Risperidone Every Two Weekly LAI

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

Risperdal

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)

1-2 L/Kg

Protein binding

  Risperidone: 88-90%
  9-hydroxyrisperidone (active metabolite): 77%

Elimination half-life (Oral)

3-6 days

Time to peak (Tmax)

30 days

Metabolism

  Risperidone: primarily CYP2D6. CYP3A4 (limited)
  9-hydroxyrisperidone (active metabolite): limited via CYP2D6 and CYP3A4

Special populations

  Renal impairment: patients with renal impairment have less ability to eliminate the active antipsychotic fraction than normal adults. If renally impaired patients require treatment with risperidone LAI, a starting dose of 0.5 mg b.i.d. oral risperidone is recommended during the first week. In the second week, 1 mg b.i.d. or 2 mg q.d. can be given. If an oral dose of at least 2 mg is well tolerated, an injection of 25 mg risperidone LAI can be administered every 2 weeks. Alternatively, a starting dose of 12.5 mg risperidone LAI may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.
  Hepatic impairment: patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone and this may result in an enhanced effect. If hepatically impaired patients require treatment with risperidone LAI, a starting dose of 0.5 mg b.i.d. oral risperidone is recommended during the first week. In the second week, 1 mg b.i.d. or 2 mg q.d. can be given. If an oral dose of at least 2 mg is well tolerated, an injection of 25 mg risperidone LAI can be administered every 2 weeks. Alternatively, a starting dose of 12.5 mg risperidone LAI may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Renal impairment

  Risperidone LAI has not been studied in renally impaired patients.
  Risperidone LAI should be used with caution in patients with renal impairment.
  Patients with renal impairment have less ability to eliminate the active antipsychotic fraction than normal adults. If renally impaired patients require treatment with risperidone LAI, a starting dose of 0.5 mg b.i.d. oral risperidone is recommended during the first week. In the second week, 1 mg b.i.d. or 2 mg q.d. can be given. If an oral dose of at least 2 mg is well tolerated, an injection of 25 mg risperidone LAI can be administered every 2 weeks. Alternatively, a starting dose of 12.5 mg risperidone LAI may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Hepatic impairment

  Risperidone LAI has not been studied in hepatically impaired patients.
  Risperidone LAI should be used with caution in patients with hepatic impairment.
  Patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone and this may result in an enhanced effect. If hepatically impaired patients require treatment with risperidone LAI, a starting dose of 0.5 mg b.i.d. oral risperidone is recommended during the first week. In the second week, 1 mg b.i.d. or 2 mg q.d. can be given. If an oral dose of at least 2 mg is well tolerated, an injection of 25 mg risperidone LAI can be administered every 2 weeks. Alternatively, a starting dose of 12.5 mg risperidone LAI may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Potential for Other Drugs to Affect Risperidone

  Risperidone is mainly metabolized through CYP2D6, and to a lesser extent through CYP3A4. Both risperidone and its active metabolite 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp). Substances that modify CYP2D6 activity, or substances strongly inhibiting or inducing CYP3A4 and/or P-gp activity, may influence the pharmacokinetics of the risperidone active antipsychotic fraction.
  Strong CYP2D6 Inhibitors: Co-administration of risperidone with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active antipsychotic fraction (risperidone and 9-hydroxyrisperidone combined). Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active antipsychotic fraction (e.g., paroxetine). When concomitant paroxetine or another strong CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
  CYP3A4 and/or P-gp Inhibitors: Co-administration of risperidone with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active antipsychotic fraction. When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
  CYP3A4 and/or P-gp Inducers: Co-administration of risperidone with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active antipsychotic fraction. When concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.

Potential for risperidone to affect other drugs

  Risperidone is a CYP2D6 and CYP3A4 substrate. Studies found that risperidone did not affect the pharmacokinetics of the following: aripiprazole, lithium, valproate, and digoxin.