NAL-byoo-feen

Therapeutic Classification: opioid analgesics

Pharmacologic Classification: opioid agonists analgesics

• Moderate to severe pain.
• Supplement to balanced anesthesia.
• Pain control during labor.
• Sedation before surgery.

• Binds to opiate receptors in the CNS.
• Alters the perception of and response to painful stimuli while producing generalized CNS depression.
• In addition, has partial antagonist properties, which may result in opioid withdrawal in physically dependent patients.

• Decreased pain.

Absorption: Well absorbed after IM and SUBQ administration. IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Mostly metabolized by the liver and eliminated in the feces via biliary excretion. Minimal amounts excreted unchanged by the kidneys.

Half-life: Children (1–8 yr): 0.9 hr; Adults: 3.5–5 hr.

(analgesia)

Contraindicated in:

• Hypersensitivity to nalbuphine or bisulfites
• Patients physically dependent on opioids and who have not been detoxified (may precipitate withdrawal).

Use Cautiously in:

• Personal or family history of substance use disorder or mental illness
• Head trauma
• ↑intracranial pressure
• Severe renal impairment
• Severe hepatic impairment
• Severe pulmonary disease
• Hypothyroidism
• Adrenal insufficiency
• Undiagnosed abdominal pain
• Prostatic hyperplasia
• Patients who have recently received opioid agonists
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk. Has been used during labor but may cause respiratory depression in the newborn; prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant. May cause respiratory depression and excessive sedation in infant
• Pedi: Safety and effectiveness not established in children
• Geri: Dose ↓ suggested in older adults.

CV: hypertension, orthostatic hypotension, palpitations.

Derm: ↑sweating, clammy feeling.

EENT: blurred vision, diplopia, miosis (high doses).

Endo: adrenal insufficiency.

GI: dry mouth, nausea, vomiting, constipation, ileus.

GU: urinary urgency.

Neuro: dizziness, headache, sedation, confusion, dysphoria, euphoria, floating feeling, hallucinations, unusual dreams.

Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA).
Misc: allodynia, opioid-induced hyperalgesia, physical dependence, psychological dependence, tolerance.

Drug-Drug:

• Use with extreme caution in patients receiving MAO inhibitors (may result in unpredictable, severe reactions; ↓ initial dose of nalbuphine to 25% of usual dose).
• Use with benzodiazepines or other CNS depressants, including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
• May precipitate withdrawal in patients who are physically dependent on opioid agonists.
• Avoid concurrent use with other opioid agonists; may diminish analgesic effect.
• Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, tramadol, trazodone, mirtazapine, 5HT₃ receptor antagonists, linezolid, methylene blue, and triptans, may ↑ risk of serotonin syndrome.

Drug-Natural Products:

• Concomitant use of kava-kava, valerian, skullcap, chamomile, or hops can ↑ CNS depression.

Analgesia

• IM, SC, IV (Adults): Usual dose is 10 mg every 3–6 hr (max = 20 mg/dose or 160 mg/day).
• IM, SC, IV (Children): 0.1–0.15 mg/kg every 3–6 hr (max = 20 mg/dose or 160 mg/day).

Supplement to Balanced Anesthesia

• IV (Adults): Initial: 0.3–3 mg/kg over 10–15 min. Maintenance: 0.25–0.5 mg/kg as needed.

(Generic available)

• Solution for injection: 10 mg/mL; 20 mg/mL;

• Assess type, location, and intensity of pain before and 1 hr after IM or 30 min (peak) after IV administration. When titrating opioid doses, increases of 25–50% should be administered until there is either a 50% ↓ in the patient’s pain rating on a numeric or visual analogue scale or the patient reports satisfactory pain relief. A repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal. Patients requiring doses higher than 20 mg should be converted to an opioid agonist. Nalbuphine is not recommended for prolonged use or as first-line therapy for acute or cancer pain.
• An equianalgesic chart (see Appendix K) should be used when changing routes or when changing from one opioid to another.
• Assess BP, HR, and respiratory rate before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Dose may need to be ↓ by 25–50%. Monitor for respiratory depression, especially during initiation or following dose ↑; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea, sleep-related hypoxemia). Nalbuphine produces respiratory depression, but this does not markedly ↑ with increased doses.
• Monitor for severe hypotension, including orthostatic hypotension and syncope, in ambulatory patients, especially in patients with compromised ability to maintain BP.
• Assess bowel function routinely. Institute prevention of constipation with ↑ intake of fluids and bulk and with laxatives to minimize constipating effects. Administer stimulant laxatives routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid-induced constipation.
• Assess previous analgesic history. Antagonistic properties may induce withdrawal symptoms (vomiting, restlessness, abdominal cramps, ↑ BP and temperature) in patients physically dependent on opioids.
• Although this drug has a low potential for dependence, prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Most patients who receive nalbuphine for pain do not develop psychological dependence. If tolerance develops, changing to an opioid agonist may be required to relieve pain.
• Assess risk for opioid addiction, abuse, or misuse prior to administration.

• May cause ↑ serum amylase and lipase.

• If an opioid antagonist is required to reverse respiratory depression or coma, naloxone is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by IV push every 2 min. For children and patients weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain.

• High Alert:Do not confuse nalbuphine with naloxone.
• Explain therapeutic value of medication before administration to enhance the analgesic effect.
  • Regularly administered doses may be more effective than as needed administration. Analgesic is more effective if administered before pain becomes severe.
  • Coadministration with nonopioid analgesics may have additive effects and permit lower opioid doses.
  • Nalbuphine should be discontinued gradually to prevent withdrawal symptoms after long-term use. Monitor frequently to manage pain and withdrawal symptoms (restlessness; lacrimation; rhinorrhea; yawning; perspiration; chills; myalgia; mydriasis; irritability; anxiety; backache; joint pain; weakness; abdominal cramps; insomnia; nausea; anorexia; vomiting; diarrhea; ↑ BP, respiratory rate, or HR). If withdrawal symptoms occur, pause the taper for a period of time or ↑ the dose of opioid analgesic to the previous dose, and then proceed with a slower taper. Also, monitor patients for changes in mood, emergence of suicidal thoughts, or use of other substances. A multimodal approach to pain management may optimize the treatment of chronic pain and assist with the successful tapering of the opioid analgesic.
• REMS: FDA strongly encourages health care professionals to complete a REMS-compliant education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain, available at OpioidAnalgesicREMSBlueprint. Information on programs can be found at 1-800-503-0784 or .
• Discuss availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing therapy, especially if patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. However, the presence of risk factors for overdose should not prevent the proper management of pain in any patient.
• IM: Administer deep into well-developed muscle. Rotate sites of injections.

IV Administration:

• May give IV undiluted.
• 10–20 mg/mL.
• Rate: Administer slowly, each 10 mg over 3–5 min.
• Y-Site Compatibility:
  • acetaminophen
  • amifostine
  • amikacin
  • aminocaproic acid
  • aminophylline
  • amiodarone
  • argatroban
  • arsenic trioxide
  • ascorbic acid
  • atropine
  • azithromycin
  • aztreonam
  • benztropine
  • bivalirudin
  • bleomycin
  • bumetanide
  • buprenorphine
  • butorphanol
  • calcium chloride
  • calcium gluconate
  • cangrelor
  • carboplatin
  • carmustine
  • caspofungin
  • cefazolin
  • cefotaxime
  • cefotetan
  • cefoxitin
  • ceftazidime
  • ceftriaxone
  • cefuroxime
  • chlorpromazine
  • cisatracurium
  • cladribine
  • clindamycin
  • cyanocobalamin
  • cyclophosphamide
  • cytarabine
  • dacarbazine
  • dactinomycin
  • daptomycin
  • daunorubicin
  • dexamethasone
  • dexmedetomidine
  • dexrazoxane
  • digoxin
  • diltiazem
  • diphenhydramine
  • dobutamine
  • dopamine
  • doxorubicin hydrochloride
  • doxorubicin liposomal
  • doxycycline
  • enalaprilat
  • ephedrine
  • epinephrine
  • epirubicin
  • epoetin alfa
  • eptifibatide
  • ertapenem
  • erythromycin
  • esmolol
  • etoposide
  • etoposide phosphate
  • famotidine
  • fentanyl
  • filgrastim
  • fluconazole
  • fludarabine
  • fluorouracil
  • foscarnet
  • fosphenytoin
  • gemcitabine
  • gentamicin
  • glycopyrrolate
  • granisetron
  • heparin
  • hetastarch
  • idarubicin
  • ifosfamide
  • insulin regular
  • irinotecan
  • isoproterenol
  • labetalol
  • LR
  • leucovorin calcium
  • levofloxacin
  • lidocaine
  • linezolid
  • lorazepam
  • magnesium sulfate
  • mannitol
  • melphalan
  • meperidine
  • mesna
  • metoclopramide
  • metoprolol
  • midazolam
  • milrinone
  • mitoxantrone
  • morphine
  • multivitamins
  • mycophenolate
  • naloxone
  • nicardipine
  • nitroglycerin
  • nitroprusside
  • norepinephrine
  • octreotide
  • ondansetron
  • oxaliplatin
  • oxytocin
  • paclitaxel
  • palonosetron
  • pamidronate
  • papaverine
  • penicillin G
  • phentolamine
  • phenylephrine
  • phytonadione
  • potassium acetate
  • potassium chloride
  • procainamide
  • prochlorperazine
  • promethazine
  • propofol
  • propranolol
  • protamine
  • pyridoxine
  • remifentanil
  • rituximab
  • rocuronium
  • sodium acetate
  • succinylcholine
  • sufentanil
  • tacrolimus
  • theophylline
  • thiamine
  • thiotepa
  • tigecycline
  • tirofiban
  • tobramycin
  • topotecan
  • vancomycin
  • vasopressin
  • vecuronium
  • verapamil
  • vinblastine
  • vincristine
  • vinorelbine
  • voriconazole
  • zoledronic acid
• Y-Site Incompatibility:
  • alemtuzumab
  • allopurinol
  • amphotericin B deoxycholate
  • amphotericin B lipid complex
  • amphotericin B liposomal
  • anidulafungin
  • azathioprine
  • cefepime
  • cyclosporine
  • dantrolene
  • diazepam
  • docetaxel
  • folic acid
  • furosemide
  • ganciclovir
  • gemtuzumab ozogamicin
  • hydrocortisone
  • imipenem/cilastatin
  • indomethacin
  • ketorolac
  • methotrexate
  • methylprednisolone
  • mitomycin
  • pantoprazole
  • pemetrexed
  • pentamidine
  • pentobarbital
  • phenobarbital
  • phenytoin
  • piperacillin/tazobactam
  • sargramostim
  • sodium bicarbonate
  • trastuzumab
  • trimethoprim/sulfamethoxazole
.

• Explain purpose and side effects of nalbuphine to patient. Instruct them how and when to ask for pain medication. Do not stop taking drug without consulting health care professional. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Medication Guidebefore starting and periodically during therapy in case of changes.
• May cause drowsiness or dizziness. Advise patient to call for assistance when ambulating and to avoid driving or other activities requiring alertness until response to the medication is known.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to notify health care professional if pain control is not adequate or if severe or persistent side effects occur.
• Emphasize the importance of aggressive prevention of constipation with the use of nalbuphine.
• Caution patient to change positions slowly to minimize orthostatic hypotension.
• Advise patient that frequent mouth rinses, good oral hygiene, and sugarless gum or candy may ↓ dry mouth.
• Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
• Advise patient to avoid concurrent use of alcohol or other CNS depressants with this medication.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal (irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, failure to gain weight); usually occur the first days after birth. Monitor infants exposed to nalbuphine through breast milk for excess sedation and respiratory depression. Chronic use may reduce fertility in females and males.

• Decrease in severity of pain without significant alteration in level of consciousness or respiratory status.

Nubain