T726 Ziconotide Adverse Events in Patients With Cancer Pain: A Multicenter Observational Study of a Slow Titration, Multidrug Protocol

Dupoiron, Denis; Monnin, Dominique; Lefebvre-Kuntz, Danièle; Boré, François; Brenet, Olivier; Lebrec, Nathalie; Bourmont, S. De; Dixmeria, F.; Buisset, N.

doi:10.1016/s1754-3207(11)70349-2

Cited by 17 publications

(30 citation statements)

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“…Bupivacaine additions revealed no statistically significant difference [42]. Dupoiron et al demonstrated efficacy in cancer pain with slow titration and multidrug use, including morphine, ropivacaine, and clonidine, with reduced side effects [47].…”

Section: Clinical Efficacymentioning

confidence: 99%

See 1 more Smart Citation

Ziconotide: a clinical update and pharmacologic review

Pope¹,

Deer

2013

Expert Opinion on Pharmacotherapy

125

110

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Ziconotide is a safe and effective strategy to treat chronic pain, although limitations remain, including a small therapeutic window. Low starting doses and slow incremental increases and long titration intervals may improve tolerability. AEs may be mitigated by also employing combination therapy, although further study is needed. Concomitant use of ziconotide and morphine is an option when considering use of FDA-labeled intrathecal drugs in those resistant to monotherapy.

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Section: Clinical Efficacymentioning

confidence: 99%

“…Dupoiron et al [47] recently surveyed the occurrence of AEs in a multicenter, observational study employing a slow titration protocol. Patients were enrolled from three comprehensive cancer centers in France, had incurable cancer, and had NRS of 6/10 or greater while on > 200 mg/day morphine equivalent.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Ziconotide: a clinical update and pharmacologic review

Pope¹,

Deer

2013

Expert Opinion on Pharmacotherapy

125

110

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“…No ITA-drug has been as thoroughly investigated as ziconotide, including three pivotal RCTs [199,229,246] and many open-label studies [2,68,73,77,196,214,247,258,260]. Typical opioid adverse events (AEs) such as respiratory depression, tolerance or dependence have not been described for ziconotide [215].…”

Section: Ziconotidementioning

confidence: 99%

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Bäckryd¹

2015

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The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain. In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question. In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor. In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses

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“…Ropivacaïne or bupivacaine are used to strengthen morphine effects by blocking nerve conduction in the sodium channels. Ziconotide is a small ω-conotoxine peptide isolated from a marine cone snail, Conus magus and acts as a selective blocker of voltage-sensitive calcium channels of N-type [8][9][10][11]. Due to its narrow therapeutic range and its potentially serious adverse effects (psychiatric and nervous system disorders), this drug is only indicated for the treatment of severe, chronic pain in adults who require intrathecal (IT) analgesia [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…Ziconotide is a particularly powerful drug. Its therapeutic index is low and adverse effects may occur at low doses (1 µg/day) [8,14,17]. The accuracy of the injected dose is therefore vital and no other clinical study has checked concentrations of ziconotide really infused.…”

Section: Introductionmentioning

confidence: 99%

Validation Study of UPLC Method for Determination of Morphine, Ropivacaïne and Ziconotide in Combination for Intrathecal Analgesia

Rossignol¹,

Sorrieul²,

Beaussart³

et al. 2016

J Anal Bioanal Tech

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Pain is often considered as the most feared symptom amongst individuals living with cancer. It can arrive at any stage during the course of the illness. In 15% to 20% of patients, conventional analgesic therapy either fails to relieve pain or induces adverse effects. Use of analgesic admixture has been recommended by the most recent consensus conferences. Several studies found evidence of synergistic effects of intrathecal analgesic admixtures, most notably these containing ziconotide, morphine and ropivacaïne, administering by a fully implantable pumps. The refills were prepared under a laminar airflow hood under strictly aseptic conditions, by the hospital pharmacist. This group of

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T726 Ziconotide Adverse Events in Patients With Cancer Pain: A Multicenter Observational Study of a Slow Titration, Multidrug Protocol

Cited by 17 publications

References 0 publications

Ziconotide: a clinical update and pharmacologic review

Ziconotide: a clinical update and pharmacologic review

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Validation Study of UPLC Method for Determination of Morphine, Ropivacaïne and Ziconotide in Combination for Intrathecal Analgesia

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