Drug reference

Olanzapine

Atypical Antipsychotic · Antipsychotic

Also known as Olanzapine pamoate

START

Confirm schizophrenia, bipolar, or approved indication. Baseline weight, BMI, waist circumference, fasting glucose, HbA1c, lipid panel, prolactin. ECG if cardiac risk. Start 5-10 mg daily (5 mg in elderly/hepatic impairment).

TYPICAL MAX

20 mg/day. No benefit from doses >20 mg; increased metabolic and extrapyramidal side effects.

STOP IF

NMS (fever, rigidity, autonomic instability), severe TD, diabetic ketoacidosis, agranulocytosis (ANC <1000), severe hepatotoxicity, pregnancy

WATCH

Weight (monthly x 3 months, then quarterly), fasting glucose/HbA1c (baseline, 12 weeks, then annually), lipid panel (baseline, 12 weeks, then every 5 years), prolactin if symptoms, movement disorder assessment (AIMS scale every 6 months), orthostatic BP

CDSCO approvedSchedule HJan AushadhiATC N05AH03

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1.6h · absorption onset
PEAK: 6.5h · 5-8 h (oral)
t½: 1.3d · 21-54 h (mean 30 h)
DURATION: 1d · 24 h (once-daily dosing)

EXCRETION

~57% urine (metabolites); ~30% fecal; hepatic glucuronidation >

route + CYP

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

FDA PLLR: Limited human data. Neonatal extrapyramidal and/or withdrawal symptoms reported with third-trimester exposure. Use only if benefit clearly outweighs risk. Risk of metabolic complications in pregnancy (gestational diabetes).

FDA category + note

Top interactionssee all 12 →

AlcoholSevereDatabase
AlfentanilSevereDatabaseDDInter
BenzhydrocodoneSevereDatabaseDDInter
Benzodiazepines (e.g., Lorazepam, Diazepam)SevereDatabase

Available in India

717 branded formulations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Olanzapine is a second-generation (atypical) antipsychotic agent that exerts its therapeutic effects through antagonism at multiple neurotransmitter receptors. It has high affinity for serotonin 5-HT2A receptors (Ki = 4 nM), dopamine D2 receptors (Ki = 11 nM), muscarinic M1 receptors (Ki = 2.5 nM), and histamine H1 receptors (Ki = 7 nM). Its antagonism at 5-HT2A receptors exceeds that at D2 receptors (5-HT2A/D2 ratio >1), which is thought to confer the 'atypical' antipsychotic profile with reduced extrapyramidal symptoms. It also blocks alpha-1 adrenergic receptors, contributing to orthostatic hypotension. The broad receptor profile explains both its efficacy in schizophrenia/bipolar disorder and its metabolic, sedative, and anticholinergic side effects.

Indications

Schizophrenia — acute and maintenance treatmentBipolar I disorder — acute manic or mixed episodes (monotherapy or with lithium/valproate)Bipolar I disorder — maintenance treatmentBipolar depression (in combination with fluoxetine — Symbyax)Treatment-resistant depression (with fluoxetine — Symbyax)Agitation associated with schizophrenia or bipolar mania (IM)Chemotherapy-induced nausea/vomiting (off-label, low-dose)Anorexia nervosa (off-label, low-dose)

Dosing

Adult: Schizophrenia: 5-10 mg PO daily initially; titrate by 5 mg/day at ≥1-week intervals; target 10-15 mg/day; max 20 mg/day. Bipolar mania: 10-15 mg PO daily initially; max 20 mg/day. Bipolar depression (with fluoxetine): olanzapine 5 mg + fluoxetine 20 mg daily. Elderly: 5 mg PO daily initially.
Pediatric: Schizophrenia/bipolar (13-17 years): 2.5-5 mg PO daily initially; titrate by 2.5-5 mg; target 10 mg/day; max 20 mg/day.
Renal adjustment: No initial adjustment. Use lower starting dose (5 mg) and titrate slowly.
Hepatic adjustment: Start 5 mg daily; titrate slowly. Increased risk of sedation and orthostatic hypotension.
Geriatric: Start 5 mg daily; max 10 mg/day. Increased risk of mortality in dementia-related psychosis (black box warning). Monitor for falls, orthostatic hypotension, sedation. Beers Criteria: potentially inappropriate for behavioral symptoms of dementia.
Max dose: 20 mg/day

Pharmacokinetics

Onset

Oral: onset within 1-2 weeks for psychotic symptoms; 4-6 weeks for full therapeutic effect. IM: rapid onset for agitation (15-45 minutes).

Peak effect

Oral: peak plasma at 5-8 hours (with or without food). IM: peak at 15-45 minutes.

Duration

24 hours (supports once-daily dosing).

Half-life

21-54 hours (mean 30 hours in healthy adults). Allows once-daily dosing. Steady-state by 7 days.

Bioavailability

~60-80% (oral); food does not affect absorption.

Protein binding

93% (bound to albumin and alpha-1-acid glycoprotein).

Metabolism

Extensive hepatic via direct glucuronidation (UGT1A4, UGT2B10 — major pathway, ~40% of dose) and CYP1A2-mediated oxidation (to N-desmethyl and 2-hydroxymethyl metabolites — minor, ~20% of dose). CYP2D6 contributes minimally.

Excretion

Urine: ~57% (7% unchanged, remainder as metabolites). Feces: ~30% (mainly as metabolites).

Contraindications

Hypersensitivity to olanzapine
Narrow-angle glaucoma (anticholinergic effects may increase intraocular pressure)
Severe CNS depression or comatose states
Paralytic ileus (anticholinergic effects may worsen)
Dementia-related psychosis (FDA black box warning — increased mortality)
Relative: known cardiovascular disease, cerebrovascular disease, history of seizures, diabetes mellitus, hyperlipidemia

Side effects

Common

Sedation, somnolence, fatigueWeight gain (mean 2-5 kg in first year; dose-dependent)Increased appetiteDry mouth (anticholinergic)Constipation (anticholinergic)Dizziness, orthostatic hypotension (alpha-1 blockade)Dyslipidemia (increased triglycerides, cholesterol)Elevated prolactin (mild, transient — less than typical antipsychotics)

Serious

METABOLIC SYNDROME — FDA warning: weight gain, diabetes mellitus, dyslipidemia, hyperglycemic hyperosmolar state, diabetic ketoacidosis (can occur without prior diabetes risk factors)
Neuroleptic malignant syndrome (NMS) — rare but fatal (hyperthermia, rigidity, autonomic instability, altered mental status, elevated CK)
Tardive dyskinesia (TD) — potentially irreversible (risk increases with duration and cumulative dose)
Agranulocytosis, neutropenia (rare)
Orthostatic hypotension and syncope (especially initial dose)
Seizures (dose-dependent lowering of seizure threshold)
Dementia-related psychosis — increased mortality (black box warning)
Hepatotoxicity (elevated transaminases, hepatitis)
Hyperprolactinemia-related effects (galactorrhea, amenorrhea, sexual dysfunction, gynecomastia)
Venous thromboembolism (increased risk)
Pancreatitis (rare)

Pregnancy & lactation

Pregnancy

Lactation

Excreted in breast milk (infant exposure ~1-3% of maternal dose). May cause infant sedation, poor feeding, extrapyramidal symptoms. Avoid breastfeeding if possible. If necessary, monitor infant closely.

Drug interactions

Alcohol

Severe

Database

Increased sedation, dizziness, orthostatic hypotension, and impaired psychomotor performance.

Advise patients to avoid alcohol consumption while taking olanzapine.

Alfentanil

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Benzhydrocodone

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Benzodiazepines (e.g., Lorazepam, Diazepam)

Severe

Database

Increased sedation, respiratory depression, and orthostatic hypotension, especially with parenteral co-administration.

Use with caution. If parenteral co-administration is necessary, monitor vital signs closely and ensure adequate resuscitation equipment is available. Consider lower doses of both agents.

Buprenorphine

Severe

Database

Drug interaction classified as: synergy.

Source: DDInter

Bupropion

Severe

Database

Drug interaction classified as: synergy.

Source: DDInter

Butorphanol

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Carbamazepine

Severe

Database

Increased clearance by 50%.

Increase olanzapine dose.

Source: DDInter

Chlordiazepoxide

Severe

Database

Drug interaction classified as: synergy.

Source: DDInter

Clonazepam

Severe

Database

Increased sedation, drowsiness, dizziness, and psychomotor impairment. Increased risk of respiratory depression.

Monitor for excessive sedation and respiratory depression. Advise caution with activities requiring mental alertness. Consider dose reduction of one or both agents, especially at initiation or dose escalation.

Source: DDInter

Clorazepic Acid

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Clozapine

Severe

Database

Drug interaction classified as: synergy.

Source: DDInter