Drug class: Opiate Partial Agonists
VA class: CN101
CAS number: 23277-43-2

Medically reviewed by Drugs.com on Mar 19, 2024. Written by ASHP.

Introduction

Analgesic; opiate partial agonist.^{a b}

Uses for Nalbuphine

Pain

Relief of pain that is severe enough to require an opiate analgesic and for which alternative treatment options (e.g., nonopiate analgesics) have not been, or are not expected to be, adequate or tolerated.⁷⁰⁴

Preoperative and postoperative sedation and analgesia.^{a b}

Supplement to balanced surgical anesthesia.^{a b}

Obstetric analgesia during labor and delivery.^{106 a b}

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.^{431 432 433 435} Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435} Optimize concomitant use of other appropriate therapies.^{432 434 435} (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

Related/similar drugs

acetaminophen, cyclobenzaprine, tramadol, naproxen, oxycodone, Tylenol, lidocaine

Nalbuphine Dosage and Administration

General

Managing Opiate Therapy for Acute Pain

• Optimize concomitant use of other appropriate therapies.^{432 434 435}

• When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Effects under Cautions.)

• When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.⁴³²

• For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435} Do not prescribe larger quantities for use in case pain continues longer than expected;^{411 432} instead, reevaluate patient if severe acute pain does not remit.^{411 431 435}

• For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.^{430 431 432}

• Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.^{430 431}

• Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.^{430 432} When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.^{430 431}

Administration

Administer by sub-Q, IM, or IV injection.^{a b}

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Rate of Administration

For induction of anesthesia: Administer IV over 10–15 minutes.^{a b}

Dosage

Available as nalbuphine hydrochloride; dosage expressed in terms of the salt.^a

Adjust dosage according to the severity of pain, physical status of the patient, and other drugs that the patient is receiving.^{a b}

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.^{411 413 431 432 435}

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.^{700 703} (See Specific Drugs and Laboratory Tests under Interactions.)

Adults

Pain

Patients Not Tolerant to Opiate Agonists

IV, IM, or Sub-Q

10 mg in a 70-kg patient (about 0.14 mg/kg).^{a b} Repeat every 3–6 hours as necessary.^{a b}

Patients Tolerant to Opiate Agonists

IV, IM, or Sub-Q

Initially, administer 25% of the usual dose of nalbuphine in patients chronically receiving morphine, meperidine, codeine, or other opiate agonists with a similar duration of action.^b

Observe the patient for signs or symptoms of withdrawal (e.g., abdominal cramps, nausea, vomiting, lacrimation, rhinorrhea, anxiety, restlessness, increased temperature, piloerection).^b If symptoms are troublesome, give IV morphine slowly in small increments until withdrawal symptoms are relieved.^b However, waiting until the abstinence syndrome abates is probably preferred.^b If withdrawal symptoms do not occur, increase dosage progressively until the desired level of analgesia is obtained.^b

Supplement to Balanced Anesthesia

IV

0.3–3 mg/kg for induction of anesthesia.^{a b} For maintenance, 0.25–0.5 mg/kg as necessary.^{a b}

Prescribing Limits

Adults

Pain

For acute pain not related to trauma or surgery, limit prescribed quantity of opiate analgesics to amount needed for the expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435}

Patients Not Tolerant to Opiate Agonists

IV, IM, or Sub-Q

Maximum 20 mg as a single dose; maximum 160 mg daily.^{a b}

Special Populations

Hepatic Impairment

Dosage reduction is recommended.^{a b}

Renal Impairment

Dosage reduction is recommended.^{a b}

Cautions for Nalbuphine

Contraindications

• Known hypersensitivity to nalbuphine or any ingredient in the formulation.^a

Warnings/Precautions

Warnings

Respiratory Effects

Possible respiratory depression.^a Administer with caution and in low doses in patients with impaired respiration caused by other drugs, uremia, bronchial asthma, severe infection, cyanosis, or respiratory obstruction.^a

Should be administered as a supplement to general anesthesia only by individuals who are experienced in the use of parenteral anesthetics and in the maintenance of an adequate airway and respiratory support.^a

Facilities and personnel necessary for intubation, administration of oxygen, and assisted or controlled respiration should be readily available; an opiate antagonist (e.g., naloxone) should also be readily available.^a

Routinely discuss availability of the opiate antagonist naloxone with all patients receiving new or reauthorized prescriptions for opiate analgesics.⁷⁵⁰

Consider prescribing naloxone for patients receiving opiate analgesics who are at increased risk of opiate overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with history of opiate or substance use disorder, those with medical conditions that could increase sensitivity to opiate effects, those who have experienced a prior opiate overdose)^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ Even if patients are not receiving an opiate analgesic, consider prescribing naloxone if the patient is at increased risk of opiate overdosage (e.g., those with current or past diagnosis of opiate use disorder [OUD], those who have experienced a prior opiate overdose).⁷⁵⁰

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiate agonists or opiate partial agonists, including nalbuphine, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiates, alcohol) may result in profound sedation, respiratory depression, coma, and death.^{416 417 418 700 701 702 703} Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.^{416 417 418 435 700 701}

Reserve concomitant use of nalbuphine and other CNS depressants for patients in whom alternative treatment options are inadequate.^{700 703} (See Specific Drugs and Laboratory Tests under Interactions.)

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.^{a b} When used in emergency procedures, keep the patient under observation until recovery from the drug’s effects that would affect driving or other potentially hazardous tasks has occurred.^{a b}

Concurrent use of other CNS depressants may potentiate CNS depression^{a b} and may result in profound sedation, respiratory depression, coma, or death.^{700 703} (See Concomitant Use with Benzodiazepines or Other CNS Depressants under Cautions.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.⁴⁰⁰ Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.⁴⁰⁰

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.⁴⁰⁰ If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.⁴⁰⁰ In some patients, switching to a different opiate improved symptoms.⁴⁰⁰

Head Injury and Increased Intracranial Pressure

Potential for elevation of CSF pressure as a result of vasodilation following carbon dioxide retention.^{a b} Opiate effects may obscure the existence, extent, or course of intracranial pathology.^{a b} Use in patients with head injury, other intracranial lesions, or preexisting elevation in intracranial pressure only if the potential benefits justify the possible risks.^{a b}

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence.^a

Prescribe cautiously for patients who are emotionally unstable or have a history of opiate abuse; closely supervise these patients when long-term therapy is contemplated.^a Avoid unnecessary increases in dose or frequency of administration; avoid use in anticipation of pain.^a

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic or anaphylactoid and other serious hypersensitivity reactions, including shock, respiratory distress, respiratory arrest, bradycardia, cardiac arrest, hypotension, and laryngeal edema, reported.¹⁰⁶

Sulfite Sensitivity

Some formulations contain sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.¹⁰⁵

General Precautions

Patients Dependent on Opiates

Use with caution in patients who have been chronically receiving opiate agonists; nalbuphine does not suppress the abstinence syndrome in these patients; high doses may precipitate withdrawal symptoms (e.g., abdominal cramps, nausea, vomiting, lacrimation, rhinorrhea, anxiety, restlessness, increased temperature, piloerection) as a result of opiate antagonist effect.^{a b} (See Patients Tolerant to Opiate Agonists under Dosage and Administration.)

Biliary Tract Surgery

Possible spasm of Oddi’s sphincter; use with caution in patients about to undergo biliary tract surgery.^a

MI

Use with caution in patients with MI who exhibit nausea and vomiting.^a

Bradycardia

During studies evaluating nalbuphine as a supplement to balanced anesthesia, increased incidence of bradycardia reported in patients who did not receive atropine preoperatively.^{a b}

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;^{400 401 402 403 404} causality not established.⁴⁰⁰ Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.⁴⁰⁰ Perform appropriate laboratory testing in patients with manifestations of hypogonadism.⁴⁰⁰

Specific Populations

Pregnancy

Category B.^a

Safe use during pregnancy (except during labor and delivery) not established.^{a b}

Administration during labor and delivery may result in fetal bradycardia or respiratory depression, apnea, cyanosis, and hypotonia in neonates at birth.^{a b} Adverse effects may resolve in some cases following maternal administration of naloxone during labor.¹⁰⁶ Fetal bradycardia may be severe and prolonged; permanent neurological damage associated with fetal bradycardia reported.¹⁰⁶ In addition, a sinusoidal fetal heart rate pattern associated with maternal use of nalbuphine.¹⁰⁶

Use with caution in women during labor and delivery, especially in those delivering premature infants; monitor neonates for respiratory depression, apnea, bradycardia, and cardiac arrhythmias.¹⁰⁶

Lactation

Distributed into milk.^a Caution if used in nursing women.^a

Pediatric Use

Safety and efficacy not established in children <18 years of age.^a

Hepatic Impairment

Use with caution and in reduced dosage.^{a b}

Renal Impairment

Use with caution and in reduced dosage.^{a b}

Common Adverse Effects

Sedation, sweatiness, clamminess, nausea, vomiting, dizziness, vertigo, dry mouth, headache.^a

Drug Interactions

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.⁴⁰⁰ May occur at usual dosages.⁴⁰⁰ Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.⁴⁰⁰ (See Advice to Patients.)

If concomitant use of other serotonergic drugs is warranted, monitor patients for serotonin syndrome, particularly during initiation of therapy and dosage increases.⁴⁰⁰

If serotonin syndrome is suspected, discontinue nalbuphine, other opiate therapy, and/or any concurrently administered serotonergic agents.⁴⁰⁰

Specific Drugs and Laboratory Tests

Nalbuphine Pharmacokinetics

Absorption

Bioavailability

Undergoes first-pass metabolism in the GI mucosa and/or liver following oral administration; only about 1/5 as effective for pain relief when given orally as when given IM.^b

Onset

Following IV administration, onset of action occurs within 2–3 minutes; peak effects occur in about 30 minutes.^{a b}

Following IM or sub-Q administration, onset of analgesia occurs within 15 minutes.^{a b}

Duration

After IV, IM, or sub-Q administration, duration of analgesia is usually 3–6 hours.^{a b}

Distribution

Extent

Crosses the placenta; fetal plasma concentrations are approximately equivalent to or higher than concurrent maternal plasma concentrations.¹⁰⁴

Distributed into milk in small amounts (<1% of administered dose).^a

Plasma Protein Binding

Not appreciably bound.^b

Elimination

Metabolism

Metabolized in the liver.^b

Elimination Route

Nalbuphine and its metabolites are excreted principally in feces via biliary secretion and to a lesser extent in urine.^b

Half-life

Plasma half-life is 5 hours.^{a b} Elimination half-life averaged 2.4 hours (range: 1.3–3.9 hours) following a single IV dose in pregnant women in active labor.¹⁰⁴

Stability

Storage

Parenteral

Injection

25°C (may be exposed to 15–30°C).^a Protect from excessive light.^a

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Actions

• Analgesic effect may result from an interaction with an opiate receptor site in the CNS (probably in or associated with the limbic system); opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but other mechanisms are probably also involved.^b

• Believed to be a partial agonist at the κ opiate receptor^{100 101 102 103 107} and an antagonist or partial antagonist at the μ receptor^{100 102 107} and to have minimal agonist activity at the Σ receptor.^{100 103}

• Analgesic activity of IM, IV, or sub-Q nalbuphine is approximately equal to that of IM, IV, or sub-Q morphine on a weight basis.^b

• Produces respiratory depression, sedation, and miosis; however, respiratory depression in healthy adults plateaus with cumulative IV doses of 30 mg (given in doses of 10 mg/hour).^b

Advice to Patients

• Potential for nalbuphine to impair mental alertness or physical coordination; do not drive or operate machinery until effects on individual are known.^a

• Risk of respiratory depression following overdosage.⁷⁵⁰ Advise patients of the benefits of naloxone following opiate overdose and of their options for obtaining the drug.⁷⁵⁰

• Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.^{700 703} Importance of informing patients that nalbuphine should not be combined with alcohol.⁷⁰⁰

• Importance of taking exactly as prescribed; do not exceed the recommended dosage.^a Do not abruptly discontinue the drug after prolonged usage.^a

• Potential risk of serotonin syndrome with concurrent use of nalbuphine and other serotonergic agents.⁴⁰⁰ Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.⁴⁰⁰

• Potential risk of adrenal insufficiency.⁴⁰⁰ Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.⁴⁰⁰

• Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.⁴⁰⁰ Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.⁴⁰⁰

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and alcohol consumption, as well as any concomitant illnesses.^b

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^a

• Importance of advising patients of other important precautionary information.^a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Medical Disclaimer