Nulphin Special Precautions

Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status (see Overdosage). Carbon dioxide (CO) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NULPHIN Injection, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of NULPHIN Injection.
To reduce the risk of respiratory depression, proper dosing and titration of NULPHIN Injection are essential (see Dosage & Administration). Overestimating the NULPHIN Injection dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NULPHIN 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 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 NULPHIN 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 Interactions).
Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: The use of NULPHIN 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: NULPHIN 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 NULPHIN Injection.
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. Monitor such patients closely, particularly when initiating and titrating NULPHIN Injection and when NULPHIN Injection is given concomitantly with other drugs that depress respiration. 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.
Severe Hypotension: NULPHIN Injection may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) (see Interactions). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NULPHIN Injection. In patients with circulatory shock, NULPHIN Injection may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NULPHIN Injection in patients with circulatory shock.
Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: In patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NULPHIN Injection may reduce respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NULPHIN Injection.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NULPHIN Injection in patients with impaired consciousness or coma.
Risks of Use in Patients with Gastrointestinal Conditions: NULPHIN Injection is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The nalbuphine in NULPHIN Injection may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
Increased Risk of Seizures in Patients with Seizure Disorders: The nalbuphine in NULPHIN Injection may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NULPHIN Injection therapy.
Withdrawal: The use of NULPHIN Injection, a mixed agonist/antagonist opioid analgesic, in patients who are receiving a full opioid agonist analgesic may reduce the analgesic effect and/or precipitate withdrawal symptoms. Avoid concomitant use of NULPHIN Injection with a full opioid agonist analgesic.
When discontinuing NULPHIN Injection in a physically-dependent patient, gradually taper the dosage (see Dosage & Administration). Do not abruptly discontinue NULPHIN Injection in these patients (see Adverse Reactions).
Use in Pregnancy (Other Than Labor): Avoid the use of NULPHIN 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 (see Use in Pregnancy & Lactation).
Use During Labor and Delivery: NULPHIN 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 NULPHIN Injection has been used (see Use in Pregnancy & Lactation).
Addiction, Abuse, and Misuse: Nalbuphine hydrochloride is a synthetic opioid agonist-antagonist analgesic. As an opioid, NULPHIN Injection exposes users to the risks of addiction, abuse, and misuse.
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NULPHIN 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 NULPHIN 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.
Impaired Renal or Hepatic Function: Because NULPHIN Injection is metabolized in the liver and excreted by the kidneys, NULPHIN Injection should be used with caution in patients with renal or liver dysfunction and administered in reduced amounts.
Myocardial Infarction: As with all potent analgesics, NULPHIN Injection should be used with caution in patients with myocardial infarction who have nausea or vomiting.
Cardiovascular System: During evaluation of NULPHIN Injection in anesthesia, a higher incidence of bradycardia has been reported in patients who did not receive atropine pre-operatively.
Laboratory Tests: NULPHIN 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.
Serotonin Syndrome: 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. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications (see Interaction).
Monoamine Oxidase Inhibitor (MAOI) Interaction: Inform patients to avoid taking NULPHIN Injection while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking NULPHIN Injection (see Interactions).
Constipation: Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
Effects on ability to drive and use machine: NULPHIN Injection may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NULPHIN Injection and know how they will react to the medication.
Maintain patient under observation until recovered from NULPHIN Injection effects that would affect driving or other potentially dangerous tasks.