Dilaudid

Boxed Warning                                                                                                                                                            12/2023

Indications and Usage (

Dosage and Administration (

Warnings and Precautions (

DILAUDID INJECTION is an opioid agonist indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate. (

Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, reserve Hydromorphone Hydrochloride Injection for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products):

• •Have not been tolerated, or are not expected to be tolerated
• •Have not provided adequate analgesia or are not expected to provide adequate analgesia

DILAUDID INJECTION should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

• •DILAUDID INJECTION should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. (
  2.1 Important Dosage and Administration Instructions

  • •
    DILAUDID 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 ]

    . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of DILAUDID INJECTION for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
  • •
    Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.
  • •
    There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse

    [see Warnings and Precautions ]

    .
  • •
    Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with DILAUDID INJECTION. Consider this risk when selecting an initial dose and when making dose adjustments

    [see Warnings and Precautions ]

    .
  • •
    Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in DILAUDID INJECTION. No loss of potency has been demonstrated. DILAUDID INJECTION is physically compatible and chemically stable for at least 24 hours at 25°C, protected from light in most common large-volume parenteral solutions.
  • •
    Discard any unused portion in an appropriate manner.
  )
• •Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of Hydromorphone Hydrochloride Injection for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. (
  2.1 Important Dosage and Administration Instructions

  • •
    DILAUDID 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 ]

    . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of DILAUDID INJECTION for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
  • •
    Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.
  • •
    There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse

    [see Warnings and Precautions ]

    .
  • •
    Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with DILAUDID INJECTION. Consider this risk when selecting an initial dose and when making dose adjustments

    [see Warnings and Precautions ]

    .
  • •
    Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in DILAUDID INJECTION. No loss of potency has been demonstrated. DILAUDID INJECTION is physically compatible and chemically stable for at least 24 hours at 25°C, protected from light in most common large-volume parenteral solutions.
  • •
    Discard any unused portion in an appropriate manner.
  ,
  5 WARNINGS AND PRECAUTIONS

  • •
    Opioid-Induced Hyperalgesia and Allodynia:
    Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation.
  • •
    Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients:
    Monitor closely, particularly during initiation and titration.
  • •
    Adrenal Insufficiency:
    If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.
  • •
    Severe Hypotension:
    Monitor during dosage initiation and titration. Avoid use of DILAUDID INJECTION in patients with circulatory shock.
  • •
    Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness:
    Monitor for sedation and respiratory depression. Avoid use of DILAUDID INJECTION in patients with impaired consciousness or coma.
  • •DILAUDID INJECTION contains sodium metabisulfite. There is a risk of anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people.

  5.1 Addiction, Abuse, and Misuse

  DILAUDID INJECTION contains hydromorphone, a Schedule II controlled substance. As an opioid, DILAUDID INJECTION exposes users to the risks of addiction, abuse, and misuse

  [see Drug Abuse and Dependence ].

  Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed DILAUDID 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 prior to prescribing DILAUDID INJECTION and monitor all patients receiving DILAUDID 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 DILAUDID INJECTION but use in such patients necessitates intensive counseling about the risks and proper use of DILAUDID 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 DILAUDID 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.

  5.2 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 (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 DILAUDID 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 DILAUDID INJECTION is essential

  [see Dosage and Administration ].

  Overestimating the DILAUDID 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 ]

  .

  5.3 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

  Profound sedation, respiratory depression, coma, and death may result from the concomitant use of DILAUDID INJECTION with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, 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 ]

  .

  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.

  5.4 Neonatal Opioid Withdrawal Syndrome

  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 ].

  5.5 Opioid-Induced Hyperalgesia and Allodynia

  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 Dependence ]

  . 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 , Warnings and Precautions ]

  .

  5.6 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

  The use of DILAUDID 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:

  DILAUDID 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 DILAUDID INJECTION

  [see Warnings and Precautions ]

  .

  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 ].

  Monitor such patients closely, particularly when initiating and titrating DILAUDID INJECTION and when DILAUDID INJECTION is given concomitantly with other drugs that depress respiration

  [see Warnings and Precautions , Drug Interactions ].

  Alternatively, consider the use of non-opioid analgesics in these patients.

  5.7 Adrenal Insufficiency

  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.

  5.8 Severe Hypotension

  DILAUDID 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 ]

  . Monitor these patients for signs of hypotension after initiating or titrating the dosage of DILAUDID INJECTION. In patients with circulatory shock, DILAUDID INJECTION may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of DILAUDID INJECTION in patients with circulatory shock.

  5.9 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 CO₂retention (e.g., those with evidence of increased intracranial pressure or brain tumors), DILAUDID INJECTION may reduce respiratory drive, and the resultant CO₂retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with DILAUDID INJECTION.

  Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of DILAUDID INJECTION in patients with impaired consciousness or coma.

  5.10 Risks of Use in Patients with Gastrointestinal Conditions

  DILAUDID INJECTION is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

  The hydromorphone in DILAUDID 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.

  5.11 Increased Risk of Seizures in Patients with Seizure Disorders

  The hydromorphone in DILAUDID 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 DILAUDID INJECTION therapy.

  5.12 Withdrawal

  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 DILAUDID INJECTION. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms

  [see Drug Interactions ]

  .

  When discontinuing DILAUDID INJECTION in a physically-dependent patient, gradually taper the dosage

  [see Dosage and Administration ].

  Do not abruptly discontinue DILAUDID INJECTION in these patients

  [see Drug Abuse and Dependence ].

  5.13 Risks of Driving and Operating Machinery

  DILAUDID 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 DILAUDID INJECTION and know how they will react to the medication.

  5.14 Sulfites

  DILAUDID INJECTION contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life- threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

  5.15 Increased Risk of Hypotension and Respiratory Depression with Rapid Intravenous Administration

  DILAUDID 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 ].
  )
• •Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. (
  2.1 Important Dosage and Administration Instructions

  • •
    DILAUDID 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 ]

    . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of DILAUDID INJECTION for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
  • •
    Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.
  • •
    There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse

    [see Warnings and Precautions ]

    .
  • •
    Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with DILAUDID INJECTION. Consider this risk when selecting an initial dose and when making dose adjustments

    [see Warnings and Precautions ]

    .
  • •
    Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in DILAUDID INJECTION. No loss of potency has been demonstrated. DILAUDID INJECTION is physically compatible and chemically stable for at least 24 hours at 25°C, protected from light in most common large-volume parenteral solutions.
  • •
    Discard any unused portion in an appropriate manner.
  )
• •Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. (
  2.1 Important Dosage and Administration Instructions

  • •
    DILAUDID 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 ]

    . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of DILAUDID INJECTION for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
  • •
    Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.
  • •
    There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse

    [see Warnings and Precautions ]

    .
  • •
    Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with DILAUDID INJECTION. Consider this risk when selecting an initial dose and when making dose adjustments

    [see Warnings and Precautions ]

    .
  • •
    Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in DILAUDID INJECTION. No loss of potency has been demonstrated. DILAUDID INJECTION is physically compatible and chemically stable for at least 24 hours at 25°C, protected from light in most common large-volume parenteral solutions.
  • •
    Discard any unused portion in an appropriate manner.
  ,
  5.1 Addiction, Abuse, and Misuse

  DILAUDID INJECTION contains hydromorphone, a Schedule II controlled substance. As an opioid, DILAUDID INJECTION exposes users to the risks of addiction, abuse, and misuse

  [see Drug Abuse and Dependence ].

  Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed DILAUDID 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 prior to prescribing DILAUDID INJECTION and monitor all patients receiving DILAUDID 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 DILAUDID INJECTION but use in such patients necessitates intensive counseling about the risks and proper use of DILAUDID 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 DILAUDID 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.
  )
• •Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Hydromorphone Hydrochloride Injection. Consider this risk when selecting an initial dose and when making dose adjustments. (
  2.1 Important Dosage and Administration Instructions

  • •
    DILAUDID 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 ]

    . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of DILAUDID INJECTION for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
  • •
    Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.
  • •
    There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse

    [see Warnings and Precautions ]

    .
  • •
    Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with DILAUDID INJECTION. Consider this risk when selecting an initial dose and when making dose adjustments

    [see Warnings and Precautions ]

    .
  • •
    Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in DILAUDID INJECTION. No loss of potency has been demonstrated. DILAUDID INJECTION is physically compatible and chemically stable for at least 24 hours at 25°C, protected from light in most common large-volume parenteral solutions.
  • •
    Discard any unused portion in an appropriate manner.
  ,
  5.2 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 (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 DILAUDID 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 DILAUDID INJECTION is essential

  [see Dosage and Administration ].

  Overestimating the DILAUDID 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 ]

  .
  )
• •
  Initial Dosage:
  • -
    Intramuscular or Subcutaneous Use:
    The usual starting dose is 1 mg to 2 mg every 2 to 3 hours as necessary. (
    2.2 Initial Dosage

    Use of DILAUDID INJECTION as the First Opioid Analgesic:

    Subcutaneous or Intramuscular Administration:

    The usual starting dose is 1 mg to 2 mg every 2 to 3 hours as necessary for pain, and 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:

    The initial starting dose is 0.2 mg to 1 mg every 2 to 3 hours. Intravenous administration should be given

    slowly

    , over at least 2 to 3 minutes, depending on the dose. The initial dose should be reduced in the elderly or debilitated and may be lowered to 0.2 mg.

    Conversion From Other Opioids to DILAUDID 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 DILAUDID INJECTION. It is safer to underestimate a patient's 24-hour DILAUDID INJECTION dosage than to overestimate the 24-hour DILAUDID 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 DILAUDID 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.
    )
  • -
    Intravenous Use:
    The usual starting dose is 0.2 mg to 1 mg every 2 to 3 hours. The injection should be given slowly
    ,
    over at least 2 to 3 minutes. (
    2.2 Initial Dosage

    Use of DILAUDID INJECTION as the First Opioid Analgesic:

    Subcutaneous or Intramuscular Administration:

    The usual starting dose is 1 mg to 2 mg every 2 to 3 hours as necessary for pain, and 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:

    The initial starting dose is 0.2 mg to 1 mg every 2 to 3 hours. Intravenous administration should be given

    slowly

    , over at least 2 to 3 minutes, depending on the dose. The initial dose should be reduced in the elderly or debilitated and may be lowered to 0.2 mg.

    Conversion From Other Opioids to DILAUDID 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 DILAUDID INJECTION. It is safer to underestimate a patient's 24-hour DILAUDID INJECTION dosage than to overestimate the 24-hour DILAUDID 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 DILAUDID 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.
    )
• •
  Hepatic Impairment:
  Initiate treatment with one-fourth to one-half the usual starting dose, depending on degree of hepatic impairment. (
  2.3 Dosage Modifications in Patients with Hepatic Impairment

  Start patients with hepatic impairment on one-fourth to one-half the usual DILAUDID INJECTION starting dose depending on the extent of impairment

  [see Clinical Pharmacology ]

  .
  )
• •
  Renal Impairment:
  Initiate treatment with one-fourth to one-half the usual starting dose, depending on degree of renal impairment. (
  2.4 Dosage Modifications in Patients with Renal Impairment

  Start patients with renal impairment on one-fourth to one-half the usual DILAUDID INJECTION starting dose depending on the degree of impairment

  [see Clinical Pharmacology ].
  )
• •Do not abruptly discontinue DILAUDID INJECTION in a physically-dependent patient. (
  2.6 Safe Reduction or Discontinuation of DILAUDID INJECTION

  When a patient who has been taking DILAUDID INJECTION regularly and may be physically dependent no longer requires therapy with DILAUDID INJECTION, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue DILAUDID INJECTION in a physically-dependent patient

  [see Warnings and Precautions , Drug Abuse and Dependence ].
  ,
  5.12 Withdrawal

  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 DILAUDID INJECTION. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms

  [see Drug Interactions ]

  .

  When discontinuing DILAUDID INJECTION in a physically-dependent patient, gradually taper the dosage

  [see Dosage and Administration ].

  Do not abruptly discontinue DILAUDID INJECTION in these patients

  [see Drug Abuse and Dependence ].
  )

DILAUDID INJECTION:

Each single-dose prefilled syringe contains 0.2 mg/mL, 0.5 mg/0.5 mL, 1 mg/mL or 2 mg/mL of hydromorphone hydrochloride in a sterile, aqueous solution.

• •Pregnancy: May cause fetal harm. (
  8.1 Pregnancy

  Risk Summary

  Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome

  [see Warnings and Precautions ]

  . There are no available data with DILAUDID 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 animal reproduction studies, reduced postnatal survival of pups, and decreased body weight were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.8 times the human daily dose of 24 mg/day (HDD), respectively. In published 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 ].

  Labor or Delivery

  Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. DILAUDID 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 DILAUDID 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

  Pregnant rats were treated with hydromorphone hydrochloride from Gestation Day 6 to 17 via oral gavage doses of 1, 5, or 10 mg/kg/day (0.4, 2, or 4 times the HDD of 24 mg based on body surface area, respectively). Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups). There was no evidence of malformations or embryotoxicity reported.

  Pregnant rabbits were treated with hydromorphone hydrochloride from Gestation Day 7 to 19 via oral gavage doses of 10, 25, or 50 mg/kg/day (8.1, 20.3, or 40.5 times the HDD of 24 mg based on body surface area, respectively). Maternal toxicity was noted in the two highest dose groups (reduced food consumption and body weights). There was no evidence of malformations or embryotoxicity reported.

  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.

  Increased pup mortality and decreased pup body weights were noted at 0.8 and 2 times the human daily dose of 24 mg in a study in which pregnant rats were treated with hydromorphone hydrochloride from Gestation Day 7 to Lactation Day 20 via oral gavage doses of 0, 0.5, 2, or 5 mg/kg/day (0.2, 0.8, or 2 times the HDD of 24 mg based on body surface area, respectively). Maternal toxicity (decreased food consumption and body weight gain) was also noted at the two highest doses tested.
  )