Nalbuphine

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• phenothiazines such as chlorpromazine (Thorazine), thioridazine (Mellaril), fluphenazine (Prolixin), perphenazine (Triavil), prochlorperazine (Compazine), and trifluoperazine (Stelazine)
• opioids such as morphine
• sedatives such as zolpidem (Ambien), diazepam (Valium)

This is not a complete list of nalbuphine drug interactions. Ask your doctor of pharmacist for more information.

You should not be treated with nalbuphine if you are allergic to it, or if you have:

• severe asthma or breathing problems; or

• a stomach or bowel obstruction (including paralytic ileus).

Your dose needs may be different if you are already using a similar opioid medicine and are tolerant to it. Before you receive nalbuphine, tell your doctor about all other pain medicines you have recently used.

To make sure nalbuphine is safe for you, tell your doctor if you have:

• any type of breathing problem or lung disease;

• problems with your pancreas or adrenal gland;

• a history of head injury, brain tumor, or seizures;

• a history of drug abuse, alcohol addiction, or mental illness;

• liver or kidney disease;

• a slow heart rate, or if you have recently had a heart attack;

• if you use an MAO inhibitor such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine; or

• if you use a sedative like Valium (diazepam, alprazolam, lorazepam, Ativan, Klonopin, Restoril, Tranxene, Versed, Xanax, and others).

Some medicines can interact with nalbuphine and cause a serious condition called serotonin syndrome. Be sure your doctor knows if you also take medicine for depression, mental illness, Parkinson's disease, migraine headaches, serious infections, or prevention of nausea and vomiting. Ask your doctor before making any changes in how or when you take your medications.

Nalbuphine is more likely to cause breathing problems in older adults and people who are severely ill, malnourished, or otherwise debilitated.

Although nalbuphine is sometimes used during labor and delivery, this medicine can cause breathing problems or life-threatening withdrawal symptoms in the newborn. If you receive nalbuphine during labor and delivery, your caregivers will watch your baby closely for any serious side effects of nalbuphine. These effects can usually be treated quickly in a hospital setting.

Unless you are given nalbuphine during labor or delivery, tell your doctor if you are pregnant before you are treated with this medicine.

Nalbuphine can pass into breast milk and may cause side effects in the nursing baby. Tell your doctor if you are breast-feeding.

• It is used to ease pain.
• It may be given to you for other reasons. Talk with the doctor.

Effects on the Endocrine System

Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date.

Nalbuphine Hydrochloride Injection is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis. Receptor studies show that Nalbuphine hydrochloride binds to mu, kappa, and delta receptors, but not to sigma receptors. Nalbuphine hydrochloride is primarily a kappa agonist/partial mu antagonist analgesic.

The onset of action of Nalbuphine hydrochloride occurs within 2 to 3 minutes after intravenous administration, and in less than 15 minutes following subcutaneous or intramuscular injection. The plasma half-life of Nalbuphine is 5 hours, and in clinical studies the duration of analgesic activity has been reported to range from 3 to 6 hours.

The opioid antagonist activity of Nalbuphine hydrochloride is one-fourth as potent as nalorphine and 10 times that of pentazocine.

Nalbuphine hydrochloride may produce the same degree of respiratory depression as equianalgesic doses of morphine. However, Nalbuphine Hydrochloride Injection exhibits a ceiling effect such that increases in dose greater than 30 mg do not produce further respiratory depression in the absence of other CNS active medications affecting respiration.

Nalbuphine hydrochloride by itself has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mµ agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), Nalbuphine hydrochloride may partially reverse or block opioid-induced respiratory depression from the mµ agonist analgesic. Nalbuphine Hydrochloride Injection may precipitate withdrawal in patients dependent on opioid drugs. Nalbuphine Hydrochloride Injection should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis.

Clinical Presentation

Acute overdose with Nalbuphine Hydrochloride Injection alone can be manifested by respiratory depression and dysphoria. Acute overdose with Nalbuphine Hydrochloride Injection and other opioids or CNS depressants can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Treatment of Overdose

In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to Nalbuphine hydrochloride overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to Nalbuphine Hydrochloride Injection overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of Nalbuphine, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product's prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.

Nalbuphine Hydrochloride Injection for intramuscular, subcutaneous, or intravenous use is a sterile solution available in:

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Protect from excessive light. Store in carton until contents have been used.

LAB-0838-2.0

1/2017

Manufactured by Hospira, Inc., Lake Forest, IL 60045 USA

N+ and NOVAPLUS are registered trademarks of Vizient, Inc.

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)

Refer to adult dosing. Initiate therapy with reduced doses and use with caution.

>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

10 mg/70 kg administered IV, IM, or subcutaneous every 3 to 6 hours as needed.
Maximum single dose: 20 mg
Maximum daily dose: 160 mg

Supplement to balanced anesthesia:
Induction dose: 0.3 to 3 mg/kg IV over 10 to 15 min.
Maintenance dose: 0.25 to 0.5 mg/kg IV once. May repeat as necessary.

Summary of Use during Lactation

Nalbuphine is excreted into breastmilk in amounts much smaller than the dose given to infants for analgesia. Because nalbuphine has poor oral absorption, it is unlikely to adversely affect the breastfed infant. No special precautions are required. Labor pain medication may delay the onset of lactation.

Drug Levels

In adults, nalbuphine has very poor oral bioavailability and is metabolized to inactive metabolites. Parenteral doses of 75 to 300 mcg/kg are used in infant and children.

Maternal Levels. Seven women who were 3 to 7 days postpartum received a single 20 mg IM dose of nalbuphine. Milk samples were collected several times beginning at 1 hour and finishing at 24 hours after the dose. The half-life of elimination from milk was about 8 hours. A reported peak milk level in one mother was about 25 mcg/L and it occurred 1 hour after the dose. The average milk level over the 24 hour study period in all 7 mothers was about 5 mcg/L (range 1.5 to 20 mcg/L).[1] Using the peak level reported in this study, an exclusively breastfed infant would receive a dosage of 3.7 mcg/kg daily, equivalent to 1.1 % of the maternal weight-adjusted dosage. Using the average milk level from this study, an exclusively breastfed infant would ingest 0.75 mcg/kg daily, equivalent to 0.2% of the maternal weight-adjusted dosage or 0.25 to 1% of the infant parenteral dosage.

Eighteen women were administered nalbuphine 0.2 mg/kg intravenously every 4 hours (average 25.5 mcg/kg daily) for pain following cesarean section. Milk samples were collected every 3 hours during the second day of drug administration. Because of small milk volumes, only 32 samples from 14 of the women were collected. The average milk nalbuphine concentration was 42 mcg/L, and the average maximum milk concentration was 61 mcg/L. The authors estimated that a fully breastfed infant would receive an average of 7 mcg/kg daily which amounts to about 0.6% of the weight-adjusted maternal dosage.[2]

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Nalbuphine can increase serum prolactin.[3] However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

A study compared women who received nalbuphine or butorphanol during labor (n = 26) to those who received no analgesia (n = 22). The time to effective breastfeeding was longer (46.5 minutes) in the analgesia group than in the no analgesia group (35.4 minutes).[4]

A national survey of women and their infants from late pregnancy through 12 months postpartum compared the time of lactogenesis II in mothers who did and did not receive pain medication during labor. Categories of medication were spinal or epidural only, spinal or epidural plus another medication, and other pain medication only. Women who received medications from any of the categories had about twice the risk of having delayed lactogenesis II (>72 hours) compared to women who received no labor pain medication.[5]

Alternate Drugs to Consider

Acetaminophen, Butorphanol, Hydromorphone, Ibuprofen, Morphine

References

1. Wischnik A, Wetzelsberger N, Lucker PW. [Elimination von nalbuphin in die muttermilch [Elimination of nalbuphine in human milk]. Arzneimittelforschung. 1988;38:1496-8. PMID: 3196391

2. Jacqz-Aigrain E, Serreau R, Boissinot C, Popon MJ et al. Excretion of ketoprofen and nalbuphine in human milk during treatment of maternal pain after delivery. Ther Drug Monit. 2007;29:815-8. PMID: 18043481

3. Saarialho-Kere U. Psychomotor, respiratory and neuroendocrinological effects of nalbuphine and haloperidol, alone and in combination, in healthy subjects. Br J Clin Pharmacol. 1988;26:79-87. PMID: 3060191

4. Crowell MK, Hill PD, Humenick SS. Relationship between obstetric analgesia and time of effective breast feeding. J Nurse Midwifery. 1994;39:150-6. PMID: 7931694

5. Lind JN, Perrine CG, Li R. Relationship between use of labor pain medications and delayed onset of lactation. J Hum Lact. 2014;30:167-73. PMID: 24451212

LactMed Record Number

371

Last Revision Date

20150310

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.