What are the typical dosing regimens for morphine (opioid analgesic) and hydromorphone (opioid analgesic)?

Morphine and Hydromorphone Dosing Regimens

For morphine, start opioid-naïve patients at 5-10 mg orally every 4 hours with the same dose available for breakthrough pain, and for hydromorphone, start at 2-4 mg orally every 4-6 hours. 1, 2

Morphine Initial Dosing

Opioid-Naïve Patients

• Start with 5 mg orally every 4 hours if transitioning directly from non-opioids (skipping WHO Step 2) 1
• Use 10 mg orally every 4 hours if converting from a Step 2 opioid (codeine, tramadol) 1
• FDA labeling supports 15-30 mg every 4 hours as needed, though this represents a more aggressive starting approach 3

Dose Titration Strategy

• Use immediate-release (normal release) morphine during titration, not extended-release formulations 1
• Immediate-release morphine peaks within 1 hour and lasts approximately 4 hours, allowing rapid assessment of efficacy 1
• Provide the full 4-hourly dose as "rescue" medication for breakthrough pain, available every 1-2 hours orally 1
• Review total daily morphine consumption (scheduled plus rescue doses) every 24 hours and adjust the regular dose accordingly 1
• Steady state is achieved within 24 hours due to morphine's 2-4 hour half-life 1

Conversion to Extended-Release Formulations

• Once pain is stable, convert to extended-release morphine using the same total daily dose divided into 12-hourly or 24-hourly dosing 1
• Continue providing immediate-release morphine (10-20% of total daily dose) for breakthrough pain 4
• A minority of patients may require 8-hourly dosing of 12-hour formulations if duration proves inadequate 1

Parenteral to Oral Conversion

• Use a 3:1 to 6:1 oral-to-parenteral ratio, with 3 mg oral morphine typically equivalent to 1 mg parenteral morphine 3

Hydromorphone Initial Dosing

Starting Doses

• Initiate at 2-4 mg orally every 4-6 hours in opioid-naïve or minimally opioid-exposed patients 2
• For patients already on opioids, calculate equianalgesic dose and reduce by 25-50% to account for incomplete cross-tolerance 5
• In acute severe pain requiring IV administration, use 0.015 mg/kg (approximately 1-1.5 mg for average adults) 5

Breakthrough Pain Dosing

• Provide 10-20% of the total 24-hour hydromorphone dose as the breakthrough dose 5
• For a patient on 0.5 mg QID (2 mg daily total), breakthrough doses of 0.2-0.4 mg are appropriate 5
• Assess efficacy every 60 minutes for oral hydromorphone 5
• For IV hydromorphone, bolus doses should be available every 15 minutes 5

Continuous Infusion Management

• If breakthrough pain occurs during continuous infusion, give a bolus equal to or double the hourly infusion rate 5
• If two bolus doses are required within one hour, double the infusion rate 5

Dose Titration

• If more than 3 breakthrough doses per day are needed, increase the scheduled dose 5
• Hydromorphone has a quicker onset (approximately 5 minutes IV) compared to morphine (6 minutes IV), making it advantageous for acute pain 5, 6
• Duration of action is approximately 120 minutes 6

Morphine-Hydromorphone Conversion

Conversion Ratios

• For IV morphine to IV hydromorphone: use a 5:1 ratio (10 mg IV morphine = 2 mg IV hydromorphone) 1, 5
• For oral-to-oral conversion: use approximately 5:1 (oral morphine to oral hydromorphone) 1
• When rotating FROM morphine TO hydromorphone, use a 5:1 ratio 7
• When rotating FROM hydromorphone TO morphine, use a more conservative 3.7:1 ratio 7

This directional difference reflects incomplete cross-tolerance—the opioid being rotated TO appears more potent than standard equianalgesic tables suggest 7

Conversion Process

• Calculate the 24-hour total of the current opioid 1
• Apply the conversion ratio, then reduce by 25-50% if pain is well-controlled to account for incomplete cross-tolerance 1, 5
• If pain control was inadequate, use 100% of the calculated equianalgesic dose or increase by 25% 1

Oral to Subcutaneous Hydromorphone

• Divide total daily oral hydromorphone by 5 to get subcutaneous dose 8
• Example: 2 mg oral daily ÷ 5 = 0.4 mg subcutaneous daily, divided into 6 doses = 0.067 mg (round to 0.1 mg) every 4 hours 8

Special Populations

Renal Impairment

• Start with one-fourth to one-half the usual dose for both morphine and hydromorphone 5, 2
• Hydromorphone appears safer than morphine in renal failure, though active metabolites can still accumulate 5
• Morphine-3-glucuronide and hydromorphone-3-glucuronide accumulate in renal failure and cause neuroexcitatory effects (myoclonus, allodynia, seizures) 9

Hepatic Impairment

• Start with one-fourth to one-half the usual hydromorphone dose depending on severity 2

Critical Safety Considerations

Monitoring

• Monitor closely for respiratory depression, especially in the first 24-72 hours and after dose increases 3, 2
• Watch for myoclonus, particularly with chronic use, renal failure, or dehydration—if present, decrease dose or rotate to a structurally different opioid 5

Constipation Prevention

• Institute a stimulant or osmotic laxative in all patients on sustained opioid therapy unless contraindicated 5

Common Pitfalls

• Never use mixed agonist-antagonist opioids (pentazocine, nalbuphine, butorphanol) with morphine or hydromorphone—this precipitates withdrawal in opioid-dependent patients 5, 4
• Avoid using modified-release morphine for initial titration—the delayed peak (2-6 hours) and prolonged duration make dose adjustments inefficient 1
• Do not make dose adjustments more frequently than every 24 hours for immediate-release morphine or 48 hours for extended-release formulations 1