Efficacy and tolerability of low-dose oral prolonged-release oxycodone/naloxone for chronic nononcological pain in older patients

Figures & data

Figure 1 Patient disposition.

Table 1 Demographic and baseline characteristics of the study population

Parameter	Value
N	53
Age, years (median; range)	81.8±5.7 (83; 70–94)
Patients >80 years, n (%)	37 (69.8%)
Females/males, n (%)	44/9 (83.0/17.0)
Pain intensity, mean NRS score*	6.7±1.2
Pain intensity at rest, NRS score	5.9±1.9
Pain intensity on movement, NRS score	8.0±0.9
Daytime pain intensity, NRS score	7.5±1.0
Nocturnal pain intensity, NRS score	5.4±2.1
Previous analgesic treatment, n (%)
Step I WHO drugs
NSAIDs	6 (11.3)
Paracetamol	36 (67.9)
Daily dosage, mg (mean)	1,796±857 mg
Step II WHO drugs	20 (37.7)
Codeine†	3 (5.6)
Daily dosage, mg (mean)	60±0
Tramadol	17 (32.0)
Daily dosage, mg (mean)	129.7±52.6
Rescue analgesics, n (%)	46 (86.8)
Cognitive state, MMSE score (median)	25.8±2.6 (26)
Daily functioning, Barthel score (median)	53.3±14.1 (55)
Bowel function, BFI score (median)	36.4±20.0 (40)

Notes: All values are expressed as numbers (percent) or mean (± standard deviation) if not otherwise reported. The sum of percentages may not equal 100, due to rounding.

* Expressed as mean of assessments for all four items (pain at rest, on movement, daytime, and nocturnal).

† At the time of this observation, available only in combination with paracetamol (30/500 mg each) without temporal limitations (currently <72 hours).

Abbreviations: BFI, Bowel Function Index; MMSE, Mini-Mental State Examination; NRS, Numeric Rating Scale; NSAIDs, nonsteroidal anti-inflammatory drugs; WHO, World Health Organization.

Figure 2 Distribution of prolonged-release oxycodone–naloxone (OXN-PR) daily dosages throughout the observation (expressed in oxycodone-equivalents). The 15 mg daily dosage was two 5/2.5 mg tablets in the morning and one in the evening, or vice versa, according to individual need and pain characteristics (three patients at day 7 [T7], one at day 14 [T14], and one at day 28 [T28]). There were two women (aged 75 and 80 years) who, after a few days of the new treatment, reduced their OXN-PR daily doses to only one 5/2.5 mg tablet in the morning because of drowsiness; in the following weeks, both increased their OXN-PR daily dose to 20/10 mg without major side effects. Two other women with severe knee pain due to osteoarthritis at the last follow-up visit had decreased their daily OXN-PR to one 5/2.5 mg tablet in the morning, nevertheless with satisfactory pain control.

Table 2 Change in pain intensity (Numeric Rating Scale score) during the 28-day observation of oxycodone/naloxone prolonged-release treatment

Parameter	Baseline	Day 7	Day 14	Day 28	Analysis of variance P-value*
Pain at rest, mean	5.9±1.9	4.6±1.6†	3.9±1.8	2.9±1.7#	<0.0001
Pain on movement, mean	8.0±0.9	6.3±1.6¶	5.3±1.9#	4.3±2.0#	<0.0001
Daytime pain, mean	7.5±1.0	5.9±1.7¶	5.0±2.1	3.9±2.3†	<0.0001
Nocturnal pain, mean	5.4±2.1	4.2±2.0#	3.5±2.1	2.5±1.9^	<0.0001

Notes: Included in this analysis were all patients completing the 28-day treatment (n=52).

* Day 28 vs baseline

^ P<0.01 vs previous observation

# P<0.01 vs previous observation

† P<0.005 vs previous observation

¶ P<0.0001 vs previous observation.

Figure 3 “Waterfall” image of ultimate individual variations in pain severity (last 7 days mean values, Numeric Rating Scale) at the end of observation after 4 weeks of treatment with prolonged-release oxycodone–naloxone among the 52 patients who completed the observation: percentage changes from baseline values are reported. Below the dashed line indicates analgesic efficacy (≥30% decrease in mean Numeric Rating Scale).

Figure 4 Proportions of patients with severe (Numeric Rating Scale [NRS] 7–10), moderate (NRS 4–6), mild (NRS 1–3), or no pain (NRS 0) at baseline and throughout the observation on prolonged-release oxycodone–naloxone (OXN-PR) (baseline: n=53; day 7 [T7], day 14 [T14], and day 28 [T28]: n=52). Four patients still complained of severe pain (mean NRS >6) after 28 days on OXN-PR. Three of them were on 20/10 mg OXN-PR daily and preferred not to further increase their daily dosage because of fear of increasing other symptoms potentially related to opioid (drowsiness in one, dry mouth in two). Another 85-year-old woman with severe osteoarthritic pain reported only modest analgesic benefit at the end of the 4-week observation on OXN-PR 10/5 mg daily. OXN-PR was deliberately not increased by her physician because of her unstable gait and history of falls.

Figure 5 Mean individual domain scores for pain-related functional impairment (measured by Numeric Rating Scale [NRS]) at baseline and at day 7 (T7), day 14 (T14), and day 28 (T28) of treatment with prolonged-release oxycodone–naloxone.

Figure 6 Constipation severity throughout the study, as assessed by Bowel Function Index (mean values ± standard deviation).

Abbreviation: NS, variations not significantly different.

Figure 7 Proportions of patients affected by disorders commonly related to opioids and their severity at different time points of the observation. Symptom severity rated on an eleven-point scale (0=absent; 1–3=mild; 4–6=moderate, 7–10=severe). All differences in frequency distributions were not significant (corresponding P-values >0.0083 at all times).