Pimavanserin Tartrate

Name: Pimavanserin Tartrate

Introduction

Atypical antipsychotic agent.1 2 5

Uses for Pimavanserin Tartrate

Parkinson's Disease Psychosis

Management of hallucinations and delusions associated with Parkinson's disease psychosis.1 2 10

Not approved for treatment of dementia-related psychosis not related to the hallucinations and delusions associated with Parkinson’s disease psychosis.1 (See Boxed Warning.)

Interactions for Pimavanserin Tartrate

Metabolized principally by CYP3A4 and 3A5.1 Does not cause clinically important inhibition or induction of CYP3A4.1 9 The active metabolite does not induce CYP3A to a clinically important extent and is not expected to induce other CYP enzymes.1 9 Neither pimavanserin nor its active metabolite appears to inhibit any of the major CYP isoenzymes involved in drug metabolism (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4).1

Not a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), or organic anion transport proteins (OATP) 1B1 and 1B3.9

Drugs Affecting Hepatic Microsomal Enzymes

Potent inhibitors of CYP3A4: Possible increased exposure of pimavanserin.1 Reduce pimavanserin dosage to 17 mg once daily.1

Potent inducers of CYP3A4: Possible decreased exposure of pimavanserin.1 Monitor patients for reduced efficacy; dosage increase of pimavanserin may be required.1

Drugs that Prolong QT Interval

Potential additive effects on QT interval prolongation, which may increase risk of cardiac arrhythmias.1 (See QT Interval Prolongation under Cautions.) Avoid concomitant use.1

Specific Drugs

Drug

Interaction

Comments

Antiarrhythmic agents, class Ia and III (e.g., amiodarone, disopyramide, procainamide, quinidine, sotalol)

Potential additive effect on QT interval prolongation1

Avoid concomitant use1

Anticonvulsants (carbamazepine, phenytoin)

Possible decreased exposure of pimavanserin1

Monitor patients for reduced efficacy of pimavanserin; may require dosage increase1

Anti-infective agents that prolong QT interval (e.g., gatifloxacin, moxifloxacin)

Potential additive effect on QT interval prolongation1

Avoid concomitant use1

Antipsychotic agents that prolong QT interval (e.g., chlorpromazine, thioridazine, ziprasidone)

Potential additive effect on QT interval prolongation1

Avoid concomitant use1

Carbidopa/levodopa

No dosage adjustment of carbidopa/levodopa necessary1

Clarithromycin

Possible increased exposure of pimavanserin1

Reduce dosage of pimavanserin to 17 mg once daily1

Indinavir

Possible increased exposure of pimavanserin1

Reduce dosage of pimavanserin to 17 mg once daily1

Itraconazole

Possible increased exposure of pimavanserin1

Reduce dosage of pimavanserin to 17 mg once daily1

Ketoconazole

Increased peak plasma concentration and AUC of pimavanserin by 1.5- and 3-fold, respectively1

Reduce dosage of pimavanserin to 17 mg once daily1

Rifampin

Possible decreased exposure of pimavanserin1

Monitor patients for reduced efficacy of pimavanserin; may require dosage increase1

St. John's wort (Hypericum perforatum)

Possible decreased exposure of pimavanserin1

Monitor patients for reduced efficacy of pimavanserin; may require dosage increase1

Pimavanserin Tartrate Pharmacokinetics

Absorption

Bioavailability

> 99.7% following oral administration.9

Exhibits dose-proportional pharmacokinetics following single oral doses (range 17–255 mg).1

Food

Food exhibits no substantial effect; peak plasma concentration decreased by approximately 9%, while AUC increased by 8% when administered with a high-fat meal.1

Distribution

Extent

Not known if distributed into human milk.1

Plasma Protein Binding

Approximately 95%.1 9

Elimination

Metabolism

Metabolized principally by CYP3A4/5, and to a lesser extent by CYP2D6, CYP2J2, and various other CYP and flavin-containing monooxygenase isoenzymes.1

Elimination Route

Approximately 0.6% of radiolabeled dose excreted in urine as unchanged drug, and 1.5% eliminated in feces after 10 days.1

<1% of administered dose of pimavanserin and its active metabolite recovered in urine.1

Half-life

Approximately 57 hours; 200 hours for active metabolite.1

Advice to Patients

  • Importance of advising patients and caregivers that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.1 3 4 Inform patients and caregivers that pimavanserin is not approved for the management of patients with dementia-related psychosis not related to the hallucinations and delusions associated with Parkinson’s disease psychosis.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Share
(web3)