mg/kg IV over 10 min | Max 4,500 mg single load | Similar results in children and adults in ESETT. |
| Status epilepticus, age 3 months to under 2 yr (house regimen), also acceptable at any age from 3 months | 40 mg/kg IV over 5 min | Max 2,500 mg single load (EcLiPSE) | EcLiPSE: 6 months to under 18 yr, IV only. ConSEPT: 3 months to 16 yr, IV or IO over 5 min (cap not stated). As effective as phenytoin, faster to give. |
| Neonatal seizures not responding to phenobarbital (specialist use) | 40 mg/kg IV; a further 20 mg/kg if seizures continue | Total 60 mg/kg | Dose used in NEOLEV2, a first-line trial against phenobarbital (40 mg/kg, escalated to 60 mg/kg). The ILAE 2023 guideline names levetiracetam as a second-line option but gives no dose. Confirm with neonatology or pharmacy. |
| Maintenance, 1 month to under 6 months | 7 mg/kg IV/PO every 12 hr; increase every 2 weeks | Recommended (target) 21 mg/kg every 12 hr (42 mg/kg/day) | Labeled dosing for partial-onset seizures. |
| Maintenance, 6 months to under 4 yr | 10 mg/kg IV/PO every 12 hr; increase after 2 weeks | Recommended (target) 25 mg/kg every 12 hr (50 mg/kg/day) | Watch diastolic BP. |
| Maintenance, 4 to under 16 yr | 10 mg/kg IV/PO every 12 hr; increase every 2 weeks | Target 30 mg/kg every 12 hr (60 mg/kg/day); max 3,000 mg/day | Same regimen for generalized tonic-clonic seizures from 6 yr. From 16 yr, use adult dosing. |
Double-check weight-based doses at pediatric weight-based dosing. The label gives no renal dosing for children.
Preparation & Administration
- Dilution (vials): Use 0.9% sodium chloride, lactated Ringer's or D5W. Adult doses of 500–1,500 mg go in 100 mL. Otherwise keep it at no more than 15 mg/mL. Use within 4 hr at room temperature.
- Status epilepticus load volume: At the label limit of 15 mg/mL, a 4,500 mg load works out to at least 300 mL. ESETT ran it at 50 mg/mL over 10 min. Protocol and pharmacy set the final concentration and volume.
- Rate: The house rate is 10 min for age 2 yr and over, adults, or 5 min for age 3 months to under 2 yr. That differs from the FDA label, a 15-minute infusion at no more than 15 mg/mL.
- Line: Use a peripheral IV (IO was used in the pediatric trials). Run it on a pump.
- Mixing with other antiseizure drugs: see Interactions & Compatibility.
- Next, use another second-line drug from the AES 2016 ladder: valproate 40 mg/kg IV (max 3,000 mg; avoid under 2 yr and in liver, mitochondrial or urea-cycle disease) or fosphenytoin 20 mg PE/kg IV (max 1,500 mg PE). Lacosamide is an option too, with less study behind it. This ladder gives no dose for it.
- Refractory status epilepticus: secure the airway (RSI), then start a continuous midazolam or propofol infusion with continuous EEG.
- Super-refractory: ketamine, pentobarbital or a phenobarbital infusion, alongside neurocritical care.
- Not waking up after the convulsions stop? Get an EEG to look for nonconvulsive status epilepticus.
Contraindications & Precautions
Contraindications
- Hypersensitivity to levetiracetam: Reactions have included anaphylaxis and angioedema. In status epilepticus, reach for fosphenytoin or valproate instead (valproate: not under 2 yr or with liver, mitochondrial or urea-cycle disease).
Precautions
- Renal impairment and older adults: Clearance falls as creatinine clearance falls. Reduce maintenance doses (see Special Populations).
- Psychiatric history: The risk of agitation, aggression, depression, psychosis and suicidal thoughts is higher.
- Children 1 month to under 4 yr: Diastolic BP rose in 17% (vs 2% on placebo). Monitor BP.
- Pregnancy: Drug levels fall, most of all in the third trimester. Watch seizure control closely.
- Stopping therapy: Taper gradually. Abrupt withdrawal can trigger seizures and status epilepticus. The exception is a serious reaction that forces a stop.
- SCN8A epilepsy: Seizures have been reported to get worse.
Hold / Reassess If
- Any rash: stop at the first sign unless clearly not drug-related; do not restart if SJS/TEN is suspected
- Facial, lip, tongue or airway swelling, hives or hypotension after a dose: stop permanently and treat as anaphylaxis
- Fever, lymph node swelling or facial edema with organ involvement: stop and evaluate for DRESS
- New severe agitation, psychosis or suicidal thoughts: notify the prescriber; dose reduction or a different drug may be needed
Adverse Effects & Toxicity
Common
- Somnolence: 15% (vs 8% on placebo); about 45% at 4,000 mg/day without titration
- Asthenia and fatigue: 15% in adults
- Dizziness: 9%; ataxia and incoordination about 3%
- Non-psychotic behavioral symptoms: 13% of adults and 38% of children 4–16 yr (irritability, agitation, aggression, anxiety, depression)
- Children: fatigue, aggression, decreased appetite, irritability
Serious / Life-Threatening
| Effect | Recognition | Management |
|---|---|---|
| Behavioral change and psychosis | Aggression, depression, paranoia, hallucinations; usually early | Notify the prescriber; reduce or switch; suicide precautions if needed |
| Anaphylaxis or angioedema | Any dose: hives, facial or airway swelling, hypotension | Stop permanently; treat as anaphylaxis with IM epinephrine |
| SJS/TEN | Rash with mucosal involvement or sloughing; median onset 14–17 days | Stop; never rechallenge |
| DRESS (multiorgan hypersensitivity) | Fever, rash, lymph node or facial swelling, eosinophilia, organ injury | Stop if no other cause; can be fatal |
| Blood dyscrasias | Recurrent infection, fever, bleeding or marked weakness | Check a CBC; significant cytopenia: notify the prescriber, consider another drug, avoid abrupt withdrawal |
Postmarketing reports also include hyponatremia, pancreatitis, hepatitis, liver failure and acute kidney injury.
Overdose & Toxicity Management
- Signs: somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma.
- Management: supportive care of airway, breathing and circulation; contact poison control.
- Antidote: none exists. Hemodialysis removes about 50% of the drug in 4 hr. Consider it in severe overdose or renal failure.
Monitoring
| Parameter | When / How Often | Target / Act If |
|---|---|---|
| Clinical: seizure activity | Continuously during and after the load | Seizures 20 min after the load started: next agent (third-line steps above) |
| Clinical: mental status and EEG | After convulsions stop | Not improving: continuous EEG to rule out nonconvulsive status epilepticus |
| Clinical: airway, RR, SpO₂, EtCO₂ | Continuously after benzodiazepines plus the load | Falling SpO₂ or rising EtCO₂: support ventilation; prepare to intubate |
| Clinical: behavior and mood | Every shift after starting or increasing the dose | New aggression, psychosis or suicidal thoughts: notify the prescriber |
| Clinical: skin | Daily for the first months | Any rash: stop unless clearly unrelated; fever with rash: evaluate for DRESS |
| Clinical: diastolic BP (age 1 month to under 4 yr) | With routine vital signs | Sustained rise: notify the prescriber |
| Laboratory: renal function | Baseline and daily in ICU (creatinine, eGFR) | CrCl below 80 mL/min/1.73 m², AKI or new dialysis: reduce maintenance doses |
| Laboratory: CBC | With weakness, fever, recurrent infection or bleeding | Significant cytopenia (agranulocytosis, pancytopenia, thrombocytopenia): notify the prescriber; consider another drug; avoid abrupt withdrawal |
| Laboratory: sodium | With confusion, new seizures or lethargy | Low sodium: evaluate; hyponatremia has been reported |
Interactions & Compatibility
Clinically Significant Interactions
| Drug / Class | Effect | What To Do |
|---|---|---|
| CNS depressants (benzodiazepines, opioids, alcohol, sedatives) | Additive somnolence and respiratory depression | Monitor airway, SpO₂ and EtCO₂, especially right after status epilepticus treatment |
| Enzyme-inducing antiseizure drugs (carbamazepine, phenytoin) | About 22% faster levetiracetam clearance in children | No dose change recommended |
| Phenytoin, valproate, warfarin, digoxin, oral contraceptives | No pharmacokinetic interaction in label studies; prothrombin time unchanged | No adjustment; levetiracetam is a good choice with complex drug lists |
| Probenecid | Raises the inactive metabolite; parent drug unchanged | No adjustment |
Levetiracetam skips CYP450 metabolism and binds less than 10% to protein. That keeps it clear of the enzyme and binding interactions that phenytoin and valproate bring.
IV Compatibility
- Diluents: 0.9% sodium chloride, lactated Ringer's, D5W.
- Admixture: compatible with lorazepam, diazepam and valproate sodium (label); no data for other antiseizure drugs.
- Verify with an institutional compatibility resource.
Special Populations
- Pediatrics: labeled from 1 month of age. Behavioral effects come up more often than in adults. Psychotic symptoms hit 17% of children under 4 yr (vs 5% on placebo). Find the doses in the Pediatric Dosing table.
- Neonates: phenobarbital stays first-line under the ILAE 2023 neonatal guideline. The exception is a likely channelopathy (a family history, for example). Then phenytoin or carbamazepine is used. Levetiracetam is second-line and may be the preferred pick with cardiac disease. It is not labeled, so this is specialist use.
- Pregnancy: Two decades of human and registry data show no higher risk of major birth defects or miscarriage. Animal studies did show developmental toxicity. The AAN/AES/SMFM 2024 guideline says to consider lamotrigine, levetiracetam or oxcarbazepine when appropriate. Give at least 0.4 mg of folic acid daily, before conception and through pregnancy. Levels drop, most of all in the third trimester. Doses may need to rise. Monitoring stays close after delivery too, especially if the dose was changed. In status epilepticus, stopping the seizure comes first. Encourage enrollment in the North American Antiepileptic Drug Pregnancy Registry.
- Lactation: It passes into breast milk. Effects on the infant are not known. Weigh the benefits of breastfeeding against the mother's need for the drug.
- Older Adults: clearance runs about 38% lower because renal function drops. Dose by creatinine clearance. Watch for somnolence and falls.
- Renal Impairment: adult maintenance by CrCl (mL/min/1.73 m²): above 80, 500–1,500 mg every 12 hr; 50–80, 500–1,000 mg every 12 hr; 30–50, 250–750 mg every 12 hr; below 30, 250–500 mg every 12 hr. Dialysis: 500–1,000 mg every 24 hr plus 250–500 mg after each dialysis. The label says nothing about loading doses or CRRT. Dose with pharmacy.
- Hepatic Impairment: no dose adjustment needed.
- Obesity / Dosing Weight: The status epilepticus load runs on actual weight, up to the 4,500 mg cap (reached at 75 kg). Adult maintenance doses are not weight-based.
Field & Transport Considerations
- Scope: This lives in the ED, the ICU and critical-care and flight transport (RN, paramedic and CCT under protocol). Some ground EMS agencies carry it too. What is allowed varies by state and agency protocol.
- Storage & Stability: Keep vials and tablets at 25°C (77°F). Excursions of 15–30°C (59–86°F) are allowed. Use a diluted dose within 4 hr at room temperature.
- Carried Concentration: vials hold 100 mg/mL (500 mg/5 mL). A full 4,500 mg load is 45 mL of concentrate (9 vials), and it gets diluted before use. At the label limit of 15 mg/mL that means at least 300 mL (ESETT used 50 mg/mL). Premixed bags hold 500, 1,000 or 1,500 mg, so a large load needs more than one bag. They are labeled for patients 16 yr and older only.
- Infusions in Transport: Run it on a pump. At handoff, confirm the total dose (mg) and the volume remaining.
- Airway: 1 in 5 patients in the ESETT levetiracetam arm (20%) needed intubation within 60 min. Have airway equipment ready after the benzodiazepines and a second-line load.
- Handoff Essentials: seizure onset time; benzodiazepine doses and times; load start and stop times and total mg; current seizure activity and mental status; home antiseizure drugs and last dose.
Clinical Pearls
- Levetiracetam 60 mg/kg (max 4,500 mg): least hypotension (0.7%); renally cleared; few drug interactions
- Fosphenytoin 20 mg PE/kg (max 1,500 mg PE): rate-limited; hypotension and arrhythmia; avoid with AV block
- Valproate 40 mg/kg (max 3,000 mg): avoid in liver, mitochondrial (POLG) or urea-cycle disease, pregnancy and under 2 yr; hyperammonemia
- Efficacy: about 47%, 45% and 46% seizure cessation at 60 min
- Safety did not differ significantly. Still, the only life-threatening arrhythmia (0.7%) and the most deaths (4.7% vs 2.4% fosphenytoin and 1.6% valproate) happened in the levetiracetam arm
Pharmacology
Mechanism of Action
- Binds synaptic vesicle protein 2A (SV2A), which regulates neurotransmitter release. That means less neuronal hyperexcitability and fewer seizures. The exact mechanism is not fully known.
- Chemically unrelated to other antiseizure drugs, and it does not block cardiac sodium channels. So there is no rate-related hypotension or conduction block, and no significant QTc prolongation at 5,000 mg.
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IV | Seizure stop: median about 10 min in a small ESETT subset (n=14; not a pharmacologic onset) | End of a 15-min infusion | About 12 hr (dosed every 12 hr) |
| PO (immediate release) | Rapid, almost complete absorption | About 1 hr | About 12 hr (dosed every 12 hr) |
- Half-life: adults 6–8 hr; children about 5 hr; longer in older adults and in renal impairment.
- Metabolism: not CYP450-dependent; 24% hydrolyzed (acetamide group) to an inactive metabolite.
- Elimination: The kidneys excrete 66% unchanged. Clearance tracks creatinine clearance.
- Protein binding / Vd: Less than 10% binds to protein, and volume of distribution sits close to total body water. Oral bioavailability is almost complete, so IV and PO doses match.
Names & Classification
- Generic Name
- Levetiracetam
- Brand Names
- Keppra (tablets, oral solution, injection), Keppra XR; generics; premixed levetiracetam in sodium chloride injection
- Pharmacologic Class
- Pyrrolidone derivative; SV2A ligand
- Therapeutic Class
- Antiseizure medication (anticonvulsant)
- Controlled Substance
- Not controlled
- ISMP High-Alert
- No
- Look-Alike / Sound-Alike
- Keppra / Keflex; Keppra / Kaletra; levETIRAcetam / lamoTRIgine; levETIRAcetam / levOCARNitine; levETIRAcetam / levoFLOXacin
References
- UCB, Inc. (2025). Keppra (levetiracetam) injection, for intravenous use [prescribing information]. DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6d5784d-abf9-45fe-ac5a-d5c53bd50f7e
- Smith, M. D., Sampson, C. S., Wall, S. P., & Diercks, D. B. (American College of Emergency Physicians Clinical Policies Subcommittee on Seizures). (2024). Clinical policy: Critical issues in the management of adult patients presenting to the emergency department with seizures. Annals of Emergency Medicine, 84(1), e1–e12. https://doi.org/10.1016/j.annemergmed.2024.02.018
- Kapur, J., Elm, J., Chamberlain, J. M., Barsan, W., et al., for the NETT and PECARN Investigators. (2019). Randomized trial of three anticonvulsant medications for status epilepticus (ESETT; landmark trial). New England Journal of Medicine, 381(22), 2103–2113. https://doi.org/10.1056/NEJMoa1905795
- Lyttle, M. D., Rainford, N. E. A., Gamble, C., Messahel, S., et al. (2019). Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): A multicentre, open-label, randomised trial (landmark trial). The Lancet, 393(10186), 2125–2134. https://doi.org/10.1016/S0140-6736(19)30724-X
- Dalziel, S. R., Borland, M. L., Furyk, J., Bonisch, M., et al., for the PREDICT research network. (2019). Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): An open-label, multicentre, randomised controlled trial (landmark trial). The Lancet, 393(10186), 2135–2145. https://doi.org/10.1016/S0140-6736(19)30722-6
- Pressler, R. M., Abend, N. S., Auvin, S., Boylan, G., et al. (2023). Treatment of seizures in the neonate: Guidelines and consensus-based recommendations. Special report from the ILAE Task Force on Neonatal Seizures. Epilepsia, 64(10), 2550–2570. https://doi.org/10.1111/epi.17745
- Sharpe, C., Reiner, G. E., Davis, S. L., Nespeca, M., et al. (2020). Levetiracetam versus phenobarbital for neonatal seizures: A randomized controlled trial (NEOLEV2). Pediatrics, 145(6), e20193182. https://doi.org/10.1542/peds.2019-3182
- Rossetti, A. O., Claassen, J., & Gaspard, N. (2024). Status epilepticus in the ICU. Intensive Care Medicine, 50(1), 1–16. https://doi.org/10.1007/s00134-023-07263-w
- American Heart Association (2025). 2025 AHA Guidelines for CPR and ECC, Part 11: Post-Cardiac Arrest Care. Circulation, 152(16 suppl 2). Hirsch, K. G., et al. https://cpr.heart.org/en/resuscitation-science/cpr-and-ecc-guidelines/post-cardiac-arrest-care
- Pack, A. M., Oskoui, M., Williams Roberson, S., et al. (AAN, AES and SMFM). (2024). Teratogenesis, perinatal, and neurodevelopmental outcomes after in utero exposure to antiseizure medication: Practice guideline. Neurology, 102(11), e209279. https://doi.org/10.1212/WNL.0000000000209279
- Glauser, T., Shinnar, S., Gloss, D., Alldredge, B., et al. (2016). Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Currents, 16(1), 48–61. https://doi.org/10.5698/1535-7597-16.1.48
- Institute for Safe Medication Practices (ISMP). (2024). ISMP List of Confused Drug Names. https://www.ismp.org/recommendations/confused-drug-names-list
Medical Disclaimer
- For Educational Purposes Only: This content is intended for educational reference and should not be used for clinical decision-making.
- Not a Substitute for Professional Judgment: Always consult your local protocols, institutional guidelines, and supervising physicians.
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