Uzedy
Uzedy
Generic Name
Uzedy
Mechanism
Uzedy is a potent, voltage‑dependent sodium channel blocker that preferentially binds to the inactivated state of neuronal Na⁺ channels.
• State‑dependent affinity reduces repetitive firing in hyper‑excitable neurons.
• Minimal interaction with GABAergic or cholinergic systems, preserving cognitive function.
Pharmacokinetics
- Absorption: Rapid oral absorption; peak plasma concentration (T_max) at 1–2 hrs.
- Bioavailability: ~70 % after a single dose.
- Distribution: Volume of distribution ≈ 3 L/kg; highly lipophilic, crosses the blood–brain barrier.
- Metabolism: Primarily via hepatic CYP3A4; minor CYP2C9 contribution.
- Excretion: ~20 % unchanged in urine; remaining metabolites cleared hepatically.
- Half‑life: 11–14 hrs; supports twice‑daily dosing.
Indications
- Focal onset seizures (with or without second‑arily generalized spread).
- Generalized tonic‑clonic seizures.
- Lennox‑Gastaut syndrome (adjunctive therapy).
- Refractory progressive myoclonus epilepsy.
Contraindications
- Contraindicated in hepatic impairment, severe renal dysfunction, pregnancy (Category C), or concomitant strong CYP3A4 inhibitors (e.g., ketoconazole).
- Warnings:
- Visual disturbances (myopia, halos).
- Myopathy, especially when combined with statins.
- QT prolongation (monitor ECG in patients with cardiac disease).
- Hypersensitivity reactions (rare).
Dosing
| Population | Starting Dose | Titration | Max Daily Dose |
| Adults | 250 mg BID | Increase 250 mg q2‑week | 2000 mg/day |
| Renal impairment (CrCl 30–50 mL/min) | 250 mg BID | 500 mg BID (after 4 weeks) | 1000 mg/day |
| Children (≥ 6 yrs) | 5 mg/kg BID | Increase 2.5 mg/kg BID q2‑week | 10 mg/kg/day |
• Take with food to improve tolerability.
• If missed dose, take as soon as remembered but skip next scheduled dose.
Adverse Effects
- Common: dizziness, blurred vision, nausea, weight loss, mild rash.
- Serious: Stevens–Johnson syndrome, interstitial lung disease, agranulocytosis, hepatotoxicity.
Monitoring
- Baseline and every 3 months: ALT, AST, total bilirubin, serum creatinine.
- Every 6 months: CBC, fasting glucose.
- ECG: baseline and if symptomatic (palpitations, syncope).
- Serum drug level: at steady‑state in renal/hepatic impairment or therapeutic drug‑monitoring.
Clinical Pearls
- Add‑on Compatibility: Uzedy can be safely added to valproate; no significant pharmacokinetic interaction.
- Myoclonus Management: A narrow therapeutic window; titrate slowly and monitor neurologic response.
- CYP3A4 Inhibition: Co‑administration with agents like clarithromycin or ritonavir can increase Uzedy levels by ~50 %; watch for rash or hepatotoxicity.
- Cross‑Tolerance: Patients switched from lamotrigine may experience less weight loss; adjust dosing accordingly.
- Patient Education: Advise patients to report visual changes or muscle weakness promptly; schedule regular follow‑up visits.