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. |
| Molecular Weight | 357.46 |
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 | Limited human data; animal studies show no teratogenicity at therapeutic doses. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; animal studies show no teratogenicity. Use only if benefit outweighs risk. |
| 3rd trimester | Prolonged use may cause neonatal opioid withdrawal syndrome. Avoid near term due to risk of respiratory depression in neonate. |
Clinical note
CNS depressants may enhance sedative effects Can cause withdrawal in patients dependent on other opioids.
| FDA category | Animal |
| Placental transfer | Crosses placenta; detectable in fetal plasma. Fetal exposure is approximately 50% of maternal levels. |
| Breastfeeding |
■ 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 componentSignificant respiratory depressionAcute or severe bronchial asthmaSuspected or known gastrointestinal obstructionUse in patients receiving MAO inhibitors 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. |
| Food/Dietary |
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| Enters breast milk in low amounts. Monitor infant for drowsiness, poor feeding, and respiratory depression. The AAP considers compatible with breastfeeding at maternal doses up to 150 mg/day. |
| Lactation Rating | L2 (Limited data - probably compatible) |
| 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. |
| 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. |
| No specific food interactions. Avoid grapefruit juice as it may theoretically increase nalbuphine levels (CYP3A4 substrate, though major metabolism via glucuronidation). Maintain adequate hydration to prevent constipation. |
| Clinical Pearls | Nalbuphine is a mixed agonist-antagonist opioid with ceiling effect on respiratory depression; less abuse liability than morphine. Useful for opioid-induced pruritus (e.g., with morphine) at low doses (0.1 mg/kg IV). May precipitate withdrawal in opioid-dependent patients. Avoid in opioid-tolerant patients on full agonists. Metabolized by liver; adjust dose in hepatic impairment. Not a controlled substance (US), but report to regulatory authorities as required. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · May cause drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how nalbuphine affects you. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of severe drowsiness, respiratory depression, coma, or death. · Do not stop suddenly after prolonged use; withdrawal symptoms may occur but are generally milder than with full agonists. · Report any signs of allergic reaction (rash, hives, swelling) or difficulty breathing immediately. · If you have been taking other opioids, inform your doctor to avoid withdrawal symptoms. · Store at room temperature away from heat, light, and moisture; keep out of reach of children. |