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Background. The short elimination half‐life of hydromorphone necessitates 4‐hourly dosing to maintain optimal levels of analgesia in patients with chronic cancer pain. The purpose of this study was to compare the clinical efficacy and safety of controlled release hydromorphone administered every 12 hours and immediate release hydromorphone administered every 4 hours in patients with chronic severe cancer pain. Methods. Forty‐eight patients with stable chronic severe cancer pain were randomized, in a double‐masked crossover study, to controlled release hydromorphone every 12 hours or immediate release hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments were made by the patient four times a day at 7: 00 a. m., 11: 00 a. m., 3: 00 p. m., and 7: 00 p. m. Use of rescue hydromorphone also was recorded by the patient. Results. Forty‐five patients completed the study (26 women, 19 men; mean age, 57.1 ± 13.6 years) and received a mean daily dose of 76 ± 133 mg (range, 6‐768 mg). There were no significant differences between controlled release hydromorphone and immediate release hydromorphone in overall VAS pain intensity scores (19 ± 14 vs. 20 ± 14 mm), ordinal pain intensity scores (1.2 ± 0.8 vs. 1.2 ± 0.8) and pain scores by day of treatment or time of day. The daily rescue analgesic consumption during controlled release hydromorphone and immediate release hydromorphone did not differ significantly overall (1.1 ± 1.1 vs. 1.0 ± 1.1 doses per day) or with respect to time of day. There were no significant differences in overall VAS sedation scores (18 ± 18 mm vs. 19 ± 18 mm) and in overall mean VAS nausea scores (12 ± 15 mm vs. 11 ± 14 mm) between controlled release hydromorphone and immediate release hydromorphone. Conclusion. Controlled release hydromorphone administered every 12 hours is as effective as immediate release hydromorphone administered every 4 hours in the management of patients with chronic severe cancer pain. The benefits of controlled release hydromorphone lie in the convenience of its capsule formulation, which can be sprinkled on soft food, and its 12‐hour duration of action, which allows patients uninterrupted sleep and improved compliance.

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Steady‐State Pharmacokinetics of Hydromorphone and Hydromorphone‐3‐Glucuronide in Cancer Patients After Immediate and Controlled‐Release Hydromorphone

Hagen

Thirlwell

Dhaliwal

et al. 1995

The Journal of Clinical Pharma

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Although the pharmacokinetics of oral hydromorphone has been evaluated in healthy volunteers after small single oral doses, data are not available regarding the disposition of hydromorphone and its principal metabolite, hydromorphone-3-glucuronide (H3G), at steady-state and after large oral doses. The authors studied the pharmacokinetics of hydromorphone and H3G after oral administration of an immediate-release (IR) and controlled-release (CR) formulation of hydromorphone at a daily dose of 48 +/- 11 mg (range 6-216 mg) in a randomized, double-blind, steady-state, two-way crossover evaluation in 18 patients with chronic cancer pain. Controlled-release hydromorphone demonstrated equivalent bioavailability and acceptable CR characteristics, when compared with IR hydromorphone (CR vs. IR: AUC0-12 123.10 +/- 20.38 vs. 118.98 +/- 20.92 ng.hr.mL-1, P = NS, Cmax 17.76 +/- 3.07 vs. 19.70 +/- 4.04 ng.mL-1, P = NS, Cmin 6.04 +/- 1.01 vs. 5.28 +/- 1.000 ng.mL-1, P = NS, and Tmax 4.78 +/- 0.78 vs. 1.47 +/- 0.22 hr, P = 0.0008). A significant linear relationship existed between hydromorphone dose and hydromorphone AUC (r = 0.8315, P = 0.0001) and between hydromorphone AUC and H3G AUC (r = 0.8048, P = 0.0001) over a wide dose range. The steady-state molar ratio of H3G to hydromorphone was 27:1. The authors conclude that CR hydromorphone provides a pharmacokinetic profile consistent with 12 hourly dosing and that at steady state, oral hydromorphone is extensively metabolized to H3G, although the pharmacologic activity of this metabolite remains unknown.

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Cited by 13 publications

References 35 publications

Management of Cancer Pain

Management of Cancer Pain

Comparative clinical efficacy and safety of immediate release and controlled release hydromorphone for chronic severe cancer pain

Steady‐State Pharmacokinetics of Hydromorphone and Hydromorphone‐3‐Glucuronide in Cancer Patients After Immediate and Controlled‐Release Hydromorphone

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