Ask the Expert: Rectally Administered Morphine
QUESTION: Can Sustained-release Morphine Tablets Be Administered Rectally?
ANSWER: Certain patients may not be able to tolerate oral morphine administration due to either intractable nausea or the inability to swallow. Although not an FDA-approved route of administration, a limited number of small studies have evaluated rectal administration of sustained-release morphine tablets.
Maloney et al reported on 39 terminally ill cancer patients who could no longer tolerate oral administration of MS Contin, either due to the inability to swallow, persistent nausea, or both. Patients were converted from oral morphine to rectal administration, with no initial change in dose. All patients maintained pain control by receiving unmodified MS Contin 30 mg tablets administered rectally (average dose: 6 tablets/d; range: 2 to 30 tablets). Patients were maintained on an every-12-hour, every-8-hour, or every-6-hour schedule and received the drug rectally for an average of 12 days (range: 1 to 30 days). Administration was assisted with a water-based lubricant, and doses that required more than one tablet were put into a gelatin capsule to allow for one-time administration. Eleven patients had their dose reduced after converting to rectal administration due to drowsiness. No patients required an increase in dosage, and there were no reports of local or systemic adverse reactions.1
Another study, an open-label crossover trial, evaluated the pharmacokinetics and efficacy of rectal versus oral administration of sustained-release morphine in 10 patients.2 Patients received their current oral dose (ranging from 20 to 220 mg) every 12 hours either by oral or rectal route, with 12 hours of blood monitoring performed after the fourth dose. The authors found no significant differences in the area under the curve (AUC) concentrations of the parent compound following oral or rectal administration (oral:rectal = 1.30, 95% CI 0.96-1.75). Oral AUCs were approximately double compared to rectal administration for the metabolites morphine-3-glucoronide (oral:rectal = 2.07, 95% CI 1.58-2.69) and morphine-6-glucoronide (oral:rectal = 2.10 95% CI 1.58-2.79). Peak morphine concentrations took longer following rectal administration (6.7 h, 95% CI 5.3-8.0 h) than oral administration (3.3 h, 95% CI 2.2-4.3 h). There were no significant differences between groups on visual analogue scales for pain or side effects. Rectal administration had a slower onset of action but lower first-pass metabolism. The authors concluded that rectal administration of sustained-release morphine tablets using the same oral dose and interval, adjusting as needed, is suitable when oral administration is not tolerated.2 As noted, although not FDA approved, rectal administration of morphine sustained-release tablets appears to be safe and effective at a 1:1 dose conversion from oral administration and 3:1 for rectal to/from parenteral in a limited number of studies. Administration with a water-based lubricant is recommended to aid in tablet dissolution. There may be patient variability with rectal administration and some patients may require a dosage reduction after converting from oral to rectal administration.1-4