KEPPRA
Clinical safety rating
cautionComprehensive clinical and safety monograph for KEPPRA (KEPPRA).
Levetiracetam binds to synaptic vesicle protein 2A (SV2A), modulating neurotransmitter release and reducing neuronal hyperexcitability. It also inhibits high-voltage N-type calcium channels and reduces GABAergic and glycinergic inhibition.
| Metabolism | Levetiracetam is not extensively metabolized; ~66% of the dose is excreted unchanged in urine. Metabolism occurs via enzymatic hydrolysis of the acetamide group, independent of cytochrome P450. Major metabolite is the carboxylic acid derivative (ucb L057), which is pharmacologically inactive. |
| Excretion | Renal: 66% unchanged; 27% as inactive metabolite; 0.3% fecal. |
| Half-life | 6-8 hours in adults; prolonged to 10-18 hours in renal impairment (CrCl <30 mL/min); clinical context: dosing interval adjustment required in renal disease. |
| Protein binding | <10% bound to plasma proteins (albumin). |
| Volume of Distribution | 0.5-0.7 L/kg; approximates total body water; clinical meaning: extensive distribution into tissues, including brain. |
| Bioavailability | Oral: 100% (immediate-release formulation); IV: 100%. |
| Onset of Action | IV: rapid (minutes) following infusion; Oral: 1-2 hours for peak plasma concentration, clinical effect onset within 1-2 doses in seizure control. |
| Duration of Action | Approximately 6-8 hours due to half-life; clinical note: regular dosing (every 12 hours) maintains therapeutic levels. |
| Molecular Weight | 170.21 |
500 mg orally twice daily, titrated up to 1500 mg twice daily as tolerated.
| Dosage form | SOLUTION |
| Renal impairment | CrCl 50-80 mL/min: 500-1000 mg every 12 hours; CrCl 30-49 mL/min: 250-750 mg every 12 hours; CrCl <30 mL/min: 250-500 mg every 12 hours; ESRD on dialysis: 500-1000 mg once daily with 250-500 mg supplemental dose after dialysis. |
| Liver impairment | No specific adjustment for hepatic impairment; use caution in severe hepatic impairment. |
| Pediatric use | 1 month to <6 months: 7 mg/kg twice daily, titrate to 21 mg/kg twice daily; 6 months to <4 years: 10 mg/kg twice daily, titrate to 25 mg/kg twice daily; 4 to <16 years: 10 mg/kg twice daily, titrate to 30 mg/kg twice daily (maximum 3000 mg/day). |
| Geriatric use | Start at 250-500 mg twice daily; titrate slowly due to age-related renal function decline. |
| 1st trimester | Levetiracetam crosses the placenta. Data from pregnancy registries do not suggest a substantially increased risk of major birth defects, but an increased risk of small for gestational age and preterm birth has been reported. Dose adjustment may be needed due to changes in clearance. |
| 2nd trimester | Monitor drug levels as clearance increases during pregnancy. Adjust dose to maintain therapeutic efficacy. Risk of fetal harm cannot be excluded, but benefits may outweigh risks for seizure control. |
| 3rd trimester | Continued monitoring and dose adjustment recommended. Neonatal withdrawal or sedation may occur if used near term. Administer vitamin K at birth due to potential risk of bleeding (not specific to levetiracetam). |
Clinical note
Comprehensive clinical and safety monograph for KEPPRA (KEPPRA).
| Placental transfer | Extensive placental transfer; cord blood concentrations approximate maternal serum levels (ratio ~0.8-1.0). |
| Breastfeeding | Levetiracetam is excreted into breast milk in low to moderate amounts (milk-to-plasma ratio ~1). Infant serum levels are 2-13% of maternal levels, which are generally below therapeutic range. No adverse effects reported in infants, but monitor for drowsiness, poor feeding, or weight gain. Benefit of breastfeeding likely outweighs minimal risk. |
| Lactation Rating | L2 (Probably Compatible) - Limited data suggest low risk. |
| Teratogenic Risk | Increased risk of major congenital malformations, particularly neural tube defects (e.g., spina bifida), cleft palate, and cardiovascular defects, especially with first trimester exposure. Risk is dose-dependent and higher with polytherapy. Second and third trimester exposure may be associated with neurodevelopmental impairments. |
| Fetal Monitoring | Monitor maternal serum levetiracetam levels (target 12-46 mcg/mL) especially during third trimester and postpartum. Perform targeted ultrasound for fetal anatomy at 18-20 weeks to screen for neural tube defects and other anomalies. Fetal echocardiography may be considered. Monitor for maternal adverse effects such as somnolence and dizziness. |
| Fertility Effects | No clinically significant effects on female fertility reported. Human data on male fertility are limited; animal studies show no adverse effects on male fertility at clinically relevant doses. |
■ FDA Black Box Warning
None
| Common Effects | Sleepiness Dizziness Fatigue Headache Decreased appetite Behavioral changes Aggressive behavior Irritation Agitation Nasal congestion stuffy nose Infection Convulsion Nasopharyngitis inflammation of the throat and nasal passages Nausea Tremors Vertigo Lethargy |
| Serious Effects |
Hypersensitivity to levetiracetam or any excipient
| Precautions | Behavioral and psychiatric symptoms: psychosis, aggression, suicidal ideation, Somnolence and fatigue, dose-dependent, Stevens-Johnson syndrome and toxic epidermal necrolysis (rare), Hematologic abnormalities: decreased red blood cell, white blood cell, and platelet counts, Acute kidney injury (rare), intercurrent illness may increase risk, Avoid abrupt discontinuation to minimize seizure exacerbation or status epilepticus |
| Food/Dietary | No significant food interactions. Levetiracetam absorption is not affected by food. Avoid alcohol as it may increase CNS depression. |
| Clinical Pearls | Levetiracetam (Keppra) is a broad-spectrum AED with minimal drug interactions. Dosing must be adjusted for renal function (CrCl <80 mL/min). Monitor for behavioral changes, especially in pediatric patients. IV formulation can be administered without ECG monitoring. No need for therapeutic drug monitoring; efficacy and tolerability guide dosing. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly as withdrawal seizures may occur. · Report any unusual mood changes, depression, or aggressive behavior to your doctor. · May cause dizziness or drowsiness; avoid driving until effects are known. · Take with or without food; do not crush extended-release tablets. · Drink plenty of fluids to prevent kidney stones, though not a common side effect. |
Loading safety data…