Relief of moderate to severe pain such as that associated with acute and chronic medical disorders including cancer, orthopedic problems, renal or biliary colic, migraine or vascular headaches, and surgery.
Avoid increases in dose or frequency of administration which in susceptible individuals might result in physical dependence.
Administration
Administer by sub-Q, IM, or IV injection.
IV Administration
For drug compatibility information, see Compatibility under Stability.
Rate of Administration
For induction of anesthesia: Administer IV over 10–15 minutes.
Dosage
Available as nalbuphine hydrochloride; dosage expressed in terms of the salt.
Adjust dosage according to the severity of pain, physical status of the patient, and other drugs that the patient is receiving.
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). Repeat every 3–6 hours as necessary.
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.
Observe the patient for signs or symptoms of withdrawal (e.g., abdominal cramps, nausea, vomiting, lacrimation, rhinorrhea, anxiety, restlessness, increased temperature, piloerection). If symptoms are troublesome, give IV morphine slowly in small increments until withdrawal symptoms are relieved. However, waiting until the abstinence syndrome abates is probably preferred. If withdrawal symptoms do not occur, increase dosage progressively until the desired level of analgesia is obtained.
Supplement to Balanced Anesthesia
IV
0.3–3 mg/kg for induction of anesthesia. For maintenance, 0.25–0.5 mg/kg as necessary.
Prescribing Limits
Adults
Pain
Patients Not Tolerant to Opiate Agonists
IV, IM, or Sub-Q
Maximum 20 mg as a single dose; maximum 160 mg daily.
Special Populations
Hepatic Impairment
Dosage reduction is recommended.
Renal Impairment
Dosage reduction is recommended.
Cautions
Contraindications
Known hypersensitivity to nalbuphine or any ingredient in the formulation.
Warnings/Precautions
Warnings
Respiratory Effects
Possible respiratory depression. 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.
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.
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.
Abuse Potential
Possible tolerance, psychologic dependence, and physical dependence.
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. Avoid unnecessary increases in dose or frequency of administration; avoid use in anticipation of pain.
CNS Depression
Performance of activities requiring mental alertness and physical coordination may be impaired. 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.
Concurrent use of other CNS depressants may potentiate CNS depression. (See Interactions.)
Head Injury and Increased Intracranial Pressure
Potential for elevation of CSF pressure as a result of vasodilation following carbon dioxide retention. Opiate effects may obscure the existence, extent, or course of intracranial pathology. Use in patients with head injury, other intracranial lesions, or preexisting elevation in intracranial pressure only if the potential benefits justify the possible risks.
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.
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.
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. (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.
MI
Use with caution in patients with MI who exhibit nausea and vomiting.
Bradycardia
During studies evaluating nalbuphine as a supplement to balanced anesthesia, increased incidence of bradycardia reported in patients who did not receive atropine preoperatively.
Specific Populations
Pregnancy
Category B.
Safe use during pregnancy (except during labor and delivery) not established.
Administration during labor and delivery may result in fetal bradycardia or respiratory depression, apnea, cyanosis, and hypotonia in neonates at birth. Adverse effects may resolve in some cases following maternal administration of naloxone during labor. Fetal bradycardia may be severe and prolonged; permanent neurological damage associated with fetal bradycardia reported. In addition, a sinusoidal fetal heart rate pattern associated with maternal use of nalbuphine.
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.
Lactation
Distributed into milk. Caution if used in nursing women.
Pediatric Use
Safety and efficacy not established in children <18 years of age.
Usual doses do not antagonize the effects of an opiate agonist administered immediately before, concurrently with, or just after nalbuphine is given inpatients who are not dependent on opiate agonists
Tests for detection of opiates
Possible interference with enzymatic methods for detection of opiates
Consult test manufacturer for specific details
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.
Onset
Following IV administration, onset of action occurs within 2–3 minutes; peak effects occur in about 30 minutes.
Following IM or sub-Q administration, onset of analgesia occurs within 15 minutes.
Duration
After IV, IM, or sub-Q administration, duration of analgesia is usually 3–6 hours.
Distribution
Extent
Crosses the placenta; fetal plasma concentrations are approximately equivalent to or higher than concurrent maternal plasma concentrations.
Distributed into milk in small amounts (<1% of administered dose).
Plasma Protein Binding
Not appreciably bound.
Elimination
Metabolism
Metabolized in the liver.
Elimination Route
Nalbuphine and its metabolites are excreted principally in feces via biliary secretion and to a lesser extent in urine.
Half-life
Plasma half-life is 5 hours. Elimination half-life averaged 2.4 hours (range: 1.3–3.9 hours) following a single IV dose in pregnant women in active labor.
Stability
Storage
Parenteral
Injection
25°C (may be exposed to 15–30°C). Protect from excessive light.
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
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.
Believed to be a partial agonist at the κ opiate receptor and an antagonist or partial antagonist at the μ receptor and to have minimal agonist activity at the Σ receptor.
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.
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).
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.
Importance of taking exactly as prescribed; do not exceed the recommended dosage. Do not abruptly discontinue the drug after prolonged usage.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and alcohol consumption, as well as any concomitant illnesses.
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
Importance of advising patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Nalbuphine Hydrochloride
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Parenteral
Injection, for IV infusion via compatible patient-controlled infusion device only
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
