Lamotrigine
Mechanism :
The precise mechanism by which lamotrigine exerts its anticonvulsant action are unknown. In animal models it was effective in preventing seizure spread in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests and prevented seizures in the visually and electrically evoked after-discharge (EEAD) tests for antiepileptic activity.
Indication :
- Tonic clonic seizures
- Absence seizures
- Atonic seizures
- Myoclonic seizures
- Partial seizures
Contraindications :
Lamotrigine is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.
Use with caution in renal failure, do not withdraw abruptly, reduce initial doses in liver disease and titrate to response.
Dosing :
Oral:
2-12 years:
0.6 mg/kg/24 hours in 1-2 doses for 2 weeks, then 1.2 mg/kg/24 hours for 2 weeks, then 5-15 mg/kg/24 hours according to response. Max: 400 mg/24 hours.
>12 years:
100-400 mg/day in 1-2 divided doses. Start with 25 mg alternate day for 2 weeks, then 25 mg daily for 2 weeks and then increase by 25-50 mg/day every 1-2 weeks. Max: 400 mg/day.
On valproate:
If the child is on valproate:
0.15 mg/kg/24 hours in 1-2 doses for 2 weeks, then 0.3 mg/kg/24 hours for 2 weeks, then 1-5 mg/kg/24 hours according to response, Max: 200 mg/24 hours.
>12 years: 50-200 mg/day in 1-2 divided doses. Start with 25 mg alternate day for 2 weeks, then 25 mg daily for 2 weeks and then increase by 25-50 mg/day every 1-2 weeks. Max: 200 mg/day.
Adverse Effect :
Measles-like skin rash, usually within first 8 weeks of commencing therapy, rarely Stevens-Johnson syndrome, nausea/vomiting, headache, dizziness, somnolence, diplopia and blurred vision, fever and ataxia.
Interaction :
Oral Contraceptives: Increased the apparent clearance of lamotrigine.
Folate Inhibitors: Lamotrigine is a weak inhibitor of dihydrofolate reductase. Prescribers should be aware of this action when prescribing other medications that inhibit folate metabolism.
Phenobarbital, Primidone: The addition of phenobarbital or primidone decreases lamotrigine steady-state concentrations by approximately 40%.
Sodium valproate: May be synergistic in absence (typical and atypical), tonic-clonic and myoclonic seizures.
Ethosuximide: May be synergistic in absence (typical and atypical) seizures.
Carbamazepine: Lamotrigine may increase the risk of adverse effects.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Caution. Start with low doses and monitor closely |
| 10-20 | Caution. Start with low doses and monitor closely |
| <10 | Caution. Start with low doses and monitor closely |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely dialysability. Dose as in GFR<10 mL/min. |
| HD | Not dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
Mild hepatic impairment: No dosage guidelines available. Use with caution.
Moderate hepatic impairment: Initial, escalation, and maintenance doses should be reduced by 25%
Severe hepatic impairment: Initial, escalation, and maintenance doses should generally be reduced by 50%.