Section 03 · Monograph
Pimavanserin
Reviewed Nov 2026FDA label
NuplazidAtypical antipsychotic
- Forms
- Tab: 34mg | Cap: 10mg
- Dose
- 34mg once daily (PD psychosis)
- MOA
- 5-HT2A inverse agonist
Black Box Warning
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death
- NUPLAZID is not approved for patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson's disease psychosis
Indications
- Treatment of hallucinations and delusions associated with Parkinson's disease psychosisFDA-labeled
Mechanism of Action
- Atypical antipsychotic acting as a selective inverse agonist/antagonist at serotonin 5-HT2A receptors, with lower affinity antagonist activity at 5-HT2C receptors
- Has negligible affinity for dopamine (including D2), histaminergic, muscarinic, or adrenergic receptors
- The precise mechanism by which this receptor activity produces efficacy in Parkinson's disease psychosis is unknown
Full Dosing
Adult / usual
- Recommended dose: 34 mg (two 17 mg capsules) taken orally once daily, without titration
- May be taken with or without food
- Capsules may be swallowed whole or the contents sprinkled on soft food (applesauce, pudding, yogurt) and consumed immediately
- With strong CYP3A4 inhibitors: reduce dose to 10 mg (one tablet) once daily
- With strong CYP3A4 inducers: avoid concomitant use (reduced efficacy)
Renal
- No dosage adjustment required for mild-to-moderate renal or hepatic impairment; not studied in severe renal/hepatic impairment
Contraindications
- Known hypersensitivity to pimavanserin or its components (e.g., prior angioedema, rash, or urticaria with pimavanserin)
Drug Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole) — increase pimavanserin exposure; reduce dose to 10 mg once daily
- Strong CYP3A4 inducers (e.g., rifampin) — decrease pimavanserin exposure; avoid concomitant use
- Other QT-prolonging drugs — additive risk of QT prolongation; avoid combination when possible
Adverse Effects
- Peripheral edema
- Confusional state
- Nausea
- Constipation
- Gait disturbance
Monitoring Parameters
- Monitor for QT interval prolongation, particularly in patients with existing QT prolongation, arrhythmia history, hypokalemia, hypomagnesemia, or those on other QT-prolonging drugs
- Monitor elderly patients closely given the boxed warning for increased mortality with antipsychotic use in dementia-related psychosis
- Assess for worsening confusion or hallucinations/delusions with continued therapy
Pregnancy & Lactation
- Pregnancy: no adequate human data; animal studies showed no teratogenicity up to 12x MRHD exposure, though maternal toxicity was seen at higher doses
- Lactation: no data on presence in human milk, effects on the breastfed infant, or milk production — weigh benefits of breastfeeding against the mother's clinical need and potential infant exposure