Buprenorphine Transdermal Patch Research Articles

Transdermal Buprenorphine Patches Applied in a 4-Day Regimen Versus a 3-Day Regimen: A Single-Site, Phase III, Randomized, Open-Label, Crossover Comparison

Background: In 2001, a transdermal matrix patch formulation of buprenorphine was approved for the treatment of moderate to severe cancer pain and severe pain that is unresponsive to nonopioid analgesics. The primary recommendation contained in the prescribing information was that transdermal patches be worn for a 3-day period before application of a new patch. Objective: This study was conducted to evaluate the potential for extending the time the buprenorphine patch is worn from 3 to 4 days. Methods: This single-center, randomized, open-label, crossover Phase III study compared the efficacy and tolerability of the buprenorphine transdermal patch applied for different durations, with patch changes every 3 days versus every 4 days (12 days each), in patients with chronic moderate or severe pain of malignant or nonmalignant origin. Study participants were aged >18 years, had already responded to at least 4 weeks of transdermal buprenorphine, and had achieved steady-state conditions for at least 2 weeks before enrollment. The primary end point was patients’ rating of the quality of treatment (analgesic efficacy and tolerability, rated on a 5-point scale: very good, good, satisfactory, poor, and inadequate) at the completion of each treatment regimen. Also recorded were physicians' ratings of the quality of treatment; pain intensity, rated on an 11-point numerical rating scale (from 0 = no pain to 10 = worst pain imaginable) and on the McGill Pain Questionnaire (MPQ) (maximum pain = 3.0); health status, assessed using the 36-item Short Form Health Survey (SF-36), expressed as a percentage of the best health condition (100%); and pain relief (5-point scale: complete, good, satisfactory, slight, and none). Local skin tolerability was evaluated for objective and subjective dermatologic symptoms at the patch application sites. Patients recorded daily pain intensities at specified times of day and night, pain relief (5-point verbal rating scale), and sleep duration (<2 hours, >2–3 hours, >3-<6 hours, or >6 hours) in a diary. The safety profile was evaluated based on standard monitoring of adverse events, vital signs, and routine laboratory tests. Results: Forty-nine white patients (25 women, 24 men) were enrolled; their mean (SD) age was 61.6 (11.5) years, and their mean weight was 74.7 (16.7) kg. The most common source of pain was musculoskeletal disorders (40 patients), followed by nervous system disorders (10), neoplasms (9), injuries (5), and other causes (6). Forty-one patients completed the study; 2 patients discontinued because of adverse events, 1 because of lack of efficacy, and 5 for nonmedical reasons. Thirty-three patients provided data per protocol. Patients in the perprotocol population received a mean (SD) transdermal buprenorphine dose of 49.9 (38.9) pg/h. The proportion of patients in the per-protocol population rating the quality of treatment as adequate (combined ratings of very good, good, and satisfactory) was 93.9% (31/33) for both regimens. The physicians' ratings indicated adequate quality of treatment in 93.8% (30/32) of patients applying 4 patches for 3 days each and 97.0% (32/33) of patients applying 3 patches for 4 days each. Mean (SD) pain intensity scores on the numerical rating scale were similar after completion of the 3− and 4-day regimens (3.73 [1.88] and 3.88 [1.75] points, respectively), as were MPQ scores (0.79 [0.67] and 0.79 [0.78]). The mean (SD) proportion of days with at least satisfactory pain relief was 83.9% (26.1%) and 85.6% (24.4%) for the 3- and 4-day regimens; the corresponding proportions of nights with at least satisfactory pain relief were 85.2% (26.6%) and 88.1% (21.4%). Continuously assessed pain intensities at specified times of day and night (numerical rating scale) did not differ significantly between regimens. Mean SF-36 health status scores did not differ significantly between regimens (total score: 37.7% [17.0%] and 37.7% [17.3%]). Mean rates of nights with good sleep quality were 28.5% (39.9%) for the 3-day regimen and 36.0% (42.6%) for the 4-day regimen. Local skin tolerability was comparable for the 3− and 4-day regimens, with objective findings (mainly erythema) at the patch-application sites in 17 of 32 and 11 of 33 patients, respectively, and subjective symptoms (mainly itching) in 16 of 32 and 13 of 33 patients. The most common adverse events in the safety population were nausea, dizziness/giddiness, and malaise/fatigue (3/49 [6.1%] each). Conclusion: Analgesic efficacy, patients' satisfaction with the quality of treatment, and skin tolerability did not differ significantly between 3 and 4 days of patch application in these patients with chronic pain who had been previously stabilized on transdermal buprenorphine.

322 Neuropathic chronic pain following traumathic brachial plexus total section managed by transdermal buprenorphine patch(tds): Original case report

Issue published online: 16 January 2012 Article first published online: 16 January 2012

Use of a transdermal matrix patch of buprenorphine in cats: preliminary pharmacokinetic and pharmacodynamic data

Six domestic shorthair cats, aged three to four years and weighing 5·1 to 7·4 kg, were used to assess the thermal antinociceptive effect of a transdermal buprenorphine patch, designed to...

Transdermales Buprenorphin in der Schwangerschaft

Buprenorphine has been widely used and studied for over 20 years and has been shown to be an effective opioid analgesic. Some years ago a buprenorphine formulation for transdermal therapy of chronic cancer-related and non-cancer-related pain became available. We report the case of a woman who received a lower dosed transdermal buprenorphine patch (3/5 of a 35 microg/h patch corresponding to release of 21 microg/h buprenorphine) during pregnancy without any complication for herself or the child. The patient has now being using the transdermal system for more than 2 years and has reported continuous excellent pain relief. The buprenorphine patch was well tolerated and produced no effect on vigilance over the whole period of administration.

Buprenorphine-induced acute respiratory depression during ifosfamide-based chemotherapy

Buprenorphine-induced acute respiratory depression during ifosfamide-based chemotherapy

Kein Opioidüberhang bei Patienten mit transdermalem Buprenorphin und Fast-Track-Anästhesie nach Eingriffen am offenen Herzen

Simultaneous use of opioids with a different pharmacological profile may lead to unexpected prolongation of effects. In an open label study possible overhang in post-operative respiratory effects and vigilance was determined in a group of patients (n = 22) carrying a transdermal buprenorphine patch for at least 2 months for treatment of chronic pain, undergoing a fentanyl-based fast-track enflurane anesthetic technique for open-heart operation. Data was compared with another randomised group (n = 21) undergoing similar open-heart procedures with no other opioid than fentanyl on board. Following induction with fentanyl and a barbiturate, depth of anesthesia with enflurane (Fi 0.5) was guided using the bispectral index (BIS). Additional doses of fentanyl were given when blood pressure and/or heart-rate increased 20% above pre-induction levels. Early postoperative extubation was initiated once the cardiovascular system was stable and there were no signs of respiratory impairment. Following a similar time of operation and anesthesia and a similar total dose of fentanyl (0.69 mg +/- 0.23 SD versus 0.67 mg +/- 0.16 SD), postoperatively, there were no significant differences between the buprenorphine- and the control group regarding the time till extubation (25.2 min +/- 6.1 versus 33.3 min +/- 5.0) and the arterial blood gases under oxygen inhalation (paO2 136 torr +/- 48 SD versus 128 torr +/- 35 SD; paCO2 43.3 torr +/- 3.3 SD versus 41.9 torr +/- 1.2 SD and the post-anesthetic vigilance and recovery score (6.8 +/- 1.0 versus 7.5 +/- 0.8) 60 minutes after end of anesthesia. Contrary to the control group, there was a lower and significant (p < 0.01) incidence of PONV in patients with transdermal buprenorphine. Patients using a buprenorphine patch for the relief of chronic pain cannot be regarded as opioid naïve. Due to adaptive mechanisms and the development of tolerance, there is no prolongation of the respiratory depression induced by intraoperative fentanyl. Long-term use of transdermal buprenorphine does not lead to potentiation or prolongation of opioid effects in cardiac surgery patients.

A comparison of the skin irritation potential of transdermal fentanyl versus transdermal buprenorphine in middle-aged to elderly healthy volunteers

ABSTRACTObjective: Establishing local tolerability of transdermal opioid systems is important as more systems become available for use in a range of indications. We compared the skin irritation potential of a single application of transdermal fentanyl (Durogesic D-trans; DDTDF) and transdermal buprenorphine (Transtec; TDB) patches in healthy volunteers.*† Durogesic and D-trans are registered trade names of Janssen-Cilag‡ Transtec is a registered trade name of Napp PharmaceuticalsMethods: 46 healthy males and females (mean age [range]: 59.6 [50–69] years) with healthy skin received a single dose of both the DDTDF 25 μg/h patch and the TDB 35 μg/h patch in a randomised order under naltrexone cover. The incidence and severity of erythema was assessed at various timepoints after patch removal.Results: There was a non-significant trend towards a higher incidence of erythema 60 min after patch removal with TDB compared with DDTDF. The severity of erythema at 60 min and the incidence of erythema at 72 h after patch removal were significantly higher with TDB than with DDTDF ( p = 0.01 and 22% versus 4.9%, p = 0.04, respectively). In general, the results from the chromametric assessment of treated skin were in agreement. The incidence of topical adverse events (AEs) was lower with DDTDF than with TDB (one versus six events) and subjects preferred the DDTDF patch and felt it was less noticeable on the skin. The DDTDF patch was considered less painful to remove, and, consistent with that, the TDB patch was judged to have better adhesion. Twenty-one subjects reported systemic AEs with DDTDF plus naltrexone and 22 with TDB plus naltrexone, most of which were considered treatment-related, 34 and 60 AEs, respectively.Conclusions: Local tolerability of transdermal opioid systems should be considered when making a therapeutic choice. Even after a single application in healthy volunteers, differences in local tolerability, assessed both clinically and by chromametry, and patch comfort were shown between DDTDF and TDB, in favour of DDTDF.

Transdermal buprenorphine in the treatment of chronic pain

The transdermal matrix patch formulation of buprenorphine has been shown to be effective in managing moderate-to-severe cancer pain and severe pain unresponsive to nonopioid analgesics. Clinical trials have revealed that it is possible to switch from weak opioids or low doses of step III opioids to transdermal buprenorphine without any problems. With buprenorphine patches, the sublingual buprenorphine intake was dose-dependently reduced and was superior to placebo in this respect. The proportion of responders increased with the buprenorphine dose, and a higher proportion of patients receiving buprenorphine patches reported uninterrupted sleep for longer than 6 h compared with those receiving placebo. In a long-term, open, follow-up study in which the mean duration of treatment was 7.5 months, analgesia was rated as at least satisfactory by 90% of patients. Almost 60% of patients could manage their pain with one patch alone or with one additional sublingual tablet a day during the whole period of treatment, indicating a low incidence of tolerance development. The buprenorphine transdermal patch was assessed as user friendly by 94.6% of patients. In a postmarketing surveillance study, pain relief with transdermal buprenorphine was rated as good or very good by 70% of the responders. Postmarketing surveillance studies have shown that transdermal buprenorphine is also effective in the management of nociceptive and neuropathic pain, which some studies have shown to be relatively insensitive to μ-opioid analgesics, such as morphine. Transdermal buprenorphine was well tolerated. Most adverse events were either local reactions to the patch that generally subsided within 24 h or systemic events typical of treatment with opioid analgesics, such as nausea, vomiting and constipation.