Long-Term Safety of NGX-4010, a High-Concentration Capsaicin Patch, in Patients with Peripheral Neuropathic Pain

Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Journal of pain and symptom management (Impact Factor: 2.8). 06/2010; 39(6):1053-64. DOI: 10.1016/j.jpainsymman.2009.11.316
Source: PubMed


Postherpetic neuralgia (PHN) and painful human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) are peripheral neuropathic pain syndromes that are difficult to treat. Current treatment options are often limited by poor tolerability.
The objective of the current open-label study was to assess the safety of repeated applications of NGX-4010, a high-concentration capsaicin patch (capsaicin 8%), over one year, in patients with moderate to severe PHN or HIV-DSP.
Patients had successfully completed a previous NGX-4010 study and had a pain level appropriate for further treatment. Eligible patients had not been treated with NGX-4010 within 12 weeks of study initiation. Patients received pretreatment with a topical local anesthetic (lidocaine 4%) for 60 minutes followed by either a 60-minute (PHN and HIV-DSP patients) or a 90-minute (HIV-DSP patients) treatment with NGX-4010. Patients could receive up to three additional treatments at intervals of > or = 12 weeks. Regardless of the number of treatments received, all patients were followed up for 48 weeks except for those withdrawing early.
A total of 106 patients were enrolled and received a total of 293 NGX-4010 treatments. The most frequently reported treatment-emergent adverse events were transient, mild-to-moderate application site erythema, pain, edema, and papules. Small, transient pain-related increases in blood pressure during and immediately after NGX-4010 application were observed. There was no evidence of an increased incidence of adverse events, dermal irritation, intolerability, or impaired neurological function with repeated treatments.
It is concluded that repeated treatments with NGX-4010 administered over a one-year period are generally safe and well tolerated.

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    • "Therapeutic potential of TRPV1 receptor agonists as analgesics has been studied extensively and analgesic effect was demonstrated in postsurgical pain, postherpetic neuralgia, mononeuropathies, radiculopathy , diabetic neuropathy, osteoarthritis, back pain, etc. (Spicarova and Palecek, 2008; Wong and Gavva, 2009; Treede et al., 2013; Schumacher and Pasvankas, 2014; Spicarova et al., 2014). Good analgesic effect of high-concentration capsaicin patch was shown especially in the treatment of postherpetic neuralgia (Backonja et al., 2010; Webster et al., 2010; Mou et al., 2013) and in the treatment of HIV-associated neuropathic pain (Simpson et al., 2010; Mou et al., 2013). Adlea (ALGRX-4975), an injectable TRPV1 receptor agonist, reduced significantly postoperative pain in patients undergoing total knee arthroplasty or bunionectomy (Remadevi and Szallisi, 2008). "
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    ABSTRACT: Allodynia and hyperalgesia present after surgical interventions are often a major complain of surgical patients. It is thought that both peripheral and central mechanisms contribute to these symptoms. In this study, the role of peripheral nerve fibres that express transient receptor potential vanilloid 1 (TRPV1) receptors in the activation of spinothalamic tract (STT) and postsynaptic dorsal column (PSDC) neurons was assessed in a model of surgical pain. Spinothalamic tract and PSDC neurons retrogradely labelled from the thalamus and nucleus gracilis were used. Activation of these projection neurons was evaluated after plantar incision as expression of the early gene product, c-Fos protein, in the nuclei of these neurons. There was a robust increase in c-Fos immunopositivity in the STT and PSDC neurons, in the control animals after a plantar incision. This increase in c-Fos expression was significantly attenuated in animals in which a single high-concentration capsaicin injection was made intradermally at the incision site 24 h before the surgery. Our results suggest that activation of both STT and PSDC neurons is involved in development of pain states present after surgical incision and that TRPV1-containing peripheral nerve fibres are needed for c-Fos expression in these dorsal horn neurons after plantar incision. © 2015 European Pain Federation - EFIC®
    Full-text · Article · Feb 2015 · European journal of pain (London, England)
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    • "Patch application results in reduced pain compared to a low concentration patch (0.04%, to control for local sensations) for up to 12 weeks in PHN (Backonja et al., 2008, 2010) and in HIV-distal polyneuropathy (Simpson et al., 2008). The long-term safety of the capsaicin patch was examined for up to 1 year with three to four patch applications at intervals of > 12 weeks; there was no evidence of impaired neurological function (Simpson et al., 2010). Post hoc analysis of controlled PHN studies of NGX-4010 indicated that patients not using oral neuropathic pain medications reported a greater reduction in pain compared to those using oral medications, suggesting lack of additivity of the topical NGX-4010 with oral medications (Irving et al., 2012). "
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    ABSTRACT: Topical analgesics applied locally to skin or to specialized compartments modify pain by actions on sensory nerve endings and/or adjacent cellular elements. With this approach, there are low systemic drug levels, good tolerability and few drug interactions, and combination with oral formulations is feasible. The goal of this review is to provide an overview of the potential for topical analgesics to contribute to improved management of neuropathic pain. Mechanistic and preclinical studies indicate much potential for development of novel topical analgesics for neuropathic pain. In humans, two topical analgesics are approved for use in post-herpetic neuralgia (lidocaine 5% medicated plaster, capsaicin 8% patch), and there is evidence for efficacy in other neuropathic pain conditions. Comparative trials indicate similar efficacy between topical and oral analgesics. Not all individuals respond to topical analgesics, and there is interest in determining factors (patient factors, sensory characteristics) which might predict responsiveness to topical analgesics. There is a growing number of controlled trials and case reports of investigational agents (vasodilators, glutamate receptor antagonists, α2-adrenoreceptor agonists, antidepressants, centrally acting drugs), including combinations of several agents, indicating these produce pain relief in neuropathic pain. There is interest in compounding topical analgesics for neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of neuropathic pain.
    Full-text · Article · Apr 2014 · European journal of pain (London, England)
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    • "A 48-week, open-label study included 52 HIV- DSN patients who had a successful response to the capsaicin 8% patch [Simpson et al. 2010]. Three to four further 60-or 90-min applications were allowed with an interval of at least 12 weeks between the two applications. "
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    ABSTRACT: In the European Union, the high-concentration capsaicin patch is licensed for the management of neuropathic pain conditions in nondiabetic patients, including postherpetic neuralgia (PHN) and HIV-associated distal sensory polyneuropathy (HIV-DSP). However, in the USA, the Food and Drug Administration approved its use only in PHN patients. Capsaicin is a transient receptor potential vanilloid-1 agonist, which increases the intracellular calcium ion concentration. This triggers calcium-dependent protease enzymes causing cytoskeletal breakdown and leads to the loss of cellular integrity and 'defunctionalization' of nociceptor fibres. Efficacy and therapeutic effect has been shown in several clinical studies of PHN and HIV-DSP. The high-concentration capsaicin patch and its practical application are different from low-concentration creams; one application can help for up to 3 months. The process of setting up of a service to use the capsaicin 8% patch is also discussed.
    Full-text · Article · Sep 2013 · Therapeutic Advances in Neurological Disorders
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