5 WARNINGS AND PRECAUTIONS

5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Antipsychotic drugs increase the all-cause risk of death in elderly patients with dementia-related psychosis. Analyses of 17 dementia-related psychosis placebo-controlled trials (modal duration of 10 weeks and largely in patients taking atypical antipsychotic drugs) revealed a risk of death in the drug- treated patients of between 1.6- to 1.7-times that in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in placebo-treated patients.

Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. NUPLAZID is not approved for the treatment of patients with dementia who experience psychosis unless their hallucinations and delusions are related to Parkinson's disease [see Boxed Warning].

5.2 QT Interval Prolongation

NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (e.g., gatifloxacin, moxifloxacin) [see Drug Interactions (7.1)]. NUPLAZID should also be avoided in patients with a 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 [see Clinical Pharmacology (12.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dose of NUPLAZID is 34 mg taken orally once daily, without titration.

2.2 Administration Information

NUPLAZID can be taken with or without food [see Clinical Pharmacology (12.3)].

NUPLAZID capsules can be taken whole, or opened and the entire contents sprinkled over a tablespoon (15 mL) of applesauce, yogurt, pudding, or a liquid nutritional supplement. Consume the drug/food mixture immediately without chewing; do not store for future use.

2.3 Dosage Modifications for Concomitant Use with CYP3A4 Inhibitors and

Inducers

• Coadministration with Strong CYP3A4 Inhibitors
  The recommended dose of NUPLAZID when coadministered with strong CYP3A4 inhibitors is 10 mg, taken orally as one tablet once daily [see Drug Interactions (7.1)].

• Coadministration with Strong or Moderate CYP3A4 Inducers
  Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID [see Drug Interactions (7.1)].

10 OVERDOSAGE

10.1 Human Experience

The pre-marketing clinical trials involving NUPLAZID in approximately 1200 subjects and patients do not provide information regarding symptoms with overdose. In healthy subject studies, dose-limiting nausea and vomiting were observed.

10.2 Management of Overdose

There are no known specific antidotes for NUPLAZID. In managing overdose, cardiovascular monitoring should commence immediately and should include continuous ECG monitoring to detect possible arrhythmias [see Warnings and Precautions (5.2)]. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine should not be used, as they have the potential for QT-prolonging effects that might be additive to those of NUPLAZID [see Drug Interactions (7.1)]. Consider the long plasma half-life of pimavanserin (about 57 hours) and the possibility of multiple drug involvement. Consult a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice.

16 HOW SUPPLIED/STORAGE AND HANDLING

NUPLAZID (pimavanserin) is available as:

34 mg Capsule:

Opaque white and light green capsule with "PIMA" and "34" printed in black.

Bottle of 30: NDC 63090-340-30

10 mg Tablet:

Orange, round, coated tablet debossed with "P" on one side and "10" on the reverse.

Bottle of 30: NDC 63090-100-30

Storage

34 mg Capsule:

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. To prevent potential capsule color fading, protect from light.

10 mg Tablet:

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Concomitant Medication

Advise patients to inform their healthcare providers if there are any changes to their current prescription or over-the-counter medications, since there is a potential for drug interactions [see Warnings and Precautions (5.2), Drug Interactions (7)].

Administration Instructions

Advise patients to take the capsule whole or sprinkled over a tablespoon (15 mL) of applesauce, yogurt, pudding, or a liquid nutritional supplement. Advise patients to consume the drug/food mixture immediately and not to store for future use [see Dosage and Administration (2.2)].