Hospice Medication Alert: Nuplazid (pimavanserin)
Nuplazid (pimavanserin) has recently received FDA approval for the treatment of hallucination and delusion associated with Parkinson’s disease. It is an antipsychotic medication targeting only on the serotonin pathway. The FDA approval was based on a 6-week, randomized, placebo-controlled study1. In this study, 199 patients were randomized in a 1:1 ratio to Nuplazid 34mg or placebo once daily. The treatment group resulted in a 37% improvement compared to a 14% improvement for those taking placebo. There are currently no head to head studies comparing Nuplazid with existing antipsychotic medications.
Typical Parkinson’s disease therapy consists of drugs that stimulate dopamine to treat the patient’s motor symptoms such as tremor and muscle rigidity. Existing antipsychotics target both the dopamine and serotonin pathways in the brain and so they can interact with the pathways that help regulate the movement disorders in Parkinson’s patients. Nuplazid, as a selective serotonin inverse agonists (SSIA), preferentially binds to 5-HT2A receptors and has no activity at dopamine receptors so it is not likely to aggravate Parkinson’s disease.
Nuplazid is supplied as tablets for oral administration and is now available in the United States. The recommended dose is 34 mg per day, taken orally as two 17-mg tablets once daily, without titration. There is no dosage adjustment needed for patients with mild to moderate renal impairment. However, the use is not recommended for patients with severe renal and hepatic impairments as it has not been evaluated in these patient populations. The dose should be reduced to 17 mg per day when taken with a potent CYP3A4 inhibitor such as statins or ketoconazolethe.
The most common adverse effects noted in the clinical trial were peripheral edema and confusion. Similar to existing antipsychotic medications, Nuplazid comes with the black box warning regarding the increased mortality in elderly patients with dementia-related psychosis. It also prolongs the QT interval so the risk of the occurrence of torsade de pointes is increased in patients with known QT prolongation or in combination with other drugs known to prolong QT interval. Therefore, Nuplazid should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval and should also be avoided in patients with a history of cardiac arrhythmias and the presence of congenital prolongation of the QT interval.
Place in Hospice Therapy
Although Nuplazid has a novel molecular approach to treat Parkinson’s psychosis, its use may be limited in the hospice setting. It has a very long half-life of 57 hours and takes 12 days to reach steady state. According to the phase 3 trial, the significant difference in the efficacy between Nuplazid and placebo was not seen until week 4. In addition, Nuplazid can be cost-prohibitive ($2340 per month) compared to existing antipsychotics, which are available as generics. Atypical antipsychotic such as Seroquel, has less anti-dopaminergic properties and demonstrated efficacy on Parkinson’s psychosis in clinical studies, so it is more cost effective than Nuplazid in the management of Parkinson’s psychosis.
1. Nuplazid® [package insert]. San Diego, CA: Arcadia Pharmaceuticals, Inc; 2016.