Paliperidone Palmitate 1-Monthly LAI (PP1M)

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 Sustenna

Monograph

Monograph Link

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.

Volume of distribution (Vd)

7.0 L/Kg

Protein binding

74% (primarily to ?1-acid glycoprotein and albumin)

Elimination half-life

25 – 49 days

Time to peak (Tmax)

13 days

Metabolism

Mostly excreted unchanged. Limited metabolism via CYP2D6 & CYP3A4.

Renal impairment

• PP1M has not been systematically studied in patients with renal impairment. For patients with mild renal impairment (creatinine clearance > 50 to < 80 mL/min), recommended initiation of PP1M is with a dose of 100 mg on treatment day 1 and 75 mg one week later, both administered in the deltoid muscle. Thereafter, follow with monthly injections of 50 mg in either the deltoid or gluteal muscle, adjusted within the range of 25 to 100 mg based on individual patient tolerability and/or efficacy.

Hepatic impairment

• PP1M 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.

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.