Hydromorphone Hydrochloride 10 mg/mL Injection, 10 ampules
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
- 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...
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- 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...
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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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💲 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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Hydromorphone Hydrochloride 10 mg/mLthis 17478-0540-01 | Akorn | 10 ampules | — | AP | Discontinued | — |
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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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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 17478-0540-01 You're viewing this | 10 AMPULE in 1 CARTON (17478-540-01) / 1 mL in 1 AMPULE | 2010-05-15 | Inactivated by FDA |
| 17478-0540-05 | 10 AMPULE in 1 CARTON (17478-540-05) / 5 mL in 1 AMPULE | 2010-05-15 | Inactivated by FDA |
| 17478-0540-50 | 1 VIAL in 1 CARTON (17478-540-50) / 50 mL in 1 VIAL | 2010-05-15 | Inactivated by FDA |
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🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS WARNING: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning. Do not confuse hydromorphone hydrochloride injection [high potency formulation (HPF)] with standard parenteral formulations of hydromorphone hydrochloride injection or other opioids, as overdose and death could result.
( 5.1 ) Hydromorphone hydrochloride injection [high potency formulation (HPF)] exposes users to risks of addictions, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing and monitor regularly for these behaviors and conditions. ( 5.2 ) Serious, life-threatening, or fatal respiratory depression may occur.
Monitor closely, especially upon initiation or following a dose increase. ( 5.3 ) Prolonged use of hydromorphone hydrochloride injection [high potency formulation (HPF)] during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
( 5.4 ) 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; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. ( 5.5 , 7 ) Risk of Medication Errors Hydromorphone hydrochloride injection [high potency formulation (HPF)] is a more concentrated solution of hydromorphone than hydromorphone hydrochloride injection, and is for use in opioid-tolerant patients only.
Do not confuse hydromorphone hydrochloride injection [high potency formulation (HPF)] with standard parenteral formulations of hydromorphone hydrochloride injection or other opioids, as overdose and death could result [see Warnings and Precautions ( 5.1 ) ]. Addiction, Abuse, and Misuse Hydromorphone hydrochloride injection [high potency formulation (HPF)] 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 hydromorphone hydrochloride injection [high potency formulation (HPF)] and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.2 ) ].
Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of hydromorphone hydrochloride injection [high potency formulation (HPF)]. Monitor for respiratory depression, especially during initiation of hydromorphone hydrochloride injection [high potency formulation (HPF)] or following a dose increase [see Warnings and Precautions ( 5.3 ) ]. Neonatal Opioid Withdrawal Syndrome Prolonged use of hydromorphone hydrochloride injection [high potency formulation (HPF)] during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions ( 5.4 ) ]. Risks From Concomitant Use With Benzodiazepin…
🎯 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. Hydromorphone hydrochloride injection [high potency formulation (HPF)] is indicated for use in opioid-tolerant patients who require higher doses of opioids for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate. Patients considered opioid tolerant are those who are taking for one week or longer, around-the-clock medicine consisting of at least 60 mg oral morphine per day, or at least 25 mcg transdermal fentanyl per hour, or at least 30 mg oral oxycodone per day, or at least 8 g oral hydromorphone per day, or at least 25 mg oral oxymorphone per day, or at least 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid for one week or longer.
Patients must remain on around-the-clock opioids while administering hydromorphone hydrochloride injection (HPF). Hydromorphone hydrochloride 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. ( 1 ) Hydromorphone hydrochloride injection [high potency formulation (HPF)] is an opioid agonist indicated for use in opioid-tolerant patients who require higher doses of opioids for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate.
Patients considered opioid tolerant are those who are taking, for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg/hr of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid daily for a week or longer. Patients must remain on around-the-clock opioids when administering hydromorphone hydrochloride injection (HPF).
Limitations of Use: Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve hydromorphone hydrochloride injection [high potency formulation (HPF)] 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 Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions ( 5.2 ) ], reserve hydromorphone hydrochloride injection [high potency formulation (HPF)] 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
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. ( 2.1 ) 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 ) - 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 ) Hydromorphone hydrochloride injection [high potency formulation (HPF)] is for opioid-tolerant patients only and should be used only if the amount of hydromorphone required can be delivered accurately with this formulation.
( 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 ) Do not stop hydromorphone hydrochloride injection [high potency formulation (HPF)] abruptly in a physically-dependent patient.
( 2.6 )
2.1Important Dosage and Administration Instructions Always initiate dosing in opioid-naïve patients using hydromorphone hydrochloride injection. Never administer hydromorphone hydrochloride injection [high potency formulation (HPF)] to opioid-naïve patients. U se the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions ( 5 ) ].
Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.2 ) ]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with hydromorphone hydrochloride injection (HPF) and adjust the dosage accordingly [see Warnings and Precautions ( 5.3 ) ].
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 hydromorphone hydrochloride injection (HPF). No loss of potency has been demonstrated.
Hydromorphone hydrochloride injection (HPF) 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. 500 mg/50 mL Vial To use this single-dose presentation, withdraw the contents using aseptic technique for preparation of a single, large volume parenteral solution.
Discard any unused portion in an appropriate manner.
2.2Initial Dosage Use of Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] as the First Opioid Analgesic Hydromorphone hydrochloride injection (HPF) is for use in opioid tolerant patients only. Do not use hydromorphone hydrochloride injection (HPF) for patients who are not tolerant to the respiratory depressant or sedating effects of opioids. Subcutaneous or Intramuscular Administration: The usual starting dose of hydromorphone hydrochloride injection is 1 mg to 2 mg every 2 to 3 hours as necessary.
Depending on the clinical situation, the initial starting dose may be lowered in patients who are opioid naïve. Intravenous Administration: The initial starting dose is 0.2 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 Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] There is inter-patient variability in the poten…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Hydromorphone Hydrochloride Injection, USP [high potency formulation (HPF)] (for use in opioid-tolerant patients only): Each amber ampule and amber single-dose vial contains 10 mg/mL of hydromorphone hydrochloride in a sterile, aqueous solution and is available in 1 mL, 5 mL ampules and in 50 mL single-dose vials † . † The Stoppers Of This Product Do Not Contain Natural Rubber Latex. Hydromorphone Hydrochloride Injection, USP [high potency formulation (HPF)]: 10 mg/mL in 1 mL, 5 mL ampule and 50 mL single-dose vial.
( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Hydromorphone hydrochloride injection [high potency formulation (HPF)] is contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.3 ) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.3 ) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.10 ) ] Hypersensitivity to hydromorphone, hydromorphone salts, any other components of the product, or sulfite containing medications (e.g., anaphylaxis) [see Warnings and Precautions ( 5.14 ) ] Hydromorphone hydrochloride injection (HPF) is contraindicated in patients who are not opioid tolerant [see Warnings and Precautions ( 5.1 ) ].
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 ) Hydromorphone hydrochloride injection [high potency formulation (HPF)]: Patients who are not opioid tolerant. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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 [high potency formulation (HPF)] 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 (HPF) in patients with impaired consciousness or coma.
( 5.9 ) Hydromorphone hydrochloride injection (HPF) contains sodium metabisulfite. There is a risk of anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people. ( 5.14 )
5.1Risk of Medication Errors Hydromorphone hydrochloride injection [high potency formulation (HPF)] is a 10 mg/mL concentrated solution of hydromorphone, and is intended for use in opioid-tolerant patients only. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/ day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid for one week or longer. Do not confuse hydromorphone hydrochloride injection (HPF) with standard parenteral formulations of hydromorphone hydrochloride injection (1 mg/mL, 2 mg/mL, 4 mg/mL) or other opioids, as overdose and death could result.
5.2Addiction, Abuse, and Misuse Hydromorphone hydrochloride injection [high potency formulation (HPF)] contains hydromorphone, a Schedule II controlled substance. As an opioid, hydromorphone hydrochloride injection (HPF) 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 (HPF).
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 hydromorphone hydrochloride injection (HPF), and monitor all patients receiving hydromorphone hydrochloride injection (HPF) 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 (HPF), but use in such patients necessitates intensive counseling about the risks and proper use of hydromorphone hydrochloride injection (HPF) along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Consider these risks when prescribing or dispensing hydromorphone hydrochloride injection (HPF). 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.
5.3Life-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 observa…
🤒 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 ( 5.2 ) ] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.3 ) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 ) ] Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions ( 5.5 ) ] Adrenal Insufficiency [see Warnings and Precautions ( 5.7 ) ] Severe Hypotension [see Warnings and Precautions ( 5.8 ) ] Seizures [see Warnings and Precautions ( 5.11 ) ] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.10 ) ] 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 [high potency formulation (HPF)] 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. Most common adverse reactions are lightheadedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Akorn, Inc. at 1-800-932-5676 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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, paresthesia, 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 [high potency formulation (HPF)]. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology ( 12.2 ) ].
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with hydromorphone hydrochloride injection [high potency formulation (HPF)]. TABLE 1. Clinically Significant Drug Interactions with Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] Benzodiazepines and other Central Nervous System Depressants (CNS) Clinical 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.
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. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions ( 5.3 ) ].
Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, 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 (HPF) 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 ( 5.3 ) ]. 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. Intervention: The use of hydromorphone hydrochloride injection (HPF) is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of hydromorphone hydrochloride injection (HPF) and/or precipitate withdrawal syndrome. 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 (HPF) and/ or the muscle relaxant as necessary. 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 (HPF) is used concomitantly with anticholinergic drugs. Serotonergic Drugs: Concomitant use may result in serotonin syn…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm. ( 8.1 )
8.1Pregnancy Risk Summary Prolonged use of opioid analgesics 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. 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 estimated 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 Prolonged use of opioid analgesics 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 antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.
Hydromorphone hydrochloride injection [high potency formulation (HPF)] 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 (HPF), 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…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Prolonged use of opioid analgesics 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. 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 estimated 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 Prolonged use of opioid analgesics 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 antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.
Hydromorphone hydrochloride injection [high potency formulation (HPF)] 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 (HPF), 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, neu…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of hydromorphone hydrochloride injection [high potency formulation (HPF)] in pediatric patients have 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 [high potency formulation (HPF)] 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.
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation Acute overdose with hydromorphone hydrochloride injection [high potency formulation (HPF)] 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 ) ].
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.
The opioid antagonists, naloxone or nalmefene are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to hydromorphone overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydromorphone overdose.
Because the duration of opioid reversal is expected to be less than the duration of hydromorphone in hydromorphone hydrochloride injection (HPF), carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product's prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist 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 antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.
🧬 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, and transient elevations in serum amylase.
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.
Chronic use of opioids 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 potent agonist opioids.
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 increasing hydromorphone plasma concentration and increasing frequ…
🧬 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 [high potency formulation (HPF)] is supplied in AMBER ampules, and AMBER single dose vials. Each 1 mL of sterile solution contains 10 mg of hydromorphone hydrochloride with 0.2% sodium citrate and 0.2% citric acid. Hydromorphone Hydrochloride Injection (HPF) is preservative-free and supplied as follows.
NDC 17478-540-01 Box of ten 1 mL (10 mg) ampules NDC 17478-540-05 Box of ten 5 mL (50 mg) ampules NDC 17478-540-50 One 50 mL (500 mg) Single-dose Vial † † The Stoppers Of This Product Do Not Contain Natural Rubber Latex. Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light until time of use.
CAUTION: DEA Order Form Required. Safety and Handling Instructions Access to drugs with a potential for abuse such as hydromorphone hydrochloride injection [high potency formulation (HPF)] 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.
📦 Storage and Handling ▾
Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light until time of use. CAUTION: DEA Order Form Required.
📋 Description ▾
11 DESCRIPTION Hydromorphone hydrochloride, a hydrogenated ketone of morphine, is an opioid agonist. Hydromorphone Hydrochloride Injection, USP [high potency formulation (HPF)] is available as a sterile, aqueous solution in AMBER ampules and in AMBER , single-dose vials for intravenous, subcutaneous, or intramuscular administration. Each ampule and single-dose vial contains 10 mg/mL of hydromorphone hydrochloride with 0.2% sodium citrate and 0.2% citric acid added as a buffer to maintain a pH of between 3.5 and 5.5.
The chemical name of hydromorphone hydrochloride is 4,5α-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride. The molecular weight is 321.80. Its molecular formula is C 17 H 19 NO 3 •HCl, 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.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their 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 telephone Akorn, Inc. at 1-800-932-5676 for information or to report adverse events on this product. AKORN Manufactured by: Akorn, Inc.
Lake Forest, IL 60045 HM00N Rev. 02/20