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Nalbuphine

Pronunciation

Pronunciation

(NAL byoo feen)

Index Terms

  • Nalbuphine HCl
  • Nalbuphine Hydrochloride
  • Nubain

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as hydrochloride:

Generic: 10 mg/mL (1 mL, 10 mL); 20 mg/mL (1 mL, 10 mL)

Pharmacologic Category

  • Analgesic, Opioid
  • Analgesic, Opioid Partial Agonist

Pharmacology

Agonist of kappa opiate receptors and partial antagonist of mu opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression

Metabolism

Hepatic; extensive first-pass metabolism (Errick 1983)

Excretion

Feces; urine (~7% eliminated as unchanged drug and metabolites) (Errick 1983); clearance decreases with increasing age (Bressolle 2011; Jaillon 1989)

Onset of Action

Peak effect: SubQ, IM: <15 minutes; IV: 2 to 3 minutes

Duration of Action

3 to 6 hours

Half-Life Elimination

Children: 0.9 to 3.5 hours; however, overall trend observed is longer half-life as age increases (Bressolle 2011; Jaillon 1989)

Adults: 5 hours

Protein Binding

~50% (Jaillon 1989)

Use: Labeled Indications

Pain, moderate to severe: Relief of moderate to severe pain

Surgical anesthesia supplement: Supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery

Use: Unlabeled

Opioid-induced pruritus

Contraindications

Hypersensitivity to nalbuphine or any component of the formulation

Documentation of allergenic cross-reactivity for morphine and related drugs is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Pain, moderate to severe: IM, IV, SubQ: Based on a 70 kg individual, administer 10 mg every 3 to 6 hours as needed; Maximum dose in nonopioid dependent patients: Single dose: 20 mg; Daily dose: 160 mg

Surgical anesthesia supplement: IV:

US labeling: Induction: 0.3 to 3 mg/kg over 10 to 15 minutes; maintenance doses of 0.25 to 0.5 mg/kg may be given as required

Canadian labeling: Induction: 0.3 mg/kg to 5 mg/kg over 10 to 15 minutes; maintenance doses of 0.25 to 0.5 mg/kg may be given as required

Adjunctive therapy in regional anesthesia: 0.2 to 0.5 mg/kg/dose

Opioid-induced pruritus (off-label use): IV: 2.5 to 5 mg; may repeat dose (Charuluxananan 1999; Charuluxananan 2001; Charuluxananan 2003; Cohen 1992; Ganesh 2007)

Dosing: Geriatric

Refer to adult dosing; use with caution.

Dosing: Pediatric

Pain, moderate to severe (off-label use): Children ≥1 year and Adolescents: IM, IV, SubQ: 0.1 to 0.2 mg/kg every 3 to 4 hours as needed; higher single doses of 0.3 mg/kg have also been used; maximum single dose: 20 mg; maximum daily dose: 160 mg (Bhatt-Mehta 1991; Kliegman 2007)

Dosing: Renal Impairment

There are no specific dosage adjustments provided in the manufacturer’s labeling; however, a reduced dose is recommended. Use with caution.

Dosing: Hepatic Impairment

There are no specific dosage adjustments provided in the manufacturer’s labeling; however, a reduced dose is recommended. Use with caution.

Administration

IM, SubQ: Administer undiluted.

IV: Administer undiluted over at least 2 to 3 minutes; larger induction doses should be administered over 10 to 15 minutes (Nursing 2016)

Compatibility

Stable in D5NS, D10W, LR, NS.

Y-site administration: Incompatible with allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, docetaxel, methotrexate, nafcillin, pemetrexed, piperacillin/tazobactam, sargramostim, sodium bicarbonate.

Compatibility in syringe: Incompatible with diazepam, dimenhydrinate, ketorolac, pentobarbital.

Storage

Store at 20°C to 25°C (68°F to 77°F). Store in original carton; protect from light.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Monitor therapy

Analgesics (Opioid): Mixed Agonist / Antagonist Opioids may diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Exceptions: Buprenorphine; Butorphanol; Nalbuphine; Pentazocine. Avoid combination

Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: Mixed Agonist / Antagonist Opioids may diminish the therapeutic effect of Buprenorphine. This combination may also induce opioid withdrawal. Avoid combination

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

May interfere with certain enzymatic methods used to detect opioids, depending on sensitivity and specificity of the test (refer to test manufacturer for details)

Adverse Reactions

>10%: Central nervous system: Sedation (36%)

1% to 10%:

Central nervous system: Dizziness (5%), headache (3%)

Dermatologic: Cold and clammy skin (9%)

Gastrointestinal: Nausea and vomiting (6%), xerostomia (4%)

<1% (Limited to important or life-threatening): Abdominal pain, abnormal dreams, agitation, anaphylactoid reaction, anaphylaxis, anxiety, asthma, bitter taste, blurred vision, bradycardia, burning sensation, cardiac arrest, confusion, crying, delusions, depersonalization, depression, derealization, diaphoresis, drowsiness, dyspepsia, dysphoria, euphoria, fever, floating feeling, flushing, hallucination, hostility, hypersensitivity reaction, hypertension, hypogonadism (Brennan, 2013; Debono, 2011), hypotension, injection site reaction (pain, swelling, redness, burning), intestinal cramps, laryngeal edema, loss of consciousness, nervousness, numbness, pruritus, pulmonary edema, respiratory depression, respiratory distress, restlessness, seizure, skin rash, speech disturbance, stridor, tachycardia, tingling sensation, tremor, urinary urgency, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac effects: Bradycardia has been reported in patients who did not receive atropine preoperatively. May cause hypotension; use with caution in patients with hypovolemia, or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease, including myocardial infarction patients who have nausea or vomiting.

• CNS depression/coma: Avoid use in patients with CNS depression or coma as these patients are susceptible to intracranial effects of CO2 retention.

• Drug abuse: Use with caution in patients with a history of drug abuse, emotionally unstable patients, or acute alcoholism; potential for drug dependency exists. Tolerance, psychological, and physical dependence may occur with prolonged use.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.

• Hepatic impairment: Use with caution and reduce dose in patients with hepatic impairment.

• Obesity: Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Renal impairment: Use with caution and reduce dose in patients with renal impairment.

• Respiratory disease: Use with caution and at low doses in patients with pre-existing respiratory compromise (eg, hypoxia and/or hypercapnia, uremia, severe infection, concomitant medications, cyanosis, bronchial asthma), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Initial dose reductions may be necessary considering reduced renal or hepatic function.

• Neonates: Neonatal withdrawal syndrome: After chronic maternal exposure to opioids, neonatal withdrawal syndrome may occur in the newborn; monitor neonate closely. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn. Opioid withdrawal syndrome in the neonate, unlike in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts.

Other warnings/precautions:

• Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.

Monitoring Parameters

Relief of pain, respiratory and mental status, blood pressure; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Nalbuphine crosses the placenta. Nalbuphine is approved for use in obstetrical analgesia during labor and delivery. When used for pain relief during labor, opioids may temporarily affect the heart rate of the fetus (ACOG 2002) and severe fetal bradycardia has been reported following use of nalbuphine in labor/delivery. Fetal bradycardia may occur when administered earlier in pregnancy (not documented). Use only if clearly needed, with monitoring to detect and manage possible adverse fetal effects. Naloxone has been reported to reverse bradycardia. Newborn should be monitored for respiratory depression or bradycardia following nalbuphine use in labor.

If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur; monitoring of the neonate is recommended. The minimum effective dose should be used if opioids are needed (Chou 2009). Neonatal abstinence syndrome following opioid exposure may present with autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, increased muscle tone, irritability, seizure, tremor) symptoms (Dow 2012; Hudak 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, fatigue, or sweating a lot. Have patient report immediately to prescriber signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), severe dizziness, passing out, severe headache, difficulty breathing, slow breathing, shallow breathing, confusion, bradycardia, tachycardia, mood changes, severe anxiety, hallucinations, polyuria, difficulty speaking, or vision changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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