Lacosamide

Lacosamide may prolong PR interval; second degree and complete AV block has also been reported. Use caution in patients with conduction problems (eg, first/second degree atrioventricular block and sick sinus syndrome without pacemaker), sodium channelopathies (eg, Brugada syndrome), myocardial ischemia, heart failure, structural heart disease, or if concurrent use with other drugs that prolong the PR interval; ECG is recommended prior to initiating therapy and when at the steady state maintenance dose. Monitor closely with IV lacosamide administration; bradycardia and AV block have occurred during infusions. Instruct patients to contact their healthcare provider if signs or symptoms of conduction problems occur (eg, low or irregular pulse, feeling of lightheadedness and fainting). During short-term trials, atrial fibrillation/flutter, or syncope occurred slightly more often in patients with diabetic neuropathy and/or cardiovascular disease. In addition, in open-label studies, syncope has been associated with a history of cardiac disease risk factors and use of drugs that slow AV conduction.

Dizziness and ataxia may occur during therapy; patients should be cautioned about performing tasks which require alertness (eg, operating machinery or driving).

Blurred vision and diplopia may occur during therapy. Patients with persistent visual disturbances may need further assessment. Consider increased monitoring in patients with preexisting ocular conditions or vision-related issues.

Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur. Disease-related concerns:

Not recommended for use in patients with severe hepatic impairment; dosage adjustment required for mild to moderate hepatic impairment. Further dosage adjustment may be necessary in patients with hepatic impairment taking concomitant strong CYP3A4 and/or CYP2C9 inhibitors.

Use caution in patients with renal impairment; dosage adjustment required for severe renal impairment (CrCl ≤30 mL/minute) and supplementation may be necessary in hemodialysis. Patients with any degree of renal impairment taking concomitant strong CYP3A4 and/or CYP2C9 inhibitors may require dosage adjustment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Some products may contain phenylalanine.

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). Other warnings/precautions:

Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually (≥1 week) to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.