paliperidone INVEGA

Class: Second Generation Antipsychotic/​Benzisothiazole Derivative
FDA Indications: Schizophrenia, Schizoaffective Disorder
Off-Label Use: Bipolar Disorder
Prescribing
Forms: 1.5, 3, 6, 9mg ER Tablets; LAI: INVEGA SUSTENNA, 39 mg, 78 mg, 117 mg, 156 mg, or 234 mg
Dose Range: 3-12 mg/day
Starting: 6 mg qd, can titrate to 9 mg qd on week 2, or up to max dose 12 mg qd on week 3
Stopping: Taper 6-8 weeks, rapid d/c can lead to rebound psychosis
Monitoring:

NAMI drug fact sheet

Precautions
Serious Side Effects: , , , , Hyperprolactinemia, QTc prolongation
Possible Risk of TdP, Drugs to Avoid in Congenital Long QT
Side Effects: headache, sedation/somnolence, dizziness, constipation, weight gain, nausea, insomnia, sexual dysfunction, anxiety, tachycardia, orthostatic hypotension, EPS
Pharmacodynamics
1° MOA: 5HT2A–D2 Antagonist
Target: Antagonism at:
Pharmacokinetics
t½: 23° TMAX: 24°
Substrate of: 1A2, 3A4
Inhibits: ∅ ; Induces:
Active Metabolites:
DDIs
  • - caution when co-prescribed with other medications that may cause orthostatic hypotension
  • - oral bioavailability was increased by 51% when coadministered with valproic acid
  • - Co-administration with carbamazepine can ↓ mean steady-state Cmax and AUC by ~37%
  • - strong 1A2 and 3A4 inhibitors can ↑ levels, likewise 1A2 and 3A4 inducers can ↓ levels
Misc
  • - active metabolite of risperidone, a.k.a. 9-hydroxy-risperidone
  • - not hepatically metabolized; its elimination is based upon urinary excretion, and it thus has few pharmacokinetic DDIs
  • - despite a similar receptor profile, paliperidone is better tolerated (less sedation, orthostasis & fewer EPS) than risperidone because its sustained-release formulation results in a much smoother dose-response curve (risperidone's side effects may may be related to its faster Tmax, higher Cmax & drug-level fluctuations)
  • - trilayer tablet consists of 3 compartments (2 containing drug, 1 a "push" compartment) and an orifice at the head of the first drug compartment; water fills the push compartment and gradually pushes drug up and out of the tablet through the orifice
  • - good evidence for treating violence
Special Populations

Category C—No reports describing the use of paliperidone in human pregnancy have been located. Developmental toxicity, in the absence of maternal toxicity, was not observed in two animal species. Risperidone was carcinogenic in rodents, but the relationship of this effect to humans has not been studied. Although there are no human pregnancy data with paliperidone, there are limited data for risperidone. However, the absence of specific information for paliperidone prevents a better assessment of the embryo-fetal risk. Nevertheless, if the mother's disease requires the use of paliperidone, the benefits to her probably outweigh any fetal risk.

No reports describing the use of paliperidone during breastfeeding have been located.

All atypicals may increase mortality in elderly patients by 1.7 times greater than placebo.

Max recommended dose 3 mg/day in moderate or severe renal impairment (CrCl < 50 mL/ min). Dose reduction (max 6 mg/day) is recommended with mild renal impairment (CrCl ≥50 mL/ min to <80 mL/ min)

No dose adjustment is required in patients with mild or moderate hepatic impairment.

logo

Developed & Designed by Kevin M. Nasky, D.O. • Built with Bootstrap, PHP & MySQL • Hosted by SiteGround
Last updated June 10 2018 15:40:14. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.