FDA-approved indicationsTreatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
Pharmacological effectsPimavanserin is an antipsychotic, but one that is very different from the first- and second-generation antipsychotics. So, how does it work? Pimavanserin is an inverse agonist and an antagonist at serotonin 2A receptors and, to a lesser extent, at serotonin 2C receptors. Wait – what is an “inverse agonist”? An inverse agonist is more than an antagonist. While an antagonist blocks the effect of the endogenous neurotransmitter at the receptor, an inverse agonist does more than that. It binds to the receptor and causes an effect opposite to that of the agonist. That’s why such drugs are called inverse agonists. Note: Others have argued that while pimavanserin appears to be an inverse agonist in the lab, this is not well-proven and that it may be an antagonist (Nutt et al., 2017). Pimavanserin has negligible binding to D1, D2, and D4 receptors and has low affinity for D3 receptors. Thus, it pretty much lacks dopamine-related effects.
PharmacokineticsPimavanserin is metabolized mainly by CYP3A4/3A5. It has an active metabolite that has a half-life of more than 200 hours. It is also a reversible inhibitor of CYP3A4.
DosageWe can start directly, without titration, at the full dose of 34 mg by mouth once daily. Note: I was initially confused because the clinical trials used 40 mg/day but the Prescribing Information says the dose is 34 mg/day. Then I found out what the reason is. In the clinical trials, the dose was based on pimavanserin tartrate and 20 mg of the tartrate salt is equivalent to 17 mg of pimavanserin. So the 40 mg/day dose used in clinical trials is the same as the 34 mg/day dose recommended in the Prescribing Information.
Potential side effectsPlease see THIS PAGE for a handout listing both the common and less common side effects of this medication along with the percentages of patients who report them.
Potential drug interactionsSince pimavanserin is used for psychosis associated with Parkinson’s disease, the patient is likely to be on the carbidopa/levodopa combination. Will the two medications interact with each other? No. According to the Prescribing Information, no dose adjustment is needed when pimavanserin is given along with carbidopa/levodopa.
Use in special populationsThe safety and efficacy of pimavanserin have not been established in pediatric patients. No dosage adjustment is needed for mild to moderate renal impairment and elderly patients. Not recommended in severe renal impairment or with hepatic impairment as safety and efficacy has not been established in these patient populations.
Dosage forms and strengthsNuplazid® is available as tablets of 34 mg and 10 mg (updated in July 2019)
Cost and availabilityPimavanserin is expensive and is only available through “specialty pharmacies”. To address both these problems, the manufacturer has a program called NUPLAZIDConnect, which is supposed to help patients with getting insurance approval and in obtaining the medication through the specialty pharmacy.
Important! Please refer to the full Prescribing Information (see link below) before prescribing this medication.
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