Hydromorphone Hydrochloride 2 mg/mL Injection, 25 vials
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Opioid Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Hydromorphone injection is used to relieve severe pain. Hydromorphone injection is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.
Read the full MedlinePlus article ↗- Hydromorphone is a strong opioid pain reliever — think of it as a more concentrated relative of morphine. Your doctor prescribed it because your pain is severe enough that other op...
- What exactly is hydromorphone and why did my doctor prescribe it instead of something else?
- This is one of the most important things to understand about hydromorphone: combining it with alcohol, benzodiazepines (like Xanax or Valium), sleep aids, or any other sedating sub...
- Is it safe to take a sleep aid, anxiety pill, or have a glass of wine while on this?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 2968PHW8QP
A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
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UNII 1Q73Q2JULR
Sodium citrate is a salt derived from citric acid. It works as a buffer to maintain the medicine's pH level and may also help improve taste or act as a preservative in the formulation.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
3 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2.740 | $68.51 / 25 ml |
| Medicaid paysCMS SDUD · 12 mo | $6.69 | $167.26 / 25 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J1171 | $0.136 / J1171 unit | — |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Hydromorphone Hydrochloride 2 mg/mLthis 00641-6151-25 | Hikma | 25 vials | $2.740 | AP | Availability likely | — |
| Hydromorphone Hydrochloride 2 mg/mL 63323-0853-25 | Fresenius | 25 vials | $2.740 | AP | Availability likely | — |
| Hydromorphone Hydrochloride 2 mg/mL 00409-1312-30 | Hospira, | 10 cartridges | $3.245 | — | Availability likely | +18% |
| Hydromorphone Hydrochloride 2 mg/mL 00409-3365-10 | Hospira, | 10 vials | — | — | FDA listed | — |
| Dilaudid 2 mg/mL 76045-0010-11 | Fresenius | 10 syringes | — | AP | FDA listed | — |
| Hydromorphone Hydrochloride 2 mg/mL 00641-2341-41 | Hikma | 20 vials | — | — | FDA listed | — |
| Hydromorphone Hydrochloride 2 mg/mL 00641-6254-01 | Hikma | 1 vial | — | — | FDA listed | — |
| Hydromorphone Hydrochloride 2 mg/mL 00641-6170-10 | Hikma | 10 syringes | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00641-6151-25 You're viewing this | 25 VIAL, SINGLE-DOSE in 1 CARTON (0641-6151-25) / 1 mL in 1 VIAL, SINGLE-DOSE (0641-6151-01) | 2018-07-01 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROMORPHONE HYDROCHLORIDE INJECTION Addiction, Abuse, and Misuse Hydromorphone Hydrochloride Injection exposes patients and other users to the 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) ] . WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROMORPHONE HYDROCHLORIDE INJECTION See full prescribing information for complete boxed warning.
Hydromorphone hydrochloride injection e xposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and monitor regularly for these behaviors and conditions. ( 5.1 ) Serious, life-threatening, or fatal respiratory depression may occur.
Monitor closely, especially upon initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of Hydromorphone Hydrochloride Injection are essential. ( 5.2 ) 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 for use in patients for whom alternative treatment options are inadequate. ( 5.3 , 7 ) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may belife-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery.
( 5.4 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Hydromorphone hydrochloride injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternate 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 (5.2) ] , 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.
Hydromorphone hydrochloride is an opioid agonist indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate. ( 1 ) 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, 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.
( 1 , 5.1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION 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. ( 2.1 ) 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 , 5 ) 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 ) 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 , 5.1 ) 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 , 5.2 ) I nitia l Dosage: - Intramuscular or Subcutaneous Use : The usual starting dose is 1 mg to 2 mg every 2 to 3 hours as necessary.
( 2.2 ) - 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 ) Hepatic Impairment : Initiate treatment with one-fourth to one-half the usual starting dose, depending on degree of hepatic impairment.
( 2.3 ) Renal Impairment: Initiate treatment with one-fourth to one-half the usual starting dose, depending on degree of renal impairment. ( 2.4 ) Periodically reassess patients receiving hydromorphone hydrochloride injection to evaluate the continued need for opioid analgesics to maintain pain control, for the signs of symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. ( 2.5 ) Do not rapidly reduce or abruptly discontinue hydromorphone hydrochloride injection in a physically dependent patient.
( 2.6 , 5.12 )
2.1Important Dosage and Administration Instructions 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 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.
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 (5.1) ]. 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 [see…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Hydromorphone hydrochloride injection is available as a 1 mL single dose vial containing 2 mg hydromorphone hydrochloride in a clear, colorless to nearly colorless aqueous sterile solution. Hydromorphone Hydrochloride Injection, USP: 2 mg/mL single dose vials ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Hydromorphone hydrochloride injection is contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.2) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.6) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.10) ] Hypersensitivity to hydromorphone, hydromorphone salts, or any other components of the product, or sulfite containing medications (e.g., anaphylaxis) [see Warnings and Precautions (5.14) ] Significant respiratory depression ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 ) Known hypersensitivity to hydromorphone, hydromorphone salts, sulfite containing medications, or any other components of the product ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when 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. ( 5.5 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Monitor closely, particularly during initiation and titration.
( 5.6 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.7 ) Severe Hypotension : Monitor during dosage initiation and titration. Avoid use of hydromorphone hydrochloride injection in patients with circulatory shock.
( 5.8 ) 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 hydromorphone hydrochloride injection in patients with impaired consciousness or coma. ( 5.9 ) Hydromorphone hydrochloride injection contains sodium metabisulfite.
There is a risk of anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people. ( 5.14 ) 5.1. Addiction, Abuse, and Misuse 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 opoid-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 longterm 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.
5.2Life-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 overdose reversal agent (e.g., naloxone, nalmefene), depending on the patient’s clinical status [see Overdosage (10) ].
Carbon dioxide (CO 2 ) retent…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2) ] Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions (5.3) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.5) ] Adrenal Insufficiency [see Warnings and Precautions (5.7) ] Severe Hypotension [see Warnings and Precautions (5.8) ] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.10) ] Seizures [see Warnings and Precautions (5.11) ] Withdrawal [see Warnings and Precautions (5.12)] 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. Serious adverse reactions associated with hydromorphone hydrochloride injection include respiratory depression and apnea and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest. The most common adverse effects are lightheadedness, 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, fatigue, injection site reactions, peripheral edema Hepatobiliary disorders: biliary colic Immune system disorders: anaphylactic reactions, hypersensitivity reactions Investigations: hepatic enzymes increased 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, convulsion, drowsiness, dyskinesia, hyperalgesia, lethargy, myoclonus, somnolence Psychiatric disorders: agitation, mood altered, nervousness, anxiety , depression, hallucination, disorientation, insomnia, abnormal dreams Renal and urinary disorders: urinary retention, urinary hesitation, antidiuretic effects Reproductive system and breast disorders: erectile dysfunction Respiratory, thoracic, and mediastinal disorders: bronchospasm, laryngospasm, dyspnea, oropharyngeal swelling 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 chronic use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY (12.2) ] .
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 le…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with hydromorphone hydrochloride injection. TABLE 1 Clinically Significant Drug Interactions with Hydromorphone Hydrochloride Injection B enzodiazepines and other Central Nervous System Depressants (CNS) C linical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. [see Warnings and Precautions (5.3) ].
In tervention: 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. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions (5.3) ].
E xamples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Serotonergic Drugs C linical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. In tervention: 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. E xamples: 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), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
M o noamine Oxidase Inhibitors (MAOIs) C linical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS AND PRECAUTIONS (5.2) ] . 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. In tervention: 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 while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. E xamples: phenelzine, tranylcypromine, linezolid M ixed Agonist/Antagonist and Partial Agonist Opioid Analgesics C linical Impact: May reduce the analgesic effect of hydromorphone hydrochloride injection and/or precipitate withdrawal syndrome. In tervention: Avoid concomitant use.
E xamples: butorphanol, nalbuphine, pentazocine, buprenorphine M uscle Relaxants C linical Impact: Hydromorphone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. In tervention: 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 C linical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
In tervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs C linical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. In tervention: Monitor patients for signs of urinary retention or reduced g…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy : May cause fetal harm. ( 8.1 )
8.1Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5 ]. 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 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 (5.5) ].
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 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 su…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of hydromorphone hydrochloride injection in pediatric patients has not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use 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 (5.7) ]. 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.
🆘 Overdosage ▾
10 OVERDOSAGE 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, 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 airway 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 techniques.
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 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 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Hydromorphone is a full opioid agonist and is relatively selective for the mu-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.
12.2Pharmacodynamics Effects on the Central Nervous System Hydromorphone produces respiratory depression by direct effect 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 origin 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.
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 , 2.2) ] . Concentration–Adverse Reaction Relationships There is a relationship between increa…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Hydromorphone is a full opioid agonist and is relatively selective for the mu-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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Hydromorphone Hydrochloride Injection, USP containing 2 mg of hydromorphone hydrochloride per mL is preservative-free and available in the following: 1 mL Single Dose vials packaged in cartons of 25s (NDC 0641-6151-25) PROTECT FROM LIGHT. Keep covered in carton until time of use. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Safety and Handling Instructions Discard any unused portion Access to drugs with a potential for abuse such as hydromorphone hydrochloride injection presents an occupational hazard for addiction in the healthcare industry. Routine procedures for handling controlled substances developed to protect the public may not be adequate to protect healthcare 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 healthcare providers.
📋 Description ▾
11 DESCRIPTION Hydromorphone hydrochloride, a hydrogenated ketone of morphine, is an opioid agonist. 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. The chemical name of hydromorphone hydrochloride is 4,5α-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride.
The structural formula is: C 17 H 19 NO 3 •HCl 321.80 Hydromorphone Hydrochloride Injection, USP is available as a sterile, aqueous solution in single dose vials for slow intravenous, subcutaneous, or intramuscular administration. Each 1 mL vial of sterile solution contains 2 mg hydromorphone hydrochloride with 0.2% sodium citrate and 0.2% citric acid solution added as a buffer to maintain a pH between 3.5 and 5.5. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION 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) ]. 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.
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 hospital.
Instruct patients to inform their healthcare providers 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) ]. Healthcare professionals can call 1-877-845-0689 for information on this product.
Manufactured by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 462-693-03