increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lasmiditanMonitor Closely (1)lasmiditan, pimavanserin. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.lefamulinContraindicated (1)lefamulin will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.lemborexantMonitor Closely (1)lemborexant, pimavanserin. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.lenacapavirMonitor Closely (1)lenacapavir will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.levodopa inhaledSerious - Use Alternative (1)pimavanserin decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Atypical (2nd generation) antipsychotics inhibit dopamine D2 receptors in varying degrees (clozapine and quetiapine are lower risk). .levoketoconazoleSerious - Use Alternative (1)levoketoconazole will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 10 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.levomilnacipranMonitor Closely (1)levomilnacipran, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).linezolidMonitor Closely (1)linezolid, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).lithiumMonitor Closely (1)lithium, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)lithium and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.lofexidineMonitor Closely (1)pimavanserin and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.lopinavirSerious - Use Alternative (2)lopinavir will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors. lopinavir and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.lorcaserinMonitor Closely (1)lorcaserin, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).lorlatinibSerious - Use Alternative (1)lorlatinib will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.lumacaftor/ivacaftorMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.macimorelinSerious - Use Alternative (1)macimorelin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.meperidineMonitor Closely (1)meperidine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).methadoneMonitor Closely (1)methadone, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).methylergonovineMonitor Closely (1)methylergonovine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).methylphenidateMonitor Closely (1)pimavanserin increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.metoclopramide intranasalSerious - Use Alternative (2)pimavanserin, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient. pimavanserin increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.midazolam intranasalMonitor Closely (1)midazolam intranasal, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.mifepristoneSerious - Use Alternative (2)mifepristone will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. mifepristone and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.milnacipranMonitor Closely (1)milnacipran, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).mirtazapineSerious - Use Alternative (1)mirtazapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.mitotaneMonitor Closely (1)mitotane will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.mobocertinibSerious - Use Alternative (1)mobocertinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.nafcillinMonitor Closely (1)nafcillin will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.naratriptanMonitor Closely (1)naratriptan, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).nefazodoneSerious - Use Alternative (1)nefazodone will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.nelfinavirSerious - Use Alternative (1)nelfinavir will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.nevirapineMonitor Closely (1)nevirapine will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.nicardipineSerious - Use Alternative (1)nicardipine will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.nilotinibSerious - Use Alternative (1)nilotinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.olanzapineSerious - Use Alternative (1)olanzapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.oliceridineMonitor Closely (1)oliceridine, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.olopatadine intranasalSerious - Use Alternative (1)pimavanserin and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. osilodrostatMonitor Closely (1)osilodrostat and pimavanserin both increase QTc interval. Use Caution/Monitor.oxaliplatinSerious - Use Alternative (1)oxaliplatin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.oxcarbazepineMonitor Closely (1)oxcarbazepine will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.ozanimodMonitor Closely (1)ozanimod and pimavanserin both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.paliperidoneSerious - Use Alternative (1)paliperidone and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.paroxetineMonitor Closely (1)paroxetine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).pentobarbitalMonitor Closely (1)pentobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.phenelzineMonitor Closely (1)phenelzine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).phenobarbitalMonitor Closely (1)phenobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.phenytoinMonitor Closely (1)phenytoin will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.pimozideSerious - Use Alternative (1)pimavanserin and pimozide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.pitolisantSerious - Use Alternative (1)pimavanserin and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.posaconazoleSerious - Use Alternative (1)posaconazole will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.primaquineSerious - Use Alternative (1)primaquine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.primidoneMonitor Closely (1)primidone will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy.