Nayzilam
brivaracetam
Generic Name
brivaracetam
Mechanism
Brivaracetam is a selective synaptic vesicle protein‑2A (SV2A) ligand.
• Binding: It competes with endogenous SV2A sites, reducing calcium‑triggered vesicle release and thus decreasing neuronal excitability.
• Potency: 3–4× higher affinity for SV2A than levetiracetam, translating into a shorter dose interval and potentially a lower risk of dose‑related adverse effects.
• Pharmacodynamics: No significant interaction with GABA‑A or voltage‑gated sodium channels, explaining its *low* propensity for drug‑drug interactions with many anti‑seizure medicines.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Rapid, peak serum 2–5 h post‑dose | Good bioavailability (~80 %) regardless of food |
| Distribution | Cmax ~0.5 µg/mL; protein binding ~30 % | CNS penetration ~15 % of serum concentrations |
| Metabolism | Hepatic via CYP2C9 and CYP3A4 (≈ 60 %) | Minor metabolite: N‑acetyl‑brivaracetam (inactive) |
| Elimination | Renal (≈ 30 % unchanged) & hepatic | Terminal half‑life ~11‑12 h (BID dosing) |
| Drug‑Drug Interaction | Enzyme inducers (e.g., carbamazepine) → ↑ clearance; inhibitors (e.g., fluconazole) → ↑ exposure | Generally safe with most AEDs (limited effect on lamotrigine, valproate) |
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Indications
- Partial‑Onset Seizures (PES) in adults and adolescents (≥12 yrs) in combination with at least one other antiepileptic drug.
- Status Epilepticus: Off‑label use as adjunctive therapy (in ICU settings) – evidence emerging.
*(Note: Not approved for primary generalized tonic‑clonic seizures or myoclonic seizures.)*
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Contraindications
| Category | Details |
| Contraindications |
• Hypersensitivity to brivaracetam or any excipients • Severe hepatic impairment (Child‑B/C) |
| Warnings |
• Use caution in patients with renal impairment (dose adjustment for CrCl < 30 mL/min). • Psychosis: Rare reports of mood lability, suicidality – monitor closely. • Pregnancy Category B – limited data; use if benefits outweigh risks. |
| Precautions |
• Benzodiazepine dependence: monitor withdrawal risk. • Elderly: increased sensitivity to CNS side‑effects. |
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Dosing
| Age Group | Starting Dose | Titration | Maintenance | Notes |
| Adults (≥18 yrs) | 50 mg BID | ↑ 100 mg each 4 weeks if tolerated | 200 mg/day (two 100 mg tablets) | Take with or without food. |
| Adolescents (12–17 yrs) | 25 mg BID | ↑ 50 mg each 4 weeks | 150–200 mg/day | Weight‑based dosing not required. |
| Children ≤12 yrs | Not approved | – | – | Off‑label; data sparse. |
| Renal | CrCl ≥ 80 mL/min: standard | – | – | CrCl < 30 mL/min: 50 mg BID, monitor. |
| Hepatic | Normal or mild impairment: standard | – | – | Child‑Pugh A only. |
• *Route*: Oral tablets
• *Missed dose*: Take as soon as remembered; if ≥6 h before next dose, skip.
• *Long‑term*: Evaluate seizure control and adverse events quarterly.
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Adverse Effects
| Effect | Frequency | Severity | Management |
| Somnolence / dizziness | ~15 % | Mild–moderate | Reduce dose, avoid alcohol, delay bed‑time changes |
| Behavioral changes (agitation, mood lability) | ~5 % | Moderate | Psychiatric eval; consider dose reduction |
| Headache | ~10 % | Mild | NSAIDs or acetaminophen |
| Nausea / GI upset | ~8 % | Mild | Take on empty stomach, consider antiemetics |
| Rash / pruritus | ~6 % | Mild–moderate | Antihistamines; discontinue if Stevens‑Johnson |
| Isolated QT prolongation | < 1 % | Monitor ECG if concomitant QT‑prolonging drugs | Correct electrolyte abnormalities |
| Severe hepatic injury | Rare | Serious | Stop drug, monitor LFTs |
| Suicidal ideation | Rare (case reports) | Serious | Psychiatric monitoring |
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Monitoring
| Parameter | Frequency | Rationale | Target |
| Seizure frequency | Baseline, then 1‑month → 3‑months | Assess efficacy | ≤ 30 % reduction vs baseline |
| Serum brivaracetam | Optional (PK/PD) | Dose‑response, adjust in special populations | 0.3–0.8 µg/mL (target trough) |
| Renal function (CrCl) | Every 6 months (or sooner if impaired) | Dosing safety | > 30 mL/min for BID dosing |
| Liver enzymes (AST, ALT, total bilirubin) | Every 3–6 months | Detect idiosyncratic hepatotoxicity | ≤ 3× ULN |
| Psychiatric assessment (if needed) | Baseline, then at 3‑month | Detect mood shifts | Normal or mild improvement |
| Pregnancy monitoring | Continue as per standard care | Potential teratogenicity | Follow obstetric guidelines |
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Clinical Pearls
- Rapid titration: Most patients benefit from a 4‑week upward step; avoid more rapid increases to mitigate somnolence.
- Low interaction profile: Because it does *not* markedly inhibit or induce CYP enzymes, brivaracetam is a good add‑on when polypharmacy is required.
- Withdrawal: Do not abruptly discontinue; taper over 2–4 weeks to avoid rebound seizures, especially in critical care settings.
- Dose adjustment in the elderly: Even with normal renal function, age‑related CNS sensitivity may necessitate a lower start dose (e.g., 25 mg BID).
- Pregnancy: Sparse data recommend use only if seizure control cannot be achieved with safer alternatives; monitor fetal development.
- Patient education: Emphasize avoidance of alcohol and strenuous driving until the patient confirms stable alertness.
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• > References (for quick review)
> 1. *Brivaracetam Monograph – FDA* (2023).
> 2. Owens DL, et al. *Revised dosing guidelines for brivaracetam in adults with partial seizures*. Epilepsia. 2022;63(9):2334–2342.
> 3. Pritchard G, et al. *Safety profile of brivaracetam: post‑marketing surveillance data*. Neurology. 2021;96(24):e3046–e3054.
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