ide injection. to reduce the risk of respiratory depression, proper dosing and titration of nalbuphine hydrochloride injection is essential [see dosage & administration ]. overestimating the nalbuphine hydrochloride injection dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. opioids can cause sleep-related breathing disorders including central sleep apnea (csa) and sleep-related hypoxemia. opioid use increases the risk of csa in a dose-dependent fashion. in patients who present with csa, consider decreasing the opioid dosage using best practices for opioid taper [see dosage & administration ]. risks from concomitant use with benzodiazepines or other cns depressants profound sedation, respiratory depression, coma, and death may result from the concomitant use of nalbuphine hydrochloride injection with benzodiazepines or other cns depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other cns depressant drugs with opioid analgesics [see precautions; drug interactions]. if the decision is made to prescribe a benzodiazepine or other cns depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. in patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other cns depressant than indicated in the absence of an opioid, and titrate based on clinical response. if an opioid analgesic is initiated in a patient already taking a benzodiazepine or other cns depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. follow patients closely for signs and symptoms of respiratory depression and sedation. advise both patients and caregivers about the risks of respiratory depression and sedation when nalbuphine hydrochloride injection is used with benzodiazepines or other cns depressants (including alcohol and illicit drugs). advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other cns depressant have been determined. screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional cns depressants including alcohol and illicit drugs [see precautions ; drug interactions and information for patients]. life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients the use of nalbuphine hydrochloride injection in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. patients with chronic pulmonary disease nalbuphine hydrochloride injection-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of use of nalbuphine hydrochloride injection [see warnings ]. elderly, cachectic, or debilitated patients life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see warnings ]. monitor such patients closely, particularly when initiating and titrating nalbuphine hydrochloride injection and when nalbuphine hydrochloride injection is given concomitantly with other drugs that depress respiration [see warnings]. alternatively, consider the use of non-opioid analgesics in these patients. adrenal insufficiency cases of adrenal insufficiency have been reported with opioid use, more often following greater than 1 month of use. presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. if adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. the information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. head injury and increased intracranial pressure the possible respiratory depressant effects and the potential of potent analgesics to elevate cerebrospinal fluid pressure (resulting from vasodilation following co2 retention) may be markedly exaggerated in the presence of head injury, intracranial lesions or a pre-existing increase in intracranial pressure. furthermore, potent analgesics can produce effects which may obscure the clinical course of patients with head injuries. therefore, nalbuphine hydrochloride injection should be used in these circumstances only when essential, and then should be administered with extreme caution. use in ambulatory patients nalbuphine hydrochloride injection may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery. therefore, nalbuphine hydrochloride injection should be administered with caution to ambulatory patients who should be warned to avoid such hazards. use in emergency procedures maintain patient under observation until recovered from nalbuphine hydrochloride injection effects that would affect driving or other potentially dangerous tasks. use in pregnancy (other than labor) severe fetal bradycardia has been reported when nalbuphine hydrochloride injection 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. avoid the use of nalbuphine hydrochloride injection in pregnant women unless 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. use during labor and delivery 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 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 has been used. addiction, abuse, and misuse nalbuphine hydrochloride is a synthetic opioid agonist-antagonist analgesic. as an opioid, nalbuphine hydrochloride injection exposes users to the risks of addiction, abuse, and misuse [see drug abuse and dependence ]. although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed nalbuphine hydrochloride injection. addiction can occur at recommended dosages and if the drug is misused or abused. assess each patient's risk for opioid addiction, abuse, or misuse. risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). the potential for these risks should not, however, prevent the proper management of pain in any given patient. opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. consider these risks when prescribing or dispensing nalbuphine hydrochloride injection. strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity. contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

tion and container permit. initial dosage 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. 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. titration and maintenance of therapy individually titrate nalbuphine hydrochloride injection to a dose that provides adequate analgesia and minimizes adverse reactions. continually reevaluate patients receiving nalbuphine hydrochloride to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring 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 unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse events. discontinuation of nalbuphine hydrochloride injection 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 ].

us: speech difficulty, urinary urgency, blurred vision, flushing and warmth. allergic reactions: anaphylactic/anaphylactoid and other serious hypersensitivity reactions have been reported following the use of nalbuphine and may require immediate, supportive medical treatment. these reactions may include shock, respiratory distress, respiratory arrest, bradycardia, cardiac arrest, hypotension, or laryngeal edema. some of these allergic reactions may be life-threatening. other allergic-type reactions reported include stridor, bronchospasm, wheezing, edema, rash, pruritus, nausea, vomiting, diaphoresis, weakness, and shakiness. events observed during post-marketing surveillance of nalbuphine hydrochloride injection due to the nature and limitations of spontaneous reporting, causality has not been established for the following adverse events received for nalbuphine hydrochloride injection: abdominal pain, pyrexia, depressed level or loss of consciousness, somnolence, tremor, anxiety, pulmonary edema, agitation, seizures, and injection site reactions such as pain, swelling, redness, burning, and hot sensations. death has been reported from severe allergic reactions to nalbuphine hydrochloride injection treatment. fetal death has been reported where mothers received nalbuphine hydrochloride injection during labor and delivery. serotonin syndrome: cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. adrenal insufficiency: cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

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.