SPRITAM
Clinical safety rating
cautionComprehensive clinical and safety monograph for SPRITAM (SPRITAM).
Spritam is a levetiracetam formulation; levetiracetam binds to synaptic vesicle glycoprotein 2A (SV2A) to modulate neurotransmitter release, reducing neuronal excitability.
| Metabolism | Hydrolysis by esterases in blood and tissues to carboxylic acid metabolite (ucb L057); not CYP450 dependent. |
| Excretion | Renal: 66% unchanged; hepatic metabolism: 24% (inactive metabolites); fecal: negligible (<1%) |
| Half-life | Terminal half-life: 6–8 hours; clinical context: requires twice-daily dosing for stable serum concentrations |
| Protein binding | <10% bound; primarily to albumin (minimal binding) |
| Volume of Distribution | 0.7–1.1 L/kg; approximates total body water, indicating extensive distribution into tissues |
| Bioavailability | Oral immediate-release: 100%; oral extended-release: approximately 100% relative to immediate-release |
| Onset of Action | Oral immediate-release: 30–60 minutes; oral extended-release: within 1 hour |
| Duration of Action | Immediate-release: 6–8 hours; extended-release: 12 hours; clinical note: therapeutic effect maintained with regular dosing |
| Molecular Weight | 170.21 |
SPRITAM is not a standard formulation; levetiracetam immediate-release: 500 mg PO BID, titrated to 1000 mg PO BID (max 1500 mg PO BID). For extended-release (Keppra XR): 1000 mg PO once daily, titrated to 2000 mg PO once daily.
| Dosage form | TABLET, FOR SUSPENSION |
| Renal impairment | CrCl >80 mL/min: 500-1500 mg BID (IR) or 1000-2000 mg once daily (XR); CrCl 50-80: 500-1000 mg BID (IR) or 1000-2000 mg once daily (XR); CrCl 30-50: 250-750 mg BID (IR) or 500-1500 mg once daily (XR); CrCl <30: 250-500 mg BID (IR) or 500-1000 mg once daily (XR); ESRD on dialysis: 500-1000 mg once daily (IR) with supplemental dose after dialysis. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): no dose adjustment required; severe hepatic impairment (Child-Pugh C): use with caution; no specific dose reduction recommended, but monitor for adverse effects. |
| Pediatric use | For immediate-release: age 1 month to <6 months: 7 mg/kg/dose BID initially, titrate to 21 mg/kg/dose BID; age 6 months to <4 years: 10 mg/kg/dose BID initially, titrate to 25 mg/kg/dose BID; age 4 to <16 years: 10 mg/kg/dose BID initially, titrate up to 30 mg/kg/dose BID (max 1500 mg/day). For extended-release: only for ≥12 years: 1000 mg once daily initially, titrate to 2000 mg once daily. |
| Geriatric use | Consider age-related renal impairment; adjust dose based on CrCl per renal adjustment. Start at lower end of dosing range; monitor for sedation, dizziness, and falls. |
| 1st trimester | Spritam (levetiracetam) is associated with an increased risk of major congenital malformations, particularly neural tube defects, when used during the first trimester. Data suggest a dose-dependent effect. |
| 2nd trimester | Exposure during the second trimester may be associated with adverse neurodevelopmental outcomes, although the absolute risk is modest. Benefits of seizure control must be weighed against potential risks. |
| 3rd trimester | Use in the third trimester may increase the risk of bleeding in the neonate due to effects on vitamin K-dependent clotting factors. Late pregnancy use also poses a risk of neonatal withdrawal symptoms, including irritability, feeding difficulties, and jitteriness. |
Clinical note
Comprehensive clinical and safety monograph for SPRITAM (SPRITAM).
| Placental transfer | Levetiracetam readily crosses the placenta with cord blood levels reaching approximately 80-100% of maternal plasma concentrations. Active transport via organic anion transporters may contribute. |
| Breastfeeding | Levetiracetam is excreted into breast milk in low concentrations. The relative infant dose is estimated to be 5-10% of the maternal weight-adjusted dose. Adverse effects reported in breastfed infants include drowsiness, poor feeding, and irritability. Caution is advised, and monitoring of the infant for sedation and adequate weight gain is recommended. The benefits of breastfeeding may outweigh potential risks in many cases. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Spritam (levetiracetam) is classified as Pregnancy Category C. In the first trimester, there is an increased risk of major congenital malformations, including neural tube defects, when used in polytherapy, but monotherapy may have a lower risk. Data from human pregnancy registries suggest a risk of major birth defects of 1.5-2.4% with monotherapy, compared to a baseline risk of 2-4%. In the second and third trimesters, exposure may lead to decreased fetal growth and transient neonatal effects such as sedation, withdrawal symptoms, and hypotonia. Levetiracetam is not highly protein-bound and crosses the placenta with a cord-to-maternal plasma ratio close to 1. |
| Fetal Monitoring | During pregnancy, monitor seizure frequency and levetiracetam levels if clinically indicated. Fetal monitoring includes ultrasound for congenital anomalies (e.g., neural tube defects) with consideration of maternal serum alpha-fetoprotein screening. In late pregnancy, fetal growth assessments should be performed. Neonates should be observed for signs of withdrawal or sedation. |
| Fertility Effects | Data on effects of levetiracetam on human fertility are limited. In animal studies, no adverse effects on fertility or reproductive performance were observed at clinically relevant doses. In humans, there are no conclusive reports of altered fertility associated with levetiracetam use. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to levetiracetam or any component of the formulationPhenylketonuria (due to aspartame content in certain formulations, e.g., Spritam contains phenylalanine)
| Precautions | Behavioral abnormalities (psychosis, aggression, suicidal ideation), Somnolence and fatigue, Dermatological reactions (e.g., Stevens-Johnson syndrome), Hematologic abnormalities, Withdrawal seizures on abrupt discontinuation |
| Food/Dietary | No significant food interactions. SPRITAM can be taken with or without food. A high-fat meal may slightly delay absorption but does not affect overall exposure. Avoid grapefruit juice? Not required; no known interaction with grapefruit. Alcohol may potentiate CNS depression and should be avoided. |
| Clinical Pearls | SPRITAM (levetiracetam) is a racetam anticonvulsant with a unique mechanism of action (SV2A binding). It exhibits linear pharmacokinetics with rapid oral absorption. No therapeutic drug monitoring required due to wide therapeutic index. Adjust dose in renal impairment (CrCl <80 mL/min). Free fraction of levetiracetam is not affected by hepatic impairment. Titrate slowly to reduce CNS side effects (somnolence, dizziness). Abrupt discontinuation may increase seizure frequency. Available in immediate-release tablets. |
| Patient Advice | Take SPRITAM exactly as prescribed; do not stop suddenly. · May cause dizziness or drowsiness; avoid driving until effects are known. · Monitor for mood changes, depression, or suicidal thoughts. · Report any skin rash or signs of allergic reaction immediately. · Use reliable contraception if applicable (no known major interaction with hormonal contraceptives). · Swallow tablets whole; do not crush or chew. · Store at room temperature, away from moisture. |
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