Controlled release formulation of oxycodone in patients with moderate to severe chronic osteoarthritis: a critical review of the literature

Figures & data

Table 1 Studies assessing safety and efficacy of oxycodone controlled release in patients with osteoarthritis

Year	Author	Duration (months)	N	Trial	Other analgesics allowed	Dose	Pain	Quality of life indicators	Discontinuations	AEs
Placebo-controlled trials
2000	Roth et al^Citation42	12	133	R, DB	Yes	10 mg every 12 hours, 20 mg every 12 hours	Oxycodone CR group Daily mean pain intensity ↓ by ≥20% at weeks one and two (four-point scale)	Oxycodone CR group Significantly improved mood, sleep, enjoyment of life, walking ability, general activity, normal work, relationships with others	Oxycodone CR group IET = 17 (19.3%) AEs = 26 (29.5%) Placebo IET = 22 AE = 2	AEs were typical opioid related. Top three AEs: constipation, nausea, somnolence
2005	Markenson et al^Citation43	3	170	R, DB	Yes	10 mg every 12 hours	Oxycodone versus placebo BPI pain intensity ↓ (5.1 ± 0.3 versus 6.0 ± 0.3; P = 0.042) WOMAC scores for pain, stiffness, and physical function significantly ↓ at 30 and 60 days. 38% versus 17.6% achieved 30% ↓ in pain. 20% versus 5.9% achieved 50% ↓ in pain	Oxycodone versus placebo BPI interference of pain scales for general activity, mood, walking ability, normal work, relations with people, sleep, and enjoyment of life significantly ↓	Oxycodone CR Group IET = 9 (16%) AEs = 20 (36%) Placebo IET = 34 (67%) AE = 2 (4%)	AEs were typical opioid related. Top three AEs: constipation, nausea, somnolence
Oxymorphone versus oxycodone
2005	Matsumoto^Citation45	1	491	R, DB, A	No	Oxymorphone ER 20 mg every 12 hours, 40 mg every 12 hours Oxycodone CR 20 mg every 12 hours	API VAS ↓ significantly for oxymorphone groups at 3 weeks and 4 weeks, trended towards significance for oxycodone group WOMAC scores for pain, physical function, and stiffness significantly ↓ in oxymorphone groups versus placebo, no significant change in oxycodone versus placebo	Oxymorphone ER superior to placebo for Patient Global Assessment, oxycodone CR was not. Oxymorphone improved quality of life with physical and mental aspects, oxycodone improved only mental. Both improved sleep	Oxymorphone IET = 14 (5.8%) AEs = 103 (43%) Oxycodone IET = 13 (10.4%) AEs = 31 (24.8%) Placebo IET = 34 (27.4%) AEs = 6 (4.8%)	At least one AE was reported for 404 patients (83%) who received study medication: 91% in the oxymorphone ER 40 mg group 95% in the oxymorphone ER 20 mg group 88% in the oxycodone CR 20 mg group 57% in the placebo group. Frequent AEs typical of opioids
Hydromorphone versus oxycodone
2007	Hale et al^Citation46	1.5	138	R, OL	Not described	Oxycodone Initial dose 10 mg every 12 hours ↑ to 80 mg every 12 hours Hydromorphone 8 mg every 24 hours up to 64 mg every 24 hours	Hydromorphone versus oxycodone Mean pain relief score of 2.3 versus 2.3 (95% CI −0.30 to ∞) Mean time to the third day of moderate to complete pain relief was 6.2 versus 5.5 days (95% CI −0.31 to ∞). Mean (SD) changes in pain intensity was −0.6 (0.80) versus −0.4 (1.15) Mean changes in WOMAC pain scale was −2.1 (1.96) versus −2.0 (2.03)	Patient/investigator global evaluations similar. Overall effectiveness of treatment rated as good, very good, or excellent by 67.2% (43/64) of patients in the OROS^® hydromorphone group and 66.7% (40/60) of patients in the ER oxycodone group. Medical Outcomes Study Sleep Problems Index I indicated significantly less sleep disruption and daytime somnolence in hydromorphone versus oxycodone	Hydromorphone IET = 1/28 AEs = 25/28 Oxycodone IET = 3/27 AEs = 22/27	Treatment-emergent AEs 78.9% versus 79.1% AEs typical of opioid treatment
Tapentadol versus oxycodone
2010	Afilalo et al^Citation48	3	1030	R, DB, A, Placebo	No	Tapentadol ER twice daily (100–250 mg) Oxycodone CR twice daily (20–50 mg)	Tapentadol ER Significantly ↓ average pain intensity versus placebo Mean difference of −0.7 (95% CI −1.04 to −0.33) and throughout the maintenance period (−0.7 [−1.00 to −0.33]). Oxycodone CR Significantly ↓ average pain intensity from baseline throughout the maintenance period versus placebo mean difference −0.3 [95% CI −0.67 to −0.00], but not at week twelve Tapentadol ER versus placebo Significantly ↑ percentage of patients achieving 50% reduction in average pain intensity (32.0% [110/344] versus 24.3% [82/337]; P = 0.027). Oxycodone CR versus placebo Percentage of patients achieving 50% reduction in average pain intensity (17.3% [59/342] versus 24.3% [82/337]; P = 0.023)	Tapentadol ER versus placebo Statistically significant improvement on the SF-36 “physical functioning,” “role-physical,” “bodily pain,” and “physical component summary” subscale scores. Significant differences in favor of placebo versus oxycodone CR for changes from baseline to end of treatment in the SF-36 “role-physical,” “vitality,” “social functioning,” “role-emotional,” “mental health,” and “mental component summary” subscale scores	Tapentadol IET = 15/163 AEs = 61/163 Oxycodone IET = 7/224 AEs = 140/224	Treatment-emergent AEs Placebo: 61.1% (206/337) Tapentadol ER: 75.9% (261/344) Oxycodone CR: 87.4% (299/342) Frequent AEs typical of opioid treatment. Constipation and nausea/vomiting significantly ↓ in tapentadol. ER group versus oxycodone CR
2010	Wild et al^Citation49	12	1117	R, OL, A	No	Tapentadol ER twice daily (100–250 mg) Oxycodone CR twice daily (20–50 mg)	Tapentadol versus oxycodone Baseline mean (SE) pain intensity scores 7.6 (0.05) versus 7.6 (0.11) At endpoint, mean pain intensity (SE) ↓ to 4.4 (0.09) versus 4.5 (0.17)	Tapentadol versus oxycodone Global assessment of excellent, very good, or good were reported by patients (75.1% versus 72.3%) and investigators (77.3% versus 72.3%)	Tapentadol IET = 72 (8.1%) AEs = 203 (22.7%) Oxycodone IET = 7 (3.1%) AEs = 82 (36.8%)	85.7% (766/894) versus 90.6% (202/223) experienced at least one treatment-emergent AE. Frequent AEs typical of opioid treatment Incidences (tapentadol versus oxycodone) Constipation: 22.6% versus 38.6% Nausea: 18.1% versus 33.2% Vomiting: 7.0% versus 13.5% Pruritus: 5.4% versus 10.3% Dizziness: 14.8% versus 19.3%
Open label trials
2011	Friedman^Citation51	12	823	OL	Yes	5–80 mg every 12 hours	Pain intensity scores significantly ↓ compared to baseline (P ≤ 0.001) Mean (SD) change in pain intensity scores at month six was −2.0 (2.6) and at month twelve was −2.1 (2.7; P ≤ 0.001)	Quality of analgesia was rated as good, very good, or excellent at months six and twelve by 61% and 64% of patients. Study drug was rated as good, very good, or excellent by 60% and 61% of patients	IET = 15/443 AEs = 173/443	678/823 (82%) experienced at least one AE Frequent AEs typical of opioid treatment

Abbreviations: A, active controlled; AE, adverse event; API, Arthritis Pain Inventory; BPI, Brief Pain Inventory; CI, confidence interval; DB, double-blind; IET, ineffective treatment; OL, open label; R, randomized; SD, standard deviation; SE, standard error; VAS, Visual Analog Scale; WOMAC, Western Ontario and McMaster University Osteoarthritis Index.

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