Xonimide ODT

Approved Uses:

• Adjunctive therapy for partial seizures in adults with epilepsy.
• Monotherapy for partial-onset seizures in adults and adolescents ≥16 years (in some regulatory jurisdictions like Japan and Europe).

Clinically Accepted Off-label Uses:

• Infantile spasms (West syndrome), as an adjunct in refractory cases.
• Generalized tonic-clonic seizures, in refractory epilepsy.
• Migraine prophylaxis, particularly in patients intolerant to first-line agents.
• Parkinson’s disease, as adjunctive therapy (studied primarily in Japan).
• Weight management/obesity, often in combination with other agents (e.g., bupropion).
• Lennox-Gastaut syndrome, as adjunct in drug-resistant cases.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Adults (Adjunctive Therapy in Partial Seizures):

• Initial dose: 100 mg once daily.
• Titrate by 100 mg increments at 2-week intervals.
• Usual maintenance dose: 300–400 mg/day (given as once or twice daily).
• Max dose: 600 mg/day (rarely used due to increased side effects).

Monotherapy in Adults:

• Start at 100 mg once daily.
• Titrate to 200 mg/day after 2 weeks, then up to 300 mg/day based on response.

Pediatric Use (off-label in some regions):

• Children ≥6 years (partial seizures): Start at 1–2 mg/kg/day, increase weekly by 1–2 mg/kg/day to 6–8 mg/kg/day divided twice daily.
• Infantile spasms or other syndromes: Use individualized dosing, typically 2–8 mg/kg/day.

Renal Impairment:

• Use with caution in moderate renal impairment.
• Contraindicated in severe renal dysfunction (CrCl <50 mL/min).

Hepatic Impairment:

• Use cautiously; no formal dosage adjustments but exposure may increase.

Geriatric:

• Start at the lowest effective dose and titrate slowly due to reduced clearance.

Administration Notes:

• Capsules may be taken with or without food.
• Swallow whole; do not crush or chew.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Zonisamide is a sulfonamide derivative that exerts its antiepileptic effects through multiple mechanisms. It blocks voltage-sensitive sodium channels, stabilizing neuronal membranes and suppressing repetitive neuronal firing. Additionally, it inhibits T-type calcium channels, which are implicated in seizure propagation. Zonisamide also modulates the release of excitatory neurotransmitters and enhances GABA-mediated inhibition. It may exert weak carbonic anhydrase inhibition, which may contribute to its side effect profile and efficacy in certain seizure types.

• Absorption: Rapid and nearly complete oral absorption; bioavailability ~100%.
• Peak plasma time: ~2–6 hours post-dose.
• Distribution: Volume of distribution ~1.5 L/kg; ~40–50% plasma protein-bound.
• Metabolism: Primarily hepatic via CYP3A4 (N-acetylation and reduction).
• Excretion: ~30% excreted unchanged in urine; remainder as metabolites.
• Half-life: ~63 hours (allows once-daily dosing).
• Steady-state: Achieved after ~2 weeks of regular dosing.

Special Populations:

• Renal impairment: Reduced clearance; drug accumulates—contraindicated in severe renal dysfunction.
• Hepatic impairment: Clearance may be decreased; use with caution.

Pregnancy:

• FDA Category: C (old classification).
• Animal studies show teratogenicity (e.g., skeletal abnormalities); human data is limited.
• Use only if potential benefit justifies risk.
• Registry monitoring is recommended for pregnant women.

Lactation:

• Zonisamide is excreted into breast milk in low concentrations.
• Possible risk of sedation or poor weight gain in breastfed infants; use caution.
• Monitor infant if used during breastfeeding.

• Primary: Antiepileptic (Anticonvulsant)
• Subclass: Sulfonamide derivative
• Secondary actions: Carbonic anhydrase inhibitor (weak)

• Hypersensitivity to zonisamide or other sulfonamide drugs
• Severe renal impairment (CrCl <50 mL/min)
• History of serious rash or drug reaction with zonisamide
• Acute metabolic acidosis in patients on carbonic anhydrase inhibitors

• Serious skin reactions: Stevens-Johnson Syndrome, toxic epidermal necrolysis—discontinue immediately if rash develops.
• Metabolic acidosis: Monitor serum bicarbonate; risk increased with concurrent use of other carbonic anhydrase inhibitors.
• Kidney stones: Monitor for hematuria; encourage fluid intake.
• Oligohidrosis and hyperthermia (especially in children): Reduced sweating—avoid overheating.
• Suicidal behavior/ideation: Monitor mood and behavior changes.
• Cognitive effects: Confusion, slowed thinking, or memory problems may occur.
• Weight loss: May occur; monitor nutritional status.
• Hypothermia risk with concomitant dopaminergic medications (e.g., levodopa).

Common (≥5%):

• CNS: Drowsiness, dizziness, ataxia, headache, fatigue, agitation, memory impairment
• GI: Anorexia, nausea
• Weight: Weight loss

Less Common / Serious:

• Dermatologic: Rash, SJS/TEN
• Renal: Nephrolithiasis
• Metabolic: Metabolic acidosis
• Hematologic: Leukopenia, anemia
• Psychiatric: Depression, irritability, psychosis
• Others: Oligohidrosis, heatstroke (especially in children)

Timing/Severity:

• Dose-related CNS effects are more prominent during titration.
• Serious skin and metabolic reactions may occur within weeks of initiation.

• CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin): May increase zonisamide clearance; reduce efficacy.
• CYP3A4 inhibitors (e.g., ketoconazole): May increase plasma levels of zonisamide.
• Other carbonic anhydrase inhibitors (e.g., topiramate, acetazolamide): Increased risk of metabolic acidosis, kidney stones.
• CNS depressants: Additive sedative effects.
• Oral contraceptives: Minimal interaction, but monitor efficacy if using enzyme inducers.

• FDA labeling continues to emphasize risk of serious skin reactions and metabolic acidosis.
• Newer epilepsy guidelines (e.g., AAN, NICE) include zonisamide as an option for adjunctive and sometimes monotherapy for focal epilepsy, especially in patients who prefer once-daily dosing or have weight concerns.
• Ongoing evaluation in pediatric epilepsy syndromes and neurodegenerative conditions is noted in clinical trials.

• Temperature: Store at 20–25°C (68–77°F).
• Excursions allowed: 15–30°C (59–86°F).
• Protect from moisture and heat.
• Keep in original container; tightly closed.
• No refrigeration or reconstitution required.
• Capsules should be stored out of reach of children and pets.