Download Nuplazid ™ - Pimavanserin Manufacturer

Nuplazid™ - Pimavanserin
Manufacturer:
Acadia Pharmaceuticals
FDA Approval Date: April 2016
Nuplazid™ - pimavanserin
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Nuplazid™ -
(pimavanserin)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Nuplazid™ (pimavanserin)
Nuplazid™ - pimavanserin
Clinical Application
• Indications:
• Parkinson’s disease psychosis
• Place in therapy:
• Alternative to quetiapine
Nuplazid™[package insert].
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].
Nuplazid™ - pimavanserin
Clinical Application
• Pregnancy:
• No human data available
• No teratogenic effect in animal studies
• Lactation:
• No data available
Nuplazid™[package insert].
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].
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].
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].
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].
Nuplazid™ - pimavanserin
Monitoring Parameters
• Efficacy Monitoring:
• Symptom improvement
• Toxicity Monitoring:
• Mental status changes
• ECG for QT prolongation
Nuplazid™[package insert].
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].
Nuplazid™ - pimavanserin
Literature Review
• Title:
Pimavanserin for patients with Parkinson’s
disease psychosis: a randomized, placebocontrolled phase 3 trial
• Objective:
• Is pimavanserin effective for treatment of
hallucinations & delusions in Parkinson’s
disease?
Cummings J, et al. Lancet. 2014;383(9916):533-40.
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):533-40.
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):533-40.
Nuplazid™ - pimavanserin
Literature Review
• Results:
Endpoint
SAPS-PD
SAPS-PD
Hallucinations
SAPS-PD
Delusions
Mean
Baseline
Score
15.9
11.1
4.8
∆ from
∆ from
Baseline in Baseline in
Placebo
pimavanserin
-2.73
-1.80
-1.01
Difference
(95% CI;
p value)
-5.79
-3.06
(-4.91 to 1.20;
p = 0.0014)
-3.81
-2.08
(-3.46 to -0.71;
p = 0.0032)
-1.95
-1.16
(-2.22 to -0.10;
p = 0.0325)
Cummings J, et al. Lancet. 2014;383(9916):533-40.
Nuplazid™ - pimavanserin
Literature Review
• Conclusions:
• Pimavanserin appears effective in
treating Parkinson’s disease psychosis
• Minimal adverse reactions
• Further studies needed regarding longterm treatment, head-to-head
comparisons, and using different
symptom scales
Cummings J, et al. Lancet. 2014;383(9916):533-40.
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
Nuplazid™ - pimavanserin
References
1. http://www.acadia-pharm.com/wpcontent/uploads/2016/04/NUPLAZIDpimavanserin-Package-Insert.pdf
2. Nuplazid™[package insert]. San Diego,
CA: ACADIA Pharmaceuticals Inc.; 2016.
3. Cummings J, et al. Lancet. 2014;383(9916)
:533-40.