Drug Interaction Report

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.

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.