Dosing of Extended Release Lamotrigine (Lamictal XR)
The recommended dosing for extended release lamotrigine (Lamictal XR) is once daily with a target maintenance dose of 200-400 mg/day for bipolar disorder and up to 600 mg/day for epilepsy, following a careful 6-8 week titration schedule to minimize the risk of serious rash. 1
Initial Titration Schedule
The dosing of lamotrigine XR requires careful titration to minimize the risk of serious adverse effects, particularly skin rash:
- Week 1-2: 25 mg once daily
- Week 3-4: 50 mg once daily
- Week 5-6: 100 mg once daily
- Week 7-8: 150 mg once daily
- Week 8+: 200 mg once daily (maintenance dose)
Further titration may be needed based on clinical response, up to 400 mg/day for bipolar disorder and 600 mg/day for epilepsy.
Dosing Adjustments Based on Concomitant Medications
Concomitant medications significantly affect lamotrigine metabolism, requiring specific dosing adjustments 1, 2:
With valproic acid (inhibits lamotrigine metabolism):
- Initial dose: 25 mg every other day
- Slower titration: increase by 25 mg every 2 weeks
- Lower target dose: approximately 50% of standard dose
With enzyme-inducing antiepileptics (carbamazepine, phenytoin, phenobarbital):
- Initial dose: 50 mg once daily
- Faster titration: may increase weekly
- Higher target dose: approximately twice the standard dose
Pharmacokinetic Considerations for Extended Release Formulation
Lamotrigine XR offers several advantages over immediate-release formulation 3:
- Once-daily dosing regardless of concomitant medications
- More stable serum drug concentrations
- Similar safety and efficacy profile to immediate-release formulation
- Potential for enhanced medication adherence
Monitoring Recommendations
- Baseline complete blood count and liver function tests before initiation
- Regular monitoring throughout treatment, especially during titration
- More frequent monitoring when adding or removing medications that affect lamotrigine metabolism
- No routine blood level monitoring required, though may be helpful in specific situations (suspected toxicity, pregnancy, significant drug interactions)
Safety Considerations
- The most common adverse events with lamotrigine XR are headache (25% of patients) and dizziness (16% of patients) 3
- Serious rash, including Stevens-Johnson syndrome, occurs in approximately 0.1% of patients 3
- Risk of serious rash is significantly higher with:
- Rapid dose escalation
- Concurrent valproic acid use
- Young age
- History of drug allergy
Clinical Pearls
- Lamotrigine XR must be taken once daily, not divided into multiple doses
- Extended-release tablets should be swallowed whole, not chewed, crushed, or divided
- If a dose is missed, patients should not double the next dose
- When discontinuing, gradual dose reduction over at least 2 weeks is recommended to prevent seizure recurrence in epilepsy patients
Lamotrigine XR exhibits linear pharmacokinetics with a half-life of approximately 24-35 hours in patients not taking enzyme-inducing or inhibiting medications 4, allowing for stable blood levels with once-daily dosing.