ZYPREXA ZYDIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZYPREXA ZYDIS (ZYPREXA ZYDIS).

How it works

Olanzapine is an atypical antipsychotic with high affinity for serotonin 5-HT2A and 5-HT2C receptors, dopamine D1-D4 receptors, muscarinic M1-M5 receptors, histamine H1 receptors, and alpha1-adrenergic receptors. Antagonism at D2 and 5-HT2A receptors is primarily responsible for its antipsychotic effects.

What the body does with it

Metabolism	Primarily metabolized by liver via direct glucuronidation and CYP1A2-mediated oxidation. Minor pathways include CYP2D6 and flavin-containing monooxygenase 3 (FMO3).
Excretion	Renal: ~57% (as metabolites); Fecal: ~30% (as metabolites); Unchanged olanzapine in urine <7%.
Half-life	Terminal elimination half-life: ~30 hours (range 21–54 hours) in healthy adults; prolonged in elderly (mean 51.8 h) and hepatic impairment.
Protein binding	~93% bound to albumin and α1-acid glycoprotein.
Volume of Distribution	Mean Vd: 14–18 L/kg (1000–1200 L), indicating extensive tissue distribution.
Bioavailability	Oral bioavailability: ~60–80% (first-pass metabolism). ODT has similar bioavailability to standard olanzapine tablets.
Onset of Action	Orally disintegrating tablet (ODT): Peak plasma concentration reached in ~5–6 hours; antipsychotic effect onset may be observed within 1–2 weeks.
Duration of Action	Dosing interval is typically once daily due to long half-life; steady-state achieved after ~1 week. Duration of clinical effect persists for at least 24 hours.

Classification & Brands

Dosing & administration

10 mg orally once daily; range 5-20 mg once daily. Initial dose 5-10 mg, titrate by 5 mg weekly. Maximum 20 mg/day. Orally disintegrating tablet.

Dosage form	TABLET, ORALLY DISINTEGRATING
Renal impairment	No dose adjustment required for renal impairment. For severe renal impairment (CrCl <10 mL/min), use with caution and consider lower initial dose of 5 mg.
Liver impairment	Child-Pugh Class A or B: Use with caution, consider lower initial dose (5 mg) and slower titration. Child-Pugh Class C: Contraindicated.
Pediatric use	Adolescents (13-17 years) with schizophrenia or bipolar I disorder: initial 2.5-5 mg orally once daily; target 10 mg/day; range 2.5-20 mg/day. For manic or mixed episodes: start 2.5 mg, increase by 2.5-5 mg daily to target 10 mg. Weight-based: not applicable.
Geriatric use	Elderly patients: lower initial dose of 5 mg orally once daily; titrate cautiously. Increased sensitivity to orthostatic hypotension, sedation, and anticholinergic effects. Monitor for falls and extrapyramidal symptoms.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZYPREXA ZYDIS (ZYPREXA ZYDIS).

Breastfeeding	Present in breast milk. M/P ratio unknown. Cases of infant somnolence, lethargy, and poor feeding reported. Use only if benefit outweighs risk. Monitor infant for sedation, irritability, and abnormal movements.
Teratogenic Risk	Pregnancy category C. First trimester: limited data; potential risk of neural tube defects? Second and third trimesters: exposure may lead to extrapyramidal symptoms and/or withdrawal symptoms in neonates including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders. Risk of gestational diabetes, weight gain, and hypertension.

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ZYPREXA ZYDIS is not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to olanzapine or any component of the formulation"]

Clinical Precautions

Precautions

["Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Hyperglycemia and diabetes mellitus","Dyslipidemia","Weight gain","Orthostatic hypotension","Seizures","Leukopenia/neutropenia/agranulocytosis","Cognitive and motor impairment","Suicide risk","Dysphagia","Anticholinergic effects","Body temperature dysregulation"]

Clinical Tips & Counseling

Drug interactions

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ZYPREXA ZYDIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZYPREXA ZYDIS (ZYPREXA ZYDIS).

How it works

What the body does with it

Metabolism	Primarily metabolized by liver via direct glucuronidation and CYP1A2-mediated oxidation. Minor pathways include CYP2D6 and flavin-containing monooxygenase 3 (FMO3).
Excretion	Renal: ~57% (as metabolites); Fecal: ~30% (as metabolites); Unchanged olanzapine in urine <7%.
Half-life	Terminal elimination half-life: ~30 hours (range 21–54 hours) in healthy adults; prolonged in elderly (mean 51.8 h) and hepatic impairment.
Protein binding	~93% bound to albumin and α1-acid glycoprotein.
Volume of Distribution	Mean Vd: 14–18 L/kg (1000–1200 L), indicating extensive tissue distribution.
Bioavailability	Oral bioavailability: ~60–80% (first-pass metabolism). ODT has similar bioavailability to standard olanzapine tablets.
Onset of Action	Orally disintegrating tablet (ODT): Peak plasma concentration reached in ~5–6 hours; antipsychotic effect onset may be observed within 1–2 weeks.
Duration of Action	Dosing interval is typically once daily due to long half-life; steady-state achieved after ~1 week. Duration of clinical effect persists for at least 24 hours.

Classification & Brands

Dosing & administration

10 mg orally once daily; range 5-20 mg once daily. Initial dose 5-10 mg, titrate by 5 mg weekly. Maximum 20 mg/day. Orally disintegrating tablet.

Dosage form	TABLET, ORALLY DISINTEGRATING
Renal impairment	No dose adjustment required for renal impairment. For severe renal impairment (CrCl <10 mL/min), use with caution and consider lower initial dose of 5 mg.
Liver impairment	Child-Pugh Class A or B: Use with caution, consider lower initial dose (5 mg) and slower titration. Child-Pugh Class C: Contraindicated.
Pediatric use	Adolescents (13-17 years) with schizophrenia or bipolar I disorder: initial 2.5-5 mg orally once daily; target 10 mg/day; range 2.5-20 mg/day. For manic or mixed episodes: start 2.5 mg, increase by 2.5-5 mg daily to target 10 mg. Weight-based: not applicable.
Geriatric use	Elderly patients: lower initial dose of 5 mg orally once daily; titrate cautiously. Increased sensitivity to orthostatic hypotension, sedation, and anticholinergic effects. Monitor for falls and extrapyramidal symptoms.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZYPREXA ZYDIS (ZYPREXA ZYDIS).

Breastfeeding	Present in breast milk. M/P ratio unknown. Cases of infant somnolence, lethargy, and poor feeding reported. Use only if benefit outweighs risk. Monitor infant for sedation, irritability, and abnormal movements.
Teratogenic Risk	Pregnancy category C. First trimester: limited data; potential risk of neural tube defects? Second and third trimesters: exposure may lead to extrapyramidal symptoms and/or withdrawal symptoms in neonates including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders. Risk of gestational diabetes, weight gain, and hypertension.

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ZYPREXA ZYDIS is not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to olanzapine or any component of the formulation"]

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…