LOREEV XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOREEV XR (LOREEV XR).
Levetiracetam is a racetam anticonvulsant that binds to synaptic vesicle glycoprotein 2A (SV2A), reducing neurotransmitter release and neuronal excitability. It also inhibits N-type calcium channels and modulates GABAergic and glutamatergic transmission.
| Metabolism | Levetiracetam undergoes hydrolysis of the acetamide group via esterases in blood and tissues to an inactive carboxylic acid metabolite (ucb L057). It is not extensively metabolized by CYP450 enzymes. Approximately 66% is excreted unchanged in urine; 24% as ucb L057. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 70% of elimination; fecal excretion accounts for approximately 30%, primarily as metabolites. |
| Half-life | Terminal elimination half-life is 6-8 hours in healthy adults; prolonged in renal impairment (up to 16 hours in severe impairment). |
| Protein binding | Approximately 35% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 1.5-2.5 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 60-70% due to first-pass metabolism; extended-release formulation has similar bioavailability. |
| Onset of Action | Oral: 30-60 minutes to initial effect; peak plasma concentrations at 3-4 hours. |
| Duration of Action | Duration of clinical effect is 8-12 hours based on extended-release formulation. |
50 mg orally once daily, preferably in the evening. Maximum dose 100 mg/day.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | eGFR 15-29 mL/min: 25 mg orally once daily. eGFR <15 mL/min or on dialysis: not recommended. |
| Liver impairment | Child-Pugh class A: no adjustment. Child-Pugh class B or C: not recommended (no data). |
| Pediatric use | Not approved for pediatric patients <18 years. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended based on age alone. Use caution due to increased sensitivity and potential for renal impairment; consider lower starting dose (25 mg) and titrate slowly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOREEV XR (LOREEV XR).
| Breastfeeding | Not known if excreted in human milk. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended. M/P ratio not available. |
| Teratogenic Risk | First trimester: Increased risk of neural tube defects and other congenital anomalies based on animal studies and limited human data. Second and third trimesters: Potential for fetal malformations and adverse effects on fetal growth and development. Placental transfer is likely. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA boxed warning for LOREEV XR. The immediate-release formulation carries no black box warning; however, levetiracetam is associated with suicidal behavior and ideation, but this is not classified as a black box warning for LOREEV XR.
| Serious Effects |
["Hypersensitivity to levetiracetam or any component of the formulation","Absolute: No other absolute contraindications known"]
| Precautions | ["Suicidal behavior and ideation: Monitor for depression and suicidality","Behavioral and psychiatric adverse reactions: Psychosis, aggression, irritability","Somnolence and dizziness: Caution with activities requiring alertness","Hematologic abnormalities: Decreased red blood cell counts, leukopenia, neutropenia, pancytopenia","Dermatologic reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis (rare)","Withdrawal seizures: Do not discontinue abruptly; taper dose gradually","Renal impairment: Dose adjustment required in patients with decreased renal function"] |
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| Monitor maternal liver function, renal function, and complete blood counts. Fetal ultrasound to assess growth and anatomy. Nonstress test or biophysical profile in third trimester if indicated. |
| Fertility Effects | May impair female fertility based on animal studies showing effects on estrous cycle and ovarian function. Reversibility in humans unknown. |