How does hydromorphone differ from morphine?

Hydromorphone vs Morphine: Key Differences

Hydromorphone is a comparable, potentially superior analgesic to morphine with a faster onset of action, greater potency (5-10 times orally, 8.5 times IV), and reduced risk of dose-stacking toxicity, particularly in renal failure. 1

Pharmacological Differences

Potency and Dosing

• Hydromorphone is 5-10 times more potent than morphine orally and approximately 8.5 times more potent intravenously 1, 2
• The equianalgesic ratio is approximately 1.5 mg hydromorphone IV = 10 mg morphine IV 1
• For oral administration, 5 mg hydromorphone provides comparable analgesia to 30 mg morphine 3
• The smaller milligram dose required (1.5 mg vs 10 mg) may reduce physician reluctance to adequately treat pain 1

Onset and Duration

• Hydromorphone has a quicker onset of action compared to morphine 1
• This faster onset reduces the risk of dose stacking that occurs with morphine's longer onset 1
• Morphine's longer onset places patients at higher risk for toxicity and hypoventilation when doses are stacked 1

Metabolism and Safety Profile

• Both drugs are mu-opioid receptor agonists with similar mechanisms of action 3
• Hydromorphone may be safer in renal failure due to morphine's greater risk of toxic metabolite accumulation 1
• Hydromorphone is a semi-synthetic congener of morphine with no major differences in efficacy when used in equianalgesic doses 1

Clinical Efficacy

Acute Pain Management

• For acute severe pain in the emergency department, hydromorphone (0.015 mg/kg IV) is recommended as comparable or potentially superior to morphine (0.1 mg/kg IV) (strong recommendation, moderate quality evidence) 1
• Meta-analysis of 8 studies (1,004 patients) showed hydromorphone provides slightly better clinical analgesia than morphine (p=0.012), though the effect size was small 4
• The analgesic advantage was more evident in higher quality studies 4

Chronic Cancer Pain

• Hydromorphone and morphine show no major differences in efficacy or adverse effects for cancer pain when dosed equianalgesically 1
• Both are effective alternatives, with hydromorphone being 5-10 times more potent orally 1
• For intrathecal delivery in refractory cancer pain, hydromorphone is noninferior to morphine for pain relief 5
• Hydromorphone doses tended to decrease over time while morphine doses increased, suggesting better long-term dose stability with hydromorphone 5

Adverse Effect Profile

Comparative Side Effects

• Side effects are generally similar between the two drugs when used in equianalgesic doses 1
• No significant differences in nausea (p=0.383), vomiting (p=0.306), or itching (p=0.249) across multiple studies 4
• Some evidence suggests hydromorphone may cause less pruritus, sedation, nausea and vomiting than morphine 2

Clinical Outcomes

• Rescue drugs are used more frequently with hydromorphone compared to morphine (p<0.01) 6
• Patients receiving hydromorphone had shorter hospital stays (approximately one day less) 6
• However, 30-day readmission rates were significantly higher with hydromorphone (p<0.01), suggesting potential implications for long-term management 6

Practical Considerations

Cost and Availability

• Hydromorphone is comparable in cost to morphine 1
• Both drugs are widely available in multiple formulations (oral, IV, subcutaneous) 1

Route-Specific Advantages

• For parenteral administration, hydromorphone is more soluble than morphine, allowing smaller volume injections 1
• The oral-to-parenteral conversion ratio is 1:2 to 1:3 for both drugs 1

When to Choose Hydromorphone Over Morphine

• Acute severe pain requiring rapid onset 1
• Patients with renal impairment (reduced risk of toxic metabolite accumulation) 1
• Situations where dose-stacking risk is high (faster onset reduces this risk) 1
• When smaller injection volumes are needed (higher solubility) 1
• Patients who develop intolerable CNS toxicity with morphine 1