Hydromorphone | Medication Reference

Bedside Snapshot

Drug Class: Semi-synthetic opioid analgesic; potent μ-opioid receptor agonist
Core Uses: Potent μ-opioid agonist used for moderate-to-severe acute and chronic pain. Compared with morphine: more potent, more lipophilic, faster onset, shorter duration, and less histamine release; unlike morphine, its primary metabolite (hydromorphone-3-glucuronide) is not analgesic but can be neurotoxic at high levels
IV Adult Dosing (Opioid-Naïve): 0.2–0.5 mg IV slowly over 2–3 minutes every 2–3 hours as needed, or 0.2–0.4 mg IV q5–10 minutes in titrated boluses. Labeling allows 0.2–1 mg IV every 2–3 hours, but most institutions use the lower end initially in opioid-naïve or high-risk patients
Oral IR (Opioid-Naïve Adults): 2–4 mg PO every 4–6 hours as needed for pain, titrated to effect
Extended-Release: Reserved for opioid-tolerant patients with severe, persistent pain requiring around-the-clock opioids
Onset: IV hydromorphone has onset within ~5 minutes, with peak effect at ~10–20 minutes and duration ~2–4 hours. Oral IR onset ~15–30 minutes, peak 30–60 minutes, duration 3–4 hours. Elimination half-life for IR formulations is ~2–3 hours
Equianalgesic Ballpark: 1.5 mg IV hydromorphone ≈ 10 mg IV morphine; 4–5 mg PO hydromorphone ≈ 20–25 mg PO morphine (roughly 1:4–5 oral potency ratio). Always apply clinical judgment and reduce doses for incomplete cross-tolerance when switching
Major Acute Risks: Respiratory depression and apnea, sedation, hypotension, bradycardia, nausea/vomiting, pruritus, and constipation. At higher doses or with accumulation of H3G in renal failure, neurotoxicity (myoclonus, agitation, hyperalgesia) can occur
Renal Impairment Considerations: Because hydromorphone has no active analgesic metabolites but relies on hepatic glucuronidation and renal excretion of H3G, it is often preferred over morphine in moderate CKD—yet severe renal impairment still warrants dose reduction or alternative opioids and close monitoring

Brand & Generic Names

Generic Name: Hydromorphone hydrochloride
Brand Names: Dilaudid (IR tablets, oral solution, injection), Exalgo (ER tablets), multiple generics—availability is region- and institution-specific

Medication Class

Semi-synthetic opioid analgesic; potent μ-opioid receptor agonist

Pharmacology

Mechanism of Action:

Hydromorphone is a semi-synthetic hydrogenated ketone of morphine and functions primarily as a potent μ-opioid receptor agonist; it has minimal activity at κ and δ receptors compared with μ
Binding to μ-opioid receptors inhibits adenylate cyclase, decreases intracellular cAMP, increases K⁺ efflux, and reduces Ca²⁺ influx at presynaptic terminals, resulting in neuronal hyperpolarization and reduced neurotransmitter release (e.g., substance P, glutamate) in nociceptive pathways
Analgesia arises from effects on ascending pain pathways (dorsal horn, thalamus, cortex) and activation of descending inhibitory pathways in the brainstem
At the medullary respiratory centers, μ-receptor activation reduces responsiveness to CO₂ and hypoxia, producing dose-dependent respiratory depression and potential apnea
Like other opioids, hydromorphone slows GI motility and increases sphincter tone, contributing to constipation and possible ileus. It causes less histamine release than morphine, so it is somewhat less likely to cause pruritus and vasodilation, but these effects can still occur

Pharmacokinetics (IV and Oral):

Formulations: Immediate-release oral tablets (2 mg, 4 mg, 8 mg), oral solution (1 mg/mL common), extended-release tablets (8, 12, 16, 32 mg), and parenteral solution for IV/IM/SC use (1–10 mg/mL). Rectal formulations exist in some regions
Onset (IV): Analgesia begins within ~5 minutes, peak effect 10–20 minutes, with duration 2–4 hours after a single bolus
Onset (PO IR): 15–30 minutes, peak plasma and effect at 30–60 minutes, duration 3–4 hours; elimination half-life ~2–3 hours
Distribution: More lipophilic than morphine, with volume of distribution around 4 L/kg and low-to-moderate protein binding (~8–19%)
Metabolism: Primarily hepatic glucuronidation to hydromorphone-3-glucuronide (H3G), which lacks analgesic activity but may be neuroexcitatory at high concentrations
Elimination: Mainly renal excretion of H3G and minor metabolites; 7% of unchanged hydromorphone and 1% via feces. Half-life is ~2–3 hours in normal renal function but can be markedly prolonged (up to tens of hours) in severe renal impairment
Renal Impairment: Accumulation of H3G increases risk for sedation, respiratory depression, myoclonus, and hyperalgesia; dose reductions, extended intervals, or alternative opioids (e.g., fentanyl) are recommended in advanced CKD/ESRD
Hepatic Impairment: Increased Cmax and AUC (up to ~4-fold in moderate hepatic impairment reported for oral doses); use lower starting doses and slower titration

Indications

Moderate-to-severe acute pain requiring opioid analgesia (trauma, post-op, abdominal pain, renal colic, cancer-related pain)
Severe chronic pain requiring around-the-clock opioid therapy when other options are inadequate (oral IR/ER, subcutaneous/IV infusions, palliative care)
Analgesic component of balanced anesthesia and procedural sedation in the OR and ICU (institution- and credentialing-dependent)
Severe musculoskeletal and trauma pain in ED/ICU/inpatient settings
Postoperative pain after major operations (e.g., joint replacement, abdominal surgery)
Cancer-related pain and advanced illness requiring parenteral or high-potency oral opioids
Renal colic, pancreatitis, sickle cell pain crises, and other severe pain states not adequately controlled by non-opioids and weaker opioids

Dosing & Administration

Available Forms:

IV/IM/SC Solution: Commonly 1 mg/mL and 2 mg/mL vials; high-potency 10 mg/mL vials exist and require extreme caution and clear labeling
Oral IR Tablets: Typically 2 mg, 4 mg, 8 mg strengths
Oral Solution: Usually 1 mg/mL; concentrated solutions also exist in some markets
Oral ER Tablets (e.g., Exalgo): 8, 12, 16, 32 mg once daily for opioid-tolerant patients only
Rectal Suppositories: Available in certain regions (e.g., 3 mg) for chronic or palliative pain

Critical Dosing Warning: Verify formulation and strength whenever drawing up hydromorphone to avoid tenfold errors and confusion between mg and mL. Hydromorphone is roughly 5–7 times as potent as IV morphine; dosing errors of a "morphine-sized" dose can be catastrophic.

Standard Dosing – Hydromorphone (IV and Oral – Always Follow Local Opioid Protocols):

Indication / Population	Dose & Route	Frequency / Titration	Notes
Adult acute moderate-to-severe pain – IV (opioid-naïve)	0.2–0.5 mg IV slowly (≈0.003–0.01 mg/kg in 70 kg)	Every 2–3 hours as needed, or smaller boluses q5–10 min titrated	Label: 0.2–1 mg IV q2–3h; start low (0.2–0.4 mg) in most patients
Adult IV PCA (example – institution-specific)	Demand 0.1–0.2 mg; lockout 6–10 min	Optional basal 0–0.4 mg/hr; hourly limit often 1–2 mg	Adjust for age, comorbidities, and opioid tolerance per protocol
Adult oral IR – opioid-naïve moderate-to-severe pain	2–4 mg PO IR	Every 4–6 hours as needed	Start at 2 mg in frail or high-risk patients; titrate based on response
Adult oral ER (Exalgo and similar) – opioid-tolerant only	8–64 mg PO once daily (varies with total daily IR dose)	Once daily; adjust every 3–4 days as needed	Reserved for severe, persistent pain in opioid-tolerant patients
Pediatric acute pain – IV (specialist-directed)	0.01–0.02 mg/kg IV (max per dose per protocol)	Every 3–4 hours or smaller boluses titrated q5–10 min	Use pediatric references and local protocols (e.g., 0.01 mg/kg bolus)
Renal impairment (adult)	Reduce IV dose (e.g., 0.1–0.2 mg) and/or extend interval	Titrate cautiously; monitor closely for sedation and neurotoxicity	Consider fentanyl or other alternatives in advanced CKD/ESRD

Equianalgesic Considerations (Approximate – Verify with Local Charts):

IV: 1.5 mg IV hydromorphone ≈ 10 mg IV morphine is a commonly cited ratio (roughly 1:6–7 potency)
Oral: About 4–5 mg PO hydromorphone ≈ 20–25 mg PO morphine (roughly 1:4–5)
When rotating opioids, calculate 24-hour morphine equivalent dose (MED) and reduce the new opioid dose by 25–50% for incomplete cross-tolerance, particularly in medically complex or frail patients
Equianalgesic tables vary; always refer to up-to-date institutional guidelines and integrate clinical response

Contraindications

Contraindications (Context-Dependent):

Significant respiratory depression in an unmonitored setting without resuscitation capability
Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment
Known hypersensitivity to hydromorphone or formulation components
Gastrointestinal obstruction, including paralytic ileus, for oral formulations

Major Precautions:

Elderly, frail, or opioid-naïve patients: Higher risk for respiratory depression and oversedation; use reduced doses and slower titration
Chronic lung disease (COPD, OSA, neuromuscular disease): Increased risk of CO₂ retention and hypoventilation; consider non-opioid adjuncts and continuous monitoring
Intracranial pathology or elevated ICP: Hypercapnia from hypoventilation may worsen ICP; monitor closely and avoid over-sedation
Hemodynamic instability: Less histamine release than morphine, but hypotension can still occur; titrate carefully in hypovolemia or shock
Renal dysfunction: Accumulation of hydromorphone-3-glucuronide (H3G) increases risk of neurotoxicity and prolonged sedation; reduce dose, extend interval, or choose an alternative opioid when possible
Hepatic impairment: Increased exposure; initiate at lower doses with slow titration
Concurrent CNS depressants (benzodiazepines, sedative-hypnotics, alcohol, gabapentinoids): Additive respiratory and CNS depression; adjust dosing and intensify monitoring
History of substance use disorder: High risk for misuse, diversion, and overdose; employ risk mitigation (PDMP, limited quantities, agreements) and multidisciplinary management

Adverse Effects

Common:

Sedation, drowsiness, dizziness
Dose-dependent respiratory depression and hypoventilation
Nausea, vomiting, and constipation
Pruritus and mild flushing
Urinary retention and dry mouth

Serious:

Severe respiratory depression and apnea: Particularly with high doses, rapid titration, or co-administered sedatives
Hypotension and bradycardia: Especially in hypovolemic or hemodynamically unstable patients
Neurotoxicity (myoclonus, agitation, hyperalgesia, seizures): Associated with accumulation of H3G, especially in renal failure
Opioid use disorder, tolerance, physical dependence, and withdrawal: With chronic use
Serotonin syndrome: When combined with other serotonergic drugs (rare but reported)
Anaphylaxis or severe hypersensitivity: Rare

Special Populations

Pediatrics: Use weight-based dosing (0.01–0.02 mg/kg IV for acute pain); requires specialist guidance and close monitoring
Pregnancy: Opioids cross the placenta; chronic use during pregnancy can lead to neonatal abstinence syndrome; use lowest effective dose for shortest duration when necessary
Older Adults: Increased sensitivity to respiratory depression and sedation; start with lower doses (e.g., 0.2 mg IV or 2 mg PO) and titrate slowly
Renal Impairment: H3G metabolite accumulates; reduce doses by 50–75% and extend intervals, or consider alternative opioids like fentanyl in severe CKD/ESRD
Hepatic Impairment: Increased exposure (up to 4-fold); start with lower doses and titrate cautiously with close monitoring

Monitoring

Pain scores and functional improvement: Vs baseline (ability to breathe deeply, move, participate in care)
Respiratory rate, pattern, and depth: Continuous pulse oximetry for high-risk patients; capnography for moderate-deep sedation, high doses, or comorbid pulmonary disease
Level of consciousness and sedation scale: (e.g., RASS, Pasero Oversedation Scale) with reassessment after dose changes
Blood pressure and heart rate: In patients with cardiovascular disease or hemodynamic instability
Bowel function: Presence of constipation, and need for prophylactic or therapeutic bowel regimens in ongoing therapy
Signs of opioid toxicity: Pinpoint pupils, somnolence, slow/shallow breathing; readiness to administer naloxone when indicated

Clinical Pearls

Critical potency awareness: Hydromorphone is roughly 5–7 times as potent as IV morphine; dosing errors of a "morphine-sized" dose can be catastrophic—always double-check concentration and units (mg vs mL).

Histamine advantage: Compared with morphine, hydromorphone often causes less pruritus and histamine-mediated hypotension, making it attractive for patients with prior morphine-related itching or vasodilation.

Renal function consideration: In moderate CKD, hydromorphone is generally safer than morphine but still not "renal-proof"; watch for neurotoxicity and consider dose reductions or alternative opioids in advanced CKD or dialysis patients.

Multimodal analgesia: Use multimodal analgesia (acetaminophen, NSAIDs when appropriate, ketamine, regional techniques) to reduce required opioid dose and adverse effects.

Naloxone reversal strategy: When reversing hydromorphone-induced respiratory depression, titrate naloxone in small aliquots (e.g., 20–40 mcg IV at a time) to restore ventilation without fully eliminating analgesia or precipitating severe withdrawal and catecholamine surge.

Safe handling and storage: As with all high-potency opioids, safe storage, disposal, and careful handoff communication are essential to reduce diversion and accidental overdose.

References

1. Abi-Aad, K. R., & Varacallo, M. (2024). Hydromorphone. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK470393/
2. U.S. Food and Drug Administration. (2009). DILAUDID (hydromorphone hydrochloride) injection prescribing information. DailyMed. https://dailymed.nlm.nih.gov
3. U.S. Food and Drug Administration. (2023). Hydromorphone hydrochloride tablets and oral solution prescribing information. DailyMed. https://dailymed.nlm.nih.gov
4. Murray, A., & Hagen, N. A. (2005). Hydromorphone. Journal of Pain and Symptom Management, 29(5S), S57–S66. https://doi.org/10.1016/j.jpainsymman.2005.01.007
5. Pereira, J., Lawlor, P., Vigano, A., Dorgan, M., & Bruera, E. (2001). Equianalgesic dose ratios for opioids: A critical review and proposals for long-term dosing. Journal of Pain and Symptom Management, 22(2), 672–687. https://doi.org/10.1016/S0885-3924(01)00294-9