paliperidone INVEGA
Class: Second Generation Antipsychotic/Benzisothiazole DerivativeFDA 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 mgDose 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:
Precautions
Serious Side Effects: , , , , Hyperprolactinemia, QTc prolongationPossible Risk of TdP
Side Effects: weight gain, sedation/somnolence, EPS, dizziness, insomnia, headache, anxiety, constipation, nausea, tachycardia, sexual dysfunction, orthostatic hypotension
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.
2019 BEE℞S Recommendation: Avoid, except in schizophrenia or bipolar disorder. Increased risk of CVA and greater rate of cognitive decline and mortality in persons with dementia. Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacological options have failed or are not possible and the older adult is threatening substantial harm to self or others.
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.