1. Nuplazid™ - Pimavanserin
Manufacturer:
Acadia Pharmaceuticals
FDA Approval Date: April 2016

2. Nuplazid™ - pimavanserin Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Nuplazid™ - (pimavanserin)
Effectively educate patients on the purpose, proper use and potential adverse effects of Nuplazid™ - (pimavanserin)

3. Nuplazid™ - pimavanserin Clinical Application
Indications:
Parkinson’s disease psychosis
Place in therapy:
Alternative to quetiapine
Nuplazid™[package insert].

4. Nuplazid™ - pimavanserin Clinical Application
Black Box Warning:
Increased mortality in elderly patients with dementia-related psychosis
Precautions:
QT interval prolongation
Orthostatic hypotension
Hazardous tasks (CNS depression)
Nuplazid™[package insert].

5. Nuplazid™ - pimavanserin Clinical Application
Pregnancy:
No human data available
No teratogenic effect in animal studies
Lactation:
No data available
Nuplazid™[package insert].

6. Nuplazid™ - pimavanserin Drug Facts
Pharmacology: Atypical antipsychotic
Antagonist/inverse agonist with high affinity for 5-HT­2A receptor & low affinity for 5-HT2C & sigma 1 receptors
No affinity for 5-HT2B, dopaminergic, muscarinic, histaminergic, or adrenergic receptors, or to calcium channels
Nuplazid™[package insert].

7. Nuplazid™ - pimavanserin Drug Facts
Pharmacokinetics: A
Not significantly affected by high-fat meals D
Volume of distribution = 2,173 L M
Primarily via CYP3A4 & CYP3A5, forming active N-desmethylated metabolite AC-279 E
Half-life pimavanserin: 57 hrs;
Active metabolite (AC-279): 200 hrs.
Minimal excretion as unchanged drug < 2%
Nuplazid™[package insert].

8. Nuplazid™ - pimavanserin Drug Interactions
Drug Interactions – Object Drugs: None
Drug Interactions – Precipitant Drugs:
Strong CYP3A4 inhibitors: Cmax150%, AUC300%
Strong CYP3A4 inducers: change in drug levels not tested
Nuplazid™[package insert].

9. Nuplazid™ - pimavanserin Adverse Effects
Common Adverse Effects: (pimavanserin%)[placebo%]
Peripheral edema (7%) [2%]
Confusional state (6%) [3%]
Nausea (7%) [4%]
Hallucination (5%) [3%]
Constipation (4%) [3%]
Gait disturbance (2%) [<1%]
Nuplazid™[package insert].

10. Nuplazid™ - pimavanserin Monitoring Parameters
Efficacy Monitoring:
Symptom improvement
Toxicity Monitoring:
Mental status changes
ECG for QT prolongation
Nuplazid™[package insert].

11. Nuplazid™ - pimavanserin Prescription Information
Dosing: 34 mg daily (two 17 mg capsules)
If taking strong CYP3A4 inhibitors, 17 mg once daily is recommended
Cost: – $2340/30 day supply ($1170 if taking only 17 mg daily)
Source—UpToDate 08/07/2016
Nuplazid™[package insert].

12. Nuplazid™ - pimavanserin Literature Review
Title:
Pimavanserin for patients with Parkinson’s disease psychosis: a randomized, placebo-controlled phase 3 trial
Objective:
Is pimavanserin effective for treatment of hallucinations & delusions in Parkinson’s disease?
Cummings J, et al. Lancet. 2014;383(9916):

13. Nuplazid™ - pimavanserin Literature Review
Treatment Group Included:
Parkinson’s disease psychosis w/ sx > 1 month, MMSE score ~26, mean age 72, ~35% female, ~95% white, 99% on dopaminergics, ~35% on cholinesterase inhibitors
Excluded:
Dementia diagnosis with or prior to Parkinson’s, stroke, MI w/in 6 months, CHF, QT prolongation, psychosis secondary to toxic or metabolic disorders
Cummings J, et al. Lancet. 2014;383(9916):

14. Nuplazid™ - pimavanserin Literature Review
Intervention: Pimavanserin PO 40mg vs. placebo once daily
Double blind randomization
n = 199
Improvement measured using SAPS-PD score
Treatment period = 43 days
Cummings J, et al. Lancet. 2014;383(9916):

15. Nuplazid™ - pimavanserin Literature Review
Results:
Endpoint
Mean Baseline Score
∆ from Baseline in Placebo
∆ from Baseline in pimavanserin
Difference
(95% CI;
p value)
SAPS-PD
15.9
-2.73
-5.79
-3.06
(-4.91 to 1.20;
p = )
SAPS-PD Hallucinations
11.1
-1.80
-3.81
-2.08
(-3.46 to -0.71;
p = )
SAPS-PD Delusions
4.8
-1.01
-1.95
-1.16
(-2.22 to -0.10;
p = )
Cummings J, et al. Lancet. 2014;383(9916):

16. Nuplazid™ - pimavanserin Literature Review
Conclusions:
Pimavanserin appears effective in treating Parkinson’s disease psychosis
Minimal adverse reactions
Further studies needed regarding long- term treatment, head-to-head comparisons, and using different symptom scales
Cummings J, et al. Lancet. 2014;383(9916):

17. Nuplazid™ - pimavanserin Summary
Nuplazid™, pimavanserin, is an atypical antipsychotic indicated for: hallucinations & delusions associated with Parkinson’s disease psychosis
Avoid in dementia-related psychosis:
Elderly patients with dementia-related psychosis are at an increased risk of death when treated with antipsychotic drugs
Serious adverse reaction: QTc prolongation
Common adverse reactions: peripheral edema, nausea, and confusion

18. Nuplazid™ - pimavanserin References
content/uploads/2016/04/NUPLAZID- pimavanserin-Package-Insert.pdf
Nuplazid™[package insert]. San Diego, CA: ACADIA Pharmaceuticals Inc.; 2016.
Cummings J, et al. Lancet. 2014;383(9916) :