NALBUPHINE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause withdrawal in patients dependent on other opioids.
Mixed agonist-antagonist at mu-opioid receptor; full agonist at kappa-opioid receptor; weak antagonist at mu-opioid receptor.
| Metabolism | Hepatic via glucuronidation; primarily metabolized by UGT2B7; minor CYP450 involvement. |
| Excretion | Primarily hepatic metabolism (CYP3A4 and glucuronidation); <5% excreted unchanged in urine; ~70% excreted as metabolites in urine, ~30% in feces. |
| Half-life | Terminal elimination half-life is approximately 5 hours (range 3-6 hours) in adults; prolonged in hepatic impairment. |
| Protein binding | Approximately 50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 2.6 L/kg (range 1.6-3.8 L/kg); indicates extensive tissue distribution. |
| Bioavailability | Intramuscular and subcutaneous: approximately 80%; oral: low (extensive first-pass metabolism, <20% oral bioavailability). |
| Onset of Action | Intravenous: 2-3 minutes; Intramuscular: <15 minutes; Subcutaneous: <15 minutes. |
| Duration of Action | 3-6 hours, dose-dependent; in hepatic insufficiency, duration may be prolonged. |
10-20 mg IM/IV/SC every 3-6 hours as needed; maximum single dose 20 mg, maximum daily dose 160 mg.
| Dosage form | SOLUTION |
| Renal impairment | CrCl 30-50 mL/min: administer 75% of normal dose; CrCl 10-29 mL/min: administer 50% of normal dose; CrCl <10 mL/min: avoid use or use with extreme caution. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 25%; Child-Pugh Class C: reduce dose by 50% or avoid. |
| 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. |
| 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.
| FDA category | Animal |
| Breastfeeding | Excreted in breast milk in small amounts; M/P ratio approximately 0.47-1.5. Limited data; caution recommended. Monitor infant for sedation and respiratory depression. Benefits of breastfeeding should outweigh risks. |
| Teratogenic Risk | Pregnancy Category C. No adequate well-controlled studies in pregnant women. Animal studies have shown no teratogenic effects but embryocidal effects at high doses. Use only if potential benefit justifies risk. In first trimester, avoid unless necessary. Second and third trimesters: risk of neonatal respiratory depression, withdrawal if chronic use. Near term: may prolong labor and cause neonatal respiratory depression. |
■ FDA Black Box Warning
Risk of respiratory depression, abuse, misuse, and addiction; concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death; neonatal opioid withdrawal syndrome with prolonged use during pregnancy.
| Common Effects | Sedation |
| Serious Effects |
Hypersensitivity to nalbuphine or any component; significant respiratory depression; acute or severe bronchial asthma; paralytic ileus; suspected or known gastrointestinal obstruction; use of MAOIs within 14 days.
| Precautions | Respiratory depression; abuse potential; neonatal opioid withdrawal syndrome; adrenal insufficiency; severe hypotension; head injury and increased intracranial pressure; severe hepatic or renal impairment. |
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| Fetal Monitoring | Monitor maternal vital signs, pain scores, respiratory rate, and sedation level. Monitor fetal heart rate during labor. Assess neonatal respiratory status and Apgar scores after delivery. Observe for signs of withdrawal in neonate after prolonged maternal use. |
| Fertility Effects | May impair fertility in females by altering pituitary gonadotropin secretion (e.g., increased prolactin). In males, may decrease libido and erectile function. Effects are generally reversible upon discontinuation. |