Atypical antipsychotic, selective 5-HT2A inverse agonist
Brand names: Nuplazid
Updated · Methodology
First line
-approved for Parkinson disease psychosis (hallucinations and delusions). Advantage over typical antipsychotics – no D2 blockade, so motor symptoms are not worsened. 2023 recommends pimavanserin as first-line pharmacotherapy after dopaminergic therapy adjustment and management of contributing factors (infections, sleep, delirium).
Sources
ICD-10: F06.0 · ICD-11: 6E61
Selective inverse agonist of cortical 5-HT2A serotonin receptors. No affinity for D2 receptors, hence the lack of extrapyramidal symptoms. Metabolised by CYP3A4. QT prolongation averages 5–8 ms. Half-life 57 hours.
Limited data. FDA boxed warning for increased mortality in elderly with dementia.
Limited milk data. Breastfeeding not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
3 pairs found. Sorted from critical to minor.
Mechanism
Additive QT prolongation (amiodarone 30-50 ms, pimavanserin 5-8 ms). recommends avoiding.
Symptoms
QT above 500 ms, torsades de pointes.
Management
Combination contraindicated.
Mechanism
Both drugs prolong QT (pimavanserin 5-8 ms, ondansetron 10-15 ms). Additive – torsades risk.
Symptoms
Syncope, torsades de pointes in patients with additional risk factors.
Management
Combination contraindicated. Use metoclopramide for nausea.
Mechanism
Clarithromycin inhibits CYP3A4 – pimavanserin rises 2-3 fold. Added QT prolongation.
Symptoms
QT prolongation, dizziness, peripheral edema.
Management
Reduce pimavanserin to 10 mg/day. Better – azithromycin.
Sources
Verbatim lines from the interaction sections, in the language of the label
«DRUG INTERACTIONS: Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of pimavanserin. ( 2.3 , 7.1 )»FDA, section 7 · Open on DailyMed
«Drugs Having Clinically Important Interactions with Pimavanserin: Intervention: Avoid the use of pimavanserin in combination with other drugs known to prolong QT interval (e.g., Class 1A…»FDA, section 7 · Open on DailyMed
«Drugs Having Clinically Important Interactions with Pimavanserin: Intervention: If pimavanserin is used with a strong CYP3A4 inhibitor, reduce the dosage of pimavanserin [see Dosage and…»FDA, section 7 · Open on DailyMed
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Pimavanserin is evaluated for the following indications with varying evidence strength: Parkinson disease psychosis (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Pimavanserin (≥ 1 in 100): Peripheral edema, Nausea, Confusion, Constipation. See the Safety section for uncommon and serious reactions.
Limited data. FDA boxed warning for increased mortality in elderly with dementia.
Limited milk data. Breastfeeding not recommended.
Pimavanserin is contraindicated in: Prior QT prolongation; Combination with QT-prolonging drugs (amiodarone, sotalol, moxifloxacin, ondansetron); Pimavanserin hypersensitivity. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Pimozide, Quetiapine, Risperidone, Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), Ziprasidone, Bromazepam, Fabomotizole, Lormetazepam