DailyMed Label: Nalbuphine Hydrochloride

DailyMed Label: Nalbuphine Hydrochloride

2024

DailyMed Prescription

Nalbuphine Hydrochloride

NALBUPHINE HYDROCHLORIDE

Hospira, Inc.

NDC: 0409-1463

NDC: 0409-1464

NDC: 0409-1465

NDC: 0409-1467

NDC: 0409-1463

NDC: 0409-1464

NDC: 0409-1465

NDC: 0409-1467

NDC: 0409-1463

NDC: 0409-1464

NDC: 0409-1465

NDC: 0409-1467

NDC: 0409-1463

NDC: 0409-1464

NDC: 0409-1465

NDC: 0409-1467

NDC: 0409-1463

NDC: 0409-1464

NDC: 0409-1465

NDC: 0409-1467

NDC: 0409-1463

NDC: 0409-1463

NDC: 0409-1465

NDC: 0409-1465

NDC: 0409-1464

NDC: 0409-1464

NDC: 0409-1467

NDC: 0409-1467

Nalbuphine hydrochloride is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. It is chemically related to both the widely used opioid antagonist, naloxone, and the potent opioid analgesic, oxymorphone. Chemically nalbuphine hydrochloride is 17-(cyclobutylmethyl)-4,5α-epoxymorphinan-3,6α,14-triol hydrochloride. Nalbuphine hydrochloride molecular weight is 393.91 and is soluble in H 2 O (35.5 mg/mL at 25ºC) and ethanol (0.8%); insoluble in CHCl 3 and ether. Nalbuphine hydrochloride has pKa values of 8.71 and 9.96. The molecular formula is C 21 H 27 NO 4 ∙ HCl. The structural formula is: Nalbuphine Hydrochloride Injection is a sterile, nonpyrogenic solution of nalbuphine hydrochloride in water for injection. This product may be administered by subcutaneous, intramuscular or intravenous injection. Each milliliter (mL) contains nalbuphine hydrochloride 10 mg or 20 mg; sodium citrate, dihydrate 0.47 mg and citric acid, anhydrous 0.63 mg added as buffers and may contain sodium hydroxide and/or hydrochloric acid for pH adjustment; pH 3.7 (3.0 to 4.5). Contains sodium chloride for tonicity adjustment. Multiple-dose vials contain 1.8 mg/mL methylparaben and 0.2 mg/mL propylparaben added as preservatives. Single-dose products contain no bacteriostat or antimicrobial agent and unused portions must be discarded. Chemical Structure

Nalbuphine Hydrochloride Injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Nalbuphine Hydrochloride Injection can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery. Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see WARNINGS ], reserve Nalbuphine Hydrochloride Injection for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): • Have not been tolerated, or are not expected to be tolerated, • Have not provided adequate analgesia, or are not expected to provide adequate analgesia. Nalbuphine Hydrochloride Injection should not be used for an extended period of time unless the pain ‎remains severe enough to require an opioid analgesic and for which ‎alternative treatment options continue to be inadequate.‎

Nalbuphine Hydrochloride Injection should be administered as a supplement to general anesthesia only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids. Naloxone, resuscitative and intubation equipment, and oxygen should be readily available. Use the lowest effective dosage for the shortest duration of time ‎consistent with individual patient treatment goals [see WARNINGS ]. ‎Because the risk of overdose increases as opioid doses increase, reserve ‎titration to higher doses of Nalbuphine Hydrochloride Injection ‎for patients in whom lower ‎doses are insufficiently effective and in whom the expected benefits of ‎using a higher dose opioid clearly outweigh the substantial risks.‎ There is variability in the opioid analgesic dose and duration needed to ‎adequately manage pain due both to the cause of pain and to individual ‎patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS ]. Respiratory depression can occur at any time during opioid therapy, ‎especially when initiating and following dosage increases with ‎Nalbuphine Hydrochloride Injection‎. Consider this risk when selecting an initial dose and when ‎making dose adjustments [see WARNINGS ].‎ Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The usual recommended adult dose is 10 mg for a 70 kg individual administered subcutaneously, intramuscularly, or intravenously; this dose may be repeated every 3 to 6 hours as necessary. Use the lowest dose necessary to achieve adequate analgesia. Titrate the ‎dose based upon the individual patient’s response to their initial dose of Nalbuphine Hydrochloride Injection. Dosage should be adjusted according to the severity of the pain, physical status of the patient, and other medications which the patient may be receiving [see WARNINGS; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ]. In nontolerant individuals, the recommended single maximum dose is 20 mg with a maximum total daily dose of 160 mg. The use of Nalbuphine Hydrochloride Injection as a supplement to balanced anesthesia requires larger doses than those recommended for analgesia. Induction doses of nalbuphine hydrochloride range from 0.3 mg/kg to 3 mg/kg intravenously to be administered over a 10 to 15 minute period with maintenance doses of 0.25 to 0.5 mg/kg in single intravenous administrations as required. The use of Nalbuphine Hydrochloride Injection may be followed by respiratory depression which can be reversed with the opioid antagonist naloxone hydrochloride. Individually titrate Nalbuphine Hydrochloride Injection to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Nalbuphine Hydrochloride Injection to assess the maintenance of pain control‎, signs and symptoms of opioid withdrawal,‎ and other adverse reactions, as well as to reassess for the development of addiction, abuse, or misuse [see WARNINGS ]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the nalbuphine hydrochloride dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed ‎(including an increase in pain after dosage increase)‎, consider reducing the dosage‎ [see WARNINGS ]. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse events. When a patient who has been taking Nalbuphine Hydrochloride Injection regularly and may be physically‑dependent no longer requires therapy with Nalbuphine Hydrochloride Injection, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue Nalbuphine Hydrochloride Injection in a physically-dependent patient [see WARNINGS , DRUG ABUSE AND DEPENDENCE ].

Nalbuphine Hydrochloride Injection is contraindicated in patients with: • Significant respiratory depression [see WARNINGS ] • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ] • Hypersensitivity to nalbuphine or to any of the other ingredients in Nalbuphine Hydrochloride Injection.

Because nalbuphine is metabolized in the liver and excreted by the kidneys, Nalbuphine Hydrochloride Injection should be used with caution in patients with renal or liver dysfunction and administered in reduced amounts. As with all potent analgesics, Nalbuphine Hydrochloride Injection should be used with caution in patients with myocardial infarction who have nausea or vomiting. During evaluation of Nalbuphine Hydrochloride Injection in anesthesia, a higher incidence of bradycardia has been reported in patients who did not receive atropine pre-operatively. Nalbuphine Hydrochloride Injection may interfere with enzymatic methods for the detection of opioids depending on the specificity/sensitivity of the test. Consult the test manufacturer for specific details. Patients should be advised of the following information: Inform patients that the use of Nalbuphine Hydrochloride Injection, even when ‎taken as recommended, can result in addiction, abuse, and misuse, which can lead to ‎overdose and death [see WARNINGS ].‎ Instruct patients not to share Nalbuphine Hydrochloride Injection with others and to take steps to protect ‎Nalbuphine Hydrochloride Injection from theft or misuse.‎ Inform patients of the risk of life-threatening ‎respiratory depression, including information that the risk is greatest when starting ‎‎Nalbuphine Hydrochloride Injection or when the dosage is increased, and that it can occur even at recommended ‎dosages [see WARNINGS ].‎ Advise patients to seek medical attention if they ‎experience symptoms of hyperalgesia, including worsening pain, increased ‎sensitivity to pain, or new pain [see WARNINGS , ADVERSE REACTIONS ].‎ Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop after discharge from the hospital. Instruct patients to inform their healthcare providers if they are taking, or plan to take serotonergic medications [see PRECAUTIONS; Drug Interactions ]. Inform patients to avoid taking Nalbuphine Hydrochloride Injection while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Nalbuphine Hydrochloride Injection [see Drug Interactions ]. Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see ADVERSE REACTIONS , CLINICAL PHARMACOLOGY ]. Although Nalbuphine Hydrochloride Injection possesses opioid antagonist activity, there is evidence that in nondependent patients it will not antagonize an opioid analgesic administered just before, concurrently, or just after an injection of Nalbuphine Hydrochloride Injection. Therefore, due to additive pharmacologic effects, the concomitant use of other opioid analgesics, benzodiazepines or other CNS depressants such as alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see WARNINGS ]. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome [see PRECAUTIONS; Information for Patients ]. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Nalbuphine Hydrochloride Injection if serotonin syndrome is suspected. Nalbuphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Nalbuphine Hydrochloride Injection and/or the muscle relaxant as necessary. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when Nalbuphine Hydrochloride Injection is used concomitantly with anticholinergic drugs. MAOI (e.g., phenelzine, tranylcypromine, linezolid) interactions with opioids may manifest as serotonin syndrome [see Drug Interactions ] or opioid toxicity (e.g., respiratory depression, coma [see WARNINGS ]). The use of Nalbuphine Hydrochloride Injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. There was no evidence of carcinogenicity in long term animal studies were performed in rats (24 months) and mice (19 months) by oral administration at doses up to 200 mg/kg [12 times the maximum recommended human daily dose (MRHD)] and 200 mg/ per day (6 times the MRDH), respectively. Nalbuphine Hydrochloride Injection induced an increased frequency of mutation in the mouse lymphoma assay. Nalbuphine Hydrochloride Injection did not have mutagenic activity in the Ames test with four bacterial strains, in the Chinese Hamster Ovary HGPRT assays or in the Sister Chromatid Exchange Assay. Clastogenic activity was not observed in the mouse micronucleus test or the cytogenicity bone marrow assay in rats. Female rats were treated with nalbuphine hydrochloride beginning 15 days prior to mating through Lactation Day 20 via subcutaneous doses of 14, 28, or 56 mg/kg/day (0.85, 1.7, or 3.4 times the MRHD of 160 mg/day based on body surface area, respectively). Male rats were treated via oral gavage with the same nalbuphine hydrochloride doses beginning 60 days prior to and throughout mating. There were no adverse effects on either male or female fertility. Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with Nalbuphine Hydrochloride Injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, nalbuphine decreased pup survival and pup body weights when pregnant female rats were treated late in gestation and throughout lactation at 1.7 times the MRHD and when female and male rats treated either prior to mating and throughout gestation and lactation. No malformations were observed in either rats or rabbits at doses 6.1 and 3.9 times the MRHD, respectively [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Severe fetal bradycardia has been reported when nalbuphine hydrochloride is administered during labor. Naloxone may reverse these effects. Although there are no reports of fetal bradycardia earlier in pregnancy, it is possible that this may occur. This drug should be used in pregnancy only if clearly needed, if the potential benefit outweighs the risk to the fetus, and if appropriate measures such as fetal monitoring are taken to detect and manage any potential adverse effect on the fetus. The placental transfer of nalbuphine is high, rapid, and variable with a maternal to fetal ratio ranging from 1:0.37 to 1:6. Fetal and neonatal adverse effects that have been reported following the administration of nalbuphine to the mother during labor include fetal bradycardia, respiratory depression at birth, apnea, cyanosis, and hypotonia. Some of these events have been life-threatening. Maternal administration of naloxone during labor has normalized these effects in some cases. Severe and prolonged fetal bradycardia has been reported. Permanent neurological damage attributed to fetal bradycardia has occurred. A sinusoidal fetal heart rate pattern associated with the use of nalbuphine has also been reported. Nalbuphine Hydrochloride Injection should be used during labor and delivery only if clearly indicated and only if the potential benefit outweighs the risk to the infant. Newborns should be monitored for respiratory depression, apnea, bradycardia and arrhythmias if Nalbuphine Hydrochloride Injection has been used. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Nalbuphine Hydrochloride Injection is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Nalbuphine Hydrochloride Injection, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Pregnant rats were treated with nalbuphine hydrochloride from Gestation Day 6 to 15 via subcutaneous doses of 7, 14, or 100 mg/kg/day (0.4, 0.85, or 6.1 times the MRHD of 160 mg/day based on body surface area, respectively). There was no evidence of malformations or embryotoxicity despite reductions in maternal weight gain in the mid- and high-dose groups. Pregnant rabbits were treated with nalbuphine hydrochloride from Gestation Day 7 to 19 via intravenous doses of 4, 8, or 32 mg/kg/day (0.5, 1, or 3.9 times the MRHD based on body surface area, respectively). There was no evidence of malformations or embryotoxicity despite reductions in maternal weight gain in the high-dose group. Pregnant rats were treated with nalbuphine hydrochloride from Gestation Day 15 to Lactation Day 20 via subcutaneous doses of 14, 28, or 56 mg/kg/day (0.85, 1.7, or 3.4 times the MRHD based on body surface area, respectively). Pup survival was decreased in the mid- and high-dose groups and neonatal body weights were dose dependently reduced. Maternal toxicity was noted in all treatment groups (reduced body weights). Female rats were treated with nalbuphine hydrochloride beginning 15 days prior to mating through Lactation Day 20 via subcutaneous doses of 14, 28, or 56 mg/kg/day (0.85, 1.7, or 3.4 times the MRHD of 160 mg/day based on body surface area, respectively). Male rats were treated via oral gavage with the same oxymorphone hydrochloride doses beginning 60 days prior to and throughout mating. There was reduced pup survival in the high dose group animals and reduced pup body weights in the mid- and high-dose groups. Limited data suggest that Nalbuphine Hydrochloride Injection is excreted in maternal milk but only in a small amount (less than 1% of the administered dose) and with a clinically insignificant effect. Infants exposed to Nalbuphine Hydrochloride Injection through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Elderly patients (aged 65 years or older) may have increased sensitivity to Nalbuphine Hydrochloride Injection. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Nalbuphine Hydrochloride Injection slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system ‎and respiratory depression [see WARNINGS ]. Nalbuphine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

The most frequent adverse reaction in 1066 patients treated in clinical studies with Nalbuphine Hydrochloride Injection was sedation 381 (36%).

Although Nalbuphine Hydrochloride Injection possesses opioid antagonist activity, there is evidence that in nondependent patients it will not antagonize an opioid analgesic administered just before, concurrently, or just after an injection of Nalbuphine Hydrochloride Injection. Therefore, due to additive pharmacologic effects, the concomitant use of other opioid analgesics, benzodiazepines or other CNS depressants such as alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see WARNINGS ]. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome [see PRECAUTIONS; Information for Patients ]. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Nalbuphine Hydrochloride Injection if serotonin syndrome is suspected. Nalbuphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Nalbuphine Hydrochloride Injection and/or the muscle relaxant as necessary. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when Nalbuphine Hydrochloride Injection is used concomitantly with anticholinergic drugs. MAOI (e.g., phenelzine, tranylcypromine, linezolid) interactions with opioids may manifest as serotonin syndrome [see Drug Interactions ] or opioid toxicity (e.g., respiratory depression, coma [see WARNINGS ]). The use of Nalbuphine Hydrochloride Injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

Nalbuphine Hydrochloride Injection is supplied as a sterile solution in single-dose ampuls and multiple‑dose fliptop vials for intramuscular, subcutaneous, or intravenous administration, and available as follows: Unit of Sale Concentration NDC 0409-1463-01 10 mg/ mL Tray of 10 – 1 mL Single-dose Ampuls NDC 0409-1465-01 20 mg/ mL Tray of 10 – 1 mL Single-dose Ampuls NDC 0409-1464-01 100 mg/10 mL Case of 25 – 10 mL Multiple-dose Fliptop Vials (10 mg/ mL) NDC 0409-1467-01 200 mg/10 mL Case of 25 – 10 mL Multiple-dose Fliptop Vials (20 mg/ mL) 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.

Nalbuphine is an agonist at kappa opioid receptors and an antagonist at mµ opioid receptors. Nalbuphine Hydrochloride Injection is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis up to a dosage of approximately 30 mg. 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 mµ opioid analgesics on a regular basis. Nalbuphine produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. However, there may be a ceiling effect for the respiratory depression caused by nalbuphine. Although a mixed agonist/antagonist, the respiratory depressant effects of nalbuphine can be reversed by naloxone. Nalbuphine causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Nalbuphine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase. During use of nalbuphine during anesthesia, a higher incidence of bradycardia has been reported in patients who did not receive atropine pre-operatively. Opioids produce peripheral vasodilation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS ]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time 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 [see ADVERSE REACTIONS ]. Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive. The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonists. The minimum effective analgesic concentration of nalbuphine for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome, and/or the development of analgesic tolerance [see DOSAGE AND ADMINISTRATION ]. The onset of action of Nalbuphine Hydrochloride Injection 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 metabolic pathway for nalbuphine has not been defined, but is likely hepatic.

NDC 0409-1463-71 1 mL Rx only Nalbuphine HCl Injection 10 mg/mL For I.V., I.M., or S.C. Use Protect from light. Dist. by Hospira, Inc. Lake Forest, IL 60045 USA RL-7150 ##-###-AA DMMMYYYY PRINCIPAL DISPLAY PANEL - 1 mL Ampule Label - 1463