NALBUPHINE HYDROCHLORIDE 
Pronounciation
Trade Name(s)
- Nubain
Individualize dose, taking into account the patient’s severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse. Use lowest effective dose for the shortest duration consistent with the patient’s treatment goals.
10 mg/70 kg. May repeat every 3 to 6 hours. In nontolerant patients, the recommended single maximum dose is 20 mg. Maximum total daily dose is 160 mg. Titrate to a dose and interval that provides adequate analgesia and minimizes adverse reactions; see Dose Adjustments.
Supplement to balanced anesthesia:
A loading dose of 0.3 to 3 mg/kg over 10 to 15 minutes. Maintain desired level of balanced anesthesia with 0.25 to 0.5 mg/kg as required. Administered only under the direction of the anesthesiologist.
Reduced dose may be required in elderly, cachectic, or debilitated patients; in impaired liver or renal function; in patients with limited pulmonary reserve; and in the presence of other CNS depressants.
■ See Drug/Lab Interactions.
May be given undiluted.
No data available from manufacturer.
Store at CRT. Avoid freezing and/or prolonged exposure to light.
Manufacturer lists as incompatible with nafcillin and ketorolac.
Other sources suggest specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Each 10 mg or fraction thereof over at least 2 to 3 minutes. Frequently titrated according to symptom relief and respiratory rate.
Supplement to balanced anesthesia:
See Usual Dose.
A synthetic narcotic agonist-antagonist analgesic. Binds to kappa and mu receptors. Acts as an agonist at kappa receptors and as an antagonist at mu receptors. It equals morphine in analgesic effect. May produce the same degree of respiratory depression as an equianalgesic dose of morphine. However, it exhibits a ceiling effect such that dose increases greater than 30 mg do not produce further respiratory depression in the absence of other CNS-active medications that affect respiration. Has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered after or concurrently with a mu agonist opioid analgesic (e.g., morphine, oxymorphone, fentanyl), nalbuphine may partially reverse or block opioid-induced respiratory depression from the mu agonist analgesic. May precipitate withdrawal in patients dependent on opioid drugs. Onset of pain relief occurs within 2 to 3 minutes and lasts about 3 to 6 hours. Metabolized in the liver. Some excretion in feces and urine. Crosses the placental barrier. Secreted in breast milk.
Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
■ Preoperative and postoperative analgesia.
■ Supplement to balanced anesthesia.
■ Obstetric analgesia during labor and delivery.
Opioid-induced pruritus.
Because of the risk for addiction, abuse, and misuse, even at recommended doses, reserve nalbuphine for use in patients for whom alternative treatment options (e.g., nonopioid analgesics or opioid combination products):
Significant respiratory depression.
■ Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.
■ Known or suspected GI obstruction, including paralytic ileus.
■ Hypersensitivity to nalbuphine or its components.
Serious, life-threatening, or fatal respiratory depression may occur, particularly when used concomitantly with other opioids or CNS depressants. Respiratory depression may occur at any time, but risk is greatest during initiation of therapy or after a dose increase. To reduce the risk of respiratory depression, proper dosing and titration are essential. Overestimating the nalbuphine dose when converting patients from another opioid product can result in a fatal overdose with the first dose.
■ Adequate facilities should be available for monitoring and ventilation. An opioid antagonist (e.g., naloxone), resuscitative and intubation equipment and oxygen should be readily available.
■ Use with extreme caution in patients with COPD, cor pulmonale, a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; these patients are at increased risk for decreased respiratory drive, including apnea, even at recommended doses. Consider using nonopioid analgesics, or administer under careful medical supervision at the lowest effective dose.
■ Use with caution and reduce initial doses in elderly, cachectic, or debilitated patients and in patients with severe impairment of hepatic, pulmonary, or renal function. Consider using nonopioid analgesics.
■ Cases of serotonin syndrome have been reported during concomitant use of nalbuphine with serotonergic drugs
■ Cases of adrenal insufficiency have been reported with opioid use, more often after more than 1 month of use. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids and wean the patient off the opioid to allow adrenal function to recover. Another opioid may be tried; some cases reported use of a different opioid without recurrence of adrenal insufficiency.
■ May cause severe hypotension, including orthostatic hypotension and syncope, in ambulatory patients or in any patient whose ability to maintain blood pressure has been compromised by depleted blood volume or concomitant administration of drugs that can cause hypotension (e.g., anesthetics, phenothiazines); see Drug/Lab Interactions. In patients with circulatory shock, nalbuphine-induced vasodilation may further reduce cardiac output and blood pressure. Use should be avoided.
■ Use caution in patients with head injury, brain tumors, or increased intracranial pressure. Respiratory depression may cause an increased PCO2, cerebral vasodilation, and increased intracranial pressure. Clinical course of head injury may be obscured. Avoid use in patients with impaired consciousness or coma.
■ Use with caution in patients with biliary tract disease, including acute pancreatitis; may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions.
■ May increase the frequency of seizures in patients with a convulsive disorder, and may induce or aggravate seizures in some clinical settings.
■ Use caution in patients with myocardial infarction who have nausea and vomiting or compromised cardiac function; effect on heart not fully evaluated.
■ When used with anesthesia, a high incidence of bradycardia has been reported in patients who did not receive atropine preoperatively.
■ Should be administered as a supplement to general anesthesia only by persons specifically trained in the use of IV anesthetics and in the management of the respiratory effects of potent opioids.
■ Do not abruptly discontinue nalbuphine in patients who are physically dependent; dose must be tapered gradually.
■ Nalbuphine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing nalbuphine, and monitor all patients regularly for the development of these behaviors and conditions. Strategies to reduce the risk of diversion or misuse should be used by health care facilities that use this and other controlled substances.
■ See prescribing information for further discussion regarding abuse, addiction, physical dependence, and tolerance.
■ Do not abruptly discontinue nalbuphine in patients who are physically dependent; dose must be tapered gradually.
Naloxone, oxygen, and equipment to establish and maintain an airway must be available.
■ Monitor for respiratory depression, especially during initiation of therapy (within the first 24 to 72 hours) or after a dose increase.
■ Assess baseline pain, reassess after administration of nalbuphine, and adjust dose or interval as required.
■ Monitor vital signs and oxygenation and observe patient frequently.
■ Keep patient supine to minimize side effects; orthostatic hypotension and fainting may occur. Observe closely during ambulation.
■ Monitor patients who may be susceptible to the intracranial effects of CO2 retention for increasing intracranial pressure and signs of sedation and respiratory depression.
■ Monitor patients with biliary tract disease for worsening of symptoms.
■ Monitor patients with a history of seizure disorders for worsening seizure control.
■ Monitor for S/S of serotonin syndrome (e.g., mental status changes [e.g., agitation, coma, hallucinations], autonomic instability [e.g., hyperthermia, labile blood pressure, tachycardia], neuromuscular aberrations [e.g., hyperreflexia, incoordination, rigidity], and/or GI symptoms [e.g., diarrhea, nausea, vomiting]). Onset of symptoms may occur within hours to days of concomitant use of opioids with serotonergic drugs.
■ Adhere to prescribed bowel care regimen to avoid constipation and/or impaction. Maintain adequate hydration.
■ See Drug/Lab Interactions.
Avoid use of alcohol, MAO inhibitors, or other CNS depressants. Review all medications for interactions.
■ Request assistance for ambulation.
■ Use caution performing any task that requires alertness; may cause dizziness, euphoria, and sedation.
■ Report unrelieved pain or side effects or S/S of serotonin syndrome.
■ May result in severe constipation. Scheduled bowel regimen recommended.
■ May result in addiction, abuse, and misuse.
Use during pregnancy (other than labor and delivery) only if benefits justify risks.
■ Prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. Infants born to mothers receiving nalbuphine during pregnancy should be monitored closely and treated for neonatal opioid withdrawal syndrome if indicated. See literature for treatment protocols.
■ Severe fetal bradycardia has been reported when nalbuphine is administered during labor. Take appropriate measures (e.g., fetal monitoring) to detect and manage potential adverse effects to the fetus.
■ Fetal and neonatal bradycardia, respiratory depression at birth, apnea, cyanosis, hypotonia, and a sinusoidal fetal heart rate pattern have been reported. Some of these events have been life-threatening. Maternal or neonatal administration of naloxone may reverse these effects. Permanent neurologic damage attributed to fetal bradycardia has occurred. Fetal death has been reported when mothers received nalbuphine during labor and delivery. Use during labor and delivery only if clearly indicated and if benefit outweighs risk. Use during or immediately before labor is not recommended when other analgesic techniques are more appropriate. Newborns should be monitored for respiratory depression, apnea, bradycardia, and arrhythmias if nalbuphine has been used.
■ Use caution with breastfeeding. Monitor infants exposed to nalbuphine through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped.
■ Safety and effectiveness in pediatric patients under 18 years of age have not been established.
May be more sensitive to effects (e.g., respiratory depression, constipation, dizziness, urinary retention). Respiratory depression is the chief risk for elderly patients treated with opioids.
■ Analgesia should be effective with lower doses.
■ Consider age-related organ impairment.
Although nalbuphine possesses opioid antagonist activity, there is evidence that it will not antagonize an opioid analgesic administered just before, concurrently, or just after an injection of nalbuphine in nondependent patients. Therefore due to additive pharmacologic effects, the concomitant use of other opioid analgesics, benzodiazepines, or other CNS depressants may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for patients for whom alternative treatment options are inadequate. Use minimum effective dose for the shortest duration possible, and monitor for S/S of respiratory depression and sedation.
■ Serotonin syndrome has been reported with the concomitant use of opioids, including nalbuphine, and other drugs that affect the serotonergic neurotransmitter system (e.g., selective serotonin reuptake inhibitors [SSRIs], serotonin and norepinephrine reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], triptans, 5-HT3 receptor antagonists, mirtazapine, trazodone, tramadol, MAO inhibitors, linezolid, and IV methylene blue). Careful observation, particularly during treatment initiation and dose adjustment, is required with concomitant use.
■ Severe and unpredictable potentiation of MAO inhibitors has been reported. MAO inhibitor interactions may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). Use of nalbuphine is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring BP and S/S of CNS and respiratory depression.
■ Nalbuphine may enhance the neuromuscular blocking action of skeletal muscle relaxants, increasing the degree of respiratory depression. Monitor patient and decrease dose if indicated.
■ Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Increase dose of diuretic if needed.
■ Concomitant use with anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
■ Use in patients who are receiving a full opioid agonist analgesic may reduce the analgesic effect and/or precipitate withdrawal symptoms. Avoid concomitant use.
■ Depending on the test used, nalbuphine may interfere with enzymatic methods for the detection of opiates.
Sedation is the most commonly reported adverse reaction. Less frequent adverse reactions are dizziness/vertigo, dry mouth, headache, nausea and vomiting, and sweaty/clammy skin. Adverse reactions that occur in 1% or fewer of patients are abdominal cramps, asthma, bitter taste, blurred vision, bradycardia, burning, CNS effects (e.g., confusion, crying, depression, dysphoria, euphoria, faintness, feeling of heaviness, floating, hallucinations, hostility, nervousness, restlessness, tingling, unreality, and unusual dreams), dyspepsia, dyspnea, flushing and warmth, hypersensitivity reactions (e.g., anaphylaxic/anaphylactoid reactions, bronchospasm, diaphoresis, edema, nausea and vomiting, pruritus, rash, shakiness, stridor, weakness, and wheezing), hypertension, hypotension, itching, respiratory depression, speech difficulties, tachycardia, urinary urgency, and urticaria.
Abdominal pain, adrenal insufficiency, agitation, anxiety, depressed level of consciousness, fever, injection site reaction, pulmonary edema, seizures, serotonin syndrome, somnolence, and tremor. Death from severe allergic reactions has been reported. Fetal death has been reported when mothers received nalbuphine during labor and delivery.
Acute overdose with nalbuphine alone can be manifested by dysphoria and respiratory depression. Acute overdose with nalbuphine and other opioids or CNS depressants can be manifested by apnea, atypical snoring, bradycardia, cardiac arrest, circulatory depression or collapse, cold and clammy skin, constricted pupils, hypotension (severe), partial or complete airway obstruction, pulmonary edema, respiratory depression or arrest, skeletal muscle flaccidity, somnolence progressing to stupor or coma, and death.
With increasing severity of any side effect or onset of symptoms of overdose, discontinue the drug and notify the physician. Naloxone hydrochloride will reverse severe cardiovascular, CNS, and respiratory reactions. Naloxone use should be reserved for situations in which clinically significant respiratory or circulatory depression is present. Titrate naloxone dose carefully to avoid precipitating an acute abstinence syndrome or uncontrolled pain. The duration of action of nalbuphine may exceed the duration of action of naloxone. Monitor patient carefully. Repeat doses of naloxone may be required. A patent airway, artificial ventilation, oxygen therapy, and other symptomatic treatment (e.g., fluids, vasopressors) must be instituted promptly. Resuscitate as necessary.