OLEPTRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OLEPTRO (OLEPTRO).

How it works

Selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuronal membrane.

What the body does with it

Metabolism	Hepatic via CYP2D6, CYP2C9, CYP3A4, and CYP2C19; active metabolite norfluoxetine (demethylation); inhibits CYP2D6.
Excretion	Renal: 70% as unchanged drug; Hepatic metabolism: 30% (minor CYP2D6), excreted in feces via bile
Half-life	Terminal elimination half-life: 12-15 hours (mean 13.5 h) in steady state; clinical context: allows twice-daily dosing, prolonged in renal impairment (up to 27 h in severe disease)
Protein binding	80-85% bound, primarily to albumin and alpha-1-acid glycoprotein; unbound fraction 15-20%
Volume of Distribution	5-10 L/kg (mean 7 L/kg); clinical meaning: extensive tissue distribution, including CNS, indicating high lipophilicity and ability to cross blood-brain barrier
Bioavailability	Oral immediate-release: 70-80% (with first-pass effect); Oral extended-release: 60-70%; Intravenous: 100%; Intramuscular: 90-100%
Onset of Action	Oral immediate-release: 1-2 hours; Oral extended-release: 2-4 hours; Intravenous: 15-30 minutes
Duration of Action	12-24 hours depending on formulation and indication; clinical notes: analgesic effects for acute pain last 6-8 h with immediate-release, extended-release provides analgesia up to 24 h

Classification & Brands

Dosing & administration

IV: 1 g every 12 hours; oral: 750 mg every 12 hours

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	CrCl ≥30 mL/min: no adjustment; CrCl 10-29: 1 g IV q24h or 750 mg oral q24h; CrCl <10 or HD: 1 g IV q48h or 750 mg oral q48h
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: not recommended
Pediatric use	1-3 months: 10-15 mg/kg IV q12h; 3 months to 12 years: 15 mg/kg IV q8h (max 4 g/day); ≥12 years: same as adult
Geriatric use	No specific adjustment beyond renal function; monitor for increased risk of adverse effects due to age-related renal decline

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OLEPTRO (OLEPTRO).

Breastfeeding	Olanzapine is excreted in human milk. The milk-to-plasma ratio is approximately 0.2-0.5. Exposure to the infant is low, but long-term effects unknown. Caution advised; monitor infant for sedation, irritability, and feeding problems.
Teratogenic Risk	OLEPTRO (olanzapine pamoate) is classified as Pregnancy Category C. First trimester: Limited human data, but animal studies show fetal harm. Second and third trimesters: Antipsychotic use may cause extrapyramidal symptoms and/or withdrawal symptoms in neonates, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults taking antidepressants. Monitor closely for worsening and emergence of suicidal thoughts and behaviors.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concomitant use with MAOIs or within 14 days of MAOI discontinuation, concomitant use with pimozide or thioridazine, hypersensitivity to fluoxetine or any component of the formulation.

Clinical Precautions

Precautions

Serotonin syndrome, discontinuation syndrome, activation of mania/hypomania, seizures, angle-closure glaucoma, hyponatremia, bleeding risk (especially with NSAIDs/aspirin), QT prolongation (dose-dependent), sexual dysfunction, weight changes.

Clinical Tips & Counseling

Drug interactions

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OLEPTRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OLEPTRO (OLEPTRO).

How it works

Selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuronal membrane.

What the body does with it

Metabolism	Hepatic via CYP2D6, CYP2C9, CYP3A4, and CYP2C19; active metabolite norfluoxetine (demethylation); inhibits CYP2D6.
Excretion	Renal: 70% as unchanged drug; Hepatic metabolism: 30% (minor CYP2D6), excreted in feces via bile
Half-life	Terminal elimination half-life: 12-15 hours (mean 13.5 h) in steady state; clinical context: allows twice-daily dosing, prolonged in renal impairment (up to 27 h in severe disease)
Protein binding	80-85% bound, primarily to albumin and alpha-1-acid glycoprotein; unbound fraction 15-20%
Volume of Distribution	5-10 L/kg (mean 7 L/kg); clinical meaning: extensive tissue distribution, including CNS, indicating high lipophilicity and ability to cross blood-brain barrier
Bioavailability	Oral immediate-release: 70-80% (with first-pass effect); Oral extended-release: 60-70%; Intravenous: 100%; Intramuscular: 90-100%
Onset of Action	Oral immediate-release: 1-2 hours; Oral extended-release: 2-4 hours; Intravenous: 15-30 minutes
Duration of Action	12-24 hours depending on formulation and indication; clinical notes: analgesic effects for acute pain last 6-8 h with immediate-release, extended-release provides analgesia up to 24 h

Classification & Brands

Dosing & administration

IV: 1 g every 12 hours; oral: 750 mg every 12 hours

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	CrCl ≥30 mL/min: no adjustment; CrCl 10-29: 1 g IV q24h or 750 mg oral q24h; CrCl <10 or HD: 1 g IV q48h or 750 mg oral q48h
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: not recommended
Pediatric use	1-3 months: 10-15 mg/kg IV q12h; 3 months to 12 years: 15 mg/kg IV q8h (max 4 g/day); ≥12 years: same as adult
Geriatric use	No specific adjustment beyond renal function; monitor for increased risk of adverse effects due to age-related renal decline

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OLEPTRO (OLEPTRO).

Breastfeeding	Olanzapine is excreted in human milk. The milk-to-plasma ratio is approximately 0.2-0.5. Exposure to the infant is low, but long-term effects unknown. Caution advised; monitor infant for sedation, irritability, and feeding problems.
Teratogenic Risk	OLEPTRO (olanzapine pamoate) is classified as Pregnancy Category C. First trimester: Limited human data, but animal studies show fetal harm. Second and third trimesters: Antipsychotic use may cause extrapyramidal symptoms and/or withdrawal symptoms in neonates, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder.

Warnings & precautions

■ FDA Black Box Warning

Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults taking antidepressants. Monitor closely for worsening and emergence of suicidal thoughts and behaviors.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concomitant use with MAOIs or within 14 days of MAOI discontinuation, concomitant use with pimozide or thioridazine, hypersensitivity to fluoxetine or any component of the formulation.