NALBUPHINE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Mixed opioid agonist-antagonist; agonist at κ-opioid receptors and antagonist/partial agonist at μ-opioid receptors.

What the body does with it

Metabolism	Hepatic metabolism primarily via glucuronidation and oxidative pathways; minor involvement of CYP450 enzymes.
Excretion	Primarily hepatic metabolism; <5% excreted unchanged in urine; about 70% excreted in feces via biliary elimination.
Half-life	Terminal elimination half-life is 5 hours; clinically, in hepatic impairment or elderly, half-life may be prolonged up to 8-10 hours.
Protein binding	Approximately 50% bound to plasma proteins, primarily albumin.
Volume of Distribution	2.3 L/kg; indicates extensive tissue distribution, consistent with moderate lipophilicity.
Bioavailability	Intravenous: 100%; Intramuscular: approximately 80%; Oral: negligible (<20%) due to extensive first-pass metabolism.
Onset of Action	Intravenous: 2-3 minutes; Intramuscular: <15 minutes; Subcutaneous: <15 minutes; Oral: not clinically used due to high first-pass metabolism.
Duration of Action	Analgesic effect: 3-6 hours; with longer duration for IM/SC vs IV; ceiling effect for respiratory depression limits dose escalation.

Classification & Brands

Dosing & administration

10-20 mg IV/IM/SC every 3-6 hours as needed for pain; maximum single dose 20 mg, maximum total daily dose 160 mg.

Dosage form	SOLUTION
Renal impairment	CrCl 30-50 mL/min: administer 75% of normal dose every 6 hours; CrCl <30 mL/min: administer 50% of normal dose every 8 hours.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50% or use alternative.
Pediatric use	0.1-0.2 mg/kg IV/IM/SC every 3-6 hours as needed; maximum single dose 20 mg.
Geriatric use	Initiate at 50% of adult dose (5-10 mg) and titrate cautiously due to increased sensitivity and risk of respiratory depression.

Use during pregnancy

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

Clinical note

CNS depressants may enhance sedative effects Can cause withdrawal in patients dependent on other opioids.

Breastfeeding	Excreted in human milk in low concentrations (M/P ratio ~0.6). Relative infant dose estimated 0.5-1% of maternal weight-adjusted dose. Monitor infant for sedation and poor feeding. American Academy of Pediatrics considers compatible with breastfeeding with caution.
Teratogenic Risk	FDA Category C. First trimester: Limited human data, no evidence of major malformations in animal studies at 4-6x MRHD. Second/third trimester: Chronic use may cause neonatal opioid withdrawal syndrome (NOWS) including irritability, hypertonia, tremors, poor feeding. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Risk of respiratory depression, particularly in opioid-naive patients; risk of dependence and abuse; concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death.

Side Effect Profile

Common Effects	Sedation
Serious Effects

Absolute Contraindications

["Hypersensitivity to nalbuphine or any component","Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting","Suspected or known gastrointestinal obstruction"]

Clinical Precautions

Precautions

["Respiratory depression may occur, especially in elderly, cachectic, or debilitated patients","Avoid use in patients with head injury or increased intracranial pressure","May precipitate withdrawal in opioid-dependent patients","Hypotension, biliary tract spasm, and seizure risk"]

Clinical Tips & Counseling

Drug interactions

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