Nalbuphine

Nalbuphine is an Opioid agonist-antagonist belonging to the analgesic class.

Nalbuphine is an opioid agonist-antagonist used to treat pain, for pre and postoperative analgesia, and for analgesia in labor and delivery.

The mean absolute bioavailability was 81% and 83% for the 10 and 20 mg intramuscular doses, respectively, and 79% and 76% following 10 and 20 mg of subcutaneous nalbuphine. Nalbuphine crosses the placenta and distributed in breast milk (small amounts). Plasma protein binding: Approx 50%. Nalbuphine undergoes extensive first-pass metabolism in GI mucosa and liver. Excretion of Nalbuphine is from urine and faeces (as unchanged drug and conjugates). The Elimination half-life is about 5 hours.

Nalbuphine shows side effects like Dry mouth, headache.

Nalbuphine is available in the form of Injectable solution.

Nalbuphine is available in India, US, China, Japan, Poland, Netherland, Canada, France, Italy, Germany and Australia.

Nalbuphine is an Analgesic belonging to the class Opioid agonist-antagonist.

Nalbuphine is an agonist of kappa opiate receptors and partial antagonist of mu opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression.

The onset of action can be observed within <15 minutes on subcutaneous and intramuscular administration, and within 2 to 3 minutes on intravenous administration.

The effect of Nalbuphine lasts for an average duration of 3 to 6 hours.

Nalbuphine is available in the form of Injectable solution.

Nalbuphine Injectable solution is given via subcutaneous, intramuscular and intravenous route.

Nalbuphine is an opioid pain medicine used to relieve moderate to severe pain. It is also used with other medications to relieve pain before, during, or after surgery and other medical procedures.

Nalbuphine is an Opioid agonist-antagonist belonging to the analgesic class.

Nalbuphine is an agonist of kappa opiate receptors and partial antagonist of mu opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression.

Nalbuphine is approved for use in the following clinical indications

• Opioid-induced pruritus, treatment
• Pain management
• Surgical anesthesia, supplement

• Opioid-induced pruritus, treatment

IV: 2 to 5 mg as a single dose.

• Pain management

IM, IV, Subcutaneous Dose: 10 mg every 3 to 6 hours as needed (based on a 70 kg patient); adjust dose according to patient response. Maximum dose in non–opioid-tolerant patients: 20 mg/dose and up to 160 mg/day.

• Surgical anesthesia, supplement

IV: Induction: 0.3 to 3 mg/kg over 10 to 15 minutes; maintenance: 0.25 to 0.5 mg/kg; repeat as needed.

Nalbuphine is available in various strengths as 10 mg/mL; 20 mg/mL.

Nalbuphine is available in the form of Injectable solution.

Nalbuphine is contraindicated in patients with

• Significant respiratory depression.
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.
• Known or suspected gastrointestinal obstruction, including paralytic ileus.
• Hypersensitivity to nalbuphine to any of the other ingredients in Nalbuphine.

• Cardiac effects

Bradycardia has been reported in patients who did not receive atropine preoperatively.

• CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Hypotension

May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute myocardial infarction [MI]), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

• Respiratory depression

Fatal respiratory depression may occur; monitor closely. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately in the event of a known or suspected overdose.

• Abdominal conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency

Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis.

• Biliary tract impairment

Use with caution in patients with biliary tract dysfunction or acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

• Cardiovascular disease

Use with caution in patients with cardiovascular disease, including MI patients who have nausea or vomiting.

• CNS depression/coma

Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO₂ retention.

• Head trauma

Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment

Use with caution in patients with hepatic impairment; dosage reduction recommended.

• Mental health conditions

Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to potential increased risk for opioid use disorder and overdose; more frequent monitoring is recommended.

• Prostatic hyperplasia/urinary stricture

Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Renal impairment

Use with caution in patients with renal impairment; dosage reduction recommended.

• Respiratory disease

Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Seizures

Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.

• Sleep-related disorders

Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and CNS depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing.

• Thyroid dysfunction

Use with caution in patients with thyroid dysfunction.

• Benzodiazepines or other CNS depressants

Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.

Consumption of alcohol is not recommended during treatment with this medicine due to the increased risk of side effects such as dizziness, lightheadedness, and fainting.

Limited data suggest that Nalbuphine (nalbuphine hydrochloride) is excreted in maternal milk but only in a small amount (less than 1% of the administered dose) and with a clinically insignificant effect. Caution should be exercised when Nalbuphine is administered to a nursing woman.

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with Nalbuphine in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

• Common

Sedation, Dizziness, headache, Cold and clammy skin, Nausea and vomiting, xerostomia.

• Rare

Abdominal pain, abnormal dreams, agitation, allodynia (opioid-induced hyperalgesia), 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, 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.

• Alizapride

May enhance the CNS depressant effect of CNS Depressants.

• Alvimopan

Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation.

• Amphetamines

May enhance the analgesic effect of Opioid Agonists.

• Anticholinergic Agents

May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination.

• Azelastine (Nasal)
• May enhance the CNS depressant effect of CNS Depressants.
• Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.

• Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Bromopride

May enhance the CNS depressant effect of CNS Depressants.

• Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

• Buprenorphine

Opioids (Mixed Agonist / Antagonist) may diminish the therapeutic effect of Buprenorphine. This combination may also induce opioid withdrawal.

• Cannabinoid-Containing Products

CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products.

• Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

• Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

• CNS Depressants

May enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

• Daridorexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended.

• Desmopressin

Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

• Dexmedetomidine

CNS Depressants may enhance the CNS depressant effect of Dexmedetomidine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression.

• Difelikefalin

May enhance the CNS depressant effect of CNS Depressants.

• Dimethindene (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Diuretics

Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.

• Droperidol

May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use.

• Eluxadoline

Opioid Agonists may enhance the constipating effect of Eluxadoline.

• Flunarizine

CNS Depressants may enhance the CNS depressant effect of Flunarizine.

• Flunitrazepam

CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available.

• Gastrointestinal Agents (Prokinetic)

Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Hydroxyzine

May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant.

• Lemborexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary.

• Lisuride

May enhance the CNS depressant effect of CNS Depressants.

• Lofexidine

May enhance the CNS depressant effect of CNS Depressants.

• Magnesium Sulfate

May enhance the CNS depressant effect of CNS Depressants.

• Methotrimeprazine

CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression.

• Metoclopramide

May enhance the CNS depressant effect of CNS Depressants.

• Metyrosine

CNS Depressants may enhance the sedative effect of Metyrosine.

• Minocycline (Systemic)

May enhance the CNS depressant effect of CNS Depressants.

• Monoamine Oxidase Inhibitors

Opioid Agonists may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

The common side effects of Nalbuphine include the following

• Common side effects

Dry mouth, headache.

• Rare side effects

Extreme tiredness, nausea, vomiting, loss of appetite, weakness, or dizziness, changes in heartbeat, agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea, inability to get or keep an erection, irregular menstruation, decreased sexual desire.

• Pregnancy

Pregnancy Category B

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with Nalbuphine in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

• Nursing Mothers

Limited data suggest that Nalbuphine (nalbuphine hydrochloride) is excreted in maternal milk but only in a small amount (less than 1% of the administered dose) and with a clinically insignificant effect. Caution should be exercised when Nalbuphine is administered to a nursing woman.

• Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Symptoms: Respiratory depression, CV effects, other CNS effects, sleepiness, mild dysphoria.

• Pharmacodynamic

Nalbuphine is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. Nalbuphine's analgesic potency is essentially equivalent to that of morphine on a milligram basis. The opioid antagonist activity of nalbuphine is about one-fourth to that of nalorphine and 10 times to that of pentazocine. Nalbuphine by itself has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mu agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), nalbuphine may partially reverse or block opioid-induced respiratory depression from the mu agonist analgesic. Nalbuphine may precipitate withdrawal in patients dependent on opioid drugs. Nalbuphine should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis.

• Pharmacokinetics

Absorption

The mean absolute bioavailability was 81% and 83% for the 10 and 20 mg intramuscular doses, respectively, and 79% and 76% following 10 and 20 mg of subcutaneous nalbuphine.

Distribution

Nalbuphine crosses the placenta and distributed in breast milk (small amounts). Plasma protein binding: Approx 50%.

Metabolism and Excretion

Nalbuphine undergoes extensive first-pass metabolism in GI mucosa and liver.

Excretion of Nalbuphine is from urine and faeces (as unchanged drug and conjugates). The Elimination half-life is about 5 hours.

• https://go.drugbank.com/drugs/DB00844
• https://medlineplus.gov/druginfo/meds/a682668.html#:~:text=Nalbuphine injection is used is,surgery and other medical procedures.
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
• https://reference.medscape.com/drug/nalbuphine-343329
• https://www.drugs.com/pregnancy/nalbuphine.html
• https://www.uptodate.com/contents/nalbuphine-drug-information?search=nalbuphine&source=panel_search_result&selectedTitle=1~120&usage_type=panel&kp_tab=drug_general&display_rank=1