Quetiapine XR

Class

Second Generation Antipsychotic

Neuroscience-based Nomenclature (NbN)

Pharmacological Target

Dopamine, serotonin

Mode of Action

Multimodal; Receptor Antagonist (D2, 5-HT2); Reuptake Inhibitor (NET) (metabolite)

Brand Name

Seroquel

Monograph

Monograph Link

Adverse effects (AEs)

Weight gain very common Sedation very common Sexual dysfunction common

Other Common Adverse Effects:

  Dizziness
  Dry mouth

Serious/Life-Threatening AEs

  Rare cases of serious hyperglycemia, including diabetic ketoacidosis and death
  Increased mortality rate vs. placebo when used in elderly patients with dementia
  Rare cases of neuroleptic malignant syndrome
  Rare venous thromboembolism

Bioavailability

  73%
  With high fat meal: Cmax increases 44-52%; UAC increases 20-22%

Volume of distribution (Vd)

10 L/Kg

Protein binding

83%

Elimination half-life

  6 – 7 hours
  N-desalkylquetiapine (active metabolite): 12 hours

Time to peak (Tmax)

6 hours

Metabolism

  Quetiapine: primarily via CYP3A4
  N-desalkylquetiapine (active metabolite): primarily formed and metabolized by CYP3A4

Excretion

  Urine: 73% (< 5% unchanged)
  Feces: 21%

Special Populations

  Renal impairment: no dosage adjustment required
  Hepatic impairment: use with caution in patients with moderate or severe hepatic impairment; lower doses may be required
  Cardiac impairment: use with caution
  Elderly: use with caution, and do not use in elderly patients with dementia
  Children and adolescents: as with other antidepressants or augmentation strategies for MDD, careful evaluation of risks vs. benefits and close monitoring for changes in behaviour and/or suicidality are recommended

Other Potential Benefits

  Antipsychotic
  Antidepressant
  Anxiolytic
  Sedative/hypnotic

Potential for Other Drugs to Affect Quetiapine

  Concomitant use of quetiapine with hepatic enzyme inducers such as carbamazepine may substantially decrease systemic exposure to quetiapine.
  Co-administration of quetiapine and another microsomal enzyme inducer, phenytoin, caused five-fold increases in the clearance of quetiapine. Increased doses of quetiapine may be required to maintain control of psychotic symptoms in patients co-administered quetiapine and phenytoin and other hepatic enzyme inducers (e.g., barbiturates, rifampicin, etc.).
  The dose of quetiapine may need to be reduced if phenytoin or carbamazepine or other hepatic enzyme inducers are withdrawn and replaced with a non-inducer (e.g., sodium valproate).
  CYP3A4 is the primary enzyme responsible for cytochrome P450-mediated metabolism of quetiapine. Thus, co-administration of compounds (such as ketoconazole, erythromycin, clarithromycin, diltiazem, verapamil, or nefazodone), which inhibit CYP 3A4, may increase the concentration of quetiapine.

Potential for Quetiapine to Affect Other Drugs

  Because of its potential for inducing hypotension, quetiapine may enhance the effects of certain antihypertensive agents.