The use of transdermal opioids

VIEWPOINT - Transdermal opioid delivery is gaining popularity. By Dr Ganesan Baranidharan, and Dr Karen Simpson.

Drugs remain the mainstay of management for many pain problems.

Strong opioids are well accepted for cancer pain and are now being used more commonly for persistent non-malignant pain. There are several choices for opioid delivery and the transdermal route is a popular option.

Second-generation matrix skin patches are easy to use, with few complications and a long duration of action. Fentanyl and buprenorphine are suitable for transdermal administration because they have a low molecular weight combined with high potency and lipid solubility.

Fentanyl and buprenorphine patches are applied every three days and buprenorphine patches every seven days.

Technique
These matrix-type patches can be cut down to give a smaller dose, although the manufacturers cannot recommend this. This technique has been used in children, the elderly and those with sensitivity to opioid side-effects, although data about this are limited and care is needed with dose accuracy.

Initial dose titration is slow, as transdermal drugs take a long time to achieve steady-state plasma concentration. However, once this is attained patches often prevent 'clock watching' and many breakthrough problems.

Disadvantages of patches include difficulty with rapid dose variation in response to circumstances. Side-effects can be slow to reverse. Some patients cannot tolerate patches because of skin irritation. Rotating the patch site and using local steroids will achieve this, but sometimes patients have to abandon patches. Some patients just do not like skin patches and healthcare professionals should respect this.

Fentanyl is a synthetic opioid agonist at the mu -receptor. The transdermal delivery system is available as 10, 25, 50, 75 and 100 mu g/h matrix patches; the bioavailability is 90 per cent.

The starting dose is high for opioid-naive patients. There are no good randomised placebo controlled trials that compare transdermal fentanyl with a standard therapy such as controlled-release morphine.

Equivalence to oral drugs
Some limited studies have shown that transdermal fentanyl produces equivalent analgesia to controlled release with strong oral opioids. Typical opioid side-effects are emesis, somnolence, confusion, myoclonus and ventilatory depression.

Buprenorphine is a potent mu-receptor partial agonist with some antagonist activity at K sites.

There were initial concerns about the possibility of its avid binding to mu -receptors leading to non-naloxone reversible ventilatory depression, increased emesis, liability to abuse and reversal of morphine analgesia leading to pain and opioid withdrawal.

These fears have been unfounded, but in some countries they have made the use of this drug unpopular.

Transdermal buprenorphine was introduced into clinical practice in 2001 as a matrix patch, allowing controlled release of the drug over about 72 hours. It is available in 35mu g/h, 52.5mu g/h and 70mu g/h patches.

A recent innovation is the buprenorphine patch that delivers 5mu g/h, 10mu g/h, or 20mu g/h for a period of seven days.

Transdermal buprenorphine has analgesic efficacy, with a low incidence of systemic adverse effects. Indications for transdermal drugs include persistent moderate to severe cancer or non-cancer pain. Patients should be physically and psychologically evaluated before initiating strong opioid therapy.

Monitoring
Patients using transdermal opioid patches should be monitored for pain control, function in its widest sense, drug use and side-effects.

Tolerance is not a major problem once the correct dose is achieved. Increased dose requirement should prompt investigation for disease progression.

Problem drug use should be assessed and managed in consultation with a specialist addiction centre.

Transdermal drug delivery provides a simple route of administration that produces stable blood opioid concentrations and good analgesia. It is one option for the third step of the WHO analgesic ladder. Transdermal drug delivery is an advance in achieving non-invasive drug administration for the management of persistent cancer and non-cancer pain.

Dr Baranidharan is a specialist registrar in anaesthesia, Hull Royal Infirmary, Hull, and Dr Simpson is consultant in pain management, St James's University Hospital, Leeds

PROS AND CONS OF TRANSDERMAL ANALGESIA

PROS
- Easy to use.

- Few complications.

- Long duration of action.

- Can be very useful in patients who cannot take oral medications such as those with gastrointestinal problems.

- Can be useful in patients with cognitive impairment.

CONS
- Difficulty with rapid dose variation in response to circumstances.

- This route should not be used in those with pain that is changing quickly or for incident or breakthrough pain.

- Can cause skin irritation.

- Transdermal drugs take a long time to achieve steady-state plasma concentration.

FURTHER READING AND RESOURCES

- The British Pain Society. Recommendations for the appropriate use of opioids in patients with persistent non-cancer-related pain. www.britishpainsociety.org

- Muijsers R B, Wagstaff A J. Transdermal Fentanyl: An updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control. Drugs 2001; 61: 2,289-307.

- Allan L. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 2001; 322, 1,154.

- Dellemijn P L, Van-Duijn H, Vanneste J A. Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Sympt Man 1998; 16: 220-9.

- Ahmedzai S, Brooks D. Transdermal fentanyl versus sustained-release oral morphine in cancer pain: Preference, efficacy, and quality of life. The TTS-fentanyl comparative trial group. J Pain Sympt Man 1997; 13: 254-61.

- Radbruch-Lukas, Vielvoye-Kerkmeer-Ans. Buprenorphine TDS: the clinical development rationale and results. Internat J Clin Pract 2003; 133: 15-18.

- Sittl-Reinhard, Griessinger-Norbert, Likar-Rudolf. Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: A multicentre, randomised, double-blind, placebo, controlled trial. Clin Ther 2003; 25: 150-68.

- Spyker D A. Long-term use of buprenorphine transdermal system in patients with chronic pain. (Abst) Journal of American Geriatric Society 2002; 50 (Suppl. 4): S66

- Spyker D A. Analgesic efficacy and safety of buprenorphine transdermal system in patients with osteoarthritis. (Abst) Journal of Pain 2002; 3 (2 Suppl 1): 12.

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