Nalbuphine

Approved Indications:

• Moderate to Severe Pain:
• Effective for managing moderate to severe acute pain, including post-operative pain, musculoskeletal trauma, and other painful conditions.
• Obstetric Analgesia:
• Used for labor pain relief without significant respiratory depression in the newborn.
• Adjunct to General Anesthesia:
• Administered before, during, or after anesthesia to supplement analgesia during surgical procedures.
• Preoperative and Postoperative Analgesia:
• Employed in hospital settings to relieve pain before or after surgery.

Clinically Accepted (Off-label) Uses:

• Opioid-Induced Pruritus:
• Used to treat itching associated with epidural or intrathecal opioid administration.
• Opioid Withdrawal Management:
• Occasionally used to relieve withdrawal symptoms in opioid-dependent patients during tapering.
• Procedural Sedation in Minor Procedures:
• Provides analgesia and sedation for short diagnostic or surgical procedures under monitored care.

Route of Administration: Intramuscular (IM), Intravenous (IV), Subcutaneous (SC)

Adults:

• Moderate to Severe Pain:
• 10 mg IM/IV/SC every 3 to 6 hours as needed.
• Maximum: 20 mg per dose; 160 mg/day.
• Adjunct to Anesthesia:
• 0.3 mg/kg IV slowly over 10 to 15 minutes, as part of surgical analgesia.
• May be repeated every 3 to 6 hours if required.
• Obstetric Analgesia (Labor Pain):
• 10 mg IV or IM every 3 hours as needed.
• Maximum: 20 mg total during labor.

Pediatric Patients (≥1 year):

• Pain Management:
• 0.1 to 0.2 mg/kg/dose IV/IM/SC every 3 to 6 hours as needed.
• Use under close clinical supervision.

Elderly:

• Start at the lower end of the dosing range (e.g., 5 mg per dose).
• Monitor closely for signs of sedation or respiratory depression.

Renal Impairment:

• Use with caution; consider dose reduction and monitor for accumulation or prolonged effect.

Hepatic Impairment:

• Reduce initial dose and extend dosing interval due to slower metabolism.
• Monitor for CNS or respiratory depression.

Nalbuphine is a mixed opioid agonist-antagonist. It acts as an agonist at kappa-opioid receptors, producing analgesia, sedation, and limited euphoria. Simultaneously, it acts as a partial antagonist at mu-opioid receptors, reducing the risk of respiratory depression, euphoria, and physical dependence typically associated with mu-agonists. This dual activity allows it to provide effective pain relief while minimizing the risk of opioid-related side effects such as overdose and addiction. The ceiling effect on respiratory depression is a significant safety advantage.

• Absorption: Rapidly absorbed following IM, IV, or SC administration.
• Peak Plasma Time:
• IV: Immediate onset
• IM: Peak effect in 30–60 minutes
• Bioavailability: 100% (IV); ~40% (IM)
• Distribution: Widely distributed; crosses placenta and may enter breast milk.
• Plasma Protein Binding: ~50%
• Metabolism: Hepatic, primarily via conjugation (glucuronidation).
• Elimination Half-life: 4.9 ± 0.8 hours
• Excretion: Primarily via urine (~80%); minor fecal excretion
• Onset of Action:
• IV: 2 to 3 minutes
• IM: 15 minutes
• Duration of Action: 3 to 6 hours

• Pregnancy Category (FDA): Category B
• No evidence of fetal harm in animal studies.
• Used during labor but may cause transient respiratory depression in the neonate if administered shortly before delivery.
• Lactation:
• Small amounts are excreted into breast milk.
• Generally considered safe during breastfeeding if used for a short duration and infant is monitored for sedation, apnea, or feeding difficulties.

• Primary Class: Opioid Analgesic
• Subclass: Mixed Opioid Agonist-Antagonist (Kappa receptor agonist / Mu receptor antagonist)

• Known hypersensitivity to nalbuphine or any of its components
• Significant respiratory depression in the absence of resuscitative equipment
• Acute bronchial asthma in an unmonitored setting
• Patients dependent on full mu-opioid agonists (risk of precipitated withdrawal)
• Head injuries or elevated intracranial pressure (may obscure neurologic evaluation)

• Respiratory Depression: May still occur, particularly in higher doses or when combined with other CNS depressants.
• Opioid Withdrawal: In opioid-dependent individuals, nalbuphine may precipitate withdrawal symptoms.
• CNS Depression: Impairs mental and physical capabilities; caution in activities requiring alertness.
• Cardiovascular Effects: May cause hypotension, especially in volume-depleted or elderly patients.
• Head Trauma: May increase intracranial pressure; use with caution.
• Hepatic/Renal Impairment: Slower metabolism or excretion may increase toxicity risk.
• Use in Neonates: Respiratory depression in newborns if administered shortly before delivery.

Common:

• Central Nervous System:
• Sedation, dizziness, headache, drowsiness
• Gastrointestinal:
• Nausea, vomiting, dry mouth, constipation
• Dermatologic:
• Sweating, pruritus

Less Common / Serious:

• Respiratory depression
• Hypotension, bradycardia
• Confusion, hallucinations, dysphoria
• Allergic reactions (rare)
• Neonatal respiratory depression (if used during labor)
• Withdrawal syndrome in opioid-dependent patients

• CNS Depressants (e.g., alcohol, benzodiazepines, sedatives):
• Additive effects → increased sedation and respiratory depression.
• Opioid Agonists (e.g., morphine, fentanyl):
• Nalbuphine may antagonize their effects or trigger withdrawal in opioid-dependent patients.
• Monoamine Oxidase Inhibitors (MAOIs):
• Use not recommended due to potential for exaggerated CNS depression or serotonin toxicity.
• Enzyme Interactions:
• Not significantly metabolized by CYP450 enzymes; low risk for major CYP450 interactions.

• Regulatory Status:
• Nalbuphine is not scheduled under the U.S. Controlled Substances Act due to low abuse potential.
• WHO & National Guidelines:
• Still recommended as a safe analgesic during labor and in post-operative settings, especially where opioid abuse is a concern.
• New Safety Data:
• No recent major safety warnings; monitoring advised for respiratory effects, especially in neonates and elderly.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Permissible Range: 15°C to 30°C
• Protection:
• Protect from light and heat.
• Keep in original packaging until use.
• Handling:
• Do not freeze.
• Inspect vial before use; discard if solution is cloudy or discolored.
• Multi-dose Containers: Use aseptic technique; follow hospital policy for expiration after opening.