Hydromorphone

Hydromorphone is a semisynthetic full mu-opioid agonist about 5 to 7 times as potent as morphine by weight. It is used as an alternative to morphine for severe pain, especially when high potency in a small volume is needed (subcutaneous infusion) or when morphine causes adverse effects. Confusion between hydromorphone and morphine doses is a recognised cause of fatal overdose.

Class. Full mu-opioid agonist (semisynthetic).

Mechanism. Mu receptor agonism.

Pharmacokinetics. Oral bioavailability about 25 to 60%. Immediate release onset 15 to 30 minutes, peak 30 to 60 minutes, duration 4 to 5 hours. Intravenous onset 5 minutes. Half-life 2 to 3 hours. Hepatic glucuronidation to hydromorphone-3-glucuronide (inactive for analgesia, can cause neuroexcitation in accumulation); fewer active metabolites than morphine; renal excretion of metabolites.

Potency. Oral hydromorphone 1.3 to 2 mg is roughly equivalent to 10 mg oral morphine in practice (conversion ratios range from 5:1 to 7.5:1 depending on the source). Parenteral hydromorphone is about 5 to 7 times as potent as parenteral morphine.

Indications are severe acute pain, cancer and palliative pain, and pain in patients who cannot tolerate morphine.

Opioid-naive adults

• Oral immediate release: 1 to 2 mg every 4 to 6 hours (some labels start at 2 mg); older or frail adults 0.5 to 1 mg.
• Intravenous: 0.2 to 0.5 mg every 5 to 10 minutes titrated, then 0.2 to 1 mg every 2 to 3 hours as needed.
• Subcutaneous: 0.5 to 1.5 mg every 4 hours. Continuous subcutaneous infusion by syringe driver in palliative care, with the daily dose calculated from oral requirement using the local conversion ratio.
• Modified release: 4 to 8 mg every 12 hours, only after the daily requirement is known.
• Patient-controlled analgesia: bolus 0.1 to 0.2 mg, lockout 6 to 10 minutes, background infusion not used in opioid-naive patients.
• No fixed maximum dose; titrate to effect with reassessment.

High-potency injection. The 10 mg/mL formulation is for opioid-tolerant patients only; never use it for opioid-naive patients.

Children. Specialist use only: oral 0.03 to 0.08 mg/kg every 4 to 6 hours; intravenous 0.005 to 0.015 mg/kg every 3 to 6 hours.

Contraindications. Respiratory depression without ventilatory support; acute severe asthma; paralytic ileus; raised intracranial pressure (relative); monoamine oxidase inhibitor within 14 days; hypersensitivity.

Boxed-warning-level risks. Addiction, abuse and misuse; life-threatening respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome; interactions with central nervous system depressants; risk of medication error from dose or unit confusion with morphine and between formulations.

Adverse effects. Common: nausea, vomiting, constipation, sedation, dizziness, pruritus. Serious: respiratory depression, hypotension, urinary retention, myoclonus, seizures with accumulation, delirium and hyperalgesia.

Interactions. Benzodiazepines, alcohol, gabapentinoids and other depressants add sedation and respiratory depression. Monoamine oxidase inhibitors risk serotonin syndrome. Anticholinergics worsen constipation. Few cytochrome interactions.

Common prescribing errors. Giving a morphine-equivalent mg dose of hydromorphone (about seven times overdose); using the high-potency formulation in opioid-naive patients; mixing up oral and parenteral doses; writing “mg” and “mL” ambiguously.

Special groups

• Pregnancy: use only if necessary, with neonatal monitoring if used near delivery.
• Breastfeeding: avoid prolonged use; single doses acceptable with infant observation.
• Older adults: start at 0.5 to 1 mg orally.
• Kidney impairment: start at one quarter to one half of the usual dose and extend the interval; metabolite accumulation is less than with morphine but can occur.
• Liver impairment: start at one quarter to one half of the usual dose; avoid in severe disease.
• Regional: availability is limited in many settings; check which concentration is stocked.

Formulations. Oral tablets (1, 2, 4, 8 mg), oral solution (1 mg/mL), modified-release capsules, injection (1, 2 and 10 mg/mL), suppositories in some markets.

Administration. Oral doses with or without food. Dilute intravenous doses in 0.9% sodium chloride and give slowly over at least 2 to 3 minutes. Write the dose in mg and the volume in mL on every chart.

Baseline. Respiratory rate, sedation score, renal and hepatic function, concurrent sedatives, opioid exposure history.

Monitoring. Pain, respiratory rate, sedation and oxygen saturation. Check 15 to 30 minutes after parenteral doses and at each titration step. Bowel function daily.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Reduce or hold for respiratory rate under 10 breaths/minute, excessive sedation, myoclonus or delirium. After more than 1 week of regular use, reduce by 10 to 25% every few days.

Referral and escalation. Respiratory depression needs airway support and naloxone, repeated as needed. Conversion between hydromorphone and other opioids in high-dose or complex pain should be reviewed by a pain or palliative care clinician.