pimavanserin 10 MG Oral Tablet [Nuplazid]

INDICATIONS AND USAGE Pimavanserin capsule is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis [see Clinical Studies (14) ]. Pimavanserin capsule is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. (1)

DOSAGE AND ADMINISTRATION Recommended dose is 34 mg taken orally once daily, without titration. ( 2.1 ) Can be taken with or without food. ( 2.2 ) Capsules may be swallowed whole or opened and entire contents sprinkled over a tablespoon of certain types of soft food. ( 2.2 ) 2.1 Recommended Dosage The recommended dose of pimavanserin capsule is 34 mg taken orally once daily, without titration. 2.2 Administration Information Pimavanserin capsule can be taken with or without food [see Clinical Pharmacology (12.3)]. Pimavanserin 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 pimavanserin capsules 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 pimavanserin capsules [see Drug Interactions (7.1) ].

WARNINGS AND PRECAUTIONS QT Interval Prolongation: Increases in QT interval; avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. (5.2) 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. Pimavanserin 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 Pimavanserin prolongs the QT interval. The use of pimavanserin 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) ] . Pimavanserin 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) ] .

CONTRAINDICATIONS Pimavanserin is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported [ see Adverse Reactions (6.2) ] . Known hypersensitivity to pimavanserin or any of its components. (4)

Mechanism of Action The mechanism of action of pimavanserin in the treatment of hallucinations and delusions associated with PDP is unclear. However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT 2A receptors and to a lesser extent at serotonin 5-HT 2C receptors.