LEVORPHANOL TARTRATE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEVORPHANOL TARTRATE (LEVORPHANOL TARTRATE).

How it works

Levorphanol is a potent opioid analgesic that acts as a mu-opioid receptor agonist. It also has NMDA receptor antagonist activity, inhibits norepinephrine and serotonin reuptake, and acts as a sigma receptor agonist, contributing to its analgesic effects and reduced tolerance development.

What the body does with it

Metabolism	Primarily hepatic via glucuronidation and N-demethylation; CYP450 involvement not fully characterized.
Excretion	Renal: approximately 30% as unchanged drug and 50% as glucuronide conjugates; fecal: 20% via biliary excretion.
Half-life	11-16 hours; extended in hepatic impairment (up to 30 hours).
Protein binding	Approximately 50% bound to albumin.
Volume of Distribution	10-15 L/kg; extensive tissue distribution.
Bioavailability	Oral: 50-70% (first-pass effect); intravenous: 100%.
Onset of Action	Intravenous: 2-5 minutes; subcutaneous/intramuscular: 10-30 minutes; oral: 30-60 minutes.
Duration of Action	Analgesia: 4-6 hours (all routes); respiratory depression may persist longer.

Classification & Brands

Dosing & administration

2 mg orally every 6-8 hours as needed for pain; for opioid-tolerant patients, doses up to 4 mg orally every 6-8 hours may be used. Parenterally: 1-2 mg subcutaneously or intramuscularly every 6-8 hours; may be given intravenously at 0.5-1 mg every 6-8 hours.

Dosage form	TABLET
Renal impairment	CrCl 10-50 mL/min: Administer 75% of usual dose at extended intervals (e.g., every 12 hours). CrCl <10 mL/min: Administer 50% of usual dose at extended intervals (e.g., every 12-24 hours). For patients on dialysis, use with caution and reduce dose; not well-studied.
Liver impairment	Child-Pugh Class A: No adjustment needed. Child-Pugh Class B: Reduce dose by 50% and administer at extended intervals (e.g., every 12 hours). Child-Pugh Class C: Avoid use; if necessary, reduce dose by 75% and monitor closely.
Pediatric use	Not recommended for use in pediatric patients due to lack of safety and efficacy data; use in children under 18 years is generally avoided. For palliative care in older children, consult specialist.
Geriatric use	Start at 50% of the usual adult dose (e.g., 1 mg orally every 6-8 hours) due to increased sensitivity and reduced clearance; titrate carefully with close monitoring for respiratory depression and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LEVORPHANOL TARTRATE (LEVORPHANOL TARTRATE).

Breastfeeding	Unknown if levorphanol is excreted in human milk; other opioids are present in breast milk. Consider benefits of breastfeeding vs. risk of infant opioid exposure (respiratory depression, withdrawal). M/P ratio not established.
Teratogenic Risk	Levorphanol is an opioid agonist; limited data in pregnancy. First trimester: potential for neural tube defects based on animal studies; human risk unclear. Second/third trimesters: risk of fetal opioid dependence, preterm labor, and intrauterine growth restriction. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Significant respiratory depression","Acute or severe bronchial asthma","Known or suspected gastrointestinal obstruction","Concurrent use of MAOIs or within 14 days","Hypersensitivity to levorphanol"]

Clinical Precautions

Precautions

["Respiratory depression: potentially fatal, especially at initiation and dose escalation","Adrenal insufficiency","Severe hypotension","Seizures","Serotonin syndrome","Risks from concomitant CNS depressants","Impaired mental or physical abilities"]

Clinical Tips & Counseling

Drug interactions

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LEVORPHANOL TARTRATE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEVORPHANOL TARTRATE (LEVORPHANOL TARTRATE).

How it works

What the body does with it

Metabolism	Primarily hepatic via glucuronidation and N-demethylation; CYP450 involvement not fully characterized.
Excretion	Renal: approximately 30% as unchanged drug and 50% as glucuronide conjugates; fecal: 20% via biliary excretion.
Half-life	11-16 hours; extended in hepatic impairment (up to 30 hours).
Protein binding	Approximately 50% bound to albumin.
Volume of Distribution	10-15 L/kg; extensive tissue distribution.
Bioavailability	Oral: 50-70% (first-pass effect); intravenous: 100%.
Onset of Action	Intravenous: 2-5 minutes; subcutaneous/intramuscular: 10-30 minutes; oral: 30-60 minutes.
Duration of Action	Analgesia: 4-6 hours (all routes); respiratory depression may persist longer.

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	CrCl 10-50 mL/min: Administer 75% of usual dose at extended intervals (e.g., every 12 hours). CrCl <10 mL/min: Administer 50% of usual dose at extended intervals (e.g., every 12-24 hours). For patients on dialysis, use with caution and reduce dose; not well-studied.
Liver impairment	Child-Pugh Class A: No adjustment needed. Child-Pugh Class B: Reduce dose by 50% and administer at extended intervals (e.g., every 12 hours). Child-Pugh Class C: Avoid use; if necessary, reduce dose by 75% and monitor closely.
Pediatric use	Not recommended for use in pediatric patients due to lack of safety and efficacy data; use in children under 18 years is generally avoided. For palliative care in older children, consult specialist.
Geriatric use	Start at 50% of the usual adult dose (e.g., 1 mg orally every 6-8 hours) due to increased sensitivity and reduced clearance; titrate carefully with close monitoring for respiratory depression and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LEVORPHANOL TARTRATE (LEVORPHANOL TARTRATE).

Breastfeeding	Unknown if levorphanol is excreted in human milk; other opioids are present in breast milk. Consider benefits of breastfeeding vs. risk of infant opioid exposure (respiratory depression, withdrawal). M/P ratio not established.
Teratogenic Risk	Levorphanol is an opioid agonist; limited data in pregnancy. First trimester: potential for neural tube defects based on animal studies; human risk unclear. Second/third trimesters: risk of fetal opioid dependence, preterm labor, and intrauterine growth restriction. Use only if benefit outweighs risk.