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: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.