LEVO-DROMORAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEVO-DROMORAN (LEVO-DROMORAN).

How it works

Levo-dromoran (levorphanol) is a potent opioid agonist primarily at mu-opioid receptors, with additional agonist activity at kappa and delta opioid receptors. It also acts as an NMDA receptor antagonist and inhibits serotonin and norepinephrine reuptake, contributing to its analgesic effects.

What the body does with it

Metabolism	Primarily hepatic via glucuronidation (UGT2B7) and N-demethylation (CYP3A4). Active metabolite: norlevorphanol.
Excretion	Primarily renal (approximately 60% as unchanged drug and metabolites); biliary/fecal elimination accounts for about 30%.
Half-life	Terminal elimination half-life is 15-30 hours (mean 22 hours) in adults; prolonged in hepatic or renal impairment, requiring dose adjustment.
Protein binding	Approximately 60-70% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	3-5 L/kg, indicating extensive tissue distribution beyond plasma volume.
Bioavailability	Oral bioavailability is about 40-60% due to first-pass metabolism; rectal bioavailability is approximately 50-70%.
Onset of Action	Oral: 30-60 minutes; Subcutaneous: 10-15 minutes; Intravenous: 5-10 minutes. Effects peak at 1-2 hours orally.
Duration of Action	Oral: 6-8 hours; Parenteral: 4-6 hours. Duration may be prolonged in elderly or debilitated patients due to reduced clearance.

Classification & Brands

Dosing & administration

2 mg orally every 6-8 hours as needed for pain; 2-4 mg intramuscularly or subcutaneously every 6-8 hours; intravenous administration: 1-2 mg slowly (over 2-3 minutes) every 6-8 hours.

Dosage form	TABLET
Renal impairment	For GFR 30-50 mL/min: administer every 8-12 hours; GFR 10-29 mL/min: administer every 12-18 hours; GFR <10 mL/min: administer every 24 hours or consider alternative.
Liver impairment	Child-Pugh Class A (mild): no adjustment necessary; Child-Pugh Class B (moderate): reduce dose by 25-50%; Child-Pugh Class C (severe): avoid use or reduce dose by 75% with extended dosing interval.
Pediatric use	Oral: 0.04-0.08 mg/kg/dose every 6-8 hours; Parenteral: 0.02-0.04 mg/kg/dose every 6-8 hours. Maximum single dose: 2 mg. Not recommended for children under 6 months.
Geriatric use	Initiate at 25-50% of adult dose (e.g., 1 mg orally every 6-8 hours) due to increased sensitivity and renal clearance decline; titrate cautiously.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LEVO-DROMORAN (LEVO-DROMORAN).

Breastfeeding	Excreted into breast milk; M/P ratio not established. Use with caution; monitor infant for sedation and respiratory depression. American Academy of Pediatrics recommends avoiding due to potential for infant toxicity.
Teratogenic Risk	First trimester: Limited human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Second and third trimesters: Chronic use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. Avoid prolonged use.

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

Hypersensitivity to levorphanol or any component, significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, suspected surgical abdomen, monoamine oxidase inhibitor use within 14 days.

Clinical Precautions

Precautions

Risk of respiratory depression, hypotension, bradycardia, increased intracranial pressure, seizures, serotonin syndrome, adrenal insufficiency, severe hypotension, and opioid-induced hyperalgesia. Avoid abrupt discontinuation.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

LEVO-DROMORAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEVO-DROMORAN (LEVO-DROMORAN).

How it works

What the body does with it

Metabolism	Primarily hepatic via glucuronidation (UGT2B7) and N-demethylation (CYP3A4). Active metabolite: norlevorphanol.
Excretion	Primarily renal (approximately 60% as unchanged drug and metabolites); biliary/fecal elimination accounts for about 30%.
Half-life	Terminal elimination half-life is 15-30 hours (mean 22 hours) in adults; prolonged in hepatic or renal impairment, requiring dose adjustment.
Protein binding	Approximately 60-70% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	3-5 L/kg, indicating extensive tissue distribution beyond plasma volume.
Bioavailability	Oral bioavailability is about 40-60% due to first-pass metabolism; rectal bioavailability is approximately 50-70%.
Onset of Action	Oral: 30-60 minutes; Subcutaneous: 10-15 minutes; Intravenous: 5-10 minutes. Effects peak at 1-2 hours orally.
Duration of Action	Oral: 6-8 hours; Parenteral: 4-6 hours. Duration may be prolonged in elderly or debilitated patients due to reduced clearance.

Classification & Brands

Dosing & administration

2 mg orally every 6-8 hours as needed for pain; 2-4 mg intramuscularly or subcutaneously every 6-8 hours; intravenous administration: 1-2 mg slowly (over 2-3 minutes) every 6-8 hours.

Dosage form	TABLET
Renal impairment	For GFR 30-50 mL/min: administer every 8-12 hours; GFR 10-29 mL/min: administer every 12-18 hours; GFR <10 mL/min: administer every 24 hours or consider alternative.
Liver impairment	Child-Pugh Class A (mild): no adjustment necessary; Child-Pugh Class B (moderate): reduce dose by 25-50%; Child-Pugh Class C (severe): avoid use or reduce dose by 75% with extended dosing interval.
Pediatric use	Oral: 0.04-0.08 mg/kg/dose every 6-8 hours; Parenteral: 0.02-0.04 mg/kg/dose every 6-8 hours. Maximum single dose: 2 mg. Not recommended for children under 6 months.
Geriatric use	Initiate at 25-50% of adult dose (e.g., 1 mg orally every 6-8 hours) due to increased sensitivity and renal clearance decline; titrate cautiously.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LEVO-DROMORAN (LEVO-DROMORAN).

Breastfeeding	Excreted into breast milk; M/P ratio not established. Use with caution; monitor infant for sedation and respiratory depression. American Academy of Pediatrics recommends avoiding due to potential for infant toxicity.
Teratogenic Risk	First trimester: Limited human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Second and third trimesters: Chronic use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. Avoid prolonged use.