A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

Figures & data

Table 1 MSN conversion guide and comparison with previously published equianalgesic data tables

	MSN conversion guide^Citation21	APS 5th ed.^Citation22	Gordon et al^Citation23	Sloan et al^Citation24	Levy^Citation25
Morphine	30 mg	30 mg	30 mg	–	–
Hydrocodone	30 mg	30 mg	30 mg	–	–
Hydromorphone	7.5 mg	7.5 mg	7.5 mg	–	–
Oxycodone	20 mg	20 mg	20–30 mg	–	–
Oxymorphone	15 mg	–	10 mg	15 mg (1:2 ratio of OM to morphine)	–
Methadone	10 mg	10 mg	3–5 mg	–	–
Trans fentanyl	12.5 µg/h = 300 µg/day	–	–	–	“µg/h dose of trans fentanyl equals one half of the mg/day dose of oral morphine”^Citation25 (ie, 12.5 µg/h patch is dosing unit closest to 15 µg/h)

Note: All conversions based on 30 mg morphine PO.

Abbreviations: APS, American Pain Society; MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; OM, oxymorphone; PO, per oral; Trans, transdermal.

Figure 1 Study flow diagram.

Notes: ^aIf a patient completes Visit 2e prior to day 42 but has not achieved a stable (effective) dose of MSN, titration visits could continue as unscheduled visits until day 42; ^bpatients who discontinued at any point in the study were to complete Visit 5 as the final visit.
Abbreviation: MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride.

Figure 2 Frequency (%) of patients achieving stable MSN dose by opioid type.

Note: Data are percent ±95% confidence interval.
Abbreviations: ER, extended-release; Excl, excluded; IR, immediate-release; MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; Trans, transdermal.

Figure 3 Number of days to reach stable MSN dose by prior opioid.

Note: Data are mean ± standard error.
Abbreviations: ER, extended-release; Excl, excluded; IR, immediate-release; MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; Trans, transdermal.

Figure 4 Number of steps to reach stable MSN dose by prior opioid.

Note: Data are mean ± standard error.
Abbreviations: ER, extended-release; Excl, excluded; IR, immediate-release; MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; Trans, transdermal.

Figure 5 Mean average pain score and mean MSN daily dose in (A) patients achieving a stable MSN dose, and in (B) patients who did not achieve a stable MSN dose.

Notes: Number of patients at each visit is not constant. Visits 2a to 2e, titration phase up to 6 weeks; Visits 2b to 2e were optional, used by subjects not on a stable dose at previous visit up to 6 weeks.
Abbreviations: MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; NA, not available.

Table 2 Brief Pain Inventory versus activity for patients at baseline (Visit 1) and patients who achieved a stable dose of MSN (Visit 3)

Activity category	Baseline Visit 1 (Safety population)		Visit 3 (Stable dose achievers)
	n	Mean (SD) score	n	Mean (SD) score
General activity	643	7.0 (2.3)	321	3.9 (2.5)
Mood	642	6.3 (2.7)	320	3.2 (2.5)
Walking ability	641	6.5 (2.8)	318	3.7 (2.7)
Normal work	637	7.2 (2.5)	320	4.0 (2.7)
Relationships with other people	644	5.4 (3.1)	319	2.6 (2.5)
Sleep	642	6.8 (2.7)	320	3.4 (2.9)
Enjoyment of life	640	7.0 (2.6)	319	3.4 (2.7)

Abbreviations: MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; SD, standard deviation.

Table 3 Number (%) of patients with treatment-emergent adverse events occurring in >5% of patients (safety population) from any prior opioid type

	TD fentanyl (n=77)	IR hydrocodone (n=164)	IR hydromorphone (n=22)	IR oxycodone (n=160)	IR morphine (n=53)	Methadone (n=64)	ER oxycodone (n=107)	ER oxymorphone (n=25)	Excluded opioid/unclassif (n=12)	Total (N=684)
Pts with ≥1 TEAE	47 (61.0)	90 (54.9)	8 (36.4)	81 (50.6)	30 (56.6)	28 (43.8)	45 (42.1)	12 (48.0)	2 (16.7)	343 (50.1)
Cardiac disorders
Dyspnea	1 (1.3)	0	0	3 (1.9)	0	1 (1.6)	0	0	1 (8.3)	6 (0.9)
Gastrointestinal disorders
Constipation	8 (10.4)	26 (15.9)	0	17 (10.6)	5 (9.4)	3 (4.7)	14 (13.1)	3 (12.0)	0	76 (11.1)
Nausea	7 (9.1)	13 (7.9)	2 (9.1)	13 (8.1)	8 (15.1)	3 (4.7)	7 (6.5)	3 (12.0)	1 (8.3)	57 (8.3)
Vomiting	4 (5.2)	11 (6.7)	1 (4.5)	7 (4.4)	2 (3.8)	4 (6.3)	3 (2.8)	2 (8.0)	0	34 (5.0)
General disorders and administration site conditions
Fatigue	4 (5.2)	3 (1.8)	0	8 (5.0)	2 (3.8)	0	2 (1.9)	1 (4.0)	0	20 (2.9)
Nervous system disorders
Dizziness	0	7 (4.3)	0	2 (1.3)	2 (3.8)	0	6 (5.6)	1 (4.0)	0	18 (2.6)
Headache	4 (5.2)	5 (3.0)	2 (9.1)	8 (5.0)	6 (11.3)	5 (7.8)	5 (4.7)	1 (4.0)	1 (8.3)	37 (5.4)
Somnolence	3 (3.9)	8 (4.9)	2 (9.1)	6 (3.8)	3 (5.7)	1 (1.6)	2 (1.9)	0	0	25 (3.7)
Tremor	1 (1.3)	0	1 (4.5)	0	1 (1.9)	0	0	0	1 (8.3)	4 (0.6)
Psychiatric disorders
Anxiety	0	0	0	0	0	0	1 (0.9)	0	1 (8.3)	2 (0.3)
Skin and subcutaneous tissue disorders
Rash	1 (1.3)	1 (0.6)	1 (4.5)	1 (0.6)	1 (1.9)	0	1 (0.9)	2 (8.0)	0	8 (1.2)

Note: An adverse event is defined as treatment emergent if it has a start date/time at any point after the patient filled the initial MSN prescription.

Abbreviations: ER, extended-release; IR, immediate-release; MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; Pts, patients; TD, transdermal; TEAE, treatment-emergent adverse event; Unclassif, unclassified.

Table 4 Investigator assessment of MSN conversion guide utility at Visit 3

Conversion guide assessment criteria	Mean (SD)	Median (range)
Usefulness of conversion guide to determine starting dose of MSNa (n=350)	7.8 (2.29)	8.0 (0–10)
Ease of use of conversion guideb (n=350)	8.4 (1.79)	9.0 (3–10)
Clarity of directions given in conversion guidec (n=350)	8.6 (1.72)	9.0 (1–10)
Satisfaction with conversion guided (n=349)	8.1 (2.11)	9.0 (2–10)

Notes:

a Scale from 0 (not useful) to 10 (very useful);

b scale from 0 (very difficult) to 10 (very easy);

c scale from 0 (very unclear) to 10 (very clear);

d scale from 0 (very dissatisfied) to 10 (very satisfied).

Abbreviations: MSN, extended-release morphine sulfate surrounding sequestered naltrexone hydrochloride; SD, standard deviation.

Table S1 Conversion factors for converting the daily dose of prior oral opioids to the daily oral dose of EMBEDA (mg/day prior opioid × factor = mg/day EMBEDA)

Prior oral opioid	Multiply dose by a factor of
Hydrocodone (including combination drugs)^Citation2^–^Citation7	1
Hydromorphone^Citation7^–^Citation9	4
Methadone^Citation2,Citation9^–^Citation12	3
Morphine	1
Oxycodone (including combination drugs)^Citation7,Citation13	1.5
Oxymorphone^Citation9,Citation14,Citation15	2

Table S2 Converting from transdermal fentanyl to EMBEDA

Transdermal fentanyl daily dose^Citation2^–^Citation6	Equianalgesic morphine daily dose, mg
12.5 µg/h = 300 µg/day	30
25 µg/h = 600 µg/day	60
50 µg/h = 1,200 µg/day	120
75 µg/h = 1,800 µg/day	180
100 µg/h = 2,400 µg/day	240

EMBEDA® (morphine sulfate and naltrexone hydrochloride) [package insert]Bristol, TNPfizer Inc2009

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