Can immediate-release (IR) morphine be given every four hours to a patient with chronic pain who is already on long-acting morphine?

Immediate-Release Morphine for Breakthrough Pain in Patients on Long-Acting Morphine

Yes, immediate-release (IR) morphine should be given every 4 hours as scheduled dosing for patients on long-acting morphine, with additional rescue doses available as frequently as every hour for breakthrough pain episodes. 1

Recommended Dosing Strategy

Scheduled IR Morphine Dosing

• Administer IR morphine every 4 hours around-the-clock as the basal regimen, even when patients are being maintained on this schedule long-term 1
• The every-4-hour interval is the standard for IR morphine and should not be increased in frequency—instead, increase the dose if pain returns before the next scheduled administration 1

Breakthrough Pain (Rescue Dose) Management

• Prescribe rescue doses of IR morphine that equal 10% of the total daily opioid dose (or approximately one-sixth of the regular 4-hourly dose for patients on IR morphine every 4 hours) 1
• Rescue doses can be administered as frequently as every hour when needed for breakthrough pain episodes 1
• For patients stabilized on 12-hourly controlled-release morphine, the appropriate rescue dose is one-third of the regular 12-hour dose (equivalent to the 4-hourly dose) 1

Dose Titration Based on Rescue Use

• Adjust the total daily dose daily based on the number of rescue doses required in the previous 24 hours 1, 2
• If pain consistently returns before the next scheduled dose, increase the regular dose rather than shortening the dosing interval 1

Transition Between IR and Long-Acting Formulations

Converting from IR to Extended-Release

• The same total daily amount of morphine is available from IR tablets and extended-release formulations 3
• Exercise caution when converting from IR to extended-release morphine because the extended duration of release results in reduced peak and increased minimum plasma concentrations, which could lead to excessive sedation at peak levels 3
• Close observation for signs of excessive sedation and respiratory depression is mandatory during conversion 3

Maintaining Both Formulations Simultaneously

• Patients on long-acting morphine should continue to have IR morphine available for breakthrough pain 1
• This is standard practice—the long-acting formulation provides baseline analgesia while IR morphine addresses episodic pain exacerbations 1

Clinical Considerations and Monitoring

Bedtime Dosing Strategy

• For patients on IR morphine every 4 hours, give a double dose at bedtime to avoid being woken by pain during the night 1
• This practice is widely adopted and effective without causing problems 1

Monitoring Requirements

• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy or following dose increases 3
• Daily self-assessment or assessment by a healthcare professional is necessary during initial titration to judge analgesic efficacy and detect side effects 1

Renal Impairment Precautions

• Use all opioids with caution at reduced doses and frequency in patients with renal impairment 1
• Morphine-6-glucuronide (active metabolite) accumulates in renal insufficiency and can worsen adverse effects 4
• Consider fentanyl or buprenorphine (transdermal or IV) as safer alternatives in chronic kidney disease stages 4-5 (eGFR <30 mL/min) 1

Common Pitfalls to Avoid

• Do not withhold rescue doses out of fear of excessive opioid use—patients can safely take rescue doses as often as hourly if needed, and this information guides appropriate dose escalation 1
• Do not crush controlled-release tablets for any route of administration, including rectal 1, 5
• Do not use intramuscular administration for chronic cancer pain—subcutaneous is simpler and less painful 1
• Do not abruptly discontinue morphine in opioid-dependent patients, as this can cause serious withdrawal symptoms, uncontrolled pain, and dangerous behaviors 3

Side Effect Management

• Routinely prescribe laxatives for both prophylaxis and management of opioid-induced constipation 1
• Use metoclopramide or antidopaminergic drugs for opioid-related nausea/vomiting 1
• Drowsiness typically occurs during titration and usually resolves within days; if persistent, consider metabolic disorders, drug interactions, or dose reduction 1