Seropin

Approved Indications:

• Schizophrenia
• Adults: Treatment of schizophrenia
• Adolescents (13–17 years): Treatment of schizophrenia (IR formulation only)
• Bipolar Disorder
• Bipolar I Disorder (manic episodes): Monotherapy or as adjunct to lithium or valproate
• Bipolar I Depression: Monotherapy for depressive episodes
• Maintenance therapy: Adjunct to mood stabilizers (lithium or valproate)
• Major Depressive Disorder (MDD)
• Adjunctive therapy in adults (extended-release formulation only)

Clinically Accepted Off-label Uses:

• Generalized Anxiety Disorder (GAD) – Low-dose XR formulation in refractory cases
• Insomnia – Off-label use at low doses for sleep initiation and maintenance
• Post-Traumatic Stress Disorder (PTSD) – Adjunctive treatment in select patients
• Delirium – Short-term management in hospital settings
• Borderline Personality Disorder – Symptom management in select cases

General Notes:

• Quetiapine may be taken with or without food.
• XR tablets must be swallowed whole (not split, crushed, or chewed).
• Dose titration is essential to minimize sedation and orthostatic hypotension.

Adults:

• Schizophrenia
• IR: Start at 25 mg twice daily. Titrate to 300–400 mg/day in divided doses. Max: 800 mg/day.
• XR: Start at 300 mg once daily. Titrate to 400–800 mg/day.
• Bipolar Mania (monotherapy or adjunct):
• IR: Start at 50 mg twice daily; increase to 400–800 mg/day by Day 4.
• XR: Day 1 – 300 mg; Day 2 – 600 mg; target 400–800 mg/day.
• Bipolar Depression:
• IR/XR: 50 mg on Day 1 → 100 mg Day 2 → 200 mg Day 3 → 300 mg Day 4. Maintenance: 300 mg at bedtime.
• Adjunctive in MDD:
• XR: Start with 50 mg nightly, titrate to 150–300 mg/day based on response.

Adolescents (13–17 years):

• Schizophrenia: Start at 25 mg twice daily; increase to 400–800 mg/day.
• Bipolar Mania: Start at 50 mg/day; titrate up to 400–600 mg/day.

Elderly:

• Start at 25 mg/day; titrate in increments of 25–50 mg/day due to sensitivity to side effects.

Renal or Hepatic Impairment:

• Initiate at 25 mg/day; increase cautiously. Close monitoring required.

Quetiapine functions as an atypical antipsychotic by modulating neurotransmission across multiple receptor types. It exhibits antagonism at serotonin 5-HT2A and dopamine D2 receptors, contributing to its antipsychotic and mood-stabilizing properties. Its lower affinity for D2 compared to 5-HT2A and rapid dissociation from the D2 receptor may result in reduced extrapyramidal symptoms. Quetiapine also blocks histamine H1 and adrenergic α1 receptors, contributing to sedation and orthostatic hypotension. The active metabolite, norquetiapine, additionally inhibits norepinephrine reuptake and acts as a partial agonist at 5-HT1A receptors, enhancing antidepressant activity.

• Absorption: Rapid oral absorption; peak plasma levels reached in ~1.5 hours (IR) and ~6 hours (XR)
• Bioavailability: ~9% due to extensive first-pass metabolism
• Distribution: Widely distributed; ~83% protein-bound
• Metabolism: Hepatic via CYP3A4 to active metabolite norquetiapine
• Half-life: ~6 hours (quetiapine), ~12 hours (norquetiapine)
• Excretion: ~73% in urine (primarily as metabolites), ~20% in feces

• Pregnancy:
  FDA Pregnancy Category C. Use only if clearly needed. Third-trimester exposure may result in extrapyramidal and/or withdrawal symptoms in neonates (e.g., agitation, respiratory distress, feeding difficulty).
• Lactation:
  Quetiapine is excreted in breast milk in low concentrations. Although adverse effects in infants are not well-documented, caution is advised. Consider discontinuing breastfeeding or quetiapine based on risk–benefit assessment.

• Primary Class: Atypical Antipsychotic
• Subclass: Dibenzothiazepine derivative
• Generation: Second-generation antipsychotic (SGA)

• Hypersensitivity to quetiapine or any of its components
• Use with strong CYP3A4 inhibitors (e.g., ketoconazole) during XR initiation
• Severe hepatic impairment without dose adjustment
• Concomitant QT-prolonging medications in susceptible patients

• Boxed Warning:
  Increased mortality in elderly patients with dementia-related psychosis. Not approved for such use.
  Increased risk of suicidal thoughts/behaviors in adolescents and young adults.
• Other Precautions:
• Risk of neuroleptic malignant syndrome (NMS)
• Tardive dyskinesia with long-term use
• Orthostatic hypotension, particularly in elderly
• Hyperglycemia and diabetes mellitus; monitor blood glucose regularly
• Metabolic changes: weight gain, dyslipidemia
• Cataract formation: long-term therapy may require periodic eye exams
• Seizures: dose-related risk
• Hepatic impairment: requires careful dose adjustment

Very Common/ Common Adverse Effects:

• CNS: Somnolence, dizziness, fatigue, headache
• Metabolic: Weight gain, increased cholesterol and triglycerides, hyperglycemia
• Cardiovascular: Orthostatic hypotension, tachycardia
• GI: Constipation, dry mouth, dyspepsia
• Other: Increased appetite, blurred vision, abnormal dreams

Serious Adverse Effects:

• Extrapyramidal symptoms (especially in pediatrics)
• Tardive dyskinesia
• Neuroleptic malignant syndrome
• Seizures
• Suicidal ideation
• Agranulocytosis and leukopenia (rare)
• Prolonged QT interval
• Cataracts (long-term use)

• CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin): ↑ plasma levels of quetiapine; avoid use
• CYP3A4 Inducers (e.g., phenytoin, carbamazepine): ↓ efficacy of quetiapine; dose increase may be necessary
• CNS Depressants (e.g., alcohol, opioids, benzodiazepines): ↑ sedation and respiratory depression risk
• QT-Prolonging Agents (e.g., methadone, amiodarone): ↑ risk of arrhythmia
• Antihypertensives: Enhanced hypotensive effects
• Dopaminergic agents (e.g., levodopa): Antagonistic effect may reduce efficacy of Parkinson’s treatments

• FDA Updates (2023–2024):
• Reinforced warnings on metabolic monitoring (glucose, lipid panel, weight)
• Caution emphasized regarding suicidality in adolescents and young adults
• Enhanced guidance on tapering doses to minimize withdrawal symptoms
• NICE Guidance (UK):
• Quetiapine XR approved for first-line use in bipolar depression
• Endorsed as adjunctive therapy for MDD resistant to first-line antidepressants
• Beers Criteria:
• Use in elderly flagged as potentially inappropriate unless for psychosis or bipolar disorder

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C
• Protect from light and moisture
• Keep in tightly closed containers
• Do not refrigerate or freeze
• XR tablets should not be crushed, split, or chewed