Drug Interactions between Di-Phen and lamotrigine

ADJUST DOSE: Coadministration with an enzyme-inducing antiepileptic agent such as phenytoin, phenobarbital, or primidone may decrease the serum concentrations of lamotrigine. The mechanism is increased clearance due to induction of lamotrigine glucuronidation in the liver. Studies have found that enzyme-inducing antiepileptic agents can reduce lamotrigine serum concentrations by approximately 40%.

MONITOR: In vitro studies have shown that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations. Lamotrigine has shown in vitro effects on the human cardiac sodium channels similar to that of other Class 1B antiarrhythmic drugs. In healthy individuals, a thorough QT study did not show slowed ventricular conduction (widen QRS) with lamotrigine; however, the risk of slow ventricular conduction and proarrhythmias, including sudden death, may be increased in patients with structural heart disease or myocardial ischemia. Based on this data, there is a concern that concomitant use of other sodium channel blockers, such as phenytoin, may increase the risk of proarrhythmias.

MANAGEMENT: When lamotrigine is added to existing therapy containing an enzyme-inducing antiepileptic agent without valproate, the initial dosage of lamotrigine should be 0.6 mg/kg/day in two divided doses (2 to 12 years of age) or 50 mg/day (older than 12 years of age) for the first 2 weeks. The initial dosage should be doubled for the next 2 weeks, then increased by 1.2 mg/kg/day or 100 mg/day every 1 to 2 weeks as needed and as tolerated. The usual maintenance dosage is 5 to 15 mg/kg/day (up to 400 mg/day) in children up to 12 years of age and 300 to 500 mg/day (400 mg/day for the treatment of bipolar disorder) in older patients. Patients should be advised to promptly notify their physician if they experience worsening of seizure control or increased adverse effects. If the enzyme-inducing antiepileptic agent is discontinued, lamotrigine half-life will be prolonged, and a dosage adjustment may be necessary. Prescribers should refer to the lamotrigine product labeling for complete dosing information. In addition, due to the potential for increased risk of proarrhythmias, the manufacturer recommends lamotrigine be avoided in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome or other sodium channelopathies). A joint task force of the International League Against Epilepsy and the American Epilepsy Society issued an advisory on Feb 25, 2021, for healthcare professionals in response to the FDA safety warning on the cardiac effects of lamotrigine. For patients under 60 years with no cardiac risk factors, they advise that clinicians should prescribe lamotrigine as usual. For patients with cardiac risk (over 60 years and under 60 years with known cardiac disease or significant risk factors), they advise clinicians to consider obtaining an ECG prior to initiating lamotrigine and repeating ECG as the serum lamotrigine level approaches the upper limit of the therapeutic range and/or with concomitant use of other sodium channel blockers or substances known to impair atrioventricular and/or intra-ventricular cardiac conduction. They also advise clinicians consider obtaining an ECG and/or cardiology consult in patients with sudden onset syncope or pre-syncope with loss of muscular tone without a clear vasovagal or orthostatic cause. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate an irregular heart rhythm such as dizziness, lightheadedness, fainting, palpitation, shortness of breath, or syncope.

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