Use of immediate-release opioids as supplemental analgesia during management of moderate-to-severe chronic pain with buprenorphine transdermal system

Figures & data

Table 1 Comparative characteristics, enrolled extension-trial population

	IR-opioid group (n=181)	No-IR-opioid group (n=173)
Mean age, years (SD)	50.9 (12.49)	51.5 (12.49)
Minimum, maximum age, years	24, 84	24, 82
Sex, n (%)
Male	102 (56)	95 (55)
Female	79 (44)	78 (45)
Race, n (%)
White	178 (98)	156 (90)
Black	2 (1)	12 (7)
Asian	0	2 (1)
Other	1 (0.6)	3 (2)
Mean days in extension trial	164	122

Abbreviations: IR, immediate-release; SD, standard deviation.

Figure 1 Mean supplemental opioid use over time (in milligrams of morphine equivalents) for patients in the IR-opioid group.

Abbreviation: IR, immediate-release.

Figure 2 Mean pain-intensity scores for patients in the IR-opioid and no-IR-opioid groups.

Notes: *P<0.05; error bars represent 95% CIs.
Abbreviations: IR, immediate-release; CIs, confidence intervals; BPI, Brief Pain Inventory.

Figure 3 Mean pain-interference scores at each assessment point for patients in the IR-opioid and no-IR-opioid groups.

Notes: *P<0.05; error bars represent 95% CIs.
Abbreviations: IR, immediate-release; CIs, confidence intervals; BPI, Brief Pain Inventory.

Table 2 Incidence of TEAEs (≥5%) during BTDS treatment for moderate–severe chronic pain: IR-opioid group vs no-IR-opioid group

	IR-opioid group (n=181)						No-IR-opioid group (n=173)
	On IR opioid		Not on IR opioid		Total
	n	%	n	%	n	%	n	%
Any TEAE	131	72.4	43	23.8	144	79.6	120	69.4
Headache	25	13.8	4	2.2	29	16	29	16.8
Application-site erythema	18	9.9	4	2.2	22	12.2	17	9.8
Application-site pruritus	17	9.4	5	2.8	22	12.2	17	9.8
Application-site rash	14	7.7	6	3.3	20	11	15	8.7
Arthralgia	17	9.4	3	1.7	20	11	9	5.2
Nausea	13	7.2	4	2.2	17	9.4	17	9.8
Back pain aggravated	10	5.5	2	1.1	12	6.6	5	2.9

Abbreviations: TEAEs, treatment-emergent adverse events; BTDS, buprenorphine transdermal system; IR, immediate-release.

Table 3 Published studies where IR opioids were used as supplemental analgesia during transdermal buprenorphine therapy for chronic pain

Study	Reported pain condition(s)	IR opioids used as supplemental analgesia	Reported dose of IR opioid
Aurilio et al^Citation32	Chronic cancer pain	Oral morphine	Mean 4–34 mg/day
Böhme and Likar^Citation33	Severe chronic pain of malignant or nonmalignant origin	Sublingual buprenorphine (Europe)*	Mean 0.3–0.4 mg/day
de Barutell and Gonzalez-Escalada^Citation34	Any type of chronic pain	Oral tramadol or oral morphine	Mean tramadol range 60–114 mg/day; mean morphine range 13–17 mg/day
Freye et al^Citation35	Pain of different origins	Oxycodone, oral morphine, sublingual buprenorphine (Europe)*	Doses not reported
Gordon et al^Citation16	Moderate or greater chronic low-back pain	Oral codeine 30 mg and APAP 300 mg	Mean 1.8±2.6 tabs/day
Likar et al^Citation8	Cancer and noncancer patients with moderate–severe chronic persistent pain	Sublingual buprenorphine (Europe)*	41% took 0 tabs (0.2 mg), 25% took 1 tab, 23% took >1 but ≤3 tabs, 11% took > 3 tabs
Menten et al^Citation36	Radiotherapy-related pain in head and neck cancer	Oral tramadol, sublingual buprenorphine (Europe),* oral morphine	Not reported
Mercadante et al^Citation37	Episodic pain in cancer patients	IV morphine	Mean 6.1 mg/day
Mercadante et al^Citation38	Cancer patients	Oral morphine	Not reported
Mercadante et al^Citation39	Cancer patients	Oral morphine	Not reported
Mordarski^Citation40	Noncancer pain in hemodialysis patients	Oral tramadol	Mean dose 61–149 mg/day
Nadezhda et al^Citation41	Moderate–severe chronic cancer pain	Oral tramadol or IM buprenorphine	Mean tramadol dose 61–147 mg/day; IM buprenorphine up to 0.6 mg/day
Pace et al^Citation42	Chronic cancer pain	Oral tramadol	Up to 200 mg/day
Poulain et al^Citation43	Severe cancer pain	Sublingual buprenorphine (Europe)*	Mean 1±1 tab/day
Ruggiero et al^Citation44	Moderate–severe cancer related pain in pediatric patients	Oral tramadol	Not reported
Setti et al^Citation45	Postoperative pain from gynecologic surgery	IV morphine	Mean up to 7.2±4.6 mg/day
Sittl et al^Citation46	Chronic severe pain due to cancer and other conditions	Sublingual buprenorphine (Europe)*	Mean 0.3 mg/day
Sorge and Sittl^Citation47	Severe chronic cancer or noncancer pain	Sublingual buprenorphine (Europe)*	Mean up to 1.1 mg/day
Zarth^Citation48	Chronic pain due to breast and bone cancer	Oral morphine, transmucosal fentanyl, sublingual buprenorphine (Europe)*	Not reported

Note:

* Sublingual buprenorphine available in Europe as a 0.2 mg dosage strength.

Abbreviations: IR, immediate-release; APAP, N-acetyl-para-aminophenol (acetaminophen); IM, intramuscular; IV, intravenous.

AurilioCPaceMCPotaVOpioids switching with transdermal systems in chronic cancer painJ Exp Clin Cancer Res2009286119422676

 PubMed Web of Science ®Google Scholar

BöhmeKLikarREfficacy and tolerability of a new opioid analgesic formulation, buprenorphine transdermal therapeutic system (TDS), in the treatment of patients with chronic pain: a randomised, double-blind, placebo-controlled studyPain Clin2003152193202

 Web of Science ®Google Scholar

de BarutellCGonzalez-EscaladaJEfficacy and safety of buprenorphine TDS in conjunction with oral tramadol or morphine as rescue medication in the treatment of 390 patients with chronic pain: a summary of two retrospective Spanish multicenter studiesJ Appl Ther Res2007621424

 Google Scholar

FreyeEAnderson-HillemacherARitzdorfILevyJVOpioid rotation from high-dose morphine to transdermal buprenorphine (Transtec) in chronic pain patientsPain Pract20077212312917559481

 PubMedGoogle Scholar

GordonACallaghanDSpinkDBuprenorphine transdermal system in adults with chronic low back pain: a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phaseClin Ther201032584486020685494

 PubMed Web of Science ®Google Scholar

LikarRKayserHSittlRLong-term management of chronic pain with transdermal buprenorphine: a multicenter, open-label, follow up study in patients from three short-term clinical trialsClin Ther200628694395216860176

 PubMed Web of Science ®Google Scholar

MentenJCarpentierIDeschutterHNuytsSVan BeekKThe use of transdermal buprenorphine to relieve radiotherapy related pain in head and neck cancer patientsCancer Invest201331641242023758187

 PubMed Web of Science ®Google Scholar

MercadanteSVillariPFerreraPSafety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphineJ Pain Symptom Manage200632217517916877185

 PubMed Web of Science ®Google Scholar

MercadanteSPorzioGFulfaroFSwitching from transdermal drugs: an observational “n of 1” study of fentanyl and buprenorphineJ Pain Symptom Manage200734553253817629666

 PubMed Web of Science ®Google Scholar

MercadanteSCasuccioATirelliWGiarratanoAEquipotent doses to switch from high doses of opioids to transdermal buprenorphineSupport Care Cancer200917671571819104845

 PubMed Web of Science ®Google Scholar

MordarskiSEfficacy and safety of buprenorphine in patients receiving haemodialysisJ Appl Ther Res2009724651

 Google Scholar

NadezhdaAOsipovaNAbuzarovaGTransdermal buprenorphine for the treatment of chronic pain syndrome in oncology patientsJ Appl Ther Res2009726572

 Google Scholar

PaceMCPassavantiMBGrellaEBuprenorphine in long-term control of chronic pain in cancer patientsFront Biosci2007121291129917127381

 PubMed Web of Science ®Google Scholar

PoulainPDenierWDoumaJEfficacy and safety of transdermal buprenorphine: a randomized, placebo-controlled trial in 289 patients with severe cancer painJ Pain Symptom Manage200836211712518411010

 PubMed Web of Science ®Google Scholar

RuggieroACocciaPArenaREfficacy and safety of transdermal buprenorphine in the management of children with cancer-related painPediatr Blood Cancer201360343343723034996

 PubMed Web of Science ®Google Scholar

SettiTSanfilippoFLeykinYTransdermal buprenorphine for postoperative pain control in gynecological surgery: a prospective randomized studyCurr Med Res Opin201228101597160822876835

 PubMed Web of Science ®Google Scholar

SittlRGriessingerNLikarRAnalgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: a multicenter, randomized, double-blind, placebo-controlled trialClin Ther200325115016812637117

 PubMed Web of Science ®Google Scholar

SorgeJSittlRTransdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled studyClin Ther200426111808182015639693

 PubMed Web of Science ®Google Scholar

ZarthRComparison of buprenorphine, morphine sulfate, and fentanyl citrate as rescue medication for breakthrough pain in cancer patientsJ Appl Ther Res2008641519

 Google Scholar