Use of Sustained-Release Morphine
34. A.J.'s pain was controlled on 40 mg of morphine solution orally every 3 hours, but he is now complaining of the frequency of the morphine dose. He wishes to have the therapy changed to allow fewer daily doses so that he may have longer periods of rest. What can be done about A.J.'s request?
Several controlled release opioid formulations are available for this patient. Morphine is available in four different formulations: MS Contin, Oramorph SR, Kadian, and Avinza. Oxycodone is also available as extended release tablet (OxyContin). Pharmacokinetic profiles differ among formulations of which clinicians need to be aware. Avinza and Kadian provide 24-hour sustained release of morphine, which leads to less fluctuation in drug levels, and therefore less frequent dosing. Avinza is always dosed once daily, whereas Kadian can be given once or twice a day. MS Contin, Oramorph SR, and OxyContin are usually dosed twice daily, whereas some patient may require doses three times a day. Whenever converting patients from one sustained-release (SR) product to a short-acting opioid, it is important to remember that SR formulations (e.g., Kadian and Avinza) will deliver morphine up to 36 hours from the last dose. This warrants intensive monitoring, especially in patients who received high doses for long periods of time.
These opioid formulations have been a target of misuse and abuse. When altering its delivery system, daily drug supply can be released immediately, potentially causing overdose and death. It is important to remember that sustained release formulations should not be crushed and chewed. Kadian and Avinza capsules can be opened and sprinkled over applesauce; however, the integrity of the beads must not be altered.
A.J.'s daily morphine requirement of 320 mg can be provided by use of an SR dosage form given every 8 to 12 hours. However, direct conversion of doses from oral morphine solutions or other immediate-release dosage forms to SR tablets often leads to oversedation initially, particularly during the first hours of the dosing period. Therefore, the SR dose should be reduced by 25% to 240 mg/day (320 mg × 75%) for A.J. This can be given as 90 mg every 8 hours or as 120 mg every 12 hours. SR morphine is available as 15-, 30-, 60-, 100-, and 200-mg tablets and 20-, 50-, and 100-mg capsules. When starting a patient on oral SR preparations, it often is desirable to try an every-8-hour regimen to prevent the initial sedation that often is associated with the larger individual doses of the 12-hour regimen. Likewise, when larger doses are needed, 8-hour dosing intervals usually cause less sedation than 12-hour intervals (i.e., during the first 2 hours of the dosing period). Some patients also may have more breakthrough pain at the end of the 12-hour dosing interval. Careful assessment of the patient's response and toxicity by the clinician is the most essential ingredient between success and failure with either product in managing the patient's pain.
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