Hydromorphone hydrochloride preservative-free (PF) injection is a compounded sterile solution of hydromorphone in water for injection, prepared without benzyl alcohol or any other preservative and filled into an ambulatory infusion cassette or syringe for continuous subcutaneous or intravenous infusion. Bayview Pharmacy prepares it to the concentration, total volume, and container the prescriber specifies for an identified individual patient.
Hydromorphone is a mu-opioid receptor agonist and a Schedule II controlled substance. In hospice and palliative care it is used for two symptoms: pain, and dyspnea. The sensation of air hunger. In plain terms, it turns down the brain's alarm signal for pain and reduces the feeling of breathlessness. Whether an opioid infusion is appropriate for a particular patient, and at what concentration and rate, is a decision for the treating clinician. Bayview compounds this as part of our hospice and palliative care compounding line.
How does it work?
Hydromorphone binds mu-opioid receptors in the central nervous system. For pain, that reduces both the transmission of the pain signal and the distress the signal produces. It turns down the brain's alarm rather than repairing the injury causing it. For dyspnea, opioids reduce the perceived intensity of breathlessness and the respiratory drive that accompanies it, which is why they are used for air hunger in advanced illness even when oxygen saturation is normal.
Given by continuous infusion, the drug is delivered at a steady rate rather than in peaks and troughs, and a pump can be programmed to allow patient- or caregiver-activated demand doses on top of the continuous rate. The pump program, the concentration, and every dose parameter are set by the prescriber.
What is it used for?
In hospice and palliative care, a continuous hydromorphone infusion is used for pain and for dyspnea when the treating clinician judges an infusion to be the appropriate route. Continuous subcutaneous infusion (CSCI) is the workhorse route when the oral route fails, dysphagia, obtundation, intractable vomiting, or bowel obstruction, and when intravenous access is absent or burdensome to maintain in the home. It is not a first-line route and it is not a substitute for a clinician's assessment of what is causing the symptom.
Why are concentrated preservative-free strengths compounded?
This is the core reason this preparation exists, and it is a volume problem rather than a potency problem.
The strengths therefore divide by need. The 5 mg/mL strength covers typical infusion requirements from opioid-naive through moderate. The 20 mg/mL and 30 mg/mL strengths exist for opioid-tolerant patients on high hourly doses, and to keep a 50, 100, or 150 mL cassette running long enough that a nurse is not driving to the home every day to change it. Cassette size is chosen the same way: rate multiplied by the desired change interval.
Commercially available preservative-free hydromorphone injection is generally capped around 1 to 10 mg/mL, so the concentrations above that range are not obtainable as a manufactured product. Persistent shortages of hydromorphone injection, which has appeared on FDA and ASHP drug shortage lists, are an additional documented reason prescribers turn to a compounding pharmacy for this preparation.
Why preservative-free matters. Benzyl alcohol and other preservatives cause local tissue irritation at a continuous subcutaneous infusion site, where the same small area is exposed for days at a time, and they accumulate when infusion volumes are high. Removing the preservative removes that source of site breakdown. It also means the preparation carries a beyond-use date rather than a multi-dose shelf life. Related hospice and palliative care preparations include Hospice & Palliative Care Compounding and Morphine Infusion (Preservative-Free). The full list is in our compounded medications catalog.
Concentrations and cassette sizes
Concentrations and volumes are listed for reference. The prescriber selects the concentration, the total volume, and the pump program.
| Concentration | Cassette volumes | Why this concentration is used |
|---|---|---|
| Hydromorphone 5 mg/mL PF | 50, 100, or 150 mL | Covers typical infusion requirements from opioid-naive through moderate |
| Hydromorphone 20 mg/mL PF | 50 or 100 mL | Opioid-tolerant patients whose hourly dose would otherwise exceed the volume the subcutaneous route absorbs |
| Hydromorphone 30 mg/mL PF | 50 mL | Highest routinely compounded concentration; high hourly doses in opioid-tolerant patients, or to extend the interval between cassette changes |
| Custom concentration | As ordered | Other concentrations, volumes, and containers as the prescriber orders |
Two cassettes are frequently dispensed together so that a spare is on hand at the home when the running cassette empties. Bayview also compounds a preservative-free morphine infusion for the same route.
Concentrations are listed for education only. Listing a concentration is not a statement that it is appropriate for any particular patient, and it is not a recommendation of a dose.
How the subcutaneous route is set up and cared for
A continuous subcutaneous infusion runs through a small butterfly needle, typically 25- or 27-gauge, placed under the skin and connected to the pump. Common sites are the upper arm, the shoulder, the abdomen, and the thigh; the chest wall is generally avoided. A site can often stay in place for up to about a week unless a local reaction develops.
What nurses and caregivers watch for. Rotate the site if there is redness, a firm or swollen lump under the skin (induration), leakage around the needle, or pain at the site. Avoid placing a site in tissue that is swollen with fluid (edematous) or that has been irradiated, because absorption there is unreliable. Keep the site clean and dry, secure the tubing so it is not tugged, and tell the hospice nurse about any change at the site rather than waiting for the next scheduled visit.
Route conversion. The evidence base for converting between intravenous and subcutaneous hydromorphone is weak; many practitioners use a 1:1 ratio. That is a practice pattern reported in the literature, not a rule, and the conversion remains the prescriber's judgment.
Titration as reported in the literature
The following describes the approach commonly reported in palliative care literature. It is provided as background for clinicians and is not a dosing recommendation; every parameter is set by the prescriber for the individual patient.
- Convert the patient's current 24-hour opioid requirement to an intravenous or subcutaneous hydromorphone equivalent, then divide by 24 to derive the continuous hourly rate.
- Because a continuous infusion takes hours to reach steady state, a loading bolus is typically used rather than waiting for the basal rate to accumulate.
- Demand (breakthrough) boluses are commonly set at 50 to 150 percent of the hourly rate, with a lockout interval of roughly 20 minutes.
- Reassess every 30 to 60 minutes until the symptom is controlled, then reassess at intervals appropriate to the clinical situation.
Renal function and metabolite accumulation
Dose reduction of approximately 25 percent at a creatinine clearance of 10 to 50 mL/min, and approximately 50 percent below 10 mL/min, is recommended in the palliative care literature. Fentanyl and methadone have no active metabolites and are the agents usually cited when metabolite accumulation is the governing concern.
Opioid neurotoxicity does not present simply as sedation. It presents as myoclonus (sudden muscle jerks), hyperalgesia (increasing pain that worsens as the dose is increased), and agitated delirium. A patient whose pain appears to escalate despite dose increases may be experiencing neurotoxicity rather than undertreatment; that distinction is a clinical assessment.
Safety
Respiratory depression is the principal risk of any opioid. Opioids titrated proportionally to symptom relief do not, in the palliative care literature, cause respiratory depression; the risk lies in non-proportional dose escalation, in opioid-naive patients, and in co-administration of benzodiazepines with opioids. Those are the situations that warrant the closest monitoring.
Equianalgesic conversion is the most common source of serious error with this class of medication. Published conversion ratios are approximations derived from limited data, and incomplete cross-tolerance means a patient tolerant to one opioid is not equally tolerant to another. A reduction of 25 to 50 percent from the calculated equianalgesic dose is the standard cautionary practice when rotating opioids. Verify every conversion independently.
Other effects reported with hydromorphone include sedation, constipation, nausea, itching (pruritus), urinary retention, and myoclonus. Constipation is effectively universal with opioids and does not improve with time, so a bowel regimen should be planned at the same time the infusion is started rather than added after a problem develops. Sedation is often greatest in the first days and may lessen; new or worsening confusion, muscle jerking, or escalating pain should be reported to the hospice team.
Naloxone reverses opioid effect and its use in a patient on a therapeutic infusion is a clinical decision, not a routine home step; follow the hospice program's written orders and call the hospice team.
Secure storage, diversion prevention, and disposal
Hydromorphone is a Schedule II controlled substance and is a target for diversion, including from within the household and by visitors to the home.
- Store cassettes in a locked box or another secured location; do not leave spare cassettes on a counter, in a shared refrigerator shelf, or in a visible bag.
- Keep a written count of cassettes received, in use, and remaining, and reconcile it at each nursing visit.
- Never share this medication. Sharing or transferring a Schedule II medication to another person is a felony, and a dose appropriate for an opioid-tolerant patient can be fatal to someone else.
- Report a missing, tampered, or leaking cassette to the hospice team promptly.
- Dispose of unused medication as the hospice program directs, and document the disposal.
Under CMS regulation at 42 CFR 418.106, a hospice must have written policies and procedures for the management and disposal of controlled drugs in the patient's home, and must provide counseling and documentation with the patient and family at the time controlled drugs are first ordered. Follow the hospice program's written policy; the program, not the pharmacy, directs disposal in the home.
Sterility and beyond-use dating
This is a compounded sterile preparation, prepared under USP General Chapter <797>. You can read how we handle sterile compounding. The 2023 revision of <797>, official November 1, 2023, replaced the former low-, medium-, and high-risk levels with Category 1, Category 2, and Category 3 compounded sterile preparations. Category 1 preparations are compounded in a primary engineering control located in an unclassified segregated compounding area and carry short beyond-use dates. Category 2 preparations require a cleanroom suite and carry beyond-use dates assigned per the chapter's Table 13. Category 3 permits longer beyond-use dates per Table 14, but only with sterility testing and expanded environmental monitoring.
The beyond-use date assigned to each preparation is printed on the label. Use the labeled date; do not extrapolate from published stability data.
Why is this compounded?
Commercial preservative-free hydromorphone injection is generally available only up to about 10 mg/mL and is supplied in vials, not in infusion cassettes. Patients who require a high hourly dose subcutaneously cannot receive it within the roughly 3 mL per hour the tissue absorbs at those concentrations, and hydromorphone injection has been subject to recurring shortages. As a 503A compounding pharmacy, Bayview prepares hydromorphone at the concentration ordered, without preservative, in the cassette volume ordered, for an identified individual patient on a valid prescription. Compounded preparations are not FDA-approved, and FDA does not verify their safety, effectiveness, or quality before marketing.
Clinical details for prescribers
Regulatory status. Hydromorphone is a Schedule II controlled substance. 21 CFR 1306.11 requires a written, signed prescription. A facsimile serves as the original written prescription with no follow-up hard copy required for (a) a Schedule II narcotic compounded for direct administration by parenteral, intravenous, intramuscular, subcutaneous, or intraspinal infusion; (b) a resident of a long-term care facility; and (c) a patient enrolled in a hospice program certified or paid for by Medicare or licensed by the state, with the prescription noted as being for a hospice patient. Compounded preparations are not FDA-approved.
Preparation. Hydromorphone HCl preservative-free in water for injection, compounded at 5, 20, and 30 mg/mL (custom concentrations available), filled into 50, 100, or 150 mL ambulatory infusion cassettes or syringes. Compounded under USP <797>; beyond-use date assigned by category and testing and printed on the label. Multiple cassettes are commonly dispensed together so a spare is on hand at the home.
Clinical points reported in the literature:
- CSCI is the preferred parenteral route at home when the oral route fails and IV access is absent or burdensome; 25 to 27 gauge butterfly, upper arm, shoulder, abdomen, or thigh, avoiding the chest wall; site may remain up to about a week absent local reaction
- Subcutaneous absorption is limited to roughly 3 mL/hr, which drives the need for concentrations above the commercial 1 to 10 mg/mL range in opioid-tolerant patients
- IV:SQ conversion evidence is weak; 1:1 is commonly used in practice
- Basal rate derived from the converted 24-hour requirement divided by 24; loading bolus used because steady state takes hours; demand bolus commonly 50 to 150% of the hourly rate with a ~20 minute lockout; reassess every 30 to 60 minutes until controlled
- Renal impairment: hydromorphone accumulates an active glucuronide metabolite in a pattern similar to morphine's M3G/M6G; approximately 25% dose reduction at CrCl 10 to 50 mL/min and approximately 50% below 10 mL/min is recommended; fentanyl and methadone have no active metabolites
- Neurotoxicity presents as myoclonus, hyperalgesia, and agitated delirium rather than sedation alone
- Incomplete cross-tolerance: reduce 25 to 50% from the calculated equianalgesic dose when rotating opioids; published ratios are approximations
- Plan a bowel regimen concurrently with initiation; constipation is effectively universal and does not remit
Ordering: send a written or valid facsimile prescription to Bayview Pharmacy, fax 401-284-4506, NCPDP 4106882. Bayview compounds for an identified individual patient on a valid prescription and does not supply office stock, agency stock, or pre-filled hospice kits. Background: PCNOW, Subcutaneous Opioid Infusions; PCNOW, Opioid Use in Renal Failure. Account setup, licensing, and ordering are covered on our for providers page.
This is a prescription compounded preparation and is not FDA-approved. Hydromorphone is a Schedule II controlled substance. This information is educational and is not medical advice, and nothing here is a recommendation of a drug or a dose for any patient. The treating clinician determines whether an opioid infusion is appropriate and sets the concentration, rate, and every dose parameter.
