Drug Interactions between 5-hydroxytryptophan / melatonin / pyridoxine and lasmiditan

MONITOR CLOSELY: Coadministration of lasmiditan and serotonergic agents may increase the risk of serotonin syndrome. Lasmiditan binds to the 5-HT(1F) receptor, where it presumably exerts therapeutic effects via agonist actions. In clinical trials, reactions consistent with serotonin syndrome were reported in patients treated with lasmiditan who were not taking any other drugs associated with serotonin syndrome. Symptoms of serotonin syndrome may include mental status changes (e.g., irritability, hallucinations, coma), autonomic dysfunction (e.g., tachycardia, hyperthermia, blood pressure lability), neuromuscular abnormalities (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or higher dose serotonergic agent.

MANAGEMENT: Caution is advised during coadministration of lasmiditan and agents that increase serotonin. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Extra caution is advised when increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. Individual product labeling for washout periods should be consulted for current recommendations. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately, and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

MONITOR: Coadministration with alcohol or other central nervous system (CNS) depressants may enhance the sedative effects of lasmiditan and increase the likelihood and/or severity of cognitive and/or neuropsychiatric adverse reactions. Patients treated with lasmiditan are at risk of CNS depression, including dizziness and sedation, as well as driving impairment. In clinical studies, dizziness and sedation were reported in up to 17% and 7%, respectively, of patients receiving lasmiditan, and dizziness was the most common adverse event resulting in discontinuation (greater than 2%). In a computer-based driving study, a significant, dose-dependent impairment of subjects' ability to drive was observed with single 50, 100, and 200 mg lasmiditan doses at 90 minutes after administration. Concomitant use of lasmiditan and CNS depressants has not been studied clinically.

MANAGEMENT: Caution is advised during coadministration of lasmiditan with alcohol, other CNS depressants, or other agents that cause sedation. Patients should be advised against driving and other activities that require complete mental alertness for at least 8 hours after lasmiditan is administered.