pimavanserin (Rx)

Parkinson Disease Psychosis

Indicated for treatment of hallucinations and delusions associated with Parkinson disease psychosis

34 mg PO qDay (without titration)

Dosage Modifications

Coadministration with strong CYP3A4 inhibitors

• Decrease dose to 10 mg PO qDay

Coadministration with strong CYP3A4 inducers

• Monitor for reduced efficacy; an increase in pimavanserin dosage may be needed

Renal impairment

• Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment required
• Severe (CrCl <30 mL/min) or end stage renal disease: Use with caution

Hepatic impairment

• No dosage adjustment recommended

Safety and efficacy not established

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; pimavanserin is not approved for dementia-related psychosis unrelated to Parkinson disease (see Black Box Warnings)

Contraindicated (1)

• lefamulin

  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.

Serious - Use Alternative (117)

• adagrasib

  adagrasib, pimavanserin. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

• alfuzosin

  alfuzosin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• amiodarone

  pimavanserin and amiodarone both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• amisulpride

  amisulpride and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amobarbital

  amobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• anagrelide

  pimavanserin and anagrelide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• apalutamide

  apalutamide will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• apomorphine

  apomorphine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• aripiprazole

  aripiprazole and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• arsenic trioxide

  pimavanserin and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• artemether

  artemether and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  pimavanserin and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• asenapine

  pimavanserin and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• asenapine transdermal

  asenapine transdermal and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• atazanavir

  atazanavir 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.

• atomoxetine

  atomoxetine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• bedaquiline

  bedaquiline and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. 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.

• buprenorphine

  buprenorphine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine buccal

  buprenorphine buccal and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine transdermal

  buprenorphine transdermal and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• ceritinib

  ceritinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.
  
  ceritinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chloramphenicol

  chloramphenicol will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• citalopram

  citalopram and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• clarithromycin

  clarithromycin 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.
  
  clarithromycin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• clozapine

  clozapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• cobicistat

  cobicistat 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.

• conivaptan

  conivaptan 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.

• crizotinib

  crizotinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• dasatinib

  dasatinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• degarelix

  degarelix and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  desflurane and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• disopyramide

  disopyramide and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• dofetilide

  dofetilide and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• dolasetron

  dolasetron and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• donepezil

  donepezil and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• efavirenz

  efavirenz and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• eliglustat

  eliglustat and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF 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.

• encorafenib

  encorafenib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

• entrectinib

  pimavanserin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

• eribulin

  eribulin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  escitalopram increases toxicity of pimavanserin by QTc interval. Avoid or Use Alternate Drug.

• fexinidazole

  fexinidazole and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels and/or prolong QT interval.
  
  fexinidazole will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fingolimod

  fingolimod and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• fosamprenavir

  fosamprenavir 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.

• gemifloxacin

  gemifloxacin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• gilteritinib

  gilteritinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• glasdegib

  pimavanserin and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

• granisetron

  granisetron and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• grapefruit

  grapefruit 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.

• hydrocodone

  hydrocodone, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. 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.

• hydroxychloroquine sulfate

  hydroxychloroquine sulfate and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyzine

  hydroxyzine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• ibutilide

  ibutilide and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• idelalisib

  idelalisib 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.

• iloperidone

  iloperidone and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• imatinib

  imatinib 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.

• indinavir

  indinavir 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.

• inotuzumab

  inotuzumab and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.

• isoflurane

  isoflurane and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• isoniazid

  isoniazid 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.

• itraconazole

  itraconazole 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.
  
  itraconazole and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  ivosidenib will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketoconazole

  ketoconazole 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.

• levodopa inhaled

  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). .

• levoketoconazole

  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.

• lithium

  lithium and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• lopinavir

  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.

• lorlatinib

  lorlatinib will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  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.

• metoclopramide intranasal

  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.

• mifepristone

  mifepristone and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.
  
  mifepristone will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mirtazapine

  mirtazapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• mobocertinib

  mobocertinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

• nefazodone

  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.

• nelfinavir

  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.

• nicardipine

  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.

• nilotinib

  nilotinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• olanzapine

  olanzapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• olopatadine intranasal

  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.

• oxaliplatin

  oxaliplatin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• paliperidone

  paliperidone and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• pimozide

  pimavanserin and pimozide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• pitolisant

  pimavanserin and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

• posaconazole

  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.

• primaquine

  primaquine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• procainamide

  pimavanserin and procainamide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• quetiapine

  pimavanserin and quetiapine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• quinidine

  pimavanserin and quinidine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• ribociclib

  ribociclib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• ritonavir

  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.

• safinamide

  pimavanserin decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

• saquinavir

  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.

• secobarbital

  secobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selinexor

  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.

• sertraline

  sertraline and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• sevoflurane

  sevoflurane and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• siponimod

  siponimod and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• solifenacin

  solifenacin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• sotalol

  pimavanserin and sotalol both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• sufentanil SL

  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.

• sunitinib

  sunitinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• tacrolimus

  tacrolimus and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• tetrabenazine

  pimavanserin and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• thioridazine

  pimavanserin and thioridazine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• tipranavir

  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.

• toremifene

  pimavanserin and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• tucatinib

  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.

• vandetanib

  pimavanserin and vandetanib both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• vemurafenib

  pimavanserin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• voriconazole

  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.

• vorinostat

  vorinostat and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• voxelotor

  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.

• ziprasidone

  pimavanserin and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

Monitor Closely (94)

• albuterol

  albuterol and pimavanserin both increase QTc interval. Use Caution/Monitor.

• alfuzosin

  pimavanserin and alfuzosin both increase QTc interval. Use Caution/Monitor.

• almotriptan

  almotriptan, 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).

• arformoterol

  arformoterol and pimavanserin both increase QTc interval. Use Caution/Monitor.

• bosentan

  bosentan 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.

• brexanolone

  brexanolone, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• buprenorphine, long-acting injection

  pimavanserin increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• carbamazepine

  carbamazepine 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.

• cenobamate

  cenobamate will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
  
  cenobamate, pimavanserin. Either increases effects of the other by sedation. Use Caution/Monitor.

• dabrafenib

  dabrafenib 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.

• daridorexant

  pimavanserin and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darunavir

  darunavir will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.

• deutetrabenazine

  pimavanserin and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.
  
  pimavanserin and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  pimavanserin and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• dexamethasone

  dexamethasone 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.

• dextromethorphan

  dextromethorphan, 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).

• difelikefalin

  difelikefalin and pimavanserin both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  dihydroergotamine, 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).

• doxepin

  doxepin and pimavanserin both increase QTc interval. Use Caution/Monitor.

• duvelisib

  duvelisib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• efavirenz

  efavirenz 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.

• elagolix

  elagolix decreases levels of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eletriptan

  eletriptan, 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).

• encorafenib

  encorafenib, pimavanserin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enzalutamide

  enzalutamide 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.

• ergoloid mesylates

  ergoloid mesylates, 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).

• ergotamine

  ergotamine, 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).

• esketamine intranasal

  esketamine intranasal, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  eslicarbazepine acetate 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.

• etravirine

  etravirine 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.

• fedratinib

  fedratinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fenfluramine

  pimavanserin decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

• fentanyl

  fentanyl, 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).

• flibanserin

  flibanserin, 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).

• fosphenytoin

  fosphenytoin 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.

• fostemsavir

  pimavanserin and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  frovatriptan, 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).

• ganaxolone

  pimavanserin and ganaxolone both increase sedation. Use Caution/Monitor.

• gemtuzumab

  pimavanserin and gemtuzumab both increase QTc interval. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• lasmiditan

  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.

• lemborexant

  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.

• lenacapavir

  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.

• levomilnacipran

  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).

• linezolid

  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).

• lithium

  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).

• lofexidine

  pimavanserin and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.

• lorcaserin

  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).

• lumacaftor/ivacaftor

  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.

• meperidine

  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).

• methadone

  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).

• methylergonovine

  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).

• methylphenidate

  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.

• midazolam intranasal

  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.

• milnacipran

  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).

• mitotane

  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.

• nafcillin

  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.

• naratriptan

  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).

• nevirapine

  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.

• oliceridine

  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.

• osilodrostat

  osilodrostat and pimavanserin both increase QTc interval. Use Caution/Monitor.

• oxcarbazepine

  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.

• ozanimod

  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.

• paroxetine

  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).

• pentobarbital

  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.

• phenelzine

  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).

• phenobarbital

  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.

• phenytoin

  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.

• primidone

  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. An increase in pimavanserin dosage may be needed.

• procarbazine

  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).

• promethazine

  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).

• quizartinib

  quizartinib, pimavanserin. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.

• remimazolam

  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.

• ribociclib

  ribociclib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  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.

• rifampin

  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.

• rifapentine

  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.

• rucaparib

  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.

• selegiline

  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).

• selpercatinib

  selpercatinib increases toxicity of pimavanserin by QTc interval. Use Caution/Monitor.

• sodium sulfate/?magnesium sulfate/potassium chloride

  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 sulfate

  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.

• St John's Wort

  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.

• stiripentol

  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.

• sumatriptan

  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 intranasal

  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).

• tazemetostat

  tazemetostat will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  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.

• tranylcypromine

  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).

• triclabendazole

  triclabendazole and pimavanserin both increase QTc interval. Use Caution/Monitor.

• valbenazine

  valbenazine and pimavanserin both increase QTc interval. Use Caution/Monitor.

• venlafaxine

  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).

• vilazodone

  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).

• voclosporin

  voclosporin, pimavanserin. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• zolmitriptan

  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).

Minor (6)

• acetazolamide

  acetazolamide will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anastrozole

  anastrozole will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• azithromycin

  azithromycin increases toxicity of pimavanserin by QTc interval. Minor/Significance Unknown.

• chloroquine

  chloroquine increases toxicity of pimavanserin by QTc interval. Minor/Significance Unknown.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• larotrectinib

  larotrectinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• adagrasib

  Serious - Use Alternative (1)adagrasib, pimavanserin. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

• albuterol

  Monitor Closely (1)albuterol and pimavanserin both increase QTc interval. Use Caution/Monitor.

• alfuzosin

  Monitor Closely (1)pimavanserin and alfuzosin both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)alfuzosin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• almotriptan

  Monitor Closely (1)almotriptan, 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).

• amiodarone

  Serious - Use Alternative (1)pimavanserin and amiodarone both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• amisulpride

  Serious - Use Alternative (1)amisulpride and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amobarbital

  Serious - Use Alternative (1)amobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• anagrelide

  Serious - Use Alternative (1)pimavanserin and anagrelide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• apomorphine

  Serious - Use Alternative (1)apomorphine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• arformoterol

  Monitor Closely (1)arformoterol and pimavanserin both increase QTc interval. Use Caution/Monitor.

• aripiprazole

  Serious - Use Alternative (1)aripiprazole and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• arsenic trioxide

  Serious - Use Alternative (1)pimavanserin and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• artemether

  Serious - Use Alternative (1)artemether and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Serious - Use Alternative (1)pimavanserin and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• asenapine

  Serious - Use Alternative (1)pimavanserin and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• asenapine transdermal

  Serious - Use Alternative (1)asenapine transdermal and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• atazanavir

  Serious - Use Alternative (1)atazanavir 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.

• atomoxetine

  Serious - Use Alternative (1)atomoxetine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• azithromycin

  Minor (1)azithromycin increases toxicity of pimavanserin by QTc interval. Minor/Significance Unknown.

• bedaquiline

  Serious - Use Alternative (1)bedaquiline and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (1)benzhydrocodone/acetaminophen, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. 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.

• bosentan

  Monitor Closely (1)bosentan 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.

• brexanolone

  Monitor Closely (1)brexanolone, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• buprenorphine

  Serious - Use Alternative (1)buprenorphine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine buccal

  Serious - Use Alternative (1)buprenorphine buccal and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  Serious - Use Alternative (1)buprenorphine subdermal implant and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine transdermal

  Serious - Use Alternative (1)buprenorphine transdermal and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine, long-acting injection

  Monitor Closely (1)pimavanserin increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.Serious - Use Alternative (1)buprenorphine, long-acting injection and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• carbamazepine

  Monitor Closely (1)carbamazepine 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.

• cenobamate

  Monitor Closely (2)cenobamate, pimavanserin. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Serious - Use Alternative (2)ceritinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.
  
  ceritinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chloroquine

  Minor (1)chloroquine increases toxicity of pimavanserin by QTc interval. Minor/Significance Unknown.

• citalopram

  Serious - Use Alternative (1)citalopram and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• clarithromycin

  Serious - Use Alternative (2)clarithromycin 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.
  
  clarithromycin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• clozapine

  Serious - Use Alternative (1)clozapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• cobicistat

  Serious - Use Alternative (1)cobicistat 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.

• conivaptan

  Serious - Use Alternative (1)conivaptan 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.

• crizotinib

  Serious - Use Alternative (1)crizotinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dabrafenib

  Monitor Closely (1)dabrafenib 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.

• daridorexant

  Monitor Closely (1)pimavanserin and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.

• dasatinib

  Serious - Use Alternative (1)dasatinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• degarelix

  Serious - Use Alternative (1)degarelix and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  Serious - Use Alternative (1)desflurane and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• deutetrabenazine

  Monitor Closely (3)pimavanserin and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  pimavanserin and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
  
  pimavanserin and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.

• dexamethasone

  Monitor Closely (1)dexamethasone 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.

• dextromethorphan

  Monitor Closely (1)dextromethorphan, 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).

• difelikefalin

  Monitor Closely (1)difelikefalin and pimavanserin both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (1)dihydroergotamine, 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).

• disopyramide

  Serious - Use Alternative (1)disopyramide and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• dofetilide

  Serious - Use Alternative (1)dofetilide and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• dolasetron

  Serious - Use Alternative (1)dolasetron and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• donepezil

  Serious - Use Alternative (1)donepezil and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• doxepin

  Monitor Closely (1)doxepin and pimavanserin both increase QTc interval. Use Caution/Monitor.

• duvelisib

  Monitor Closely (1)duvelisib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• efavirenz

  Monitor Closely (1)efavirenz 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.Serious - Use Alternative (1)efavirenz and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (1)elagolix decreases levels of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eletriptan

  Monitor Closely (1)eletriptan, 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).

• eliglustat

  Serious - Use Alternative (1)eliglustat and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Serious - Use Alternative (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF 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.

• encorafenib

  Monitor Closely (1)encorafenib, pimavanserin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.Serious - Use Alternative (1)encorafenib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

• entrectinib

  Serious - Use Alternative (1)pimavanserin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

• enzalutamide

  Monitor Closely (1)enzalutamide 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.

• ergoloid mesylates

  Monitor Closely (1)ergoloid mesylates, 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).

• ergotamine

  Monitor Closely (1)ergotamine, 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).

• eribulin

  Serious - Use Alternative (1)eribulin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  Serious - Use Alternative (1)escitalopram increases toxicity of pimavanserin by QTc interval. Avoid or Use Alternate Drug.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate 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.

• etravirine

  Monitor Closely (1)etravirine 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.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fenfluramine

  Monitor Closely (1)pimavanserin decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

• fentanyl

  Monitor Closely (1)fentanyl, 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).

• fexinidazole

  Serious - Use Alternative (2)fexinidazole and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels and/or prolong QT interval.
  
  fexinidazole will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fingolimod

  Serious - Use Alternative (1)fingolimod and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• flibanserin

  Monitor Closely (1)flibanserin, 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).

• fosamprenavir

  Serious - Use Alternative (1)fosamprenavir 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.

• fosphenytoin

  Monitor Closely (1)fosphenytoin 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.

• fostemsavir

  Monitor Closely (1)pimavanserin and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  Monitor Closely (1)frovatriptan, 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).

• ganaxolone

  Monitor Closely (1)pimavanserin and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Serious - Use Alternative (1)gemifloxacin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• gemtuzumab

  Monitor Closely (1)pimavanserin and gemtuzumab both increase QTc interval. Use Caution/Monitor.

• gilteritinib

  Serious - Use Alternative (1)gilteritinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• glasdegib

  Serious - Use Alternative (1)pimavanserin and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

• granisetron

  Serious - Use Alternative (1)granisetron and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• grapefruit

  Serious - Use Alternative (1)grapefruit 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.

• hydrocodone

  Serious - Use Alternative (1)hydrocodone, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. 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.

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)hydroxychloroquine sulfate and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyzine

  Serious - Use Alternative (1)hydroxyzine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• ibutilide

  Serious - Use Alternative (1)ibutilide and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• idelalisib

  Serious - Use Alternative (1)idelalisib 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.

• iloperidone

  Serious - Use Alternative (1)iloperidone and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• imatinib

  Serious - Use Alternative (1)imatinib 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.

• indinavir

  Serious - Use Alternative (1)indinavir 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.

• inotuzumab

  Serious - Use Alternative (1)inotuzumab and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.

• isoflurane

  Serious - Use Alternative (1)isoflurane and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• isoniazid

  Serious - Use Alternative (1)isoniazid 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.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Serious - Use Alternative (2)itraconazole 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.
  
  itraconazole and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketoconazole

  Serious - Use Alternative (1)ketoconazole 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.

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lasmiditan

  Monitor 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.

• lefamulin

  Contraindicated (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.

• lemborexant

  Monitor 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.

• lenacapavir

  Monitor 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 inhaled

  Serious - 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). .

• levoketoconazole

  Serious - 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.

• levomilnacipran

  Monitor 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).

• linezolid

  Monitor 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).

• lithium

  Monitor 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.

• lofexidine

  Monitor Closely (1)pimavanserin and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.

• lopinavir

  Serious - 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.

• lorcaserin

  Monitor 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).

• lorlatinib

  Serious - 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/ivacaftor

  Monitor 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.

• macimorelin

  Serious - 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.

• meperidine

  Monitor 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).

• methadone

  Monitor 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).

• methylergonovine

  Monitor 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).

• methylphenidate

  Monitor 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 intranasal

  Serious - 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 intranasal

  Monitor 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.

• mifepristone

  Serious - 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.

• milnacipran

  Monitor 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).

• mirtazapine

  Serious - Use Alternative (1)mirtazapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• mitotane

  Monitor 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.

• mobocertinib

  Serious - 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.

• nafcillin

  Monitor 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.

• naratriptan

  Monitor 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).

• nefazodone

  Serious - 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.

• nelfinavir

  Serious - 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.

• nevirapine

  Monitor 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.

• nicardipine

  Serious - 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.

• nilotinib

  Serious - 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.

• olanzapine

  Serious - Use Alternative (1)olanzapine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• oliceridine

  Monitor 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 intranasal

  Serious - 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.

• osilodrostat

  Monitor Closely (1)osilodrostat and pimavanserin both increase QTc interval. Use Caution/Monitor.

• oxaliplatin

  Serious - Use Alternative (1)oxaliplatin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• oxcarbazepine

  Monitor 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.

• ozanimod

  Monitor 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.

• paliperidone

  Serious - 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.

• paroxetine

  Monitor 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).

• pentobarbital

  Monitor 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.

• phenelzine

  Monitor 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).

• phenobarbital

  Monitor 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.

• phenytoin

  Monitor 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.

• pimozide

  Serious - 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.

• pitolisant

  Serious - Use Alternative (1)pimavanserin and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

• posaconazole

  Serious - 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.

• primaquine

  Serious - Use Alternative (1)primaquine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• primidone

  Monitor 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. An increase in pimavanserin dosage may be needed.

• procainamide

  Serious - 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.

• procarbazine

  Monitor 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).

• promethazine

  Monitor 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).

• quetiapine

  Serious - 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.

• quinidine

  Serious - 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.

• quizartinib

  Monitor Closely (1)quizartinib, pimavanserin. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.

• remimazolam

  Monitor 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.

• ribociclib

  Monitor 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.

• rifabutin

  Monitor 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.

• rifampin

  Monitor 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.

• rifapentine

  Monitor 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.

• ritonavir

  Serious - 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.

• rucaparib

  Monitor 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.

• safinamide

  Serious - 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.

• saquinavir

  Serious - 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.

• secobarbital

  Serious - Use Alternative (1)secobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selegiline

  Monitor 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).

• selinexor

  Serious - 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.

• selpercatinib

  Monitor Closely (1)selpercatinib increases toxicity of pimavanserin by QTc interval. Use Caution/Monitor.

• sertraline

  Serious - Use Alternative (1)sertraline and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• sevoflurane

  Serious - Use Alternative (1)sevoflurane and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• siponimod

  Serious - Use Alternative (1)siponimod and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor 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 sulfate

  Monitor 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.

• solifenacin

  Serious - Use Alternative (1)solifenacin and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• sotalol

  Serious - 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 Wort

  Monitor 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.

• stiripentol

  Monitor 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 SL

  Serious - 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.

• sumatriptan

  Monitor 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 intranasal

  Monitor 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).

• sunitinib

  Serious - Use Alternative (1)sunitinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• tacrolimus

  Serious - Use Alternative (1)tacrolimus and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor 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.

• tetrabenazine

  Serious - 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.

• thioridazine

  Serious - 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.

• tipranavir

  Serious - 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.

• toremifene

  Serious - 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.

• tranylcypromine

  Monitor 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).

• triclabendazole

  Monitor Closely (1)triclabendazole and pimavanserin both increase QTc interval. Use Caution/Monitor.

• tucatinib

  Serious - 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.

• valbenazine

  Monitor Closely (1)valbenazine and pimavanserin both increase QTc interval. Use Caution/Monitor.

• vandetanib

  Serious - 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.

• vemurafenib

  Serious - 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.

• venlafaxine

  Monitor 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).

• vilazodone

  Monitor 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).

• voclosporin

  Monitor Closely (1)voclosporin, pimavanserin. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

  Serious - 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.

• vorinostat

  Serious - Use Alternative (1)vorinostat and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• voxelotor

  Serious - 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.

• ziprasidone

  Serious - 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.

• zolmitriptan

  Monitor 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).