Nalbuphine (Nubain, Nalbin) is a synthetic opioid analgesic used in the management of pain that is refractory to non-steroidal anti-inflammatory drugs and other analgesics.

Nalbuphine Uses:

• Pain management:

  • Used to control pain that is severe enough to need an opioid analgesic and for which no other options are effective.

    Limitations of use:

• • Nalbuphine should only be used on patients for whom other treatment alternatives (such as nonopioid analgesics) are ineffective, poorly tolerated, or would otherwise fall short of adequately managing their pain.

• Surgical anesthesia supplement:

  • Supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery.

• Off Label Use of Nalbuphine in Adults:

  • Opioid-induced pruritus

Nalbuphine Dose in Adults

Nalbuphine Dose for the management of pain:

• IM, IV, SubQ:

  • 10 mg every 3 to 6 hours as needed (based on a 70 kg patient);
  • may titrate dose to appropriate effect.
  • Maximum dose in nonopioid-tolerant patients: 20 mg/dose; 160 mg/day.

• Discontinuation of therapy:

  • When discontinuing chronic opioid therapy, the dose should be gradually tapered down.
  • An optimal universal tapering schedule for all patients has not been established.
  • Proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days).
  • Tapering schedules should be individualized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmacokinetics of the opioid being tapered.
  • An even slower taper may be appropriate in patients who have been receiving opioids for a long duration (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events.
  • Monitor carefully for signs/symptoms of withdrawal.
  • If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms.
  • Continue to offer nonopioid analgesics as needed for pain management during the taper;
  • Consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI complaints, muscle spasm) as needed.

Nalbuphine dose in the treatment of Surgical anesthesia supplement:

Intravenous:

• Induction: 0.3 to 3 mg/kg over 10 to 15 minutes
• Maintenance: 0.25 to 0.5 mg/kg as required.

Nalbuphine dose in the treatment of Opioid-induced pruritus (off-label):

Intravenous:

• 2.5 to 5 mg; may repeat the dose.

Nalbuphine Dose in Childrens

Nalbyphine dose in the treatment of moderate to severe Analgesia in children and adolescents:

• Children 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 as a one-time dose perioperatively
• maximum single dose: 20 mg/dose
• maximum daily dose: 160 mg/day.

Nalbuphine Pregnancy Risk Category: D

• In some studies on animal reproduction, adverse events were observed.
• Nalbuphine crosses the placenta.
• Nalbuphine can be used to analgeize labor and delivery with approval
• Using opioids during labour may momentarily change the fetus's heart rate. Severe foetal bradycardia has occasionally occurred after the birth of nalbuphine.
• If administered in the first trimester of pregnancy, fetal bradycardia could occur (not documented).
• Only use if absolutely necessary. Monitor to detect and manage any adverse effects on the fetus.
• Reports have indicated that Naloxone reverses bradycardia.
• After nalbuphine is used in labor, newborns should be closely monitored for signs of respiratory depression and bradycardia.
• A pregnant woman who has been exposed to chronic opioids during pregnancy may experience withdrawal symptoms in her newborn. It is important to monitor the neonate.
• If opioids are required, the minimum effective dosage should be used.
• Neonatal abstinence syndrome may manifest after opioid exposure as autonomic symptoms (such as temperature instability, fever), gastrointestinal symptoms (such as diarrhoea, vomiting), poor feeding/weight gain, or neurologic symptoms (such as high-pitched crying, increased muscle tone, and irritability).

Nalbuphine use during breastfeeding:

• Breast milk contains a small amount of nalbuphine (1% of the maternal dose).
• The natural instinct to nurse in the first hours of birth can be affected by the use of parenteral opioids during labor.
• It is important to monitor the mother and baby for any psychotomimetic reactions if nalbuphine has been given to a pregnant woman.
• Monitor nursing infants who have been exposed to high doses of opioids for prolonged periods should be checked for sedation and apnea.

Nalbuphine Dose in Kidney Disease:

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

Nalbuphine dose in Liver disease:

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

Side Effects of Nalbuphine (Nalbin, Nubain):

• Central nervous system:

  • Sedation
  • Dizziness
  • Headache

• Dermatologic:

  • Cold And Clammy Skin

• Gastrointestinal:

  • Nausea And Vomiting
  • Xerostomia

Contraindications to Nalbuphine (Nubain, Nalbin):

• Hypersensitivity to nalbuphine and any component of the formulation
• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting, or without resuscitative devices
• GI obstruction, including paralytic ileus (known and suspected).

There is not much evidence of cross-reactivity between opioids and allergenic opioids. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

• Surgical abdomen (eg acute appendicitis or pancreatitis).
• Mild pain can be managed by other pain medication
• Acute alcoholism
• Delirium tremens
• Convulsive disorders
• Severe CNS depression
• Elevated cerebrospinal and intracranial pressure
• Head injury
• Monoamine oxidase inhibitor therapy (MAO) can be used concurrently or within 14 days.
• Pregnancy
• Breastfeeding

Warnings and precautions

• Cardiac effects:

  • Patients who received atropine postoperatively have been known to develop Bradycardia.

• CNS depression:

  • CNS depression can lead to impairment of mental or physical abilities. Patients should be cautious about driving or operating machinery that requires mental alertness.

• Hypotension

  • Can cause severe hypotension (including orthostatic hypertension and syncope).
  • Patients with hypovolemia, heart disease (including acute MI), and drugs that can exaggerate hypotensive effects (such as phenothiazines and general anesthetics) should be cautious.
  • After dose titration or initiation, monitor for hypotension symptoms.
  • Patients with circulatory shock should not use this product.

• Respiratory depression [US Boxed Warning]

  • It is possible to develop severe, life-threatening or fatal respiratory depression.
  • You should monitor your respiratory health, especially during dose escalation or initiation.
  • The sedating effects of opioids can be exacerbated by carbon dioxide retention due to opioid-induced respiratory depression.

• Conditions abdominales:

  • Patients with acute abdominal conditions may not be diagnosed or treated appropriately.

• Adrenocortical Insufficiency

  • Patients with adrenal insufficiency (including Addison disease) should be cautious.
  • Long-term opioid abuse can lead to secondary hypogonadism. This could cause infertility, sexual dysfunction, mood disorders, and osteoporosis.

• Insufficiency of the biliary tract:

  • Patients with acute pancreatitis or biliary dysfunction should be cautious
  • Opioids can cause constriction in the sphincter Oddi.

• Cardiovascular disease

  • Patients with heart disease and myocardial injury, as well as patients suffering from nausea or vomiting, should be cautious.

• CNS depression and coma

  • Patients with impaired consciousness and coma should not be given carbon monoxide. They are more susceptible to the intracranial effects.

• Delirium tremens:

  • Patients with delirium-tremens should be cautious.

• Head trauma

  • Patients with intracranial injuries, elevated intracranial pressure, or head injuries should be used with caution
  • It is possible to experience an exaggerated elevation in ICP.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.
  • It is recommended to reduce dosage.

• Obesity:

  • Patients who are obese or morbidly overweight should be treated with caution.

• Prostatic hyperplasia, urinary stricture

  • Patients with prostatic hyperplasia or urinary stricture should be cautious.

• Psychosis:

  • Patients with toxic psychosis should be treated cautiously

• Renal impairment

  • Patients with impaired renal function should be cautious; dosage reduction is recommended.

• Respiratory disease

  • Patients with severe chronic obstructive lung disease or cor pulmonale should be monitored for signs of respiratory depression.
  • Even with therapeutic doses, severe respiratory depression can occur.
  • You might consider using non-opioid analgesics for these patients.

• Seizures:

  • Patients with seizure disorders should be cautious.
  • May cause or exacerbate preexisting seizures.

• Sleep-disordered breathing

  • Patients with sleep-disordered or HF breathing should be advised to avoid opioids for chronic pain.
  • Patients with severe or moderate sleep-disordered breathing should avoid opioids

• Thyroid dysfunction:

  • Patients with thyroid dysfunction should be cautious.

Nalbuphine: Drug Interaction

Monitoring parameters:

• Relief of pain
• Respiratory and mental status
• Blood pressure
• Bowel function

How to administer Nalbuphine (Nubain, Nalbin)?

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.

Mechanism of action of Nalbuphine (Nubain, Nalbin):

• An inhibitor of ascending pain pathways that modifies perception and reaction to pain. It is an antagonist of the kappa opiate receptors in the CNS and a partial antagonist of the mu opiate receptors.
• CNS depression is produced

The onset of action: Peak effect:

• SubQ, IM: <15 minutes
• IV: 2 to 3 minutes

Duration of action:

• 3 to 6 hours

Protein binding:

• ~50%.

Metabolism:

• Hepatic; extensive first-pass metabolism.

Half-life elimination:

• Children: 0.9 to 3.5 hours; however, the overall trend observed is longer half-life as age increases.
• Adults: 5 hours

Excretion:

• Feces
• Urine (~7% eliminated as unchanged drug and metabolites).
• Clearance decreases with increasing age.

International Brand Names of Nalbuphine:

• Nubain
• Analin
• Azerty
• Bain
• Bufigen
• Bufimorf
• Fabitec
• Intapan
• Mexifin
• Nalbufina
• Nalbuk
• Nalbun
• Nalbuphin OrPha
• Nalbutin
• Nalcryn SP
• Nalpain
• Nalphin
• Nubain
• Nubaina
• Nukaine
• Onfor
• Raltrox

Nalbuphine Injection Brand Names in Pakistan: