Buprenorphine transdermal

Generic Name buprenorphine transdermal delivery system... 

Buprenorphine transdermal dehvery system (BTDS) patches have heen shown to successfully treat moderate to severe chronic pain. Douhle-hhnd studies have demonstrated its effectiveness in treating cancer pain as well as chronic Imnhar pain [4] and chronic osteoarthritis pain of the hip and knee. 

Steiner D, Munera, C, Hale, M, Ripa, S, Landau, C, The efficacy and safety of buprenorphine transdermal system (BTDS) in subjects with moderate to severe low back pain. APS 28th Annual Meeting, San Diego, CA. May 8, 2009. 

KapU RP, Cipriano A, Michels GH, Perrino P, O Keefe SA, Shet MS, et al. Effect of ketoconazole on the pharmacokinetic profile of buprenorphine following adininistration of a once-weekly buprenorphine transdermal system. Clin Drug Invest September 1,2012 32(9) 583-92. 

A quantum leap in pain therapy with distinct advantages in the form of reduced side-effects and application frequency was achieved with transdermal opioid administration. Transdermal application requires a number of characteristics on the part of the active substance (Fig. 7), the most restrictive being the daily dose, and only very potent opioids which are effective in very low doses, such as fentanyl and buprenorphine, are an option (Sittl and Likar, 2001). 

Buprenorphine, the other option for transdermal application on account of its potency, is more difficult to apply dermally in therapeutic doses (Roy et al., 1994 Grond et al., 2000). A surrogate parameter for skin penetration, provided the other prerequisites are fulfilled (Fig. 7), is the melting point of the active substance. With buprenorphine base this is 209°C and about 260°C for buprenorphine hydrochloride, compared with, for example, 83°C for fentanyl base and 150°C for fentanyl dihydrogen citrate. The DDS developer LTS devised a technical solution for reliable transdermal buprenorphine administration in the form of a matrix patch (Fig. 9). 

In contrast to reservoir patches, there is no risk of dosedumping a with matrix patch, which releases buprenorphine from a prolonged-release matrix in direct contact with the skin for at least 3 days. The improved solubility necessary to achieve an adequate concentration of dissolved buprenorphine base is obtained by means of well tolerated organic acids that do not form practically insoluble salts with buprenorphine in the undercooled mass in the matrix of the TTS. In Europe transdermal buprenorphine was developed by Grunenthal as Transtec , which was launched in Germany in 2001 and recently approved in major Europoean markets with dosages of 35, 52.5 and 70 pg/h containing 20, 30 and 40 mg buprenorphine per TDS respectively (Fig. 10 Terlinden et al., 2000). 

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

Because faster onset of action is associated with higher potential for abuse, abuse-liability assessment should include consideration of whether a formulation can be altered to increase the speed of onset. There are numerous examples of abuse of a medication by a route other than that intended by the manufacturer. The sustained-release oral form of oxycodone, designed to deliver an initial rapid dose followed by slow release, has been widely abused by chewing the tablet, thus releasing the entire content of the tablet at once.65 There is also evidence for intravenous use of sublingual buprenorphine tablets.66 Transdermal systems developed to deliver medication slowly for extended periods of time have been prime targets for misuse,67 as discussed below in the case study of fentanyl. 

Fang, J.Y., et al. 2002. The effects of iontophoresis and electroporation on transdermal delivery of buprenorphine from solutions and hydrogels. J Pharm Pharmacol 54 1329. 

ALFENTANIL, BUPRENORPHINE, FENTANYL, TRAMADOL PROTEASE INHIBITORS Possibly t adverse effects when buprenorphine is co administered with indinavir, ritonavir (with or without lopinavir) or saquinavir Inhibition of CYP3A4 (CYP2D6 in the case of tramadol) Halve the starting dose and titrate to effect. For single injection of fentanyl, monitor sedation and respiratoiy function closely. If continued use of fentanyl, i dose may be required. Concomitant use of ritonavir and transdermal fentanyl is not recommended... 

Bohme K. Buprenorphine in a transdermal therapeutic system—a new option. Clin Rheumatol 2002 21(Suppl 1) S13-16. 

Transtec Transdermal Patch (Buprenorphine). Napp Pharmaceuticals Ltd. UK Summary of product characteristics. May 2007. 

Wirz S, Wittmann M, Schenk M, Schroeck A, Schaefer N, Mueller M, Standop J, Kloecker N, Nadstawek J. Gastrointestinal symptoms under opioid therapy a prospective comparison of oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine. Eur J Pain 2009 13(7) 737-A3. 

Transdermal patches registered at present are patches containing active substances such as buprenorphine, estradiol, fentanyl, glyceryl trinitrate, nicotine, oxybutynine, rivastigmine, rotigotine and scopolamine. These transdermal patches are used in the treatment of a variety of diseases. They release the active substance during a period of 24 up to 72 h, depending on the type of patch used and the active substance. After application of the patch plasma concentration slowly rises until a steady concentration is reached. 

Naing C, Aung K, Racloz V, Yeoh PN (2013) Safety and efficacy of transdermal buprenorphine for the relief of cancer pain. J Cancer Res CUn Oncol 139 1963-1970 Nelson LS, Perrone J, JuurUnk DN (2014) Painful decision-making at FDA. Expert Opin Drug Saf 13 407 10... 

Chapter 35 - Buprenorphine intravenous neuraxial and transdermal applications... 

Buprenorphine can also be used intramuscularly where it provides an analgesic onset at 15 minutes, peak effect at 1 hour and a duration of 6 hours. The development and use of transdermal buprenorphine for the treatment of chronic pain is ongoing and is discussed in Chapter 121. Buprenorphine in conjunction with local anesthetic has been used intra-articularly for control of pain after knee arthroscopy [21] and for perivascular axillary brachial plexus block [22]. It was seen that buprenorphine in conjunction with local anesthetic produced analgesia that was three times longer than the analgesia produced by the use of bupivacaine alone. Buprenorphine added to the local anesthetic for axillary brachial plexus block prolongs post-operative analgesia [23]. 

Transdermal buprenorphine has a latency to onset and peak effect, and is not recommended for analgesia in the immediate post-operative period, or when analgesic requirements are varying rapidly. 

The advantages of transdermal buprenorphine are primarily related to the convenience and improved compliance associated with a 7-day analgesic delivery system. The preparation may be particularly useful in elderly patients with moderate pain that cannot be controlled with non-opioid analgesics and others who are at risk for respiratory depression with pure mu agonists. 

The safety of transdermal buprenorphine has been reviewed [182 ]. Buprenorphine can be effectively and safely combined with full g receptor agonists, and switching between buprenorphine and other opioids at equianalgesic doses is not associated with inadequate analgesic efficacy. The risk of... 

Drug administration ronte Transdermal buprenorphine has been studied in children with cancer pain in three case studies. An adverse event occurred in only one case— erythema and pruritus at the patch site [192 ]. 

In 30 adults, transdermal buprenorphine 35 micrograms/hour produced adequate pain relief, but there was a high incidence of adverse events patients developed constipation n = 3), hypotension (3), urinary retention (2), or paradoxical hyperalgia (1) nine discontinued treatment mostly because of nausea and daytime sleepiness [194 ]. 

Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain 2009 13(3) 219-30. 

Arlotta A, Chiaretti A, Riccardi R. Transdermal buprenorphine in children with cancer-related pain. Pediatr Blood Cancer 2009 52(1) 125-7. 

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