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Drug Reference

hydromorphone

opioid analgesic· Brands: Dilaudid, PalladoneIMIVPOPRSC

Mechanism of action
Hydromorphone is an opioid analgesic that acts as an agonist at mu-opioid receptors. It activates G-protein coupled receptors, which inhibits adenylate cyclase and reduces cyclic AMP production. This leads to decreased neurotransmitter release, particularly substance P and glutamate, resulting in analgesia, sedation, and euphoria. It also has effects on brainstem respiratory centres, causing respiratory depression, and on the chemoreceptor trigger zone, causing nausea and vomiting.
Pharmacokinetics
Hydromorphone is well absorbed after oral administration, but oral bioavailability is approximately 24 per cent due to first-pass metabolism.
Indications & dosing

Moderate to severe acute pain

Use low end of dose range in opioid-naive patients; titrate to analgesic effect.

  • adult · IV: 0.5–1 mg every 2 to 4 hours · Use low end of dose range in opioid-naive patients; titrate to analgesic effect.

Severe chronic pain in opioid-tolerant patients

For opioid-tolerant patients; initiate at lower dose in opioid-naive and titrate carefully.

  • adult · PO: 2–4 mg every 4 to 6 hours · For opioid-tolerant patients; initiate at lower dose in opioid-naive and titrate carefully.

Pain in malignancy

Titrate to pain relief; consider longer-acting formulations for stable pain.

  • adult · PO: 2–4 mg every 4 to 6 hours · Titrate to pain relief; consider longer-acting formulations for stable pain.
Contraindications & precautions
  • Hypersensitivity to hydromorphone or any excipient · Includes anaphylaxis and angioedema.
  • Significant respiratory depression · Risk of severe and fatal respiratory insufficiency.
  • Acute severe asthma or severe COPD without adequate monitoring · Opioids can worsen airway obstruction.
  • Paralytic ileus · Opioids reduce gastrointestinal motility.
  • Severe hepatic impairment · Metabolism of hydromorphone may be impaired; use with caution and consider lower doses.
  • Severe renal impairment · Risk of accumulation; consider extended dosing intervals.
  • Monitor respiratory rate and depth, especially during the first 24 hours after starting therapy or after a dose increase.
  • Use with caution in patients with renal or hepatic impairment; consider dose reduction or extended dosing intervals.
  • Avoid concurrent use of other CNS depressants, including alcohol, benzodiazepines, and other opioids, as this increases the risk of respiratory depression.
  • Taper the dose gradually to avoid withdrawal symptoms; do not discontinue abruptly.
  • Use caution in patients with hypotension, hypovolemia, or reduced respiratory reserve.
  • Caution in patients with a history of substance misuse or dependence.
Adverse effects
  • Constipation
  • Nausea
  • Vomiting
  • Drowsiness
  • Dizziness
  • Respiratory depressionserious
  • Hypotensionserious
  • Bradycardiaserious
  • Allergic reactionsserious
Renal & hepatic adjustment
  • eGFR 30–59: Use with caution; consider reducing the dose or increasing the dosing interval.
  • eGFR 0–29: Avoid or use extreme caution; consider an alternative opioid. (avoid)
  • Hepatic impairment (mild): No adjustment required, but monitor closely.
  • Hepatic impairment (moderate): Reduce the initial dose and titrate cautiously.
  • Hepatic impairment (severe): Avoid or use with extreme caution; consider an alternative opioid. (avoid)
Monitoring, pregnancy & toxicity
  • Pain score · At each assessment and after dose changes
  • Respiratory rate · Regularly during treatment, especially during dose titration
  • Sedation score · Regularly during treatment, especially when starting or increasing the dose
  • Blood pressure · Monitor for hypotension, especially during initial therapy
  • Bowel function · Assess regularly for constipation
  • Signs of opioid dependence or withdrawal · Monitor with prolonged use
  • Pregnancy: Hydromorphone crosses the placenta. Use only if the potential benefit outweighs the risk to the fetus. Prolonged use during pregnancy can cause neonatal abstinence syndrome. If used, use the lowest effective dose for the shortest duration and monitor the neonate for withdrawal symptoms.
  • Toxicity: Respiratory depression · Administer naloxone, provide supportive care, and monitor respiratory status.
  • Toxicity: CNS depression (sedation, confusion, coma) · Administer naloxone if indicated, provide airway support, and monitor level of consciousness.
  • Toxicity: Miosis · Generally not treated unless accompanied by other serious signs; monitor for concomitant opioid toxicity.
  • Toxicity: Hypotension · Administer fluids and consider vasopressors if needed; naloxone may reverse opioid-induced hypotension.
Antidotes & reversal
  • Naloxone · Titrate to ventilation; watch for re-sedation.
Clinical notes
Hydromorphone is used for the management of moderate to severe pain including acute and chronic pain. It is approximately five to ten times more potent than morphine on a milligram basis, so dose adjustment is essential. The oral dose is about five times the parenteral dose. It can be given by oral, intravenous, intramuscular, subcutaneous, and rectal routes. Common adverse effects include constipation, nausea, vomiting, respiratory depression, and sedation. Tolerance and dependence may develop with prolonged use. Caution is needed in patients with renal impairment, hepatic impairment, or respiratory disease. In the UK, it is a controlled drug.

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BNF; local formulary