An increase in pimavanserin dosage may be needed.procainamideSerious - Use Alternative (1)pimavanserin and procainamide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.procarbazineMonitor Closely (1)procarbazine, 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).promethazineMonitor Closely (1)promethazine, 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).quetiapineSerious - Use Alternative (1)pimavanserin and quetiapine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.quinidineSerious - Use Alternative (1)pimavanserin and quinidine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.remimazolamMonitor Closely (1)remimazolam, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ribociclib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.rifabutinMonitor Closely (1)rifabutin 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.rifampinMonitor Closely (1)rifampin 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.rifapentineMonitor Closely (1)rifapentine 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.ritonavirSerious - Use Alternative (1)ritonavir 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.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.safinamideSerious - Use Alternative (1)pimavanserin decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.saquinavirSerious - Use Alternative (1)saquinavir 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.secobarbitalSerious - Use Alternative (1)secobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.selegilineMonitor Closely (1)selegiline, 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).selinexorSerious - Use Alternative (1)selinexor, pimavanserin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.selpercatinibMonitor Closely (1)selpercatinib increases toxicity of pimavanserin by QTc interval. Use Caution/Monitor.sertralineSerious - Use Alternative (1)sertraline and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.sevofluraneSerious - Use Alternative (1)sevoflurane and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.siponimodSerious - Use Alternative (1)siponimod and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.sodium sulfate/?magnesium sulfate/potassium chlorideMonitor Closely (2)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of pimavanserin by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. . sodium sulfate/?magnesium sulfate/potassium chloride increases effects of pimavanserin by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.sodium sulfate/potassium sulfate/magnesium sulfateMonitor Closely (2)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of pimavanserin by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. . sodium sulfate/potassium sulfate/magnesium sulfate increases effects of pimavanserin by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.solifenacinSerious - Use Alternative (1)solifenacin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.sotalolSerious - Use Alternative (1)pimavanserin and sotalol both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.St John's WortMonitor Closely (1)St John's Wort 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.stiripentolMonitor Closely (1)stiripentol, pimavanserin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.sufentanil SLSerious - Use Alternative (1)sufentanil SL, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. 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.sumatriptanMonitor Closely (1)sumatriptan, 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).sumatriptan intranasalMonitor Closely (1)sumatriptan intranasal, 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).sunitinibSerious - Use Alternative (1)sunitinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.tacrolimusSerious - Use Alternative (1)tacrolimus and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.tetrabenazineSerious - Use Alternative (1)pimavanserin and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.thioridazineSerious - Use Alternative (1)pimavanserin and thioridazine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.tipranavirSerious - Use Alternative (1)tipranavir 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.toremifeneSerious - Use Alternative (1)pimavanserin and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.tranylcypromineMonitor Closely (1)tranylcypromine, 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).triclabendazoleMonitor Closely (1)triclabendazole and pimavanserin both increase QTc interval. Use Caution/Monitor.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valbenazineMonitor Closely (1)valbenazine and pimavanserin both increase QTc interval. Use Caution/Monitor.vandetanibSerious - Use Alternative (1)pimavanserin and vandetanib both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.vemurafenibSerious - Use Alternative (1)pimavanserin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.venlafaxineMonitor Closely (1)venlafaxine, 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).vilazodoneMonitor Closely (1)vilazodone, 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).voclosporinMonitor Closely (1)voclosporin, pimavanserin. Either increases effects of the other by QTc interval. Use Caution/Monitor.voriconazoleSerious - Use Alternative (1)voriconazole 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.vorinostatSerious - Use Alternative (1)vorinostat and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.ziprasidoneSerious - Use Alternative (1)pimavanserin and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.zolmitriptanMonitor Closely (1)zolmitriptan, 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). 1-10% Nausea (7%) Peripheral edema (7%) Confusional state (6%) Hallucinations (5%) Constipation (4%) Gait disturbance (2%) Postmarketing Reports Rash Urticaria Reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) Somnolence, falls Agitation Aggression Black Box Warnings Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death Pimavanserin is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson disease psychosisContraindications Documented hypersensitivity reaction to drug or components; rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) Cautions Antipsychotic drugs increase the all-cause risk of death in elderly patients with dementia-related psychosis (see Black Box Warnings) Pimavanserin is a substrate of CYP3A4; strong CYP3A4 inhibitor or inducers affect systemic exposure (see Dosage Modifications and Interactions) QT prolongation Prolongs QT interval Avoid use in patients with known QT prolongation or in combination with other drugs known to prolong QT interval, including class 1A antiarrhythmics (eg, quinidine, procainamide) or class 3 antiarrhythmics (eg, amiodarone, sotalol), certain antipsychotic medications (eg, ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (eg, gatifloxacin, moxifloxacin) Avoid with history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or