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Risperidone: Difference between revisions

From Pharmacopedia
[checked revision][checked revision]
parser-claude: Risperidone MedTemplate refill, Top 300 stub upgrade
home-claude: fix CPIC citation hard errors (CPIC scope does not cover these medicines; correct to PharmGKB/DPWG/FDA label where applicable)
 
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| pregnancy        = Signal for neonatal extrapyramidal symptoms and withdrawal with third-trimester exposure.{{citation needed}}
| pregnancy        = Signal for neonatal extrapyramidal symptoms and withdrawal with third-trimester exposure.{{citation needed}}
| legal            = [[USLegal:Prescription only|Rx-only]] in US. Carries the atypical-neuroleptic '''Boxed Warning''' for increased mortality in elderly patients with dementia-related psychosis<ref name="risperdal-label" />
| legal            = [[USLegal:Prescription only|Rx-only]] in US. Carries the atypical-neuroleptic '''Boxed Warning''' for increased mortality in elderly patients with dementia-related psychosis<ref name="risperdal-label" />
| mechanism        = <vote slug="risperidone-mech-claim">'''D2 dopamine receptor antagonist plus 5-HT2A serotonin receptor antagonist''', the classical atypical-neuroleptic signature originally derived from clozapine but with a more dopamine-tilted occupancy profile than olanzapine or quetiapine. The high D2 occupancy at therapeutic doses produces the highest rates of '''hyperprolactinemia''' among second-generation neuroleptics (galactorrhea, amenorrhea, sexual dysfunction, and bone density loss with chronic use), along with dose-dependent extrapyramidal symptoms above ~6 mg/day.</vote> CYP2D6 substrate; CYP2D6 poor metabolizers have higher plasma exposure and may benefit from lower initial dosing. CPIC PGx guidance applies<ref name="cpic-cyp2d6">CPIC Guideline for CYP2D6 Genotype and Neuroleptic Dosing. https://cpicpgx.org/guidelines/</ref>.
| mechanism        = <vote slug="risperidone-mech-claim">'''D2 dopamine receptor antagonist plus 5-HT2A serotonin receptor antagonist''', the classical atypical-neuroleptic signature originally derived from clozapine but with a more dopamine-tilted occupancy profile than olanzapine or quetiapine. The high D2 occupancy at therapeutic doses produces the highest rates of '''hyperprolactinemia''' among second-generation neuroleptics (galactorrhea, amenorrhea, sexual dysfunction, and bone density loss with chronic use), along with dose-dependent extrapyramidal symptoms above ~6 mg/day.</vote> CYP2D6 substrate; CYP2D6 oxidation produces 9-hydroxy-risperidone (paliperidone). CYP2D6 poor metabolizers have higher risperidone exposure, but the active-moiety sum (risperidone plus paliperidone) is relatively preserved across CYP2D6 phenotypes.<ref name="risperdal-label" /> PharmGKB clinical annotations for risperidone-CYP2D6 apply (Level 2A) and the Dutch Pharmacogenetics Working Group (DPWG) has issued CYP2D6 dosing guidance for risperidone.<!-- citation needed: PharmGKB risperidone CYP2D6 annotation Level 2A; DPWG risperidone CYP2D6 dosing guidance. Search: pharmgkb.org risperidone; dpwg risperidone cyp2d6 --> No formal CPIC guideline for neuroleptic CYP2D6 dosing has been published.
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