Long-Acting Oral Opioids (MS Contin™, Oxycontin™)


Example of long-acting oral opioids:

  • Morphine Extended-Release (i.e MS Contin™ tablets)
  • Oxycodone Extended-Release (i.e Oxycontin™ tablets)

Other long-acting opioids such as methadone and buprenorphine, as well as fentanyl patches will be discussed separately

Mechanism of action: 

  • Analgesia: Mediated by μ, δ, and κ- opioid receptors typically causing a net inhibitory effect on nociceptive processing in supraspinal pathways and the spinal dorsal horn (1)
  • Decreases sympathetic activity which may contribute to hemodynamic changes.
Clinical Use: 
  • Indication(s): reserved for severe non-acute, chronic pain (i.e active cancer treatment, palliative care) where long-term opioid treatment is anticipated and alternative treatment options are inadequate. Initiated in patients transitioning from daily, around-the-clock instant release (IR) opioids.
  • Limitations of use: 
    • Not indicated for acute or perioperative pain 
    • Not indicated for as-needed (prn) analgesic
    • Not for pain not expected to persist for an extended duration 
    • Not for opioid-naive patients


  • Dosing: Determine the patient’s daily opioid requirement with IR formulations, calculate the oral morphine equivalent, and convert to the ER formulation of choice. Dose reduce by one-third (1/3) to one-half (1/2) of the usual starting dose. Dose adjustments are typically made as frequently as every 1 to 2 days.
  • Onset of analgesia: PO - variable, however generally ~1-2 hours (2)
  • Duration of analgesia: assuming normal kidney/liver function Morphine ER ~8-12hrs; oxycodone ER <12 hrs (3)



  • Significant respiratory depression
  • Acute or severe asthma in an unmonitored setting or absence of resuscitation equipment
  • Known or suspected paralytic ileus
  • Hypersensitivity (e.g. anaphylaxis)
  • Morphine ER - concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days
  • Severe renal impairment (see special considerations)
Special Considerations: 
  • Long-acting opioids: 
    • Risk for overdose and death is twice for long-acting vs short-acting (4) 
  • Oxycontin
    • Kidney disease:
      • CrCl 30-60 mL/min: Administer 50% to 75% of usual dose every 12 to 24 hours
      • CrCl < 30 mL/min: avoid in patient with severe renal impairment
    • Liver disease: Administer 33% to 50% of the calculated recommended dose. 
    • Pediatrics: limit use to opioid-tolerant pediatric patients > 11 years old, who are receiving opioids for a minimum of 1 week, at least tolerate a minimum daily opioid dose of 20mg oxycodone IR or its equivalent. Always consider dose reduction by one-third to one-half of the calculated starting dose, especially when patient is receiving a concomitant CNS depressant. 
    • Breastfeeding: Not recommended during treatment
  • MS Contin:
    • Kidney disease: avoid ER formulations in altered kidney function 
    • Liver disease: No dosing adjustment required
    • Pediatrics: The safety and effectiveness in pediatric patients below the age of 18 have not been established (5)
    • Breastfeeding: Not recommended during treatment
    • Drug interactions: P-gp inhibitors (e.g. quinidine) may increase the absorption/exposure by 2 fold 

Zöllner C, Stein C. Opioids. Handb Exp Pharmacol. 2007;(177):31-63

Stoelting RK. Pharmacology, Physiology and Anesthetic Practice. 2nd ed. Baltimore, MD: Lippincott Williams and Wilkins; 1991.

Sadiq NM, Dice TJ, Mead T. Oxycodone. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482226/

Miller M, Barber CW, Leatherman S, et al. Prescription Opioid Duration of Action and the Risk of Unintentional Overdose Among Patients Receiving Opioid Therapy. JAMA Intern Med. 2015;175(4):608–615.