Opioids
Strong opioids
Oxycodone hydrochloride
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Prolonged release oxycodone hydrochloride tablets (12-hourly) |
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Immediate release oxycodone hydrochloride capsules, liquid and concentrate (4 - 6 hourly p.r.n) |
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Oxycodone hydrochloride solution for injection or infusion |
Oxycodone is a full opioid agonist with affinity for mu and kappa receptors. Its opioid agonist actions are similar to those of other opioid analgesics, primarily affecting the central nervous system and smooth muscle. The pharmacological effects of oxycodone include analgesia as well as the known side effects of sedation, nausea, vomiting and decreased gastrointestinal motility. As with all pure opioid agonists, there is no ceiling effect to the analgesia seen with oxycodone.
Oxycodone has been in clinical use for more than 80 years and has been commercially available in the UK as OxyContin® tablets (prolonged release oxycodone hydrochloride tablets) and the OxyNorm® range [immediate release (IR) oxycodone hydrochloride oral capsules, solution and concentrate, and solution for injection or infusion] since 2000. Clinical studies show it to be effective for managing moderate to severe cancer1-9 and post-operative10-14 pain and severe non-cancer pain.15-19
To view animations of the mode of action of OxyContin® tablets, please click here 
To view case studies using the OxyContin® / OxyNorm® product range, click here
OxyContin® tablets prescribing information click here.
OxyNorm® (oral range) prescribing information click here.
OxyNorm® (injection) prescribing information click here.
Hydromorphone
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Hydromorphone hydrochloride capsules |
Experience with the Palladone® range is especially well documented in severe tumour pain.20 Most cancer patients are on multiple concomitant medications as their disease progresses. In addition, renal impairment frequently becomes apparent as the disease proceeds.
Hydromorphone has no therapeutically active metabolites and can be used in patients who have renal impairment and in those requiring dialysis (low dose might be required). Hydromorphone is metabolised mainly by glucuronyl transferase and therefore largely independently of cytochrome P450. This, together with its low plasma protein binding of 8%, is another reason for the low interaction potential of the Palladone® range.21,22
To view case studies of patients treated with the Palladone® range, click here.
Buprenorphine
Buprenorphine is a low molecular weight, highly lipophilic, semi-synthetic opioid analgesic. It acts as a partial agonist at mu opioid receptors and as an antagonist at kappa opioid receptors.23-25 The pharmacological effects of buprenorphine are qualitatively the same as those seen with full mu agonists. However, as a partial mu receptor agonist, buprenorphine has significant pharmacological differences compared with full agonists and may have advantages, such as a lower risk of some side effects.
In Europe, buprenorphine is available in parenteral, sublingual and transdermal formulations. It has been used in the clinical setting for approximately 30 years and has been shown to be effective for the relief of severe pain in a variety of therapeutic settings. BuTrans® patches (buprenorphine) allow for the delivery of a consistent and steady dose of buprenorphine with limited fluctuation over a 7-day period.
Clinical studies have shown BuTrans® patches to be effective in the treatment of severe osteoarthritis pain,26,27 severe chronic back pain28-30 and other severe chronic non-malignant pain syndromes.31,32
To download guidelines on the primary care treatment and management of chronic osteoarthritic pain, click here.
To view prescribing information for BuTrans® patches, click here
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Buprenorphine |
The Transtec® patch is available in three dose strengths, which continuously deliver buprenorphine over a period of 96 hours at a rate of 35 µg/h, 52.5 µg/h or 70 µg/h.
Pharmacokinetic and clinical data show that Transtec® patches:
- achieve a clinically effective level of buprenorphine after approximately 1 day, and this level is maintained during the 3- to 4-day application period;33
- provide effective relief of chronic, moderate to severe malignant pain, and chronic, severe non-malignant pain;34-38
- markedly improve pain relief, decrease pain intensity, and increase the duration of sleep uninterrupted by pain, compared with the use of buprenorphine sublingual tablets alone;34-38
- are well-tolerated;37-40
- satisfied 90% of patients.37
To download the Transtec® patches product monograph, click here.
To view case studies using Transtec® patches, click here.
To view key information about Transtec® patches, click here
Transtec® patches patient information booklet click here
Transtec® patches patient progress log click here
References:
1) Mucci-LoRusso P, Berman BS, Silberstein PT, et al. Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study. Eur J Pain 1998; 2:239-49.
2) Citron ML, Kaplan R, Parris WC-V, et al. Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Cancer Invest 1998; 16:562-71.
3) Kaplan R, Parris WC-V, Citron ML, et al. Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain. J Clin Oncol 1998; 16:3230-7.
4) Parris WC-V, Johnson BW, Croghan MK, et al. The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study. J Pain Symptom Manage 1998; 16:205-11.
5) Hagen NA, Babul N. Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain. Cancer 1997; 79:1428-37.
6) Kalso E, Vainio A. Morphine and oxycodone hydrochloride in the management of cancer pain. Clin Pharmacol Ther 1990; 47:639-46.
7) Kalso E, Vainio A, Mattila MJ, et al. Morphine and oxycodone in the management of cancer pain: plasma levels determined by chemical and radioreceptor assays. Pharmacol Toxicol 1990; 67:322-8.
8) Maddocks I, Somogyi A, Abbott F, et al. Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone. J Pain Symptom Manage 1996; 12:182-9.
9) Gagnon B, Bielech M, Watanabe S, et al. The use of intermittent subcutaneous injections of oxycodone for opioid rotation in patients with cancer pain. Support Care Cancer 1999; 7:265-70.
10) Sunshine A, Olson NZ, Colon A, et al. Analgesic efficacy of controlled-release oxycodone in postoperative pain. J Clin Pharmacol 1996; 36:595-603.
11) Curtis GB, Johnson GH, Clark P, et al. Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model. Eur J Clin Pharmacol 1999; 55:425-9.
12) Cheville A, Chen A, Oster G, et al. A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty. J Bone Joint Surg 2001; 83-A:572-6.
13) McCroskery E, Kaiko R. Open-label, clinical-use study of controlled-release (CR) oxycodone in patients with postoperative pain. Proceedings of the 9th World Congress on Pain; 1999 Aug 17-22; Vienna, Austria. Seattle: IASP Press®; 1999. p. 606.
14) Napp Pharmaceuticals Limited. A randomised, double-blind, parallel group, multicentre study to compare the tolerability, safety and efficacy of oxycodone with morphine in patients using i.v. patient-controlled analgesia (PCA) for acute postoperative pain. Data on file, study code: OXI3201.
15)Watson CPN, Babul N. Efficacy of oxycodone in neuropathic pain. A randomized trial in postherpetic neuralgia. Neurol 1998; 50:1837-41.
16) Watson CPN, Moulin D, Watt-Watson J, et al. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain 2003; 105:71-8.
17) McCroskery E, Croft J, Markenson J, et al. 3-month efficacy and safety study of OxyContin® in osteoarthritis patients. Proceedings of EFIC; 2000 Sep 26-29; Nice, France.
18) Hale ME, Fleischmann R, Salzman R, et al. Efficacy and safety of controlled-release versus immediate-release oxycodone: randomized, double-blind evaluation in patients with chronic back pain. Clin J Pain 1999; 15:179-83.
19) Roth SH, Fleischmann RM, Burch FX et al. Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain. Placebo-controlled trial and long-term evaluation. Arch Intern Med 2000; 160:853-60.
20) Hays H, Hagen N, Thirlwell M, et al. Cancer 1994; 74;1808-16.
21) Parab PV, Coyle DE, Streng WH et al. Pharma Ind 1987; 49;951-6.
22) Lötsch J, Skarke C, Tegeder I, et al. Clin Pharmacokinet 2002; 41(1);31-57.
23) Martin WR, Eades CG, Thompson JA, et al. The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 1976; 197:517-32.
24) Lewis JW. Buprenorphine. Drug Alcohol Depend 1985; 14:363-72.
25) Leander JD. Buprenorphine is a potent ?-opioid receptor antagonist in pigeons and mice. Eur J Pharmacol 1988; 151:457-61.
26) Napp Pharmaceuticals Limited. A double-blind, placebo-controlled study of BuTrans® (buprenorphine) patches in patients with osteoarthritis of the hip or knee. Data on file. Study code: BP99-0203.
27) Napp Pharmaceuticals Limited. A double-blind, parallel group study to compare the efficacy and tolerability of BuTrans® (buprenorphine) patches with sublingual buprenorphine tablets in patients with moderate to severe osteoarthritis pain Data on file. Study code: BUPN.CLIN0001.
28) Spyker DA, Hale ME, Karpow SE, et al. Effectiveness of buprenorphine transdermal system (BTDS) compared with oxycodone/acetaminophen and placebo in the treatment of patients with chronic back pain [abstract]. Anesthesiol 2001; 95:A-826.
29) Spyker D, Hale M, Munera C, et al. Effectiveness and safety of buprenorphine transdermal system (BTDS) compared with hydrocodone/acetaminophen in the treatment of patients with chronic low back pain [abstract]. J Pain 2002;3(Suppl 1):14. Abstract 653.
30) Hale ME, Munera CL, Spyker DA, et al. Treatment of patients with chronic low back pain with buprenorphine transdermal system (BTDS) compared with hydrocodone/acetaminophen. Abstract presented at the National Clinical Symposium of the American College of Nurse Practitioners; 2003 Oct 20; Atlanta, Georgia, USA.
31) Napp Pharmaceuticals Limited. Efficacy of 7-day BuTrans® (buprenorphine) transdermal patches compared with placebo in the management of chronic non-malignant pain syndromes. Data on file. Study code: BUP3201.
32) Spyker DA, Hale ME, Lederman M, et al. Long-term use of buprenorphine transdermal system (BTDS) in patients with chronic pain [abstract]. J Am Geriatr Soc 2002; 50(Suppl 4):S66.
33) Likar R, Allard R. Efficacy and safety of a buprenorphine-containing transdermal patch with 4 days’ wearing time compared to the current application period 3 days - randomized cross-over study (abstract). 4th International Conference on Pain Control and Regional Anaesthesia. 2005,18-22nd Nov. Cape Town, South Africa.
34) Böhme K, Likar R. Efficacy 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 study. The Pain Clinic 2003; 15:193-202.
35) Sittl R, Griessinger N, Likar R. Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: a multicentre, randomized, double-blind, placebo-controlled trial. Clin Ther 2003; 25:150-68
36) Sorge J, Sittl R. Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Clin Ther 2004; 26:1808-20.
37) Kopp M. Buprenorphine transdermal system (TDS) (delivery rate 35 µg/h) in an open long-term study with chronic pain patients [abstract]. Pain in Europe III, Nice, 2000. Abstract 260.
38) Muriel C y Grupo de Estudio de Opioides de la Sociedad Española del Dolor. [Assessment of buprenorphine transdermal patch in patients with cancer pain.] Rev Soc Esp Dolor 2004; 11:41-8. Spanish.
39) Böhme K. Buprenorphine in a transdermal therapeutic system – a new option. Clin Rheumatol 2002; Suppl 1:S13-6.
40) Radbruch L. Efficacy and tolerability of buprenorphine TDS in cancer pain patients. Eur J Palliat Care 2003; 10(1):13-6.