Drug Interactions between lacosamide and troleandomycin

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Antiepileptic drugs can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Dose dependent prolongation in PR interval has been observed with the use of lacosamide. This drug should be used with caution in patients with known conduction abnormalities (AV block, sick sinus syndrome) in patients with sodium channelopathies (e.g., Brugada syndrome), with severe cardiac disease (myocardial ischemia, heart failure, structural disease), or in treatment with other drugs that also prolong PR interval. An ECG is recommended before beginning treatment, and after dose titration to a steady maintenance dose.

Dose dependent prolongation in PR interval has been observed with the use of lacosamide. This drug should be used with caution in patients with known conduction abnormalities (AV block, sick sinus syndrome) in patients with sodium channelopathies (e.g., Brugada syndrome), with severe cardiac disease (myocardial ischemia, heart failure, structural disease), or in treatment with other drugs that also prolong PR interval. An ECG is recommended before beginning treatment, and after dose titration to a steady maintenance dose.

Patients with mild to moderate hepatic impairment should be observed closely during lacosamide dose titration. A maximum dose of 300 mg/day is recommended for these patients. Lacosamide has not been evaluated in patients with severe hepatic impairment, so its use is not recommended in this group of patients.

Dose dependent prolongation in PR interval has been observed with the use of lacosamide. This drug should be used with caution in patients with known conduction abnormalities (AV block, sick sinus syndrome) in patients with sodium channelopathies (e.g., Brugada syndrome), with severe cardiac disease (myocardial ischemia, heart failure, structural disease), or in treatment with other drugs that also prolong PR interval. An ECG is recommended before beginning treatment, and after dose titration to a steady maintenance dose.

A maximum dose of 300 mg/day of lacosamide is recommended for patients with severe renal impairment (CrCl <30 mL/min) and in patients with end stage renal disease. Lacosamide is effectively removed from plasma by hemodialysis and a dose supplementation of 50% should be considered following this procedure. Dose titration should be done with caution in all renally impaired patients.