Addiction, Abuse, and Misuse Because the use of Hydromorphone Hydrochloride Injection exposes patients and other users to risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1) ] . Life-Threatening Respiratory Depr...
Hydromorphone Hydrochloride Injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use: Because of the risks of addiction, abuse, misuse, overdose, and death , which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions (5.1) ] , reserve opioid analgesics, i...
• Hydromorphone Hydrochloride Injection should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. • Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions (5) ]. Because the risk of overdose increases as opioid doses increase, reserve t...
Safety and Handling Instructions Access to drugs with a potential for abuse such as Hydromorphone Hydrochloride Injection presents an occupational hazard for addiction in the health care industry. Routine procedures for handling controlled substances developed to protect the public may not be adequate to protect health care workers. Implementation of more effective accounting procedures and measures to restr...
www.fda.gov.medwatch
www.pfizermedinfo.comAddiction, Abuse, and Misuse
Because the use of Hydromorphone Hydrochloride Injection exposes patients and other users to risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1)].
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of Hydromorphone Hydrochloride Injection, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of Hydromorphone Hydrochloride Injection are essential [see Warnings and Precautions (5.2)].
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of Hydromorphone Hydrochloride Injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3), Drug Interactions (7)].
Neonatal Opioid Withdrawal Syndrome (NOWS)
Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions (5.4)].
Hydromorphone Hydrochloride Injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Limitations of Use:
Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions (5.1)], reserve opioid analgesics, including Hydromorphone Hydrochloride Injection, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
Use of Hydromorphone Hydrochloride Injection as the First Opioid Analgesic
Subcutaneous or Intramuscular Administration
Initiate treatment in a dosing range of 1 mg to 2 mg every 2 to 3 hours as necessary for pain, and at the lowest dose necessary to achieve adequate analgesia. Depending on the clinical situation, the initial starting dose may be lowered in patients who are opioid naïve. Titrate the dose based upon the individual patient’s response to their initial dose of Hydromorphone Hydrochloride Injection.
Intravenous Administration
Initiate treatment in a dosing range of 0.2 mg to 1 mg every 2 to 3 hours as necessary for pain control, and at the lowest dose necessary to achieve adequate analgesia. Intravenous administration should be given slowly, over at least 2 to 3 minutes, depending on the dose. Titrate the dose to achieve acceptable pain management and tolerable adverse events. The initial dose should be reduced in the elderly or debilitated and may be lowered to 0.2 mg.
Conversion from Other Opioids to Hydromorphone Hydrochloride Injection
There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of Hydromorphone Hydrochloride Injection. It is safer to underestimate a patient's 24-hour Hydromorphone Hydrochloride Injection dosage than to overestimate the 24-hour Hydromorphone Hydrochloride Injection dosage and manage an adverse reaction due to overdose. If the decision is made to convert to Hydromorphone Hydrochloride Injection from another opioid analgesic using publicly available data, convert the current total daily amount(s) of opioid(s) received to an equivalent total daily dose of Hydromorphone Hydrochloride Injection and reduce by one-half due to the possibility of incomplete cross tolerance. Divide the new total amount by the number of doses permitted based on dosing interval (e.g., 8 doses for every-three-hour dosing). Titrate the dose according to the patient's response.
Start patients with hepatic impairment on one-fourth to one-half the usual dose of Hydromorphone Hydrochloride Injection depending on the extent of impairment [see Clinical Pharmacology (12.3)].
Start patients with renal impairment on one-fourth to one-half the usual starting dose of Hydromorphone Hydrochloride Injection depending on the degree of impairment [see Clinical Pharmacology (12.3) ].
Titrate the dose based upon the individual patient’s response to their initial dose of Hydromorphone Hydrochloride Injection. Individually titrate Hydromorphone Hydrochloride Injection to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Hydromorphone 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 and Precautions (5.1, 5.12) ]. 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 Hydromorphone Hydrochloride Injection dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after a dosage increase), consider reducing the dosage [see Warnings and Precautions (5)]. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
When a patient who has been taking Hydromorphone Hydrochloride Injection regularly and may be physically dependent no longer requires therapy with Hydromorphone 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 rapidly reduce or abruptly discontinue Hydromorphone Hydrochloride Injection in patients who may be physically dependent on opioids [see Warnings and Precautions (5.12), Drug Abuse and Dependence (9.3)].
Hydromorphone Hydrochloride Injection, USP is available as:
|
|
The drug product is a clear, colorless to nearly colorless aqueous sterile solution. Each 1 mL of sterile solution contains 1 mg, 2 mg or 4 mg of hydromorphone hydrochloride.
Hydromorphone Hydrochloride Injection is contraindicated in patients with:
Hydromorphone Hydrochloride Injection contains hydromorphone, a Schedule II controlled substance. As an opioid, Hydromorphone Hydrochloride Injection exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)].
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Hydromorphone Hydrochloride Injection. Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions (6)].
Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing Hydromorphone Hydrochloride Injection, and monitor all patients receiving Hydromorphone Hydrochloride Injection for the development of these behaviors and conditions. 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. Patients at increased risk may be prescribed opioids such as Hydromorphone Hydrochloride Injection but use in such patients necessitates intensive counseling about the risks and proper use of Hydromorphone Hydrochloride Injection along with intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing Hydromorphone 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.
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 overdose reversal agent (e.g., naloxone, nalmefene), depending on the patient's clinical status [see Overdosage (10)]. Carbon dioxide (CO2) 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 Hydromorphone Hydrochloride Injection, the risk is greatest during the initiation of therapy or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of Hydromorphone Hydrochloride Injection are essential [see Dosage and Administration (2.1)]. Overestimating the Hydromorphone 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 and Administration (2.1)].
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Hydromorphone Hydrochloride Injection with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids). 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 Drug Interactions (7)].
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. Monitor 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 Hydromorphone 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 Drug Interactions (7)].
Use of Hydromorphone Hydrochloride Injection for an extended period of time during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life‑threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for an extended period of time of the risk of neonatal opioid withdrawal syndrome and ensure that management by neonatology experts will be available at delivery [see Use in Specific Populations (8.1)].
Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect [see Drug Abuse and Dependence (9.3)]. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non‑painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.
Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching the patient to a different opioid moiety) [see Dosage and Administration (2.6) , Warnings and Precautions (5.12)].
The use of Hydromorphone 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: Hydromorphone 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 hydromorphone hydrochloride [see Warnings and Precautions (5.2)].
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 and Precautions (5.2)].
Monitor such patients closely, particularly when initiating and titrating Hydromorphone Hydrochloride Injection and when Hydromorphone Hydrochloride Injection is given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2, 5.3) , Drug Interactions (7)]. Alternatively, consider the use of non-opioid analgesics in these patients.
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one 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.
Hydromorphone Hydrochloride 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 Drug Interactions (7)]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of Hydromorphone Hydrochloride Injection. In patients with circulatory shock, Hydromorphone Hydrochloride Injection may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Hydromorphone Hydrochloride Injection in patients with circulatory shock.
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), Hydromorphone Hydrochloride Injection may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for worsening of signs of increasing intracranial pressure. Monitor patients for signs of sedation and respiratory depression, particularly when initiating therapy with Hydromorphone Hydrochloride Injection.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Hydromorphone Hydrochloride Injection in patients with impaired consciousness or coma.
Hydromorphone Hydrochloride Injection is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The hydromorphone in Hydromorphone Hydrochloride 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.
Cases of opioid-induced esophageal dysfunction (OIED) have been reported in patients taking opioids. The risk of OIED may increase as the dose and/or duration of opioids increases. Regularly evaluate patients for signs and symptoms of OIED (e.g., dysphagia, regurgitation, non-cardiac chest pain) and, if necessary, adjust opioid therapy as clinically appropriate [see Clinical Pharmacology (12.2)].
The hydromorphone in Hydromorphone Hydrochloride 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 Hydromorphone Hydrochloride Injection therapy.
Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including Hydromorphone Hydrochloride Injection. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].
When discontinuing Hydromorphone Hydrochloride Injection, in a physically-dependent patient, gradually taper the dosage [see Dosage and Administration (2.6)]. Do not rapidly reduce or abruptly discontinue Hydromorphone Hydrochloride Injection in these patients [see Drug Abuse and Dependence (9.3)].
Hydromorphone Hydrochloride 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 Hydromorphone Hydrochloride Injection and know how they will react to the medication.
Hydromorphone Hydrochloride Injection may be given intravenously, but the injection should be given very slowly. Rapid intravenous injection of opioid analgesics increases the possibility of side effects such as hypotension and respiratory depression [see Dosage and Administration (2.1)].
The following serious adverse reactions are described, or described in greater detail, in other sections:
The following adverse reactions associated with the use of hydromorphone were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The most common adverse effects are light-headedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus. These effects seem to be more prominent in ambulatory patients and in those not experiencing severe pain.
Less Frequently Observed Adverse Reactions
Cardiac disorders: tachycardia, bradycardia, palpitations
Eye disorders: vision blurred, diplopia, miosis, visual impairment
Gastrointestinal disorders: constipation, ileus, diarrhea, abdominal pain
General disorders and administration site conditions: weakness, feeling abnormal, chills, injection site urticaria
Hepatobiliary disorders: biliary colic
Metabolism and nutrition disorders: decreased appetite
Musculoskeletal and connective tissue disorders: muscle rigidity
Nervous system disorders: headache, tremor, paraesthesia, nystagmus, increased intracranial pressure, syncope, taste alteration, involuntary muscle contractions, presyncope
Psychiatric disorders: agitation, mood altered, nervousness, anxiety, depression, hallucination, disorientation, insomnia, abnormal dreams
Renal and urinary disorders: urinary retention, urinary hesitation, antidiuretic effects
Respiratory, thoracic and mediastinal disorders: bronchospasm, laryngospasm
Skin and subcutaneous tissue disorders: injection site pain, urticaria, rash, hyperhidrosis
Vascular disorders: flushing, hypotension, hypertension
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.
Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Hydromorphone Hydrochloride Injection.
Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time.
Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration. [see Warnings and Precautions (5.5)].
Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).
Opioid-induced esophageal dysfunction (OIED): Cases of OIED have been reported in patients taking opioids and may occur more frequently in patients taking higher doses of opioids, and/or in patients taking opioids longer term [see Warnings and Precautions (5.10)].
Adverse Reactions from Observational Studies
A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90-day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months.
Over 12 months:
A retrospective, observational cohort study estimated the risk of opioid-involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days’ supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database. The 5-year cumulative incidence estimates for opioid-involved overdose or opioid overdose-related death ranged from approximately 1.5% to 4% across study sites, counting only the first event during follow-up. Approximately 17% of first opioid overdoses observed over the entire study period (5-11 years, depending on the study site) were fatal. Higher baseline opioid dose was the strongest and most consistent predictor of opioid-involved overdose or opioid overdose-related death. Study exclusion criteria may have selected patients at lower risk of overdose, and substantial loss to follow-up (approximately 80%) also may have biased estimates.
The risk estimates from the studies described above may not be generalizable to all patients receiving opioid analgesics, such as those with exposures shorter or longer than the duration evaluated in the studies.
Table 1 includes clinically significant drug interactions with Hydromorphone Hydrochloride Injection.
Benzodiazepines and other Central Nervous System (CNS) Depressants | |
Clinical Impact: | Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death [see Warnings and Precautions (5.3)]. |
Intervention: | 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. Monitor patients closely for signs of respiratory depression and sedation. |
Examples: | Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. |
Serotonergic Drugs | |
Clinical Impact: | The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. |
Intervention: | If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Hydromorphone Hydrochloride Injection if serotonin syndrome is suspected. |
Examples: | 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), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). |
Monoamine Oxidase Inhibitors (MAOIs) | |
Clinical Impact: | MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2) ]. |
Intervention: | The use of Hydromorphone 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. |
Examples: | phenelzine, tranylcypromine, linezolid |
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics | |
Clinical Impact: | May reduce the analgesic effect of Hydromorphone Hydrochloride Injection and/or precipitate withdrawal symptoms. |
Intervention: | Avoid concomitant use. |
Examples: | butorphanol, nalbuphine, pentazocine, buprenorphine |
Muscle Relaxants | |
Clinical Impact: | Hydromorphone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. |
Intervention: | Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Hydromorphone Hydrochloride Injection and/or the muscle relaxant as necessary. |
Examples: | cyclobenzaprine, metaxalone |
Diuretics | |
Clinical Impact: | Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. |
Intervention: | Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. |
Anticholinergic Drugs | |
Clinical Impact: | The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. |
Intervention: | Monitor patients for signs of urinary retention or reduced gastric motility when Hydromorphone Hydrochloride Injection is used concomitantly with anticholinergic drugs. |
Risk Summary
Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4) ]. There are no available data with Hydromorphone Hydrochloride Injection in pregnant women to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. There are adverse outcomes reported with fetal exposure to opioid analgesics [see Clinical Considerations ].
In published animal reproduction studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6.4 times the HDD and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 3 times the HDD to pregnant mice. No malformations were noted at 4 or 40.5 times the HDD in pregnant rats or rabbits, respectively [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus.
The 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 to 4% and 15 to 20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.4) ].
Labor or Delivery
Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid‑induced respiratory depression in the neonate. Hydromorphone 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 Hydromorphone 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.
Data
Animal Data
No effects on teratogenicity or embryotoxicity were observed in pregnant rats given oral doses up to 7 mg/kg/day which is 3-fold higher than the human dose of 24 mg Hydromorphone Hydrochloride Injection (4 mg every 4 hours), on a body surface area basis.
In a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on Gestation Day 8 to pregnant hamsters (6.4 to 87.2 times the HDD of 24 mg/day based on body surface area). The findings cannot be clearly attributed to maternal toxicity. No neural tube defects were noted at 14 mg/kg (4.7 times the human daily dose of 24 mg/day).
In a published study, CF-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.5, 3, or 6.1 times the human daily dose of 24 mg based on body surface area) via implanted osmotic pumps during organogenesis (Gestation Days 7 to 10). Soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 3 times the human dose of 24 mg/day based on body surface area. The findings cannot be clearly attributed to maternal toxicity.
Risk Summary
Low levels of opioid analgesics have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Hydromorphone Hydrochloride Injection and any potential adverse effects on the breastfed infant from Hydromorphone Hydrochloride Injection or from the underlying maternal condition.
Clinical Considerations
Monitor infants exposed to Hydromorphone Hydrochloride Injection through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped.
Infertility
Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6), Clinical Pharmacology (12.2)].
The safety and effectiveness of Hydromorphone Hydrochloride Injection in pediatric patients has not been established.
Elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. 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 Hydromorphone Hydrochloride Injection slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.6) ].
Hydromorphone 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 pharmacokinetics of hydromorphone are affected by hepatic impairment. Due to increased exposure of hydromorphone, patients with moderate hepatic impairment should be started at one fourth to one half the recommended starting dose depending on the degree of hepatic dysfunction and closely monitored during dose titration. The pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. A further increase in Cmax and AUC of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see Clinical Pharmacology (12.3)].
The pharmacokinetics of hydromorphone are affected by renal impairment. In addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life. Start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. Patients with renal impairment should be closely monitored during dose titration [see Clinical Pharmacology (12.3)].
Hydromorphone Hydrochloride Injection contains hydromorphone, a Schedule II controlled substance.
Hydromorphone Hydrochloride Injection contains hydromorphone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1) ].
Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.
Abuse is the intentional non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug, use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
Misuse and abuse of Hydromorphone Hydrochloride Injection increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of Hydromorphone Hydrochloride Injection with alcohol and/or other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.
All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Hydromorphone Hydrochloride Injection abuse include those with a history of prolonged use of any opioid, including products containing hydromorphone, those with a history of drug or alcohol abuse, or those who use Hydromorphone Hydrochloride Injection in combination with other abused drugs.
“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.
Hydromorphone Hydrochloride Injection, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Risks Specific to Abuse of Hydromorphone Hydrochloride Injection
Abuse of Hydromorphone Hydrochloride Injection poses a risk of overdose and death. The risk is increased with concurrent use of Hydromorphone Hydrochloride Injection with alcohol and/or other CNS depressants.
Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
Both tolerance and physical dependence can develop during use of opioid therapy.
Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.
Hydromorphone Hydrochloride Injection should not be rapidly reduced or abruptly discontinued in a physically-dependent patient [see Dosage and Administration (2.6)]. If Hydromorphone Hydrochloride Injection is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur, typically characterized by restlessness, lacrimation, rhinorrhea, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
Infants born to mothers physically-dependent on opioids will also be physically-dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].
Clinical Presentation
Acute overdose with hydromorphone can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2)]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication.
Treatment of Overdose
In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures.
For clinically significant respiratory or circulatory depression secondary to hydromorphone overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene.
Because the duration of opioid reversal is expected to be less than the duration of action of hydromorphone in Hydromorphone Hydrochloride Injection, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product's prescribing information.
In an individual physically-dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered. If a decision is made to treat serious respiratory depression in the physically-dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of the reversal agent.
Hydromorphone Hydrochloride Injection is an opioid agonist and available as an aqueous sterile solution, for use for intravenous, intramuscular and subcutaneous administration. It contains hydromorphone as active pharmaceutical ingredient in the form of hydrochloride salt. The chemical name of hydromorphone hydrochloride is 4,5α- epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride. The molecular weight is 321.8 and it has the following chemical structure.
Hydromorphone hydrochloride is a white or almost white crystalline powder that is freely soluble in water, very slightly soluble in ethanol (96%), and practically insoluble in methylene chloride.
Each mL of Hydromorphone Hydrochloride Injection sterile solution contains 1 mg, 2 mg, or 4 mg of Hydromorphone Hydrochloride USP, equivalent to 0.89 mg, 1.77 mg or 3.55 mg of hydromorphone free base, respectively, 0.24 mg of Lactic Acid USP, 5.40 mg of Sodium Chloride as isotonicity agent, 8.93 mg of Sodium Lactate USP as buffering agent, and Lactic Acid USP and Sodium Hydroxide NF as pH adjusters, in Water for Injection. Hydromorphone Hydrochloride Injection pH range is 3.5 to 5.5.
Hydromorphone is a full opioid agonist and is relatively selective for the mµ-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of hydromorphone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
Effects on the Central Nervous System
Hydromorphone 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.
Hydromorphone 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.
Effects on the Gastrointestinal Tract and Other Smooth Muscle
Hydromorphone 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, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED).
Effects on the Cardiovascular System
Hydromorphone produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/or orthostatic hypotension.
Effects on the Endocrine System
Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions (6)]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon [see Adverse Reactions (6)].
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 (6)].
Effects on the Immune System
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.
Concentration–Efficacy Relationships
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 hydromorphone 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 (2.1, 2.5) ].
Concentration–Adverse Reaction Relationships
There is a relationship between increasing hydromorphone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see Dosage and Administration (2.1, 2.5 )].
Distribution
At therapeutic plasma levels, hydromorphone is approximately 8–19% bound to plasma proteins. After an intravenous bolus dose, the steady state of volume of distribution [mean (%cv)] is 302.9 (32%) liters.
Elimination
The systemic clearance is approximately 1.96 (20%) liters/minute. The terminal elimination half-life of hydromorphone after an intravenous dose is about 2.3 hours.
Metabolism
Hydromorphone is extensively metabolized via glucuronidation in the liver, with greater than 95% of the dose metabolized to hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.
Excretion
Only a small amount of the hydromorphone dose is excreted unchanged in the urine. Most of the dose is excreted as hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.
Specific Populations
Hepatic Impairment
After oral administration of hydromorphone at a single 4 mg dose (2 mg hydromorphone immediate-release tablets), mean exposure to hydromorphone (Cmax and AUC∞) is increased 4 fold in patients with moderate (Child-Pugh Group B) hepatic impairment compared with subjects with normal hepatic function. Patients with moderate hepatic impairment should be started at one fourth to one half the recommended starting dose and closely monitored during dose titration. The pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. A further increase in Cmax and AUC of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see Use in Specific Populations (8.6)].
Renal Impairment
The pharmacokinetics of hydromorphone following an oral administration of hydromorphone at a single 4 mg dose (2 mg hydromorphone immediate-release tablets) are affected by renal impairment. Mean exposure to hydromorphone (Cmax and AUC0–∞) is increased by 2 fold in patients with moderate (CLcr = 40 – 60 mL/min) renal impairment and increased by 4 fold in patients with severe (CLcr < 30 mL/min) renal impairment compared with normal subjects (CLcr > 80 mL/min). In addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life (40 hr) compared to patients with normal renal function (15 hr). Start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. Patients with renal impairment should be closely monitored during dose titration [see Use in Specific Populations (8.7)].
Age: Geriatric Population
In the geriatric population, age has no effect on the pharmacokinetics of hydromorphone.
Sex
Sex has little effect on the pharmacokinetics of hydromorphone. Females appear to have a higher Cmax (25%) than males with comparable AUC0–24 values. The difference observed in Cmax may not be clinically relevant.
Carcinogenesis
Long-term studies in animals to evaluate the carcinogenic potential of hydromorphone have not been conducted.
Mutagenesis
Hydromorphone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames assay). Hydromorphone was not clastogenic in either the in vitro human lymphocyte chromosome aberration assay or the in vivo mouse micronucleus assay.
Impairment of Fertility
No effects on fertility, reproductive performance, or reproductive organ morphology were observed in male or female rats given oral doses up to 7 mg/kg/day which is 2.8 times the human dose of 24 mg hydromorphone hydrochloride injection (4 mg every 4 hours), on a body surface area basis.
Safety and Handling Instructions
Access to drugs with a potential for abuse such as Hydromorphone Hydrochloride Injection presents an occupational hazard for addiction in the health care industry. Routine procedures for handling controlled substances developed to protect the public may not be adequate to protect health care workers. Implementation of more effective accounting procedures and measures to restrict access to drugs of this class (appropriate to the practice setting) may minimize the risk of self-administration by health care providers.
How Supplied
Hydromorphone Hydrochloride is as a sterile solution in single-dose ampules, single-dose CarpujectTM cartridges with Luer Lock for use with CarpujectTM Syringe System and Carpuject Holder ONLY, and single-dose vials for intravenous, intramuscular, and subcutaneous administration, and available as follows:
| Unit of Sale | Concentration (per total volume) |
|---|---|
NDC 0409-2552-01 | 1 mg/mL |
NDC 0409-3356-01 | 2 mg/mL |
NDC 0409-2540-01 | 4 mg/mL |
NDC 0409-3365-01 | 2 mg/mL |
NDC 0409-3365-10 | 2 mg/mL |
NDC 0409-1283-31 | 1 mg/mL |
NDC 0409-1312-30 | 2 mg/mL |
NDC 0409-1304-31 | 4 mg/mL |
Carpuject™ Single-dose cartridges with Luer Lock are packaged in a Slim-Pak™ tamper detection package. Note that a needle is not included.
PROTECT FROM LIGHT
Keep covered in carton until time of use. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
Addiction, Abuse, and Misuse
Inform patients that the use of Hydromorphone Hydrochloride Injection, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1) ]. Instruct patients not to share Hydromorphone Hydrochloride Injection with others and to take steps to protect Hydromorphone Hydrochloride Injection from theft or misuse.
Life-Threatening Respiratory Depression
Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Hydromorphone Hydrochloride Injection or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.2)].
Hyperalgesia and Allodynia
Advise patients to inform their healthcare provider if they experience symptoms of hyperalgesia, including worsening pain, increased sensitivity to pain, or new pain [see Warnings and Precautions (5.5), Adverse Reactions (6) ].
Serotonin Syndrome
Inform patients that opioids could cause a rare but potentially life-threatening condition called serotonin syndrome 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 physicians if they are taking, or plan to take serotonergic medications [see Drug Interactions (7)].
Constipation
Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6)].
For Medical Information about Hydromorphone Hydrochloride, please visit www.pfizermedinfo.com or call 1‑800-438-1985.
Distributed by Hospira, Inc., Lake Forest, IL 60045 USA
LAB-0856-7.0
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if color is darker than pale yellow, if it is discolored in any other way, or if it contains a precipitate.
Instructions for use - Carpuject™ Single-dose Cartridge
Carpuject™ Single-dose cartridges with Luer Lock are packaged in a Slim-Pak™ tamper detection package. Note that a needle is not included.
Before use, read all instructions for using the Carpuject™ Syringe, which are contained in the product insert for the reusable Carpuject™ Holder.
Carpuject™ Single-dose cartridges are to be used ONLY with Carpuject™ Holders.
NOTE: To prevent needlestick injuries, do not recap, purposely bend, or break by hand used needles. Do not recap, purposely bend, or break by hand blunt Cannulas.
LAB-1381-3.0
Revised: 11/2025
RL - 4950
NDC 0409-2552-11
Rx only
1 mL
Single-use ampul
HYDROmorphone HCl
Injection, USP
CII
1 mg/mL
PROTECT FROM LIGHT
Hospira, Inc.,
Lake Forest, IL 60045 USA
Hospira
1 mL 10 Single-use ampuls
NDC 0409-2552-01
Rx only
HYDROmorphone HCl
Injection, USP
1 mg/mL
CII
For Intravenous, Intramuscular, or Subcutaneous Use
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
PROTECT FROM LIGHT.
Do not use if solution is discolored or contains a precipitate.
Usual Dosage: See insert.
Hospira
RL - 4973
Rx only
NDC 0409-3356-11
1 mL Single-use ampul
HYDROmorphone HCl
Injection, USP
CII
2 mg/mL
PROTECT FROM LIGHT
Hospira, Inc.,
Lake Forest, IL 60045 USA
Hospira
1 mL 10 Single-use ampuls
NDC 0409-3356-01
Rx only
HYDROmorphone HCl
Injection, USP
2 mg/mL
CII
For Intravenous, Intramuscular, or Subcutaneous Use
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
PROTECT FROM LIGHT.
Do not use if solution is discolored or contains a precipitate.
Usual Dosage: See insert.
Hospira
RL - 4949
NDC 0409-2540-11
Rx only
1 mL
Single-use ampul
HYDROmorphone HCl
Injection, USP
CII
4 mg/mL
PROTECT FROM LIGHT
Hospira, Inc.,
Lake Forest, IL 60045 USA
Hospira
1 mL 10 Single-use ampuls
NDC 0409-2540-01
Rx only
HYDROmorphone HCl
Injection, USP
4 mg/mL
CII
For Intravenous, Intramuscular, or Subcutaneous Use
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
PROTECT FROM LIGHT.
Do not use if solution is discolored or contains a precipitate.
Usual Dosage: See insert.
Hospira
1mL Single-dose vial
Rx only
NDC 0409-3365-11
HYDROmorphone HCl
Injection, USP
2 mg/mL
CII
PROTECT FROM LIGHT
Dist. by Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
1 mL 10 Single-dose vials
Rx only
NDC 0409-3365-10
Contains 10 of NDC 0409-3365-11
HYDROmorphone HCl
Injection, USP
2 mg/mL
CII
For Intravenous, Intramuscular, or Subcutaneous Use
Distributed by Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
1 mL Single-dose Carpuject™
Sterile Cartridge Unit with Luer Lock
NDC 0409-1283-03
Rx only
HYDROmorphone HCl
Injection, USP
1 mg/mL
CII
PAA198794
PROTECT FROM LIGHT
Distributed by
Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
#####AA
DMMMYYYY
NDC 0409-1283-31
Contains 10 of NDC 0409-1283-03
Rx only
1 mL
Single-dose
10 Carpuject™
Sterile Cartridge Units
with Luer Lock
Needle not included
SLIM-PACK™
Tamper Detection Package
HYDROmorphone HCl
Injection, USP
1 mg/mL
CII
For Intravenous,
Intramuscular, or
Subcutaneous Use
Carpuject Cartridges are to be used
ONLY with Carpuject Holders.
Hospira
1 mL Single-dose Carpuject™
Sterile Cartridge Unit with Luer Lock
NDC 0409-1312-03
Rx only
HYDROmorphone HCl
Injection, USP
2 mg/mL
CII
PROTECT FROM LIGHT
Distributed by Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
PAA198795
#####AA
DMMMYYYY
NDC 0409-1312-30
Contains 10 of NDC 0409-1312-03
Rx only
1 mL
Single-dose
10 Carpuject™
Sterile Cartridge Units
with Luer Lock
Needle not included
SLIM-PAK™
Tamper Detection Package
HYDROmorphone HCl
Injection, USP
2 mg/mL
CII
For Intravenous,
Intramuscular, or
Subcutaneous Use
Carpuject Cartridges are to be used
ONLY with Carpuject Holders.
Hospira
1 mL Single-dose Carpuject™
Sterile Cartridge Unit with Luer Lock
NDC 0409-1304-03
Rx only
HYDROmorphone HCl
Injection, USP
4 mg/mL
CII
PROTECT FROM LIGHT
Distributed by
Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
PAA198796
#####AA
DMMMYYYY
NDC 0409-1304-31
Contains 10 of NDC 0409-1304-03
Rx only
1 mL
Single-dose
10 Carpuject™
Sterile Cartridge Units
with Luer Lock
Needle not included
SLIM-PAK™
Tamper Detection Package
HYDROmorphone HCl
Injection, USP
4 mg/mL
CII
For Intravenous,
Intramuscular, or
Subcutaneous Use
Carpuject Cartridges are
to be used ONLY with
Carpuject Holders.
Hospira
| RxCUI | RxNorm string | TTY | SPL version |
|---|---|---|---|
| 1724383 | HYDROmorphone HCl 1 MG in 1 ML Cartridge | PSN | 33 |
| 897653 | HYDROmorphone HCl 1 MG in 1 ML Injection | PSN | 33 |
| 897756 | HYDROmorphone HCl 1 MG in 1 ML Prefilled Syringe | PSN | 33 |
| 1724644 | HYDROmorphone HCl 2 MG in 1 ML Cartridge | PSN | 33 |
| 1724276 | HYDROmorphone HCl 2 MG in 1 ML Injection | PSN | 33 |
| 897757 | HYDROmorphone HCl 2 MG in 1 ML Prefilled Syringe | PSN | 33 |
| 897758 | HYDROmorphone HCl 4 MG in 1 ML Cartridge | PSN | 33 |
| 897753 | HYDROmorphone HCl 4 MG in 1 ML Injection | PSN | 33 |
| 1724383 | 1 ML hydromorphone hydrochloride 1 MG/ML Cartridge | SCD | 33 |
| 897653 | 1 ML hydromorphone hydrochloride 1 MG/ML Injection | SCD | 33 |
| 897756 | 1 ML hydromorphone hydrochloride 1 MG/ML Prefilled Syringe | SCD | 33 |
| 1724644 | 1 ML hydromorphone hydrochloride 2 MG/ML Cartridge | SCD | 33 |
| 1724276 | 1 ML hydromorphone hydrochloride 2 MG/ML Injection | SCD | 33 |
| 897757 | 1 ML hydromorphone hydrochloride 2 MG/ML Prefilled Syringe | SCD | 33 |
| 897758 | 1 ML hydromorphone hydrochloride 4 MG/ML Cartridge | SCD | 33 |
| 897753 | 1 ML hydromorphone hydrochloride 4 MG/ML Injection | SCD | 33 |
| 1724383 | hydromorphone HCl 1 MG per 1 ML Cartridge | SY | 33 |
| 897653 | hydromorphone HCl 1 MG per 1 ML Injection | SY | 33 |
| 897756 | hydromorphone HCl 1 MG per 1 ML Prefilled Syringe | SY | 33 |
| 1724644 | hydromorphone HCl 2 MG per 1 ML Cartridge | SY | 33 |
| 1724276 | hydromorphone HCl 2 MG per 1 ML Injection | SY | 33 |
| 897757 | hydromorphone HCl 2 MG per 1 ML Prefilled Syringe | SY | 33 |
| 897758 | hydromorphone HCl 4 MG per 1 ML Cartridge | SY | 33 |
| 897753 | hydromorphone HCl 4 MG per 1 ML Injection | SY | 33 |
| Class | Version | Type | Effective |
|---|---|---|---|
| HYDROMORPHONE Pharmacologic Class Indexing | 2 | Indexing - Pharmacologic Class | 20180813 |
| Resource | Code type | Value | Equivalent identifiers | Source image |
|---|---|---|---|---|
| Barcode | DataBar Limited | (01)00304091283039 | GTIN-14: 00304091283039 GTIN-12: 304091283039 UPC-A: 304091283039 EAN-13: 0304091283039 GTIN storage (14 digits): 00304091283039 | hydromorphone-18.jpg |
| Barcode | DataBar Limited | (01)00304091304031 | GTIN-14: 00304091304031 GTIN-12: 304091304031 UPC-A: 304091304031 EAN-13: 0304091304031 GTIN storage (14 digits): 00304091304031 | hydromorphone-31.jpg |
| Barcode | DataBar Limited | (01)00304091312036 | GTIN-14: 00304091312036 GTIN-12: 304091312036 UPC-A: 304091312036 EAN-13: 0304091312036 GTIN storage (14 digits): 00304091312036 | hydromorphone-26.jpg |
| Barcode | DataBar Limited | (01)00304092540117 | GTIN-14: 00304092540117 GTIN-12: 304092540117 UPC-A: 304092540117 EAN-13: 0304092540117 GTIN storage (14 digits): 00304092540117 | hydromorphone-14.jpg |
| Barcode | DataBar Limited | (01)00304092552110 | GTIN-14: 00304092552110 GTIN-12: 304092552110 UPC-A: 304092552110 EAN-13: 0304092552110 GTIN storage (14 digits): 00304092552110 | hydromorphone-10.jpg |
| Barcode | DataBar Limited | (01)00304093356113 | GTIN-14: 00304093356113 GTIN-12: 304093356113 UPC-A: 304093356113 EAN-13: 0304093356113 GTIN storage (14 digits): 00304093356113 | hydromorphone-12.jpg |
| Barcode | DataBar Stacked | (01)00304093365115 | GTIN-14: 00304093365115 GTIN-12: 304093365115 UPC-A: 304093365115 EAN-13: 0304093365115 GTIN storage (14 digits): 00304093365115 | hydromorphone-16.jpg |
| Product concept | Relation | Version | Effective |
|---|---|---|---|
| c92985da-a658-b186-e763-2287eda87a86 | Product name | 3 | 20250221 |
| 96c475b3-58c7-b955-d715-0111804a3e50 | Product name | 5 | 20210512 |
| 1dd54659-b775-4fa8-a858-7f0e521fbadc | Product name | 4 | 20200925 |
| 444b3e50-f226-46ef-bfca-2e7035d140cd | Product name | 1 | 20190611 |
| 597b1cfd-7b31-5048-62be-ca5cd740da2f | Product name | 1 | 20140508 |
| ec2149b3-5c6d-5344-f757-c86411073075 | Product name | 1 | 20140508 |
| Package NDC | Product | Description | Form | Quantity | Strength | SPL version |
|---|---|---|---|---|---|---|
| 0409-1283-03 | Hydromorphone Hydrochloride | 1 mL in 1 CARTRIDGE | INJECTION, SOLUTION | 1 | 33 | |
| 0409-1283-31 | Hydromorphone Hydrochloride | 10 in 1 CARTON | INJECTION, SOLUTION | 10 | 33 | |
| 0409-1304-03 | Hydromorphone Hydrochloride | 1 mL in 1 CARTRIDGE | INJECTION, SOLUTION | 1 | 33 | |
| 0409-1304-31 | Hydromorphone Hydrochloride | 10 in 1 CARTON | INJECTION, SOLUTION | 10 | 33 | |
| 0409-1312-03 | Hydromorphone Hydrochloride | 1 mL in 1 CARTRIDGE | INJECTION, SOLUTION | 1 | 33 | |
| 0409-1312-30 | Hydromorphone Hydrochloride | 10 in 1 CARTON | INJECTION, SOLUTION | 10 | 33 | |
| 0409-2540-01 | Hydromorphone Hydrochloride | 10 in 1 CARTON | INJECTION, SOLUTION | 10 | 33 | |
| 0409-2540-11 | Hydromorphone Hydrochloride | 1 mL in 1 AMPULE | INJECTION, SOLUTION | 1 | 33 | |
| 0409-2552-01 | Hydromorphone Hydrochloride | 10 in 1 CARTON | INJECTION, SOLUTION | 10 | 33 | |
| 0409-2552-11 | Hydromorphone Hydrochloride | 1 mL in 1 AMPULE | INJECTION, SOLUTION | 1 | 33 | |
| 0409-3356-01 | Hydromorphone Hydrochloride | 10 in 1 CARTON | INJECTION, SOLUTION | 10 | 33 | |
| 0409-3356-11 | Hydromorphone Hydrochloride | 1 mL in 1 AMPULE | INJECTION, SOLUTION | 1 | 33 | |
| 0409-3365-01 | Hydromorphone Hydrochloride | 25 in 1 TRAY | INJECTION, SOLUTION | 25 | 33 | |
| 0409-3365-10 | Hydromorphone Hydrochloride | 10 in 1 CARTON | INJECTION, SOLUTION | 10 | 33 | |
| 0409-3365-11 | Hydromorphone Hydrochloride | 1 mL in 1 VIAL, SINGLE-DOSE | INJECTION, SOLUTION | 1 | 33 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| HYDROMORPHONE HYDROCHLORIDE | ACTIVE INGREDIENT | L960UP2KRW | 12 | |
| HYDROMORPHONE | ACTIVE MOIETY | Q812464R06 | 12 | |
| LACTIC ACID, UNSPECIFIED FORM | INACTIVE INGREDIENT | 33X04XA5AT | 12 | |
| SODIUM CHLORIDE | INACTIVE INGREDIENT | 451W47IQ8X | 12 | |
| SODIUM HYDROXIDE | INACTIVE INGREDIENT | 55X04QC32I | 12 | |
| SODIUM LACTATE | INACTIVE INGREDIENT | TU7HW0W0QT | 12 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 0409-1283 | 0409-1283-03, 0409-1283-31 |
| 0409-1304 | 0409-1304-03, 0409-1304-31 |
| 0409-1312 | 0409-1312-03, 0409-1312-30 |
| 0409-2540 | 0409-2540-11, 0409-2540-01 |
| 0409-2552 | 0409-2552-11, 0409-2552-01 |
| 0409-3356 | 0409-3356-11, 0409-3356-01 |
| 0409-3365 | 0409-3365-11, 0409-3365-01, 0409-3365-10 |
Every source-derived ingredient row is available through these pages.
| Version | Effective date | Source | Hydrated |
|---|---|---|---|
| 32 | 2025-12-08 | monthly-update | 2026-06-03 17:48:23 |
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / SUBCUTANEOUS | 1 %w/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAVENOUS | 78 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAMUSCULAR | 78 mg | ||
| LACTIC ACID, UNSPECIFIED FORM | LACTIC ACID | 33X04XA5AT | INJECTION, SOLUTION / INTRAVENOUS | 87 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAVENOUS | 78 mg | ||
| LACTIC ACID, UNSPECIFIED FORM | LACTIC ACID | 33X04XA5AT | INJECTION, SOLUTION / INTRAVENOUS | 87 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAMUSCULAR | 78 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAMUSCULAR | 1486 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / SUBCUTANEOUS | 1 %w/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAMUSCULAR | 78 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAMUSCULAR | 1486 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAMUSCULAR | 78 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAMUSCULAR | 78 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / SUBCUTANEOUS | 1 %w/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / SUBCUTANEOUS | 1 %w/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / SUBCUTANEOUS | 1486 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 18.7 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / SUBCUTANEOUS | 1486 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION / INTRAVENOUS | 54 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAMUSCULAR | 78 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAVENOUS | 78 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / SUBCUTANEOUS | 1486 mg | ||
| LACTIC ACID, UNSPECIFIED FORM | LACTIC ACID | 33X04XA5AT | INJECTION, SOLUTION / INTRAVENOUS | 87 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / SUBCUTANEOUS | 1 %w/v | ||
| LACTIC ACID, UNSPECIFIED FORM | LACTIC ACID | 33X04XA5AT | INJECTION, SOLUTION / INTRAVENOUS | 87 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / SUBCUTANEOUS | 1486 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / SUBCUTANEOUS | 1 %w/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAMUSCULAR | 1486 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAMUSCULAR | 1486 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION / INTRAVENOUS | 54 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAVENOUS | 78 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / SUBCUTANEOUS | 1486 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAVENOUS | 78 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION / INTRAVENOUS | 54 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION / INTRAVENOUS | 54 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| LACTIC ACID, UNSPECIFIED FORM | LACTIC ACID | 33X04XA5AT | INJECTION, SOLUTION / INTRAVENOUS | 87 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 18.7 mg | ||
| LACTIC ACID, UNSPECIFIED FORM | LACTIC ACID | 33X04XA5AT | INJECTION, SOLUTION / INTRAVENOUS | 87 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION / INTRAVENOUS | 54 mg | ||
| SODIUM HYDROXIDE | SODIUM HYDROXIDE | 55X04QC32I | INJECTION, SOLUTION / INTRAVENOUS | 78 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAVENOUS | 2916 mg | ||
| SODIUM CHLORIDE | SODIUM CHLORIDE | 451W47IQ8X | INJECTION, SOLUTION / INTRAMUSCULAR | 1486 mg | ||
| SODIUM LACTATE | SODIUM LACTATE | TU7HW0W0QT | INJECTION, SOLUTION / INFILTRATION | 0.17 %v/v |
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| N200403-001 | HYDROMORPHONE HYDROCHLORIDE | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 |
| N200403-002 | HYDROMORPHONE HYDROCHLORIDE | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 |
| N200403-003 | HYDROMORPHONE HYDROCHLORIDE | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 |
| N200403-004 | HYDROMORPHONE HYDROCHLORIDE | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | RLD | 2022-06-13 | |
| N200403-005 | HYDROMORPHONE HYDROCHLORIDE | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | RLD | 2023-03-03 |
| Application-product | TE code |
|---|---|
| N200403-001 | AP |
| N200403-002 | AP |
| N200403-003 | AP |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-10-15 13:18:30 | 2026-09 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | RLD | 2022-06-13 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | RLD | 2023-03-03 | c2088c7a36db… | |
| 2026-09-14 22:38:34 | 2026-08 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | RLD | 2011-12-01 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | RLD | 2022-06-13 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | RLD | 2023-03-03 | 84e616aacf4f… | |
| 2026-08-18 06:07:40 | 2026-07 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | 2022-06-13 | caaa826d4ba7… | ||
| 2026-08-18 06:07:40 | 2026-07 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | 2023-03-03 | caaa826d4ba7… | ||
| 2026-02-19 14:30 UTC | 2026-02 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | 2022-06-13 | 011fe1cb6892… | ||
| 2026-02-19 14:30 UTC | 2026-02 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | 2023-03-03 | 011fe1cb6892… | ||
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | 2022-06-13 | 31067a03dcf5… | ||
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | 2023-03-03 | 31067a03dcf5… | ||
| 2025-08-23 18:47 UTC | 2025-08 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | 2022-06-13 | 6a471c1ec25d… | ||
| 2025-08-23 18:47 UTC | 2025-08 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | 2023-03-03 | 6a471c1ec25d… | ||
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | 2022-06-13 | fd3edfee7708… | ||
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | 2023-03-03 | fd3edfee7708… | ||
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-001 | HYDROMORPHONE HYDROCHLORIDE | 1MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-002 | HYDROMORPHONE HYDROCHLORIDE | 2MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-003 | HYDROMORPHONE HYDROCHLORIDE | 4MG/ML | INJECTABLE / INJECTION | AP | 2011-12-01 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-004 | HYDROMORPHONE HYDROCHLORIDE | 0.5MG/0.5ML | INJECTABLE / INJECTION | 2022-06-13 | b8a1b40f171c… | ||
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-005 | HYDROMORPHONE HYDROCHLORIDE | 0.25MG/0.5ML | INJECTABLE / INJECTION | 2023-03-03 | b8a1b40f171c… |
| Captured | Edition | Application-product | TE code | Order | Source SHA-256 |
|---|---|---|---|---|---|
| 2026-10-15 13:18:30 | 2026-09 | N200403-001 | AP | 1 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N200403-002 | AP | 1 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N200403-003 | AP | 1 | c2088c7a36db… |
| 2026-09-14 22:38:34 | 2026-08 | N200403-001 | AP | 1 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N200403-002 | AP | 1 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N200403-003 | AP | 1 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | N200403-001 | AP | 1 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N200403-002 | AP | 1 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N200403-003 | AP | 1 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | N200403-001 | AP | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N200403-002 | AP | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N200403-003 | AP | 1 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-001 | AP | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-002 | AP | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N200403-003 | AP | 1 | 31067a03dcf5… |
| 2025-08-23 18:47 UTC | 2025-08 | N200403-001 | AP | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N200403-002 | AP | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N200403-003 | AP | 1 | 6a471c1ec25d… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-001 | AP | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-002 | AP | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N200403-003 | AP | 1 | fd3edfee7708… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-001 | AP | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-002 | AP | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N200403-003 | AP | 1 | b8a1b40f171c… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N200403-001 | AP | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N200403-002 | AP | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N200403-003 | AP | 1 | 03ed91905a0d… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N200403-001 | AP | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N200403-002 | AP | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N200403-003 | AP | 1 | 2680178bc6a6… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N200403-001 | AP | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N200403-002 | AP | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N200403-003 | AP | 1 | 5bbf6a4d5a75… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N200403-001 | AP | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N200403-002 | AP | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N200403-003 | AP | 1 | d8e5a09893c0… |
| 2024-10-29 15:01 UTC | 2024-10 | N200403-001 | AP | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N200403-002 | AP | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N200403-003 | AP | 1 | d06236e962d9… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N200403-001 | AP | 1 | 79d66fd596c7… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| Hydromorphone Hydrochloride | HYDROMORPHONE HYDROCHLORIDE | Hospira, Inc. | f9ca2ef5-46d8-475a-a26e-f7c8becd6db7 | 2026-02-04 | Boxed warning, Warnings, Adverse reactions | 0409-1312 0409-1283 |
| Hydromorphone Hydrochloride | HYDROMORPHONE HYDROCHLORIDE | Hospira, Inc. | e9c9ef18-7dfc-4322-b2fc-29b934c30f8b | 2025-12-31 | Boxed warning, Warnings, Adverse reactions | 0409-3356-01 0409-2540-01 0409-3365-10 0409-2552-11 0409-3365-11 0409-1304-31 0409-1312-30 0409-3356-11 0409-3365-01 0409-2552-01 0409-1283-31 0409-2540-11 0409-1283-03 0409-1304-03 0409-1312-03 0409-1312 0409-1283 0409-1304 0409-2552 0409-2540 0409-3365 0409-3356 00409130403 00409335601 00409336510 00409131203 00409128303 00409131230 00409255201 00409130431 00409336501 00409335611 00409336511 00409254011 00409128331 00409254001 00409255211 a3ebafac-648e-47b1-a6f5-1e3bff1e3e08 e9c9ef18-7dfc-4322-b2fc-29b934c30f8b |
Adverse event summaries are temporarily unavailable. Other product information remains available.