Olixar

Approved Indications:

• Schizophrenia (Adults and Adolescents ≥13 years):
  For the treatment of acute and chronic manifestations, including positive and negative symptoms.
• Bipolar I Disorder (Adults and Adolescents ≥13 years):
• Acute manic or mixed episodes, either as monotherapy or in combination with lithium or valproate.
• Maintenance treatment to delay recurrence of mood episodes.
• Bipolar Depression (Adults):
  In combination with fluoxetine (as fixed-dose combination or separate agents).
• Agitation associated with schizophrenia and bipolar mania (Adults):
  Short-acting intramuscular formulation indicated for the rapid control of agitation.

Important Off-label / Clinically Accepted Uses:

• Treatment-resistant depression: In combination with fluoxetine.
• Psychotic depression: As an adjunctive agent.
• Borderline personality disorder: For mood instability and impulsivity (specialist use).
• Behavioral disturbances in dementia: Not routinely recommended due to increased risk of stroke and mortality.
• Post-traumatic stress disorder (PTSD): Adjunctive use in severe cases.
• Delusional parasitosis: Rare but documented use in psychodermatologic conditions.

Route of Administration: Oral (tablets, orally disintegrating tablets) and intramuscular (IM) injection.

Adults:

• Schizophrenia:
  Initial: 5–10 mg once daily.
  Usual target: 10–20 mg/day.
  Max: 20 mg/day.
• Bipolar Mania or Mixed Episodes:
  Initial: 10–15 mg once daily.
  Maintenance: 5–20 mg/day.
  Max: 20 mg/day.
• Bipolar Depression (with fluoxetine):
  Olanzapine 5–12.5 mg + Fluoxetine 20–25 mg once daily.
• IM for Agitation:
  10 mg intramuscularly as a single dose.
  May repeat once after ≥2 hours.
  Maximum: 30 mg in 24 hours.

Adolescents (13–17 years):

• Start with 2.5–5 mg/day.
  Titrate based on response.
  Max: 20 mg/day.
  Use with caution due to greater metabolic sensitivity.

Elderly:

• Start with lower doses (2.5–5 mg/day).
  Monitor for sedation, orthostasis, and metabolic changes.

Renal Impairment:

• No dose adjustment typically required.
  Monitor clinical status.

Hepatic Impairment:

• Start at lower doses.
  Titrate cautiously.
  Monitor liver function.

Discontinuation:

• Taper gradually over weeks to minimize withdrawal symptoms and relapse.

Olanzapine is a second-generation (atypical) antipsychotic that acts by antagonizing dopamine D₂ and serotonin 5-HT₂A receptors in the brain. It also affects other receptors, including 5-HT₂C, 5-HT₃, 5-HT₆, histamine H₁, muscarinic M₁–₅, and α₁-adrenergic receptors. Antagonism of D₂ receptors helps reduce psychotic symptoms, while 5-HT₂A antagonism improves mood and reduces extrapyramidal symptoms. Its antihistaminic and antimuscarinic actions contribute to sedation and anticholinergic effects, respectively. This broad receptor activity accounts for its antipsychotic, antimanic, and mood-stabilizing properties.

• Absorption: Rapid and nearly complete; not significantly affected by food.
• Bioavailability: Approximately 60% (due to first-pass hepatic metabolism).
• Time to Peak Plasma Concentration (Tmax):
• Oral: ~5 to 8 hours
• IM: ~15 to 45 minutes
• Distribution: Extensive (Volume of distribution ~1000 L); ~93% protein-bound.
• Metabolism: Hepatic metabolism primarily via CYP1A2, with minor contribution from CYP2D6.
• Active Metabolites: No pharmacologically active metabolites.
• Half-life:
• Adults: ~30 to 38 hours
• Elderly: ~51 hours
• Elimination:
• ~57% via urine (as inactive metabolites)
• ~30% via feces

• Pregnancy:
• Classified as Category C (under the former FDA system).
• Risk of neonatal extrapyramidal or withdrawal symptoms if used in the third trimester.
• Use only if benefits outweigh potential risks.
• Lactation:
• Olanzapine is excreted into breast milk.
• Potential infant effects: sedation, poor feeding, irritability, or extrapyramidal symptoms.
• Breastfeeding is not recommended, or infant should be closely monitored if continued.

• Primary Class: Atypical Antipsychotic (Second-generation).
• Chemical Subclass: Thienobenzodiazepine derivative.

• Known hypersensitivity to olanzapine or any formulation excipients.
• Acute intoxication with alcohol, benzodiazepines, or other CNS depressants.
• Known risk for narrow-angle glaucoma (due to anticholinergic activity).
• Comatose or severely sedated states.

• Black Box Warning:
• Elderly patients with dementia-related psychosis: Increased risk of death due to cardiovascular or infectious causes.
• Metabolic Risks:
• Weight gain, dyslipidemia, and new-onset or worsened hyperglycemia/diabetes mellitus.
• Regular monitoring of weight, fasting glucose, and lipid profile is mandatory.
• Neuroleptic Malignant Syndrome (NMS):
• Rare but potentially fatal. Requires immediate discontinuation and supportive care.
• Tardive Dyskinesia:
• Risk increases with duration of treatment; may be irreversible.
• Orthostatic Hypotension:
• Especially in elderly or volume-depleted individuals.
• Cognitive and Motor Impairment:
• May impair activities requiring alertness (e.g., driving).
• Hepatic Dysfunction:
• Use with caution. Monitor liver enzymes.
• Seizures:
• Use with caution in patients with seizure history or risk factors.

Common Adverse Effects (≥1%):

• CNS: Somnolence, dizziness, headache
• Metabolic: Weight gain, increased appetite, hyperlipidemia, hyperglycemia
• Gastrointestinal: Dry mouth, constipation
• General: Fatigue, asthenia

Serious / Rare Adverse Effects:

• Tardive dyskinesia
• Neuroleptic malignant syndrome (NMS)
• Agranulocytosis
• Seizures
• Hepatotoxicity
• QT interval prolongation
• Hyperprolactinemia → galactorrhea, gynecomastia, amenorrhea
• Increased mortality in elderly with dementia

Onset:

• Sedation and orthostatic effects may occur within hours or days.
• Metabolic disturbances may take weeks to months.

• CYP1A2 Inhibitors (e.g., Fluvoxamine):
  ↑ Olanzapine levels → Increased side effect risk
• CYP1A2 Inducers (e.g., Smoking, Carbamazepine):
  ↓ Olanzapine levels → Reduced efficacy
• Fluoxetine (CYP2D6 inhibitor):
  ↑ Olanzapine levels when coadministered
• CNS Depressants (e.g., Alcohol, Benzodiazepines):
  Additive sedation and respiratory depression
• Antihypertensives:
  Additive hypotensive effects
• Anticholinergics:
  Enhanced peripheral and central anticholinergic effects
• Dopaminergic Drugs (e.g., Levodopa):
  Antagonized by olanzapine

• Regulatory Alerts:
• Reinforcement of warnings for metabolic complications and use in elderly dementia-related psychosis.
• Caution against overuse in off-label indications without proper risk assessment.
• Clinical Practice Guidelines:
• APA and NICE recommend olanzapine only after considering its metabolic risks.
• Baseline and periodic monitoring of weight, lipids, fasting glucose, and BMI is essential.
• Consider alternative agents in patients at high risk for diabetes or obesity.

• Oral Tablets and ODTs:
• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep in original packaging until use.
• Intramuscular Injection:
• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Do not freeze.
• Protect from light.
• Handling:
• Keep out of reach of children.
• Do not use expired or damaged products.