Dosing and uses of Nuplazid (pimavanserin)
Adult dosage forms and strengths
tablet
- 17mg
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 17 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): Not evaluated
Hepatic impairment
- Not recommended (not evaluated)
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
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)
Nuplazid (pimavanserin) adverse (side) effects
1-10%
Nausea (7%)
Peripheral edema (7%)
Confusional state (6%)
Hallucinations (5%)
Constipation (4%)
Gait disturbance (2%)
Warnings
Black box warnings
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death
Pimavanserin is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson disease psychosis
Contraindications
None
Cautions
Antipsychotic drugs increase the all-cause risk of death in elderly patients with dementia-related psychosis (see Black box warnings)
Pimavanserin is a substrate of CYP3A4; strong CYP3A4 inhibitor or inducers affect systemic exposure (see Dosage modifications and Interactions)
QT prolongation
- Prolongs QT interval
- Avoid use in patients with known QT prolongation or in combination with other drugs known to prolong QT interval, including class 1A antiarrhythmics (eg, quinidine, procainamide) or class 3 antiarrhythmics (eg, amiodarone, sotalol), certain antipsychotic medications (eg, ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (eg, gatifloxacin, moxifloxacin)
- Avoid with history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia, or hypomagnesemia, and the presence of congenital prolongation of the QT interval
Pregnancy
Pregnancy
There are no data for use in pregnant women that would allow assessment of the drug-associated risk of major congenital malformations or miscarriage
In animal reproduction studies, no adverse developmental effects were seen when pimavanserin was administered orally to rats or rabbits during the period of organogenesis at doses up to 10 or 12 times the maximum recommended human dose (MRHD) of 34 mg/day, respectively
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Nuplazid (pimavanserin)
Mechanism of action
Selective serotonin inverse agonist and antagonist activity preferentially targeting 5-HT2A receptors believed to play an important role in psychosis
Absorption
Peak plasma time: 6 hr (range 4-24 hr)
Time to active metabolite formation: 6 hr
Distribution
Protein bound: ~95%
Vd: 2173 L
Metabolism
Predominantly metabolized by CYP3A4 and CYP3A5 and to a lesser extent by CYP2J2, CYP2D6, and various other CYP and FMO enzymes
CYP3A4 is the major enzyme responsible for the formation of its major active metabolite (AC-279)
Elimination
Half-life: 57 hr (pimavanserin); 200 hr (active metabolite)
Excretion (after 10 days): ~0.55 unchanged in urine; 1.53% unchanged in feces; <1% of the administered dose and active metabolite recovered in urine
Administration
Oral Administration
May take with or without food
Storage
Store at controlled room temperature (20-25°C [68-77°F]); excursions permitted between 15-30°C (59-86°F)
