What is the recommended dosing for Lamictal (lamotrigine)?

Lamotrigine (Lamictal) Dosing

Start lamotrigine at 25 mg once daily for the first two weeks, then increase to 50 mg daily, with subsequent titration to a target maintenance dose of 200 mg/day for bipolar disorder or 100-500 mg/day for epilepsy, using strict adherence to slow titration schedules to minimize serious rash risk. 1

Standard Initial Dosing Protocol

• Begin with 25 mg once daily for 14 days, followed by an increase to 50 mg daily 1
• The standard titration takes approximately 6 weeks to reach the target dose of 200 mg/day 2
• Never exceed recommended dose escalation rates, as exceeding the initial dosage is a major risk factor for serious rash including Stevens-Johnson syndrome 3, 4

Maintenance Dosing by Indication

Epilepsy

• Target dose range: 100-500 mg/day for seizure control 1, 5
• Monotherapy doses of 100-300 mg/day show similar efficacy to carbamazepine and phenytoin for partial onset seizures 5
• In elderly patients (>65 years), lower doses are effective: mean dose of 72 mg/day, with 52% maintaining control on just 50 mg/day 6

Bipolar Disorder

• Target maintenance dose: 200 mg/day 1, 2
• Continue maintenance treatment for at least 2 years after the last bipolar episode 4
• Lamotrigine is FDA-approved for maintenance therapy in adults with bipolar I disorder 4

Critical Dosage Adjustments for Drug Interactions

With Valproic Acid (Enzyme Inhibitor)

• Reduce lamotrigine dose by 50% when coadministered with valproate 4, 2
• Valproic acid increases lamotrigine half-life to 48.3-59 hours (from baseline 22.8-37.4 hours) 4, 7
• Dosage adjustment is essential to prevent toxicity 4

With Enzyme-Inducing Antiepileptic Drugs

• Phenytoin, carbamazepine, or phenobarbital reduce lamotrigine half-life to 13.5-15 hours 7
• Higher doses and more rapid titration may be required, but must still follow safety protocols 8, 2
• Therapeutic drug monitoring is recommended when significant drug interactions are present 8, 1

With Hormonal Contraceptives

• Combined hormonal contraceptives may reduce lamotrigine effectiveness 4
• Check lamotrigine levels when patients are on hormonal contraceptives 4

Special Populations

Elderly Patients

• Start with 25 mg/day for 15 days, then increase to 50 mg/day 6
• Mean effective dose is significantly lower (72 mg/day) compared to younger adults 6
• Many elderly patients achieve seizure control on just 50 mg/day 6

Restarting After Discontinuation

• Do not restart at full dose—always re-titrate from the beginning using the standard slow titration schedule 1
• Exception: A loading dose of 6.5 mg/kg can be used only in patients previously on lamotrigine for >6 months without rash history who have been off lamotrigine for <5 days 1, 3
• Never use loading doses in lamotrigine-naive patients or those with prior rash history due to severe rash risk 3

Therapeutic Monitoring

• Putative therapeutic plasma range: 1-4 mg/L 1, 7
• Monitor levels in cases of known or suspected malabsorption, poor treatment response, or significant drug interactions 1
• Some patients tolerate concentrations >10 mg/L with benefit and without toxicity 7
• Baseline laboratory tests should include complete blood count, liver function tests, and renal function tests 4

Administration Considerations

• Available formulations include regular tablets (swallow whole with water), extended-release tablets, and dissolving tablets (place on tongue, do not chew, crush, or break) 4, 9
• Extended-release tablets are available in 25,50,100,200,250, and 300 mg strengths 9

Safety Warnings

• Strict adherence to slow titration is the primary strategy to minimize serious rash risk 1
• Skin rash occurs in approximately 10% of patients and is the most common cause of treatment withdrawal 5
• Incidence of serious rash is 0.1% in bipolar disorder studies 2
• Educate patients to report any rash immediately 1