How is morphine administered for analgesia?

How Morphine is Administered for Analgesia

Primary Route of Administration

The optimal route for morphine administration is oral, using immediate-release formulations for dose titration and controlled-release formulations for maintenance treatment. 1

Oral Administration Strategy

Initial Dose Titration

• Start with immediate-release morphine given every 4 hours, with the same dose available for breakthrough pain 1
• The rescue dose may be given as frequently as every hour if needed 1
• Adjust the total daily dose based on how many rescue doses were required in the previous 24 hours 1
• If pain consistently returns before the next scheduled dose, increase the regular dose 1

Maintenance Treatment

• Once pain is controlled, transition to controlled-release formulations for convenience 1
• Controlled-release morphine is typically given every 12 hours, though every 8-hour dosing may occasionally be necessary 1
• For patients on immediate-release morphine every 4 hours, give a double dose at bedtime to prevent nocturnal pain awakening 1

Critical Safety Warning

• Never crush controlled-release morphine tablets, as this destroys the extended-release mechanism and can cause dose dumping, leading to respiratory depression, overdose, and death 2
• Controlled-release tablets should not be used for rectal or vaginal administration 1

Alternative Routes When Oral Administration is Not Possible

Preferred Alternatives

If patients cannot take oral medications, the preferred alternative routes are subcutaneous and rectal 1, 2

Rectal Administration

• The bioavailability and duration of analgesia are identical to oral administration 1
• The potency ratio of oral to rectal morphine is 1:1 (use the same dose) 1
• Only use immediate-release formulations rectally, never controlled-release tablets 1

Subcutaneous Administration

• Morphine can be given subcutaneously either as bolus injections every 4 hours or by continuous infusion 1, 3
• The potency ratio of oral to subcutaneous morphine is approximately 1:2 (subcutaneous dose should be half the oral dose) 1, 3
• For breakthrough pain, use the same dose as the regular 4-hourly dose, available as often as every hour 3
• A double dose at bedtime prevents nocturnal pain awakening 3

Contraindications to Subcutaneous Administration

Subcutaneous morphine may not be practical in patients with: 1, 3

• Generalized edema, soreness, or sterile abscesses
• Erythema at injection sites
• Coagulation disorders
• Very poor peripheral circulation

Intravenous Administration

• The potency ratio of oral to intravenous morphine is approximately 1:3 (intravenous dose should be one-third the oral dose) 1
• Intravenous administration is preferred when immediate-release oral formulations are unavailable and treatment must be started with controlled-release morphine 1
• For breakthrough pain, an intravenous dose equal to one-fifth of the calculated equianalgesic total daily dose provides rapid relief (typically within 17 minutes) 4
• Intravenous morphine is particularly useful for severe breakthrough pain requiring rapid onset of analgesia 5

Intramuscular Administration

• There is generally no indication for intramuscular morphine in chronic cancer pain, as subcutaneous administration is simpler and less painful 1, 3

Routes NOT Recommended

Buccal, sublingual, and nebulized routes are not recommended, as there is no evidence of clinical advantage over conventional routes 1

Special Considerations

Alternative Opioids for Parenteral Use

• Other opioids may be preferred for parenteral administration due to greater solubility: diamorphine in Britain and hydromorphone elsewhere 1

Neuraxial Administration

• For the 20% of patients who do not achieve adequate pain control with standard routes, consider spinal administration of opioids alone or combined with local anesthetics 1
• The optimal single-shot intrathecal dose is 0.075-0.15 mg, and the ideal single-shot epidural dose is 2.5-3.75 mg 6

Pharmacokinetic Considerations

• Oral bioavailability of morphine is less than 40% with large inter-individual variability due to extensive first-pass metabolism 7
• Maximum analgesic effect occurs approximately 60 minutes after oral administration 7
• Food does not significantly affect absorption, though it may slightly delay time to peak concentration 7