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
Monograph
DOSING AND ADMINISTRATION
Therapeutic Dose Range
Schizophrenia: 3-12 mg/day. The recommended starting and target dose is 6 mg/day
Time of Day
Once a day, preferably in the morning
Effect of food
May be taken with or without food. Tablets should not be crushed or cut; they should be swallowed while.
Effect of smoking
Smoking has no effect on paliperidone metabolism
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
Bioavailability
28%
With high fate meal: Cmax increase 60% and AUC increases 54%
Volume of distribution (Vd)
7.0 L/Kg
Protein binding
74% (primarily to ?1-acid glycoprotein and albumin)
Elimination half-life
23 hours
Time to peak (Tmax)
Oral: 24 hours
Metabolism
Mostly excreted unchanged. Limited metabolism via CYP2D6 & CYP3A4.
Excretion
Urine:80% (approx. 59% unchanged)
Feces:11%
MORE INFORMATION
Renal impairment
For patients with mild renal impairment (creatinine clearance = 50 to < 80 mL/min), the maximum recommended initial dose of paliperidone is 3 mg once daily. The dose may be increased to a maxiumum of 6 mg once daily based on clinical response and tolerability.
For patients with moderate to severe renal impairment (creatinine clearance = 10 to < 50 mL/min), the recommended initial dose of paliperidone is 1.5 mg once daily which may then be increased to 3 mg once daily after clinical reassessment.
As paliperidone has not been studied in patients with creatinine clearance < 10 mL/min, use is not recommended in such patients.
Hepatic impairment
No dose adjustment is required in patients with mild to 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.