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Hydromorphone Hydrochloride 4 mg/mL Injection, Solution, 25 vials — NDC 63323-0854-10 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Hydromorphone Hydrochloride 4 mg/mL Injection, Solution, 25 vials — NDC 63323-854-10 (Billing 63323-0854-10)

by Fresenius Kabi USA, LLC · 25 VIAL, SINGLE-DOSE in 1 CARTON / 1 mL in 1 VIAL, SINGLE-DOSE

This is a package of 25 vials of Hydromorphone Hydrochloride 4 mg/mL Injection, Solution from Fresenius Kabi USA, LLC, marketed since Dec 2017 and currently FDA-listed. It is this product's only package size.

NDC 63323-0854-10
🏷️ FDA NDC (as labeled) 63323-854-10 billing pads the product segment with a zero
Rx only Brand On market CII ⚠ On shortage ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Sep 10, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 63323-854-10 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
63323 labeler · 854 product · 10 package
Package marketed since
Dec 15, 2017
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC)
0363323851071, 0363323854034, 0363323852030, 0363323851507 +2 more
Medicaid fills, this package
12 prescriptions in the last four reported quarters
FDA record last changed
Sep 10, 2026
⚠️
Active FDA shortage. Hydromorphone Hydrochloride Injection is currently reported in shortage by the FDA. Available Shortage details →

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 63323-854-10
Product NDC 63323-854
11-digit billing NDC 63323085410
NCPDP billing unit ML — per mL (volume)
RxCUI 897653, 897753, 1724276, 1724338, 1724340, 1724341
UNII L960UP2KRW
UPC 0363323851071, 0363323854034, 0363323852030, 0363323851507 +2 more
Application # NDA019034
SPL Set ID e034eb96-03e0-46e1-8b92-5e1f94555e7b
Established class (EPC) Opioid Agonist
Mechanism of action Full Opioid Agonists
DEA schedule CII
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-12-15
Route INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance HYDROMORPHONE HYDROCHLORIDE
TE code (Orange Book) AP · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 078551
GCN 44897
HICL code 034805
Ingredient (HICL) Hydromorphone Hcl/Pf
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H3
Therapeutic class — intermediate (HIC2) Analgesics
HIC3 code H3A
Therapeutic class — specific (HIC3) Opioid Analgesics
AHFS code 28:08.08.00
AHFS class Opioid Agonists (28:08)
FDB label name HYDROMORPHONE 4 MG/ML VIAL
FDB brand name Hydromorphone Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 078551
  • GCN: 44897
  • HICL (First Databank): 034805
  • AHFS class code: 28:08.08.00
  • RxCUI (RxNorm): 897653
Why two NDCs? The FDA registers this code as 63323-854-10 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 63323-0854-10. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Opioid Agonist class.

Pharmacologic class Opioid Agonist
Drug family (ATC) Natural opium alkaloids
How it works Full Opioid Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name HYDROMORPHONE 4 MG/ML VIAL Ingredient Hydromorphone Hcl/Pf
📖 What it is MedlinePlus · NLM

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 ↗
📗 Our plain-language guide HelloPharmacist
  • It treats severe pain when other treatments haven’t worked or can’t be used. The high potency version (HPF) is only for people who are already tolerant to opioids.
  • Dizziness, sleepiness, nausea, vomiting, sweating, flushing, dry mouth, and itching are the most common. Tell your care team if they bother you.
  • Get help right away for slow or shallow breathing, hard-to-wake sleepiness, fainting, or swelling and wheezing. The risk is highest after a first dose or dose increase.
  • No, not unless your prescriber specifically says so. Alcohol, benzodiazepines, and other sedating drugs can cause dangerous sedation, slowed breathing, coma, and death.
📖 Read our full Hydromorphone Injection guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $4.32 $108.00 / 25 ml
Medicare drug plans payPart D · Q2 2026 $3.56 $89.12 / 25 ml
Medicare Part B allowsASP · J1171 $0.136 / J1171 unit —
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Billing & reimbursement

FDA NDC (as labeled)63323-854-10
11-digit billing NDC63323-0854-10
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ1171
DescriptorINJECTION, HYDROMORPHONE, 0.1 MG
Billing units / pkg40 units
How the units are derivedThis package is 1 ML; the HCPCS unit is 0.1 MG, so one package = 40 billing units.
Medicare Part B spend (2026 (Q1))$54,468 · 1,926 claims · $28.28 per claim (all NDCs under J1171)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
63323-0854-10 You're viewing this Main listing 25 VIAL, SINGLE-DOSE in 1 CARTON / 1 mL in 1 VIAL, SINGLE-DOSE 2017-12-15 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Hydromorphone Hydrochloride 4 mg/mLthis 63323-0854-10 Fresenius 25 vials — AP FDA listed —
Hydromorphone Hydrochloride 4 mg/mL 00409-1304-31 Hospira, 10 cartridges — AP FDA listed —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2020
First FDA approval
Jan 2020
📍
2026
Currently FDA-listed
6 years listed
🛡️
2034
Latest patent/protection listed
not a guaranteed launch date
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Mar 2034. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jan 16, 2020 AP TE-rated RLD RS ⏳ ~7.4 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 9248229 — drug product
US 9248229 — drug product
US 9731082 — drug product
US 9248229 — drug product
US 9731082 — drug product
US 9731082 — drug product
US 9248229 — drug product
US 9248229 — drug product
US 9248229 — drug product
US 9731082 — drug product
US 9731082 — drug product
US 9731082 — drug product
US 9248229 — drug product
US 9731082 — drug product
2020 2022 2024 2026 2028 2030 2032 2034
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (14)
PatentTypeUse codeExpires
US 9248229 ↗ Drug product — Mar 12, 2034
US 9248229 ↗ Drug product — Mar 12, 2034
US 9731082 ↗ Drug product — Apr 23, 2032
US 9248229 ↗ Drug product — Mar 12, 2034
US 9731082 ↗ Drug product — Apr 23, 2032
US 9731082 ↗ Drug product — Apr 23, 2032
US 9248229 ↗ Drug product — Mar 12, 2034
US 9248229 ↗ Drug product — Mar 12, 2034
US 9248229 ↗ Drug product — Mar 12, 2034
US 9731082 ↗ Drug product — Apr 23, 2032
US 9731082 ↗ Drug product — Apr 23, 2032
US 9731082 ↗ Drug product — Apr 23, 2032
US 9248229 ↗ Drug product — Mar 12, 2034
US 9731082 ↗ Drug product — Apr 23, 2032
Common questions
Is there a generic version of HYDROMORPHONE 4 MG/ML VIAL?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for HYDROMORPHONE 4 MG/ML VIAL. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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.

🧪 Avoiding an ingredient? See Hydromorphone Injection inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 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.
  • 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.

2 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerFresenius Kabi USA, LLC
Application holderFRESENIUS KABI USA LLC
FDA applicationNDA019034 (NDA)
Labeler code63323
First marketedDec 2017
DEA scheduleCII
Product typeHuman Prescription Drug
Portfolio556 products on file

More NDCs from Fresenius Kabi USA, LLC labeler code 63323

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~2 min read ▾

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROMORPHONE HYDROCHLORIDE INJECTION AND HYDROMORPHONE HYDROCHLORIDE INJECTION (HPF) 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 Because the use of Hydromorphone Hydrochloride Injection and 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 and reassess 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 or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)], especially during initiation or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] are essential [see Warnings and Precautions ( 5.3 )] . 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 or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions ( 5.4 ), 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 ( 5.5 )] . WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROMORPHONE HYDROCHLORIDE INJECTION AND HYDROMORPHONE HYDROCHLORIDE INJECTION (HPF) 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 and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and reassess regularly for these behaviors and conditions. ( 5.2 ) • Serious, life-threatening, or fatal respiratory depression may occur, especially during initiation or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection (HPF) are essential. ( 5.3 ) • 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.

( 5.4 , 7 ) • Advise pregnant women using opioids for an extended… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE Hydromorphone Hydrochloride Injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative 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). 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 ( 5.3 )] , reserve opioid analgesics, including Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] 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 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, 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 or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)], 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 , 5.2 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection (HPF) 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 or Hydromorphone Hydrochloride Injection (HPF) 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 , 5.2 ) • Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection (HPF). Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.3 ) • 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 ) • Periodically reassess patients receiving Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection (HPF) to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or 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 or Hydromorphone Hydrochloride Injection (HPF) in a physically-dependent patient. ( 2.6 , 5.13 )

2.1Important Dosage and Administration Instructions • Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection (HPF) 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 or Hydromorphone Hydrochloride Injection (HPF) 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… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 116 words ▾

3 DOSAGE FORMS AND STRENGTHS Hydromorphone Hydrochloride Injection: Each 1 mL colorless single dose vial contains 1 mg/mL, 2 mg/mL, or 4 mg/mL of hydromorphone hydrochloride in a sterile, aqueous solution. Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] (for use in opioid-tolerant patients only): Each amber single dose vial contains 10 mg/mL of hydromorphone hydrochloride in a sterile, aqueous solution and is available in 1 mL, 5 mL and 50 mL single dose vials. • Hydromorphone Hydrochloride Injection, 1 mg/mL, 2 mg/mL, or 4 mg/mL in single dose colorless vials, and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)], 10 mg/mL, available in 1 mL, 5 mL, and 50 mL single dose amber vials.

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⛔ Contraindications 188 words ▾

4 CONTRAINDICATIONS Both Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] are 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 ( 5.7 )] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.11 )] • Hypersensitivity to hydromorphone, hydromorphone salts, any other components of the product, or sulfite containing medications (e.g., anaphylaxis) [see Warnings and Precautions ( 5.15 )] 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.

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⚠️ Warnings and Cautions ~3 min read ▾

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. ( 5.6 ) • Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Monitor closely, particularly during initiation and titration.

( 5.7 ) • Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.8 ) • Severe Hypotension : Monitor during dosage initiation and titration. Avoid use of Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] in patients with circulatory shock.

( 5.9 ) • 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 or Hydromorphone Hydrochloride Injection (HPF) in patients with impaired consciousness or coma. ( 5.10 ) • Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection (HPF) contain sodium metabisulfite.

There is a risk of anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people. ( 5.15 )

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 and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] contain hydromorphone, a Schedule II controlled substance. As an opioid, Hydromorphone Hydrochloride Injection and 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 or Hydromorphone Hydrochloride Injection (HPF).

Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions ( 6.2 )] .

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection (HPF), and monitor all patients receiving Hydromorphone Hydrochloride Injection or 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 or Hydromorphone Hydrochloride Injection (HPF… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

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 )] • Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions ( 5.4 )] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] • Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.6 )] • Adrenal Insufficiency [see Warnings and Precautions ( 5.8 )] • Severe Hypotension [see Warnings and Precautions ( 5.9 )] • Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.11 )] • Seizures [see Warnings and Precautions ( 5.12 )] • Withdrawal [see Warnings and Precautions ( 5.13 )] 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 and 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. 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 and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)]. Androgen deficiency : Cases of androgen deficiency have occurred with 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… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with Hydromorphone Hydrochloride Injection and/or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)]. TABLE 1. Clinically Significant Drug Interactions with Hydromorphone Hydrochloride Injection and/or 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. [see Warnings and Precautions ( 5.4 )] Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Limit dosages and durations to the minimum required. Monitor patients closely for signs of respiratory depression and sedation [see Warnings and Precautions ( 5.4 )]. Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol.

Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Hydromorphone Hydrochloride Injection and 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 or Hydromorphone Hydrochloride Injection (HPF) 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.

Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of Hydromorphone Hydrochloride Injection and 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 and Hydromorphone Hydrochloride Injection (HPF) and/or the muscle relaxant as necessary. Examples: cyclobenzaprine, metaxalone Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monit… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

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 or 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 or 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 Gest… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

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 or 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 or 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,… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 26 words ▾

8.4Pediatric Use The safety and effectiveness of Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] in pediatric patients has not been established.

🧓 Geriatric Use 188 words ▾

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 or 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 ( 5.7 )]. 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 ~1 min read ▾

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, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis, rather than miosis, may be seen with hypoxia in overdose situations [ see Clinical Pharmacology ( 12.2 )]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication .

Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent 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 measures.

For clinically significant respiratory or circulatory depression secondary to hydromorphone overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. Because the duration of opioid reversal is expected to be less than the duration of hydromorphone in Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection (HPF), carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of the reversal agent.

🧬 Clinical Pharmacology ~3 min read ▾

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 inc… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 114 words ▾

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 ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Hydromorphone Hydrochloride Injection Hydromorphone Hydrochloride Injection is supplied in single dose colorless vials. Each mL of sterile, aqueous solution contains 1 mg, 2 mg, or 4 mg of hydromorphone hydrochloride with 0.2% sodium citrate and 0.2% citric acid solution. Hydromorphone Hydrochloride Injection is preservative free and is supplied as follows: Product Code Unit of Sale Strength Each 852101 NDC 63323-852-25 Unit of 25 1 mg per mL NDC 63323-852-03 1 mL Single Dose Vial 853101 NDC 63323-853-25 Unit of 25 2 mg per mL NDC 63323-853-03 1 mL Single Dose Vial 854101 NDC 63323-854-10 Unit of 25 4 mg per mL NDC 63323-854-03 1 mL Single Dose Vial Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] Hydromorphone Hydrochloride Injection (HPF) is supplied in single dose amber vials.

Each single dose vial of sterile aqueous solution contains 10 mg of hydromorphone hydrochloride with 0.2% sodium citrate and 0.2% citric acid solution. Hydromorphone Hydrochloride Injection (HPF) is preservative free and is supplied as follows: Product Code Unit of Sale Strength Each 851101 NDC 63323-851-10 Unit of 10 10 mg per mL NDC 63323-851-03 1 mL Single Dose Vial 851105 NDC 63323-851-15 Unit of 10 50 mg per 5 mL (10 mg per mL) NDC 63323-851-07 5 mL Single Dose Vial 851150 NDC 63323-851-50 Individually Packaged 500 mg per 50 mL (10 mg per mL) NDC 63323-851-50 50 mL Single Dose Vial PROTECT FROM LIGHT.

Protect from light 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 Access to drugs with a potential for abuse such as Hydromorphone Hydrochloride Injection and 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.

📋 Description 213 words ▾

11 DESCRIPTION Hydromorphone Hydrochloride, a hydrogenated ketone of morphine, is an opioid agonist. Hydromorphone Hydrochloride Injection is available as a sterile, aqueous solution in single dose colorless vials for slow intravenous, subcutaneous, or intramuscular administration. Each mL contains 1 mg, 2 mg, or 4 mg 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.

Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] is available as a sterile, aqueous solution in single dose amber vials for intravenous, subcutaneous, or intramuscular administration. Each 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 ꞏHCl, 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. The inactive ingredients in Hydromorphone Hydrochloride Injection include: 0.2% sodium citrate and 0.2% citric acid added as a buffer to maintain a pH between 3.5 and 5.5. hydro-struc-01.jpg

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Addiction, Abuse, and Misuse Inform patients that the use of Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection (HPF), 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 Hydromorphone Hydrochloride Injection (HPF) 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 ( 5.6 ); Adverse Reactions (6.2)]. Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition called serotonin syndrome resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop after discharge from the hospital.

Instruct patients to inform their 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 Fresenius Kabi USA, LLC at 1-800-551-7176 for information or to report adverse events on this product. www.fresenius-kabi.com/us 451503E hydro-img-01.jpg

🍼 Nursing Mothers 55 words ▾

8.3Females and Males of Reproductive Potential Infertility Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions ( 6 ), Clinical Pharmacology ( 12.2 ), Nonclinical Toxicology ( 13.1 )].

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Distribution At therapeutic plasma levels, hydromorphone is approximately 8-19% bound to plasma proteins. After an intravenous bolus dose, the steady state of volume of distribution [mean (%CV)] is 302.9 (32%) liters. Elimination The systemic clearance is approximately 1.96 (20%) liters/minute.

The terminal elimination half-life of hydromorphone after an intravenous dose is about 2.3 hours. Metabolism Hydromorphone is extensively metabolized via glucuronidation in the liver, with greater than 95% of the dose metabolized to hydromorphone-3- glucuronide along with minor amounts of 6-hydroxy reduction metabolites. Excretion Only a small amount of the hydromorphone dose is excreted unchanged in the urine.

Most of the dose is excreted as hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites. Special Populations Hepatic Impairment After oral administration of hydromorphone at a single 4 mg dose (2 mg hydromorphone immediate-release tablets), mean exposure to hydromorphone (C max and AUC∞) is increased 4-fold in patients with moderate (Child-Pugh Group B) hepatic impairment compared with subjects with normal hepatic function. Patients with moderate hepatic impairment should be started at one-fourth to one-half the recommended starting dose and closely monitored during dose titration.

The pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. A further increase in C max and AUC of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see Use in Specific Populations ( 8.6 )]. Renal Impairment The pharmacokinetics of hydromorphone following an oral administration of hydromorphone at a single 4 mg dose (2 mg hydromorphone immediate-release tablets) are affected by renal impairment.

Mean exposure to hydromorphone (C max and AUC0-∞) is increased by 2-fold in patients with moderate (CLcr = 40 - 60 mL/min) renal impairment and increased by 4-fold in patients with severe (CLcr< 30 mL/min) renal impairment compared with normal subjects (CLcr> 80 mL/min). In addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life (40 hr) compared to patients with normal renal function (15 hr). Start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment.

Patients with renal impairment should be closely monitored during dose titration [see Use in Specific Populations ( 8.7 )]. Geriatric Population In the geriatric population, age has no effect on the pharmacokinetics of hydromorphone. Sex Sex has little effect on the pharmacokinetics of hydromorphone.

Females appear to have a higher C max (25%) than males with comparable AUC 0-24 values. The difference observed in C max may not be clinically relevant.

🧬 Pharmacodynamics ~2 min read ▾

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 increasing hydromorphone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression.

In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see Dosage and Administration ( 2.1 , 2.2 ) ].

🔒 Drug Abuse and Dependence ~3 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] contain hydromorphone, which is a Schedule II controlled substance.

9.2Abuse Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] contains hydromorphone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions ( 5.2 )]. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death.

The risk is increased with concurrent abuse of Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] with alcohol and/or other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] abuse include those with a history of prolonged use of any opioid, including products containing hydromorphone, those with a history of drug or alcohol abuse, or those who use Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] in combination with other abused drugs. “Drug-seeking” behavior is very common in persons with substance use disorders.

Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Hydromorphone Hydrochloride Injection or Hydromorphone Hydrochloride Injection [high potency formulation (HPF)], like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] Abuse of Hydromorphone Hyd… [Excerpted — this section continues on DailyMed.]

🔒 Controlled Substance 23 words ▾

9.1Controlled Substance Hydromorphone Hydrochloride Injection and Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] contain hydromorphone, which is a Schedule II controlled substance.

🧪 Nonclinical Toxicology 176 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long term studies in animals to evaluate the carcinogenic potential of hydromorphone have not been conducted. Mutagenesis Hydromorphone was positive in the mouse lymphoma assay in the presence of metabolic activation, but was negative in the mouse lymphoma assay in the absence of metabolic activation. Hydromorphone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames assay).

Hydromorphone was not clastogenic in either the in vitro human lymphocyte chromosome aberration assay or the in vivo mouse micronucleus assay. Impairment of Fertility Reduced implantation sites and viable fetuses were noted at 2.1 times the human daily dose of 32 mg/day in a study in which female rats were treated orally with 1.75, 3.5, or 7 mg/kg/day hydromorphone hydrochloride (0.5, 1.1, or 2.1 times a human daily dose of 24 mg/day (HDD) based on body surface area) beginning 14 days prior to mating through Gestation Day 7 and male rats were treated with the same hydromorphone hydrochloride doses beginning 28 days prior to and throughout mating.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 173 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long term studies in animals to evaluate the carcinogenic potential of hydromorphone have not been conducted. Mutagenesis Hydromorphone was positive in the mouse lymphoma assay in the presence of metabolic activation, but was negative in the mouse lymphoma assay in the absence of metabolic activation. Hydromorphone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames assay).

Hydromorphone was not clastogenic in either the in vitro human lymphocyte chromosome aberration assay or the in vivo mouse micronucleus assay. Impairment of Fertility Reduced implantation sites and viable fetuses were noted at 2.1 times the human daily dose of 32 mg/day in a study in which female rats were treated orally with 1.75, 3.5, or 7 mg/kg/day hydromorphone hydrochloride (0.5, 1.1, or 2.1 times a human daily dose of 24 mg/day (HDD) based on body surface area) beginning 14 days prior to mating through Gestation Day 7 and male rats were treated with the same hydromorphone hydrochloride doses beginning 28 days prior to and throughout mating.

📄 Recent Major Changes 32 words ▾

Boxed Warning 12/2025 Indications and Usage ( 1 ) 12/2025 Dosage and Administration ( 2.6 ) 12/2025 Warnings and Precautions ( 5.2 , 5.3 , 5.4 , 5.11 , 5.13 ) 12/2025

📄 Package Label / Principal Display Panel ~2 min read ▾

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 1 mg Vial Label NDC 63323-852-03 852101 HYDROmorphone Hydrochloride Injection, USP 1 mg per mL For IM, IV or SC use. Preservative free. Protect from light. 1 mL Single Dose Vial Rx only hydro-label-01.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 1 mg Carton Label NDC 63323-852-25 852101 HYDROmorphone Hydrochloride Injection, USP 1 mg per mL For intramuscular, intravenous or subcutaneous use. Preservative free. Rx only 25 x 1 mL Single Dose Vials hydro-label-02.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 2 mg Vial Label NDC 63323-853-03 853101 HYDROmorphone Hydrochloride Injection, USP 2 mg per mL For IM, IV or SC use. Preservative free. Protect from light. 1 mL Single Dose Vial Rx only hydro-label-03.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 2 mg Carton Label NDC 63323-853-25 853101 HYDROmorphone Hydrochloride Injection, USP 2 mg per mL For intramuscular, intravenous or subcutaneous use. Preservative free. Rx only 25 x 1 mL Single Dose Vials hydro-label-04.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 4 mg Vial Label NDC 63323-854-03 854101 HYDROmorphone Hydrochloride Injection, USP 4 mg per mL For IM, IV or SC use. Preservative free. Protect from light. 1 mL Single Dose Vial Rx only hydro-label-05.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 4 mg Carton Label NDC 63323-854-10 854101 HYDROmorphone Hydrochloride Injection, USP 4 mg per mL For intramuscular, intravenous or subcutaneous use. Preservative free. Rx only 25 x 1 mL Single Dose Vials hydro-label-06.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 10 mg Vial Label NDC 63323-851-03 851101 HYDROmorphone Hydrochloride Injection, USP 10 mg per mL HIGH POTENCY FORMULA Preservative free. Protect from light. 1 mL Single Dose Vial Rx only hydro-label-07.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 10 mg Carton Label HIGH POTENCY FORMULA FOR USE IN THE PREPARATION OF LARGE-VOLUME PARENTERAL SOLUTIONS. NDC 63323-851-10 851101 HYDROmorphone Hydrochloride Injection, USP 10 mg per mL Preservative free. Rx only 10 x 1 mL Single Dose Vials hydro-label-08.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 50 mg Vial Label NDC 63323-851-07 851105 HYDROmorphone Hydrochloride Injection, USP 50 mg per 5 mL (10 mg per mL) HIGH POTENCY FORMULA FOR USE IN THE PREPARATION OF LARGE-VOLUME PARENTERAL SOLUTIONS. 5 mL Single Dose Vial Rx only hydro-label-09.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 50 mg Carton Label HIGH POTENCY FORMULA FOR USE IN THE PREPARATION OF LARGE-VOLUME PARENTERAL SOLUTIONS. NDC 63323-851-15 851105 HYDROmorphone Hydrochloride Injection, USP 50 mg per 5 mL (10 mg per mL) Preservative free. Rx only 10 x 5 mL Single Dose Vials hydro-label-10.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 500 mg Vial Label NDC 63323-851-50 851105 HYDROmorphone Hydrochloride Injection, USP 500 mg per 50 mL (10 mg per mL) HIGH POTENCY FORMULA FOR USE IN THE PREPARATION OF LARGE-VOLUME PARENTERAL SOLUTIONS. 50 mL Single Dose Vial Rx only hydro-label-11.jpg

PACKAGE LABEL - PRINCIPAL DISPLAY - Hydromorphone Hydrochloride 500 mg Individual Carton Label HIGH POTENCY FORMULA FOR USE IN THE PREPARATION OF LARGE-VOLUME PARENTERAL SOLUTIONS. NDC 63323-851-50 851150 HYDROmorphone Hydrochloride Injection, USP 500 mg per 50 mL (10 mg per mL) Preservative free. Rx only 1 x 50 mL Single Dose Vial hydro-label-12.jpg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
12
Units reimbursed last 4 qtrs
12
Gross reimbursed last 4 qtrs
$51.84
Avg / prescription
$4.32
Avg / unit
$4.3200
Latest quarter Q1 2026
0Rx
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 12 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: 12 units · 0.3 per 100k residents KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
0.30.3
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Kentucky 0.3 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
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 ✓ Available
Inactive ingredients (structured) ✓ 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 ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Fresenius Kabi USA, LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Fresenius Kabi USA, LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J1171 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 63323-0853-25 · Fresenius 63323-0865-02 · Fresenius →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.