DRUG INFORMATION
Class
Second Generation Antipsychotic
Neuroscience-based Nomenclature (NbN)
Pharmacological Target
Dopamine, serotonin, norepinephrine
Mode of Action
Receptor Antagonist (D2, 5-HT2, NE alpha-2)
Brand Name
Invega Trinza
Monograph
DOSING AND ADMINISTRATION
Therapeutic Dose Range
Schizophrenia: 175-535 every three months. May be given up to 7 days before or after the monthly time point to avoid a missed dose. Is only to be used after paliperidone palmitate once-monthly has been established as adequate treatment for at least four months.
Time of Day
Not applicable
Effect of food
Not applicable
Effect of smoking
Smoking has no effect on paliperidone palmitate injectable
ADVERSE EFFECTS
Adverse Reactions
EPS
Galactorrhea
Sedation
Dizziness
Weight gain
Risk of tardive dyskinesia
NMS
Warnings
Class Warning: Increased Mortality in Elderly Patients with Dementia Elderly patients with dementia treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of thirteen placebo-controlled trials with various atypical antipsychotics (modal duration of 10 weeks) in these patients showed a mean 1.6-fold increase in the death rate in the drug-treated patients. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.
Class Warning: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.
PHARMACOKINETICS
Volume of distribution (Vd)
7.0 L/Kg
Protein binding
74% (primarily to alpha 1-acid glycoprotein and albumin)
Elimination half-life
The median apparent half-life of PP3M following administration over the dose range of 175-525 mg ranged from 52-86 days following deltoid injections and 69-120 days following gluteal injections.
Time to peak (Tmax)
24-34 days
Metabolism
Mostly excreted unchanged. Limited metabolism via CYP2D6 & CYP3A4.
MORE INFORMATION
Renal impairment
For patients with mild renal impairment (creatinine clearance > 50 to < 80 mL/min), adjust dosage and stabilize the patients using PP1M, then transition to PP3M in a 3.5 to 1 ratio. The maximum recommended dose of PP3M in patients with mild renal impairment is 350 mg. PP3M is not recommended in patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min).
Hepatic impairment
PP3M has not been studied in patients with hepatic impairment. Based on a study with oral paliperidone, no dose adjustment is required in patients with mild or moderate hepatic impairment. Paliperidone has not been studied in patients with severe hepatic impairment.
DRUG-DRUG INTERACTIONS
Potential for Other Drugs to Affect Paliperidone
Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, CYP2C19, and CYP3A5. This suggests that an interaction with inhibitors or inducers of these isozymes is unlikely.
Potential for Paliperidone to Affect Other Drugs
Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P-450 isozymes. In vitro studies in human liver microsomes showed that paliperidone does not substantially inhibit the metabolism of drugs metabolized by cytochrome P450 isozymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5. Therefore, paliperidone is not expected to inhibit clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner. Paliperidone is also not expected to have enzyme-inducing properties
Because of its potential for inducing orthostatic hypotension, an additive effect may be observed when paliperidone is administered with other therapeutic agents that have this potential.