Instructions for use Nalbuphine-Darnitsa solution for injection 10 mg/ml in ampoules 2 ml No. 5
Composition
active ingredient: nalbuphine hydrochloride;
1 ml of solution contains nalbuphine hydrochloride 10 mg;
Excipients: sodium citrate, citric acid monohydrate, sodium chloride, sodium hydroxide or hydrochloric acid, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent, colorless or almost colorless liquid.
Pharmacotherapeutic group
Analgesics. Opioids. Morphine derivatives.
ATX code N02A F02.
Pharmacological properties
Pharmacodynamics.
Nalbuphine hydrochloride is an agonist of kappa-opioid receptors and an antagonist of mu-opioid receptors.
Nalbuphine is a potent analgesic whose analgesic effect is equivalent to that of morphine in milligrams at a dosage of approximately 30 mg.
The opioid antagonist activity of nalbuphine is one quarter lower than that of nalorphine and 10 times higher than that of pentazocine.
Nalbuphine may cause respiratory depression similar to equivalent analgesic doses of morphine.
However, nalbuphine exhibits a saturation effect, so increasing the dose above 30 mg does not cause further respiratory depression in the absence of other central nervous system (CNS)-active drugs that affect respiration.
Nalbuphine has potent opioid antagonist activity at doses equal to or less than its analgesic dose.
When administered after or simultaneously with mu-opioid receptor agonists (e.g., morphine, oxymorphone, fentanyl), nalbuphine may partially reduce or eliminate the respiratory depression caused by them. Nalbuphine may cause withdrawal symptoms in patients dependent on opioid drugs. Nalbuphine should be used with caution in patients who have been regularly receiving mu-opioid analgesics.
Effects on the CNS.
Nalbuphine causes respiratory depression by direct action on the respiratory centers of the brainstem. Respiratory depression results from a decrease in the sensitivity of the respiratory centers of the brainstem to increases in carbon dioxide pressure and to electrical stimulation. However, a saturation effect may be observed for the respiratory depression caused by nalbuphine. Although nalbuphine is a mixed agonist/antagonist, naloxone can counteract its respiratory depressant effects.
Nalbuphine causes miosis even in complete darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pons lesions of hemorrhagic or ischemic origin may have similar symptoms). Due to hypoxia resulting from overdose, marked mydriasis rather than miosis may be observed.
Effects on the gastrointestinal tract and other smooth muscles.
Nalbuphine causes a decrease in motility associated with an increase in the tone of the smooth muscles of the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are reduced. Propulsive waves of peristalsis in the colon are reduced and tone may increase to the point of spasm, leading to constipation. Other opioid effects may include decreased biliary and pancreatic secretions, spasm of the sphincter of Oddi, and a transient increase in serum amylase.
Effect on the cardiovascular system.
When nalbuphine was used during anesthesia, there were reports of a higher incidence of bradycardia in patients who did not receive atropine before surgery.
Opioids cause peripheral vasodilation, which can lead to orthostatic hypotension or syncope.
Manifestations of histamine release and/or peripheral vasodilation may include itching, flushing, red eyes, sweating, and/or orthostatic hypotension.
Impact on the endocrine system.
Opioids suppress the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans. They also stimulate the secretion of prolactin, growth hormone (GH), and pancreatic secretion of insulin and glucagon.
Long-term opioid use can affect the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency, which may manifest as decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.
The causal role of opioids in the clinical syndrome of hypogonadism is unknown because various medical, physical, and psychological stressors and lifestyle factors that may affect gonadal hormone levels have not been adequately controlled in studies conducted to date.
Impact on the immune system.
Opioids have been shown to differentially affect components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids are mildly immunosuppressive.
Concentration-efficiency ratio.
The minimum effective analgesic concentration will vary widely among patients, especially those previously treated with strong opioid agonists. The minimum effective analgesic concentration of nalbuphine hydrochloride for an individual patient may increase over time due to increased pain, development of a new pain syndrome, and/or development of tolerance.
The onset of action of nalbuphine is within 2–3 minutes after intravenous administration and less than 15 minutes after subcutaneous or intramuscular injection. The plasma half-life of nalbuphine is 5 hours. In clinical studies, the duration of analgesic action was 3 to 6 hours.
The metabolic pathway of nalbuphine has not been determined, but metabolism probably occurs in the liver.
Indication
Nalbuphine-Darnitsa is prescribed for the treatment of severe pain syndrome for which the use of opioid analgesics is justified and for which alternative treatment methods are ineffective. The drug Nalbuphine-Darnitsa is also recommended as an additional therapy in mixed anesthesia for the purpose of preoperative and postoperative analgesia, as well as for obstetric analgesia during childbirth.
Application restrictions
Due to the risk of addiction, abuse and misuse associated with opioid analgesics, even when taken at recommended doses (see section "Special instructions"), the use of the drug Nalbuphine-Darnitsa should be limited to patients in whom alternative treatments (e.g., non-opioid analgesics) are not available:
- associated with intolerance or suspected intolerance;
- do not provide adequate analgesia or adequate analgesic effect is not expected when taken.
Contraindication
- Hypersensitivity to nalbuphine hydrochloride or to any other component of the drug.
- Known or suspected gastrointestinal obstruction, including paralytic ileus.
- Use of the drug in acute inflammatory diseases of the abdominal organs (in particular, acute appendicitis or pancreatitis), as this may complicate diagnosis.
- Mild pain that can be relieved with other pain medications.
- Acute or severe bronchial asthma, chronic airway obstruction or asthmatic status.
- Severe respiratory depression, elevated blood carbon dioxide levels, and pulmonary cor pulmonale.
- Acute alcohol poisoning, delirium, or seizures.
- Severe CNS depression, increased intracranial pressure, head injury.
- Use of monoamine oxidase inhibitors (MAOIs) and within 14 days of stopping MAOI therapy.
- Pregnancy or breastfeeding (except for use during childbirth).
Interaction with other medicinal products and other types of interactions
Benzodiazepines and other CNS depressants.
Although Nalbuphine-Darnitsa has opioid receptor antagonist activity, there is evidence that in non-addicted patients it will not antagonize an opioid analgesic administered immediately before, simultaneously with, or immediately after Nalbuphine-Darnitsa. Therefore, due to additive pharmacological effects, concomitant use of nalbuphine hydrochloride with other opioid analgesics, benzodiazepines, or other CNS depressants (e.g., alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, neuroleptics, and other opioids) may increase the risk of respiratory depression, deep sedation, coma, and death.
Concomitant use of such drugs should be limited to patients in whom alternative therapies are ineffective. Doses and duration of use should be minimized. Patients should be carefully monitored for signs of respiratory depression and sedation.
Serotonergic drugs.
Concomitant use of opioid analgesics with other drugs that affect the serotonergic neurotransmission system (e.g., selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmission system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (e.g., cyclobenzaprine, metaxalone) and MAOIs (drugs intended for the treatment of psychiatric disorders and others, e.g., linezolid and methylene blue for intravenous administration)) leads to the occurrence of serotonin syndrome.
If concomitant use of such drugs is warranted, the patient should be closely monitored, especially at the beginning of treatment and during dose adjustment. If serotonin syndrome is suspected, the use of Nalbuphine-Darnitsa should be discontinued.
Muscle relaxants.
The drug Nalbuphine-Darnitsa may enhance the neuromuscular blockade of skeletal muscle relaxants and lead to severe respiratory depression.
Patients should be monitored for symptoms of respiratory depression, which may be more severe than expected, and the dose of nalbuphine and/or muscle relaxants should be reduced if necessary.
Diuretics.
Opioid analgesics may reduce the effectiveness of diuretics by activating the release of antidiuretic hormone.
Patients should be monitored for signs of decreased diuresis and/or effects on blood pressure and the dose of diuretics should be increased if necessary.
Concomitant use of nalbuphine hydrochloride with anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
When using Nalbuphine-Darnitsa with anticholinergic drugs, patients should be carefully monitored for symptoms of urinary retention or decreased gastric motility.
MAO inhibitors.
Interaction of MAO inhibitors (e.g., phenelzine, tranylcypromine, linezolid) with opioid analgesics may result in serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
The use of the drug Nalbuphine-Darnitsa is not recommended for patients taking MAO inhibitors, as well as within 14 days after discontinuing their use.
In case of urgent need for opioid analgesics, it is recommended to use trial doses and frequently increase small doses to treat pain, carefully monitoring blood pressure, signs and symptoms of CNS depression and respiration.
Application features
Life-threatening respiratory depression.
Serious, life-threatening, or fatal cases of respiratory depression have been reported with opioid use, even when used as directed. Respiratory depression, if not promptly recognized and treated, can lead to respiratory arrest and death. Treatment of respiratory depression may include close monitoring, supportive measures, and the use of opioid receptor antagonists, depending on the clinical condition of the patient. Carbon dioxide (CO2) retention resulting from respiratory depression caused by opioid analgesics may enhance the sedative effects of such analgesics.
Although life-threatening respiratory depression can occur at any time during the use of nalbuphine, the risk is greatest at the beginning of therapy or after dose increases. Patients should be closely monitored for respiratory depression, especially during the first 24–72 hours after starting therapy and after increasing the dose of nalbuphine.
Proper dosing and dilution of Nalbuphine-Darnitsa is important to reduce the risk of respiratory depression. Incorrect calculation of the nalbuphine dose when transferring a patient from another opioid drug may result in a fatal first-dose overdose.
Opioid analgesics can cause sleep-disordered breathing, including central sleep apnea and sleep hypoxemia. The use of opioid analgesics increases the risk of central sleep apnea in a dose-dependent manner. For patients presenting with central sleep apnea, consideration should be given to reducing the dose of opioid analgesics using best practices for gradual dose reduction.
Risks associated with concomitant use of benzodiazepines or other CNS depressants.
Concomitant use of Nalbuphine-Darnitsa with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, neuroleptics, other opioid analgesics, alcohol) may result in profound sedation, respiratory depression, and death. Because of these risks, the use of nalbuphine hydrochloride with these drugs should be limited to patients for whom alternative treatment options are inadequate.
Observational studies have shown that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared with opioid analgesics alone. Given their similar pharmacological properties, it is reasonable to expect similar risks when other CNS depressants are used concomitantly with opioid analgesics.
Patients and caregivers should be informed of the risk of respiratory depression and sedation when using Nalbuphine-Darnitsa with benzodiazepines or other CNS depressants, including alcohol and narcotics. Patients should be advised to refrain from driving or operating machinery until the effects of concomitant use of nalbuphine hydrochloride with a benzodiazepine or other CNS depressant are known. Patients should be screened for the risk of substance use disorders, including abuse and misuse of opioid analgesics, and informed of the risk of overdose and death from additional CNS depressants, including alcohol and narcotics.
Life-threatening respiratory depression in patients with chronic lung disease, in elderly, cachectic, or debilitated patients.
The use of the drug Nalbuphine-Darnitsa in patients with acute or severe bronchial asthma in the absence of appropriate monitoring or resuscitation equipment is contraindicated.
Patients with chronic lung disease
Patients with significant chronic obstructive pulmonary disease or cor pulmonale, as well as patients with significantly reduced lung capacity, hypoxia, hypercapnia, or existing respiratory depression, are at increased risk of decreased respiratory center activity, including apnea, even when using Nalbuphine-Darnitsa at recommended doses.
Elderly, cachectic, or debilitated patients
Life-threatening respiratory depression is most likely to occur in elderly, cachectic, or debilitated patients due to possible changes in pharmacokinetic parameters or clearance compared to younger, healthier patients. Such patients should be closely monitored, especially at the beginning of treatment, when the dose of Nalbuphine-Darnitsa is increased, and when it is co-administered with other drugs that cause respiratory depression. Non-opioid analgesics should be considered as an alternative for such patients.
Adrenal cortex insufficiency.
Adrenal insufficiency has been reported with opioid analgesics, most commonly after use for more than 1 month. Symptoms of adrenal insufficiency may include nonspecific symptoms and signs, including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension. If adrenal insufficiency is suspected, the diagnosis should be confirmed as soon as possible by diagnostic testing. If adrenal insufficiency is diagnosed, treatment should be with physiologic replacement doses of corticosteroids. Patients should be gradually withdrawn from opioid analgesics to allow adrenal function to recover, and corticosteroids should be continued until adrenal function has fully recovered. A switch to another opioid analgesic may be considered, as there have been reports of a few cases of switching to another opioid analgesic without recurrence of adrenal insufficiency. It is not known from the available data which opioid analgesics are more likely to be associated with adrenal insufficiency.
Severe hypotension.
Nalbuphine-Darnitsa may cause severe hypotension, including orthostatic hypotension and syncope, in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure is already compromised due to volume depletion or the concomitant use of certain CNS depressants, such as phenothiazines, tricyclic antidepressants, hypnotics, sedatives or general anesthetics. These patients should be monitored for signs of hypotension after initiation or dose increase of Nalbuphine-Darnitsa. In patients with circulatory shock, nalbuphine hydrochloride may cause vasodilation, which may further lead to decreased cardiac output and decreased blood pressure. Nalbuphine-Darnitsa should be avoided in patients with circulatory shock.
Risks of use in patients with increased intracranial pressure, brain tumors, head injuries, or impaired consciousness.
In patients susceptible to the intracranial effects of CO2 retention (e.g., patients with signs or symptoms of increased intracranial pressure or brain tumors), Nalbuphine-Darnitsa may reduce the activity of the respiratory center, and the associated CO2 retention may further increase intracranial pressure. Such patients should be monitored for signs of sedation and respiratory depression, especially at the beginning of the drug. In addition, nalbuphine may cause confusion, miosis, vomiting, and other side effects that mask the clinical course in patients with head injury.
The use of Nalbuphine-Darnitsa should be avoided in cases of impaired consciousness or coma.
The drug Nalbuphine-Darnitsa is contraindicated in patients with existing or suspected gastrointestinal obstruction, including paralytic ileus.
Nalbuphine hydrochloride may cause spasms of the sphincter of Oddi. Opioid analgesics may cause elevations in serum amylase levels. Patients with bile duct disease, including acute pancreatitis, should be monitored for worsening of symptoms.
Increased risk of seizures in patients with seizure disorders.
Nalbuphine may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in other clinical conditions associated with seizures. Patients with a history of seizure disorders should be monitored for worsening seizure control during nalbuphine therapy.
Discontinuation of treatment (withdrawal syndrome).
The use of the drug Nalbuphine-Darnitsa, a mixed opioid analgesic of the opiate receptor agonist-antagonist group, in patients using an analgesic that is a full opiate receptor agonist may lead to a decrease in the analgesic effect and/or provoke withdrawal symptoms. The simultaneous use of the drug Nalbuphine-Darnitsa with an analgesic that is a full opioid receptor agonist should be avoided.
When discontinuing Nalbuphine-Darnitsa in physically dependent patients, the dose should be reduced gradually. Such patients should not abruptly discontinue the use of this drug.
Dependence, abuse and misuse.
Nalbuphine hydrochloride is a synthetic opioid receptor agonist-antagonist analgesic. The use of nalbuphine hydrochloride as an opioid exposes the patient to the risk of dependence, abuse, and misuse.
Addiction can occur when using the drug both in recommended doses and in case of abuse or improper use.
The risk of opioid dependence, abuse, or misuse should be assessed for each patient. The risk is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or dependence) and in patients with psychiatric illness (e.g., severe depression). The existence of these risks should not prevent appropriate pain management for each individual patient.
Opioids used by patients with drug addiction may be used for criminal purposes. These risks should be considered when prescribing nalbuphine hydrochloride. To reduce these risks, the drug should be prescribed at the lowest possible dose.
Abuse and Dependence: Nalbuphine hydrochloride is subject to abuse, misuse, dependence, and illegal resale.
All patients treated with opioid analgesics require close monitoring for symptoms of abuse and dependence, as the use of such substances carries a risk of dependence even when used medically appropriate.
Abuse of a prescription drug is intentional when it is used not for therapeutic purposes, even if it occurs once, but to obtain psychological and physiological effects.
Drug dependence is a set of behavioral, cognitive, and physiological phenomena that develop after repeated use of a substance and includes a strong desire to take the drug, difficulty controlling its use and continuing to take it despite harmful consequences, greater priority given to taking the drug over other activities and responsibilities, increased tolerance to the drug, and sometimes physical withdrawal symptoms.
Drug-seeking behaviors are common among people with substance use disorders. Drug-seeking tactics include making urgent calls or visits late at work, refusing to undergo appropriate examinations, tests, or referrals, “losing” prescriptions, forging prescriptions, and failing to provide previous medical records or contact information to other providers. Visiting multiple doctors to obtain additional prescriptions is common among people with drug dependence and those with untreated addiction. Concern about achieving adequate pain relief may be a relevant behavior in patients with inadequate pain management.
Abuse and dependence are distinct concepts and are distinct from physical dependence and tolerance. Clinicians should be aware that not all addicts will develop tolerance and symptoms of physical dependence. In addition, opioid analgesic abuse can occur in the absence of true dependence.
Appropriate measures to help limit the misuse of opioid analgesics include proper patient assessment, proper prescribing practices, periodic evaluation of therapy, and proper dispensing and storage. Misuse of nalbuphine can lead to overdose and death. The risks are increased when nalbuphine is used concomitantly with other CNS depressants and alcohol. Misuse of parenteral drugs is commonly associated with the transmission of infectious diseases, such as hepatitis and HIV.
Dependence. Both tolerance and dependence can develop with prolonged therapy with opioid analgesics. Tolerance is the need for increased doses of opioid analgesics to maintain a certain effect, such as pain relief (in the absence of disease progression or other external factors). Tolerance can be caused by both desired and adverse effects of drugs and develops differently for different effects.
Physical dependence leads to the development of withdrawal symptoms after abrupt cessation of use or a significant reduction in the dose of the drug. The withdrawal syndrome can also be reduced by drugs with antagonistic activity at opioid receptors (e.g., naloxone, nalmefene), analgesics belonging to the class of opioid receptor agonist-antagonists (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Clinically significant degrees of physical dependence may not appear until several days or even weeks after continuous administration of opioid analgesics.
It is not recommended to stop using nalbuphine hydrochloride suddenly. If a patient with physical dependence suddenly stops using the drug Nalbuphine-Darnitsa, he may experience a withdrawal syndrome. Some or all of the following symptoms may characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, increased sweating, chills, muscle pain, and mydriasis. Other signs and symptoms may also develop, including irritability, restlessness, back pain, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or an increase in blood pressure, respiratory rate, or pulse.
Children born to women who are physically dependent on opioid analgesics will also suffer from physical dependence and may have breathing difficulties and withdrawal symptoms.
Impaired kidney or liver function.
Since nalbuphine is metabolized in the liver and excreted by the kidneys, this drug should be used with caution in patients with impaired renal or hepatic function and administered at reduced doses.
Myocardial infarction.
The drug Nalbuphine-Darnitsa, like other potent analgesics, should be used with caution in patients with myocardial infarction who experience nausea and vomiting.
Cardiovascular system.
When evaluating the use of the drug Nalbuphine-Darnitsa during anesthesia, there were reports of an increased incidence of bradycardia in patients who did not receive atropine before surgery.
Laboratory tests.
The drug Nalbuphine-Darnitsa may interfere with enzymatic methods for detecting opioids depending on the specificity/sensitivity of the test. For more detailed information, please contact the manufacturer of the test system.
Serotonin syndrome.
Opioid analgesics may rarely lead to a potentially life-threatening condition due to concomitant use of serotonergic drugs. Immediate medical attention should be sought if symptoms of serotonin syndrome occur. In such cases, the serotonergic drug should be discontinued and symptomatic treatment initiated. The physician should be informed of any serotonergic drug being taken or planned.
The drug Nalbuphine-Darnitsa should not be used together with MAO inhibitors, serotonin precursors, or other agents that affect the serotonergic neurotransmitter system.
Interaction with MAO inhibitors.
The use of Nalbuphine-Darnitsa with any MAO inhibitor should be avoided (see section “Interaction with other medicinal products and other types of interactions”).
Constipation.
Severe constipation may develop (see sections "Pharmacological properties" and "Adverse reactions").
Use in elderly patients.
Elderly patients (65 years of age and older) may be more sensitive to nalbuphine. In general, caution should be exercised when selecting a dose for an elderly patient, usually starting at the low end of the dosing range, because this population is more likely to have decreased hepatic, renal, or cardiac function, concomitant disease, or use of other medications.
Nalbuphine is known to be largely excreted by the kidneys and the risk of adverse reactions is higher in patients with impaired renal function. Since these patients are more likely to have decreased renal function, caution should be exercised in dose selection and renal function should be monitored whenever possible.
Carcinogenesis.
In long-term studies conducted in rats (24 months) and mice (19 months) with oral administration at doses of 200 μg/ml (12 times the maximum recommended human daily dose (MRDL)) and 200 mg/day (6 times the MRDL), respectively, there was no evidence of carcinogenicity.
Mutagenesis.
Nalbuphine hydrochloride caused an increased frequency of mutations in a mouse lymphoma assay. The drug did not exhibit mutagenic activity in the Ames test with four bacterial strains, in the Chinese hamster ovary GHPT assay, or in the sister chromatid exchange assay. Clastogenic activity was not observed in the mouse micronucleus test or in the rat bone marrow cytogenicity assay.
Important information about excipients.
The drug Nalbuphine-Darnitsa contains less than 1 mmol (23 mg)/dose of sodium, i.e. it is essentially sodium-free.
Use during pregnancy or breastfeeding.
Pregnancy.
No human studies have been conducted. Nalbuphine crosses the placental barrier and is contraindicated in pregnant women.
Prolonged use of opioid analgesics during pregnancy may lead to neonatal withdrawal syndrome. Neonatal opioid withdrawal syndrome can be life-threatening.
The potential human risk of serious birth defects and miscarriage in this population is unknown. There is a potential risk of birth defects, miscarriage, or other adverse outcomes at all stages of pregnancy.
In animal reproduction studies, nalbuphine reduced pup survival and body weight when administered to female rats during late pregnancy and lactation at 1.7 times the maximum recommended human dose, and when administered to female and male rats both prior to mating and throughout pregnancy and lactation. No developmental defects were observed in either rat or rabbit at 6.1 and 3.9 times the maximum recommended human dose, respectively. The estimated background risk of major birth defects and miscarriage in humans is unknown. All pregnancies carry a background risk of birth defects, miscarriage, or other adverse outcomes. In the general US population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Adverse reactions in the fetus/neonatal infant.
Severe fetal bradycardia has been reported with nalbuphine hydrochloride during labor. Reversibility of these effects can be achieved with naloxone. There are no reports of fetal bradycardia in early pregnancy, but this risk exists. The drug should be used during pregnancy only if clearly needed, when the potential benefit outweighs the potential risk to the fetus and with appropriate measures such as fetal monitoring to detect and manage any potential adverse effects.
Labor and delivery.
Placental transfer of nalbuphine is high, rapid, and variable at maternal-fetal ratios ranging from 1:0.37 to 1:6. Adverse fetal and neonatal effects reported following maternal administration of nalbuphine during labor include fetal bradycardia, neonatal respiratory depression, apnea, cyanosis, and hypotension. Some of these effects have been life-threatening. Administration of naloxone to the mother during labor has resulted in some recovery. Severe and prolonged fetal bradycardia has been reported. There have been reports of permanent neurological damage associated with fetal bradycardia.
Changes in heart rate have also been reported with nalbuphine. Nalbuphine should be used during labor and delivery only if clearly needed and only if the potential benefit to the mother outweighs the risk to the infant. If nalbuphine is used during labor, the neonate should be monitored for respiratory depression, apnea, bradycardia, and arrhythmias.
The drug Nalbuphine-Darnitsa is not recommended for use by pregnant women.
