KEPPRA XR
Clinical safety rating
cautionComprehensive clinical and safety monograph for KEPPRA XR (KEPPRA XR).
Levetiracetam binds to synaptic vesicle glycoprotein 2A (SV2A), modulating neurotransmitter release and reducing neuronal excitability.
| Metabolism | Metabolized primarily by hydrolysis of the acetamide group via enzymatic hydrolysis (not CYP450 dependent); forms inactive metabolite (UCB L057); ~24% of dose undergoes oxidative metabolism. |
| Excretion | Renal: 66% as unchanged drug; 27% as inactive metabolite (uch L057); biliary/fecal: negligible (<1%). |
| Half-life | 7.1 ± 1.1 hours in adults; 10–11 hours in elderly; prolonged in renal impairment (up to 25 hours in severe renal failure). |
| Protein binding | <10%; binding to albumin (not extensive). |
| Volume of Distribution | 0.5–0.7 L/kg; suggests distribution into total body water. |
| Bioavailability | 100% for oral tablet (immediate-release); 100% for extended-release (relative to immediate-release). |
| Onset of Action | 7–14 days for steady-state antiepileptic effect with extended-release formulation. |
| Duration of Action | 12 hours with twice-daily dosing; sustained release maintains therapeutic levels over 24 hours with BID dosing. |
| Molecular Weight | 170.21 |
| Action Class | Synaptic vescicle 2 A protein ligand (AED) |
| Brand Substitutes | Acolev 500mg Tablet, Levepsy 500 Tablet, Levefree 500mg Tablet, Levigress 500 Tablet, Seiz-Free 500 Tablet, Levetee Syrup, Levipace Syrup, Vitisun 100mg Syrup, Axitam 100mg Syrup, Levipil Syrup, Epicetam 250mg Tablet, Verocet 250mg Tablet, Seiz-Free 250 Tablet, Levigress 250 Tablet, Levecad 250mg Tablet, Levepsy 750 Tablet, Seiz-Free 750mg Tablet, Verocet 750mg Tablet, Levacetam 750mg Tablet, Levipil 750 Tablet, Levilex 1000 Tablet, Livrich 1000mg Tablet, Levepsy 1000 Tablet, Livogrid 1000 Tablet, Epifast 1000 Tablet, Babicetom L Injection, Epilive Premix 500mg Injection, Levitrend 500mg Injection, Sezlev 500mg Injection, Torleva Injection |
1500 mg orally once daily (2 tablets of 750 mg). Extended-release formulation is taken once daily; immediate-release is dosed twice daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For CrCl > 80 mL/min: 1500 mg once daily; CrCl 50-80 mL/min: 1000 mg once daily; CrCl 30-49 mL/min: 500 mg once daily; CrCl < 30 mL/min: 250 mg once daily. ESRD on dialysis: 500 mg once daily with 250 mg supplemental dose post-dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). For severe hepatic impairment (Child-Pugh C), reduce dose by 50%. |
| Pediatric use | For children ≥12 years (≥40 kg): 1500 mg orally once daily. Not FDA-approved for <12 years; use immediate-release formulation for pediatric patients <12 years: starting dose 10 mg/kg twice daily, titrated to 30 mg/kg twice daily. |
| Geriatric use | Elderly patients often have reduced creatinine clearance; dose should be adjusted based on renal function. Monitor for drowsiness, dizziness, and ataxia. Start at lower end of dosing range and titrate cautiously. |
| 1st trimester | Levetiracetam is associated with a small increased risk of major congenital malformations, primarily neural tube defects, especially during the first trimester. The absolute risk is low, around 2-3%. |
| 2nd trimester | During the second trimester, levetiracetam exposure may be associated with reduced head circumference and possible neurodevelopmental effects. Therapeutic drug monitoring is recommended. |
| 3rd trimester | Third trimester exposure may lead to neonatal withdrawal symptoms (e.g., sedation, irritability) or bleeding tendencies. Dose adjustments may be needed due to altered pharmacokinetics. |
Clinical note
Comprehensive clinical and safety monograph for KEPPRA XR (KEPPRA XR).
| Placental transfer | Levetiracetam readily crosses the placenta, with umbilical cord plasma levels approximating maternal plasma levels (near 100% transfer). It is not highly protein bound, facilitating transfer. |
| Breastfeeding | Levetiracetam is excreted into breast milk in low amounts, with relative infant doses estimated at 1-3% of maternal weight-adjusted dose. No adverse effects on breastfed infants have been reported in small studies; however, monitor for drowsiness, poor feeding, or growth. Benefits of breastfeeding generally outweigh risks, especially when maternal epilepsy is well-controlled. |
| Lactation Rating | L2 (Possibly Compatible) |
| Teratogenic Risk | Pregnancy Category C. First trimester: Increased risk of major congenital malformations (e.g., neural tube defects, cleft palate) with antiepileptic drug polytherapy; monotherapy association unclear but may be dose-dependent. Second/third trimester: Risk of fetal growth restriction, hemorrhagic disease of newborn (vitamin K deficiency due to enzyme induction). Perinatal: Neonatal withdrawal syndrome, sedation, and coagulopathy. |
| Fetal Monitoring | Pre-conception: Folate supplementation (at least 0.4 mg/day). First trimester: High-resolution ultrasound and fetal echocardiography for structural anomalies. Throughout pregnancy: Serial growth scans (every 4–6 weeks) for intrauterine growth restriction. Third trimester: Vitamin K1 10 mg/day orally from 36 weeks to prevent neonatal hemorrhagic disease. At delivery: Neonatal vitamin K prophylaxis. Postpartum: Monitor maternal therapeutic levels and adjust dose. |
| Fertility Effects | No known significant effect on fertility in humans. Levetiracetam does not appear to alter sex hormone levels or menstrual cycle regularity. Limited animal studies show no impairment of fertility at clinically relevant doses. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to levetiracetam or any excipient
| Precautions | Behavioral abnormalities including psychosis, aggression, hostility, irritability, and suicidal ideation/behavior, Somnolence and fatigue, Serious dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), Hematologic abnormalities (decreased red blood cell, white blood cell, and platelet counts), Increased blood pressure in pediatric patients, Withdrawal seizures upon abrupt discontinuation |
| Food/Dietary | No significant food interactions. Grapefruit juice does not affect levetiracetam. Avoid alcohol as it may exacerbate CNS depression. |
| Clinical Pearls | Keppra XR (levetiracetam extended-release) is dosed once daily due to its prolonged absorption profile. Therapeutic drug monitoring is not routinely required because of its predictable pharmacokinetics and wide therapeutic index. Adjust dose in renal impairment (CrCl < 80 mL/min) using ideal body weight; supplement dose after hemodialysis. May cause somnolence, dizziness, and behavioral changes (e.g., aggression, psychosis) especially in pediatric and elderly patients. Stevens-Johnson syndrome and angioedema are rare but serious adverse effects. Sudden discontinuation may precipitate withdrawal seizures; taper over at least 2 weeks. |
| Patient Advice | Take exactly as prescribed once daily with or without food, at the same time each day. · Swallow tablet whole; do not crush, chew, or break. · Do not drive or operate heavy machinery until you know how this medicine affects you. · Contact your doctor immediately if you experience skin rash, blistering, swelling of face/lips, or difficulty breathing. · Inform your doctor of any history of depression, mood swings, aggressive behavior, or suicidal thoughts. · Report any worsening of seizures or new types of seizures. · If you are on dialysis, take the recommended supplement dose after each session. · Do not stop taking this medicine suddenly as it may cause withdrawal seizures. · Avoid alcohol while taking Keppra XR; it may increase drowsiness and dizziness. |
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