It binds mu, delta, and kappa opioid receptors in the brain and spinal cord, blunting pain perception while also depressing the cough reflex, the respiratory drive, and GI motility (the source of the near-universal constipation). Avoid it in asthma and COPD, and use caution in any condition that already compromises breathing.
Generic and Brand Names
Generic: hydromorphone (dihydromorphinone).
Brand names: Dilaudid, Dilaudid-HP (high potency), Dilaudid-5 and Dilaudid-8 (oral solution), Hydromorphone Hydrochloride, Exalgo (extended-release tablet), Hydromorph Contin (extended-release tablet), Palladone (extended-release capsule), and Jurnista. Other brand names exist by country or region.
Drug Classification
Therapeutic class: opioid analgesics (also used as an antitussive). Pharmacologic class: opioid agonists.
Indications
Hydromorphone relieves moderate to severe pain: acute pain from surgery or injury, chronic pain in cancer, arthritis, or neuropathic conditions, pain in palliative and terminal care, and pain in opioid-tolerant patients who have outgrown other opioids. In low doses it also works as an antitussive.
Mechanism of Action
Binding mu-opioid receptors in the CNS raises the release of neurotransmitters such as dopamine and serotonin, which inhibits pain perception and produces sedation and euphoria. It also dampens sympathetic activity, lowering heart rate, blood pressure, and respiratory rate, and slows the GI tract, which drives constipation.
Precautions and Contraindications
Respiratory depression is the lead concern and can be life-threatening, so use caution in COPD, sleep apnea, and other respiratory disease. Use caution with head injury or increased intracranial pressure, where respiratory depression raises the risk further, and in hypotension, which is dangerous in cardiovascular disease.
Hydromorphone is metabolized in the liver largely to hydromorphone-3-glucuronide; this metabolite accumulates in kidney disease and can cause opioid neurotoxicity. Avoid it with other CNS depressants, sedatives, or narcotic analgesics in severe hypothyroidism, where significant respiratory depression can occur. Use caution with GI obstruction (worsened constipation), in pregnancy and breastfeeding (crosses the placenta, present in breast milk), and in the elderly, who are more sensitive to its effects. It is not recommended in children under 6 years. As a controlled substance it carries real potential for addiction, abuse, and misuse, and must be kept secure.
Drug Interactions
Drug-drug. Benzodiazepines, alcohol, and other CNS depressants raise the risk of sedation and respiratory depression. Other opioids add overdose risk. Antidepressants and antipsychotics increase sedation and respiratory depression. Hypnotics, anxiolytics, general anesthetics, and muscle relaxants can cause profound sedation, respiratory depression, coma, and death. Certain antibiotics and antifungals can decrease effectiveness. Partial antagonists (buprenorphine, butorphanol, nalbuphine, pentazocine) may precipitate withdrawal in physically dependent patients; nalbuphine or pentazocine may decrease analgesia. Serotonergic drugs (tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5-HT3 receptor antagonists, linezolid, methylene blue, triptans) raise the risk of serotonin syndrome.
Drug-natural products. Kava-kava, valerian, chamomile, or hops increase CNS depression.
Adverse Effects
Common: nausea and vomiting, constipation, drowsiness and dizziness (fall and impairment risk), dry mouth, headache, sweating, itching (often with rash or hives, histamine-mediated), loss of appetite, fatigue, and weakness.
More serious: respiratory depression (the major concern with all opioids), confusion, addiction or dependence, low blood pressure including orthostatic hypotension, slow heart rate (bradycardia, more likely at higher doses or with other rate-slowing drugs), seizures (more likely at high doses or with a seizure history), blurred vision, and fainting. The elderly carry higher risk across most of these.
Administration Considerations
Available Forms
- Immediate-release tablets: 2 mg, 4 mg, 8 mg.
- Extended-release tablets (abuse-deterrent): 4 mg, 8 mg, 12 mg, 16 mg, 32 mg.
- Controlled-release capsules: 3 mg, 4.5 mg, 6 mg, 9 mg, 12 mg, 18 mg, 24 mg, 30 mg.
- Oral solution: 1 mg/mL.
- Injection: 1 mg/mL, 2 mg/mL, 4 mg/mL, 10 mg/mL.
- Suppositories: 3 mg.
Dosage for Children
Analgesic
- PO (Children <50 kg): 0.06 mg/kg every 3 – 4 hr initially; younger children may require smaller initial doses of 0.03 mg/kg. Maximum dose 5 mg.
- IV, IM, Subcut (Children <50 kg): 0.015 mg/kg every 3 – 4 hr as needed initially; may be increased.
Antitussive
- PO (Children >12 yr): 1 mg every 3 – 4 hr.
- PO (Children 6–12 yr): 0.5 mg every 3–4 hr.
Dosage for Adults
Analgesic
- PO (Adults ≥50 kg): Immediate-release, 4 – 8 mg every 3 – 4 hr initially (some patients respond to doses as small as 2 mg initially); or once the 24-hr opioid requirement is determined, convert to extended-release by giving the total daily oral dose once daily.
- PO (Adults <50 kg): 0.06 mg/kg every 3 – 4 hr initially; younger patients may require smaller initial doses of 0.03 mg/kg. Maximum dose 5 mg.
- IV, IM, Subcut (Adults ≥50 kg): 1.5 mg every 3 – 4 hr as needed initially; may be increased.
- IV, IM, Subcut (Adults <50 kg): 0.015 mg/kg every 3 – 4 hr as needed initially; may be increased.
- IV (Adults): Continuous infusion (unlabeled), 0.2 – 3 mg/hr depending on previous opioid use. An initial bolus of twice the hourly rate in mg may be given, with subsequent breakthrough boluses of 50 – 100% of the hourly rate in mg.
- Rect (Adults): 3 mg every 6 – 8 hr initially as needed.
- Hepatic impairment, PO (Adults): Moderate impairment (extended-release), decrease initial dose by 75%.
- Renal impairment, PO (Adults): Moderate impairment (extended-release), decrease initial dose by 50%; severe impairment (extended-release), decrease initial dose by 75%.
Antitussive
- PO (Adults): 1 mg every 3 – 4 hr.
Pharmacokinetics
Rapid onset and a relatively short half-life, with peak effect typically 30 minutes to 2 hours after administration depending on route.
- Absorption. Rapidly absorbed after oral administration; bioavailability approximately 100%.
- Distribution. Widely distributed and highly protein-bound.
- Metabolism and excretion. Metabolized in the liver by the cytochrome P450 system to hydromorphone-3-glucuronide and hydromorphone-6-glucuronide, which are excreted in the urine.
- Half-life. Oral immediate-release or injection, typically 2-4 hours, prolonged in liver or kidney impairment; oral extended-release, 8 – 15 hr.
Nursing Considerations
Nursing Assessment
Assess BP, pulse, and respirations before and periodically during administration. If the respiratory rate is <10/min, assess the level of sedation; the dose may need to be decreased by 25 – 50%. Initial drowsiness diminishes with continued use.
Assess the type, location, and intensity of pain before dosing, then 1 hour after IM or PO and 5 min (peak) after IV to judge effectiveness. When titrating, increase by 25 – 50% until there is either a 50% reduction in the pain rating on a numerical or visual analogue scale or the patient reports satisfactory relief. With short-acting hydromorphone, a repeat dose can be safely given at the time of the peak if the previous dose was ineffective and side effects are minimal.
Patients on a continuous infusion should have additional bolus doses every 15 – 30 minutes as needed for breakthrough pain; the bolus is usually set to the amount infused each hour. Patients on extended-release hydromorphone may need additional short-acting or rapid-onset opioid for breakthrough pain, equivalent to 10 – 20% of the 24-hour total and given every 2 hours as needed.
Assess geriatric and pediatric patients frequently, since both are more sensitive to opioids and more prone to side effects and respiratory complications. Monitor for respiratory depression, sedation, and changes in blood pressure, heart rate, and mental status. Assess bowel function routinely and prevent constipation with fluids, bulk, and laxatives.
Individualize the dose. Prolonged use can lead to physical and psychological dependence and tolerance, but that should not block adequate analgesia; most patients treated for pain do not develop psychological dependence, though progressively higher doses may be needed over long-term therapy. Assess the risk for addiction, abuse, or misuse before administering. Crushing, chewing, snorting, or injecting extended-release product delivers uncontrolled hydromorphone and can cause overdose and death; Exalgo is abuse-deterrent and turns to gel if crushed. Monitor for withdrawal if the drug is abruptly stopped (taper gradually). Reassess pain, since non-opioid strategies such as physical therapy or nerve blocks may suit some pain better. During antitussive use, assess cough and lung sounds; hydromorphone depresses the cough reflex through a direct effect on the cough center in the medulla and depresses respiration through a direct effect on brainstem respiratory centers.
Review the medication list before administering for interactions with benzodiazepines, alcohol, and anti-anxiety drugs that can deepen sedation or respiratory depression.
Naloxone (Narcan) is the antidote when an opioid antagonist is needed to reverse respiratory depression or coma. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by IV push every 2 min. For children and patients weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg every 2 min. Titrate to avoid withdrawal, seizures, and severe pain.
Nursing Diagnoses
Acute pain, chronic pain, ineffective breathing pattern, risk for injury, risk for constipation, and deficient knowledge.
Nursing Interventions
Verify patient identity and the order against the MAR and label before administering. Calculate doses carefully (accidental opioid overdose has been fatal, and errors are common in pediatrics), and check infusion pump settings before starting.
Do not confuse hydromorphone with morphine or oxymorphone, and do not confuse high-potency (HP) forms with regular forms; fatalities have occurred. Hydromorphone and morphine are different drugs, both high-alert. Oxymorphone is a semisynthetic mu opioid agonist 1.2 times as potent as morphine. Run an Independent Double Check (IDC) when giving any high-risk drug.
Explain the therapeutic value before administration to enhance the analgesic effect. Watch for respiratory depression, drowsiness, or confusion. Scheduled dosing is often more effective than prn, since analgesia works better given before pain becomes severe. Document time, dose, and patient response immediately to prevent an unintended repeat dose. Coadministration with nonopioid analgesics can add analgesic effect and allow lower opioid doses. Discontinue gradually after long-term use to prevent withdrawal.
Dose conversions: when moving from immediate-release to extended-release, give the total daily oral dose once daily and titrate the ER product every 3 – 4 days. To convert from another opioid, calculate the total daily hydromorphone dose, give 50% of it as extended-release once daily, then titrate every 3 – 4 days. When converting from transdermal fentanyl, start extended-release hydromorphone 18 hours after removing the patch; for each 25 mcg/hr fentanyl transdermal dose, the equianalgesic dose of extended-release hydromorphone is 12 mg once daily (initiate at 50% of this calculated total daily dose given once daily).
Give Dilaudid with food or milk to minimize GI irritation. Tell the patient to swallow extended-release tablets whole and not to break, crush, dissolve, or chew them.
IV push. Dilute with at least 5 mL of sterile water or 0.9% NaCl for injection. Inspect for particulate matter; a slight yellow color does not alter potency. Store at room temperature. Administer slowly, at a rate not to exceed 2 mg over 3 – 5 min; rapid administration can cause increased respiratory depression, hypotension, and circulatory collapse.
Y-site compatibility: acetaminophen, acyclovir, alemtuzumab, allopurinol, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, amphotericin B colloidal, amphotericin B lipid complex, amphotericin B liposome, ampicillin/sulbactam, anidulafungin, argatroban, atracurium, atropine, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, busulfan, calcium chloride, calcium gluconate, cangrelor, carboplatin, carmustine, caspofungin, cefepime, cefotaxime, cefoxitin, ceftaroline, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, cladribine, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daptomycin, daunorubicin hydrochloride, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doxorubicin, doxorubicin liposome, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, epirubicin, eptifibatide, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hetastarch, hydralazine, hydrocortisone, idarubicin, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meropenem, mesna, methotrexate, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, micafungin, midazolam, milrinone, mitoxantrone, mitomycin, morphine, mycophenolate, nafcillin, naloxone, nesiritide, nicardipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, pemetrexed, penicillin G potassium, pentamidine, pentobarbital, phenylephrine, piperacillin/tazobactam, posaconazole, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propofol, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rituximab, rocuronium, scopolamine, sodium acetate, sodium phosphates, streptozocin, succinylcholine, tacrolimus, teniposide, theophylline, thiotepa, tigecycline, tirofiban, tobramycin, topotecan, trastuzumab, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, zidovudine, zoledronic acid.
Y-site incompatibility: dantrolene, dimenhydrinate, minocycline, phenytoin, sargramostim, thiopental.
Patient Education and Teaching
Take only as prescribed and do not change the dose without consulting a professional. Hydromorphone has known abuse potential: guard it against theft and never give it to anyone else. Do not crush, break, or chew the tablet, which can cause rapid release and increased side effects. Call for assistance when ambulating or smoking. Avoid alcohol and other CNS depressants. Change positions slowly to minimize orthostatic hypotension. Store in a secure place, out of reach of children and pets, and dispose of unused medication per the pharmacist's instructions. Tell every provider about all medications and supplements, and report side effects to a physician immediately. Avoid driving or operating heavy machinery until the drug's effects are known. Do not stop abruptly, which can cause withdrawal. Turn, cough, and breathe deeply every 2 hr to prevent atelectasis. Notify a professional if pregnancy is planned or suspected, or if breastfeeding. Teach patients and family how and when to administer the drug, safe storage, and infusion equipment care. For children, teach caregivers to measure liquid medication accurately using only the device dispensed with it. Stress aggressive prevention of constipation.
Evaluation and Desired Outcomes
Effective relief of moderate to severe pain (analgesia), reduced anxiety and relaxation in patients with chronic pain, and suppression of cough during antitussive use (hydromorphone depresses the cough reflex by direct effect on the cough center in the medulla and depresses respiration by direct effect on brainstem respiratory centers).
Frequently Asked Questions
How much stronger is hydromorphone than morphine? Roughly five to seven times more potent by the oral and IV routes, with about 0.9 to 1.2 mg of hydromorphone equal to 10 mg of morphine (Opioid Equivalency, StatPearls). Because of that, the two drugs are never interchangeable milligram for milligram, and confusing them has caused fatal overdoses.
What is the antidote for an overdose? Naloxone (Narcan). For respiratory depression, dilute a 0.4 mg ampule in 10 mL of 0.9% sodium chloride and give 0.5 mL (0.02 mg) by IV push every 2 minutes, titrating to restore breathing while avoiding withdrawal, seizures, and a sudden return of severe pain (Hydromorphone, StatPearls).
Why is hydromorphone called a high-alert medication? A small dosing error carries a large risk because the drug is so potent, and its name and high-potency (HP) forms are easy to confuse with morphine and with standard-concentration hydromorphone. Run an independent double check, verify the order and pump settings, and never assume HP and regular vials are equivalent.
Why does almost every patient get constipated? Opioids slow GI motility through their effect on the gut, and unlike most side effects this one does not fade with time. Start a bowel regimen with fluids, fiber, and a stimulant laxative early rather than waiting for the problem to appear.
Who is at highest risk for respiratory depression? Patients with COPD, sleep apnea, or other respiratory disease, the elderly, the very young, and anyone also taking benzodiazepines, alcohol, or other CNS depressants. Assess respiratory rate and sedation before and during therapy, and hold or reduce the dose if the rate falls below 10 per minute.
Why must extended-release tablets be swallowed whole? Crushing, chewing, or dissolving them releases the full dose at once, which can cause a fatal overdose. Only immediate-release forms are used for breakthrough pain, and extended-release products are reserved for opioid-tolerant patients.