Trip Answers

Question answered:12/06/08

We found no guidance or studies on the management of severe osteoathritic pain in patients with fibrosing alveolitis.

 

However, the Medline database contains three clinical studies of fentanyl patches for the treatment of osteoarthritic pain and all appear to demonstrate their effectiveness to improve pain control. We will present brief details of these studies and will ask you to access the full abstracts of the studies by following the links given.

 

Langford R, McKenna F and Ratcliffe S et al. Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial. Arthritis Rheum. 2006 Jun;54(6):1829-37.Comment in: Arthritis Rheum. 2007 Feb;56(2):697-8. ( Medline abstract at: http://www.hubmed.org/display.cgi?uids=16729276)

 

“RESULTS: Data were available for 399 patients (202 receiving TDF [transdermal fentanyl], 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group. CONCLUSION: TDF can reduce pain and improve function in patients with knee or hip OA.”

 

Le Loët X, Pavelka K and Richarz U et al. Transdermal fentanyl for the treatment of pain caused by osteoarthritis of the knee or hip: an open, multicentre study. BMC Musculoskelet Disord. 2005 Jun 15;6:31. (http://www.hubmed.org/display.cgi?uids=15958159)

 

“…: Of the 159 patients recruited, 75 with OA knee and 44 with OA hip completed the treatment phase, 30 knee and 18 hip patients entered the one-week taper-off phase. The most frequently used maximum dose of TDF was 25 microg/hr. The number of patients with adequate pain control increased during the run-in period from 4% to 27%, and further increased during TDF treatment to 88% on day 28. From baseline to endpoint, there were significant reductions in pain (p < 0.001) and improvements in functioning (p < 0.001) and physical (p < 0.001) and mental (p < 0.05) health. Scores for 'pain right now' decreased significantly within 24 hours of starting TDF treatment. TDF was assessed favourably and 84% of patients would recommend it for OA-related pain. Nausea and vomiting were the most common adverse events (reported by 32% and 26% of patients respectively), despite prophylaxis with metoclopramide, which showed limited efficacy in this setting.”

 

Pavelka K, Le Loet X and Bjorneboe O et al. Benefits of transdermal fentanyl in patients with rheumatoid arthritis or with osteoarthritis of the knee or hip: an open-label study to assess pain control. Curr Med Res Opin. 2004 Dec;20(12):1967-77. (http://www.hubmed.org/display.cgi?uids=15701214)

 

“…CONCLUSIONS: TDF significantly improved pain control and quality of life, and was well tolerated in patients with RA or knee/hip OA who continued to experience pain on their current analgesic treatment. Treatment could be discontinued without issues. Nausea and vomiting was usually mild during treatment initiation. Patients' well being could be further accommodated by optimising prophylactic treatment.”

 

However, we consulted the SPC for Fentanyl to check the special warnings and precautions for use and found the following information:

 

“Fentanyl patches
4.4 Special warnings and precautions for use
Use of Durogesic DTrans in opioid-naïve patients has been associated with very rare cases of significant respiratory depression and/or fatality when used as initial opioid therapy. The potential for serious or life-threatening hypoventilation exists even if the lowest dose of Durogesic DTrans is used in initiating therapy in opioid naïve patients. It is recommended that Durogesic DTrans be used in patients who have demonstrated opioid tolerance (See Section 4.2).

 

When Durogesic DTrans is administered for chronic intractable pain that will require prolonged treatment, it is strongly recommended that the physician defines treatment outcomes with regards to pain relief and functional improvement in accordance with locally defined pain management guidelines. Physician and patient should agree to discontinue treatment if these objectives are not met.

Respiratory depression
As with all potent opioids, some patients may experience significant respiratory depression with Durogesic DTrans; patients must be observed for these effects. Respiratory depression may persist beyond the removal of the Durogesic DTrans patch. The incidence of respiratory depression increases as the Durogesic DTrans dose is increased (see Section 4.9). CNS active drugs may increase the respiratory depression (see section 4.5).

 

Interactions with CYP3A4 Inhibitors
The concomitant use of Durogesic DTrans with cytochrome P450 3A4 inhibitors (e.g. ritonavir, ketoconazole, itraconazole, clarithromycin, erythromycin, nelfinavir, verapamil, diltiazem, and amiodarone) may result in an increase in fentanyl plasma concentrations, which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression. In this situation special patient care and observation are appropriate. Therefore the concomitant use of transdermal fentanyl and cytochrome P450 3A4 inhibitors is not recommended unless the patient is closely monitored. Patients, especially those who are receiving Durogesic DTrans and CYP3A4 inhibitors should be monitored for signs of respiratory depression and dosage adjustments should be made if warranted.” [1]

 

In addition, we located one study evaluating the use of lidocaine 5% patch (a 2-week pilot study) and one assessing a topical diclofenac patch in patients with OA. In brief, the authors report:

 

Gammaitoni AR, Galer BS and Onawola R et al. Lidocaine patch 5% and its positive impact on pain qualities in osteoarthritis: results of a pilot 2-week, open-label study using the Neuropathic Pain Scale. Curr Med Res Opin. 2004;20 Suppl 2:S13-9. (http://www.hubmed.org/display.cgi?uids=15563742)

 

“CONCLUSIONS: In patients with moderate-to-severe OA of the knee, 2 weeks of treatment with the lidocaine patch 5% significantly reduces the intensity of pain qualities as measured by all 4 NPS composite measures. Our results coincide with previously reported improvements in pain and physical function in the same patient population, as measured by the Western Ontario and McMaster Universities OA Index. Measuring the various qualities of pain appears to be a valid approach for assessing clinical outcomes in the treatment of OA pain. Pain measures such as the NPS can capture the multi-dimensional properties of a patient's pain experience and may offer clinicians the possibility to identify differential effects of analgesic treatments on various pain qualities associated with OA.”

 

Finally, Bruhlmann and Michel note in the Medline abstract of their article:

 

“OBJECTIVE: To assess the efficacy and safety of a diclofenac hydroxyethylpyrrolidine (DHEP) patch in the treatment of symptomatic osteoarthritis (OA) of the knee joint. METHODS: A double-blind, randomised, placebo-controlled trial was carried out on 103 outpatients for 2 weeks. The main efficacy parameters were spontaneous pain and Lequesne's Index. Secondary endpoints were walking time over a standard distance, global assessment of efficacy and tolerability, and paracetamol consumption. RESULTS: The active treatment group showed a significant improvement in pain, Lequesne's Index, and the physician's and patient's global assessment of efficacy. For these parameters the difference between groups was statistically significant in favour of the DHEP patch. Adverse reactions were seen in a small number of probands and were similar in both groups.

 

CONCLUSIONS: The results of this trial suggest that the DHEP patch appears to be an effective and safe treatment for patients suffering from symptomatic knee OA.” [2]

 

We were unable to locate a SPC for lidocaine. However, the SPC for voltarol gel patch notes in section 4.4. entitled, ‘Special Warning and Precautions for Use’:

 

“Do not administer concurrently, by either the topical or the systemic route, any medicinal product containing diclofenac or other NSAIDs.
- Although systemic effects should be low, the plaster should be used with caution in patients with renal, cardiac or hepatic impairment, history of peptic ulceration or inflammatory bowel disease or bleeding diathesis. Non-steroidal anti-inflammatory drugs should be used with particular caution in elderly patients who are more prone to adverse events.
- This medicinal product contains methylparahydroxybenzoate and propylparahydroxybenzoate. It may cause allergic reactions (possibly delayed). It also contains propylene glycol, which may cause skin irritation.
- Patients should be warned against exposure to direct and solarium sunlight in order to reduce the risk of photosensitivity.
- Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergenic disease or allergy to acetylsalicylic acid or other NSAID. The medicated plaster should be used with caution in patients with or without chronic asthma in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin or other nonsteroidal anti-inflammatory agents (see 4.3 Contraindications).” [3]

 

As we have only be able to offer general information on the use of transdermal analgesia in OA and not specifically in patients with fibrosing alveolitis , we would suggest contacting a local specialist for further assistance with this query.

References
1. SPC for  Durogesic DTrans 12/25/50/75/100. December 2007. (http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=17086)
2. Brühlmann P and Michel BA.Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Clin Exp Rheumatol. 2003 Mar-Apr;21(2):193-8. (http://www.hubmed.org/display.cgi?uids=12747273)
3. SPC. Voltarol gel pathc. September 2007. (http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=16903)

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