PIMAVANSERIN Drug Interactions: What You Need to Know

INTERACTIONS Strong CYP3A4 Inhibitors: Reduce pimavanserin dose to 10 mg once daily. ( 2.3 , 7.1 ) Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of pimavanserin. ( 2.3 , 7.1 )

7.1 Drugs Having Clinically Important Interactions with Pimavanserin Table 2 Clinically Important Drug Interactions with Pimavanserin QT Interval Prolongation Clinical Impact: Concomitant use of drugs that prolong the QT interval may add to the QT effects of pimavanserin and increase the risk of cardiac arrhythmia. Intervention: Avoid the use of pimavanserin in combination with other drugs known to prolong QT interval (e.g., Class 1A antiarrythmics, Class 3 antiarrythmics, certain antipsychotics or antibiotics) <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2)]</span> . Strong CYP3A4 Inhibitors Clinical Impact: Concomitant use of pimavanserin with a strong CYP3A4 inhibitor increases pimavanserin exposure <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span> . Intervention: If pimavanserin is used with a strong CYP3A4 inhibitor, reduce the dosage of pimavanserin <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span>. Strong or Moderate CYP3A4 Inducers Clinical Impact: Concomitant use of pimavanserin with strong or moderate CYP3A4 inducers reduces pimavanserin exposure [ see Clinical Pharmacology (12.3) ]. Intervention: Avoid concomitant use of strong or moderate CYP3A4 inducers with pimavanserin <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .

7.2 Drugs Having No Clinically Important Interactions with Pimavanserin Based on pharmacokinetic studies, no dosage adjustment of carbidopa/levodopa is required when administered concomitantly with pimavanserin [ see Clinical Pharmacology (12.3) ] .

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)

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 <span class="opacity-50 text-xs">[see Boxed Warning]</span> .

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) ] .