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D. Dupoiron - One of the best experts on this subject based on the ideXlab platform.
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Intrathecal pain management with Ziconotide: Time for consensus?
Brain and behavior, 2021Co-Authors: Georgios Matis, D. Dupoiron, Pasquale De Negri, Rudolf Likar, Xander Zuidema, Dirk RascheAbstract:This article summarizes recommendations made by six pain specialists who discussed the rationale for Ziconotide intrathecal analgesia (ITA) and the requirement for evidence-based guidance on its use, from a European perspective. Riemser Pharma GmbH (Greifswald, Germany), which holds the European marketing authorization for Ziconotide, hosted the meeting. The group agreed that ITA is under-used in Europe, adding that Ziconotide ITA has potential to be a first-line alternative to morphine; both are already first-line options in the USA. Ziconotide ITA (initiated using a low-dose, slow-titration approach) is suitable for many patients with noncancer- or cancer-related chronic refractory pain and no history of psychosis. Adopting Ziconotide as first-line ITA could reduce opioid usage in these patient populations. The group advocated a risk-reduction strategy for all candidate patients, including compulsory prescreening for neuropsychosis, and requested US-European alignment of the licensed starting dose for Ziconotide: the low-and-slow approach practiced in the USA has a better tolerability profile than the fixed high starting dose licensed in Europe. Of note, an update to the European Summary of Product Characteristics is anticipated in early 2021. The group acknowledged that the Polyanalgesic Consensus Conference (PACC) treatment algorithms for Ziconotide ITA provide useful guidance, but recommendations tailored specifically for European settings are required. Before a consensus process can formally begin, the group called for additional European prospective studies to investigate Ziconotide in low-and-slow dosing strategies, in different patient settings. Such data would enable European guidance to have the most appropriate evidence at its core.
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Stability Study of Admixtures Combining Ziconotide With Morphine or Sufentanil in Polypropylene Syringes.
Neuromodulation : journal of the International Neuromodulation Society, 2020Co-Authors: Jérémy Sorrieul, D. Dupoiron, Julien Robert, Catherine DevysAbstract:Background The association of morphine Ziconotide or sufentanil Ziconotide was used to manage cancer pain. Moving these patients is sometimes difficult. In order to transport these syringes for pump refilling, it could be interesting to demonstrate the stability of the mixture and so to be able to ensure the best transport conditions of syringes. Materials and methods A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Fur mixtures of each association have been stored in 5 ± 3°C and 25 ± 2°C and were evaluated for seven days and compared to the initial observed concentrations. Results The stability of these associations was demonstrated at 5°C for seven days thanks to relative concentrations (95% confidence intervals of the mean of three samples) systematically positioned between 95% and 105%. No degradation product was observed during the stability study. Conclusion This study shows the stability of these association morphine Ziconotide or sufentanil Ziconotide at 5°C for seven days in polypropylen syringes. This result will allow the transport of the preparation under optimal conditions. Advance preparations for intrathecal pump refills could also be feasible.
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Study of Physicochemical Stability of Ziconotide in Medication Cassette Reservoir.
Neuromodulation : journal of the International Neuromodulation Society, 2020Co-Authors: Julien Robert, Jérémy Sorrieul, D. Dupoiron, Amelie Andrieu, Freddy Mounsef, Catherine DevysAbstract:OBJECTIVE To determine the physicochemical stability of Ziconotide solutions for intrathecal administration in the Medication Cassette Reservoir (MCR). MATERIALS AND METHODS A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Two mixtures of Ziconotide (0.40 μg/mL and 0.60 μg/mL) stored in MCR stored at 25 ± 2°C were evaluated for 14 days and compared to the initial observed concentrations. RESULTS The physicochemical stability of the two solutions was demonstrated for two days thanks to relative concentrations, pH measurement, visual inspections, and turbidity assays. A degradation product was observed and increased during the study. CONCLUSION This study showed a very low physicochemical stability of diluted Ziconotide stored at 25 ± 2°C in the MCR. The intrathecal administration of Ziconotide does not seem appropriate with this device for outpatients.
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Simultaneous Determination of Sufentanil and Ziconotide in Combination for Intrathecal Analgesia by UPLC-UV
Pharmaceutical Technology in Hospital Pharmacy, 2016Co-Authors: Jérémy Sorrieul, Vincent Gibory, Hélène Kieffer, Caroline Folliard, D. Dupoiron, Chau Phi Dinh, Catherine DevysAbstract:AbstractIntrathecal analgesia has increased over the past two decades based on high level proof of efficacy in patients with cancer. Morphine and Ziconotide remains the reference. Polyanalgesic Consensus Conference IT treatment algorithm recommends as the second line therapy opioids/Ziconotide combination. Sufentanil and Ziconotide combination can be used. The implantable pumps development helped to improve the comfort of the patient. The refills were prepared under a laminar airflow hood under strictly aseptic conditions, by the hospital pharmacist. In order to secure the process, a new analytical method by simple liquid chromatography ultraviolet spectrometry method was developed for the simultaneous quantification of two analgesic drugs (sufentanil, Ziconotide). The method was validated according to the recommendation of the US Food and Drug Administration (FDA). The method was linear between 0.1 to 4 μg/mL for Ziconotide and 3.125 to 50 µg/mL for sufentanil. This routine quality control analysis secures the production process.
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in vitro stability of low concentration Ziconotide alone or in admixtures in intrathecal pumps
Neuromodulation, 2014Co-Authors: D. Dupoiron, Catherine Devys, Hélène Richard, Pierre Leynia, Vincent Chabertdesnot, Michele BoisdroncelleAbstract:Objectives Ziconotide is often administered in combination with other analgesics via an intrathecal pump. Studies have established that Ziconotide is stable when delivered alone in high concentrations. No stability data are available, however, for Ziconotide given in low concentrations and/or with other analgesics as usually occurs in clinical oncology practice. The objective of this study was to assess the in vitro stability of Ziconotide alone and combined with other analgesics in intrathecal pumps at 37°C, as well as in syringes at 5°C, to evaluate conditions for storing and transporting preparations. Materials and Methods Various Ziconotide concentrations (0.1, 0.25, 0.5, and 0.75 μg/mL) were combined with an admixture of ropivacaine (7.5 mg/mL), morphine (7.5 mg/mL), and clonidine (15 μg/mL) in 20-mL intrathecal pumps at 37°C and in syringes at 5°C. Solutions of Ziconotide alone in concentrations of 0.25, 0.5, 0.75, and 1 μg/mL were introduced into pumps at 37°C and syringes at 5°C. Assays were performed using ultra high pressure liquid chromatography. Results In admixtures, mean Ziconotide concentrations decreased linearly to 53.4% (±3.33%) of baseline after 35 days. When Ziconotide was introduced alone in pumps at 37°C, the residual concentration on day 31 was 35.54% (±0.04%) with 0.25 μg/mL, 39.37% (±0.15%) with 0.5 μg/mL, and 44.49% (±0.18%) with 1 μg/mL. Ziconotide alone or combined with the other analgesics was stable in syringes stored at 5°C. The preparations complied with the prescriptions, with a mean error of less than 10%, except with the lowest Ziconotide concentration (0.1 μg/mL). Conclusions At the low Ziconotide concentrations studied, the degradation of Ziconotide admixed with other drugs was linear and only weakly influenced by the baseline concentration. Linear regression with intrapolation to 30 days showed that the degradation of Ziconotide admixed with other drugs was consistent with previously published data.
Mark S. Wallace - One of the best experts on this subject based on the ideXlab platform.
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Effectiveness and Safety of Intrathecal Ziconotide: Final Results of the Patient Registry of Intrathecal Ziconotide Management (PRIZM).
Pain medicine (Malden Mass.), 2020Co-Authors: Gladstone C. Mcdowell, Richard Rauck, Philip Kim, Michael Saulino, Mark S. Wallace, Eric Grigsby, I-zu Huang, Geertrui F. Vanhove, Robert Ryan, Timothy R. DeerAbstract:Background and objectives The Patient Registry of Intrathecal Ziconotide Management evaluated the long-term effectiveness and safety of intrathecal Ziconotide. Methods The study was a prospective, multicenter observational study of intrathecal Ziconotide in US clinical practice. Patients were adults with severe chronic pain that warranted intrathecal therapy. Ziconotide was initiated as the single agent in the pump; however, other intrathecal medications were permitted. The primary efficacy outcome was ≥30% reduction in numeric pain rating scale score from baseline at week 12. A secondary outcome was patient global impression of change. Adverse events were solicited at each visit. Results The registry enrolled 93 patients. Seventy-four and 28 patients completed 12 weeks and 18 months of treatment, respectively. In the overall patient population, 17.4% had ≥30% pain reduction from baseline at week 12, with a mean reduction in pain of 10.9%. At month 18, 38.5% of patients had ≥30% pain reduction from baseline, with a mean pain reduction of 24.7%. Patient-rated improvement was reported in 67% of patients at week 12 and 71% at month 18. Almost all patients experienced adverse events, the most common of which were nausea (25.8%), confusional state (22.6%), and dizziness (20.4%). Conclusions Final study analyses showed that intrathecal Ziconotide provided clinically meaningful pain relief in 17.4% and 38.5% of patients at week 12 and month 18, respectively. At these same time points, patient-rated improvement was reported in at least two-thirds of patients. The safety profile was consistent with that listed in the Ziconotide prescribing information.
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Effectiveness and Safety of Intrathecal Ziconotide: Interim Analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM)
Pain practice : the official journal of World Institute of Pain, 2017Co-Authors: Timothy R. Deer, Richard Rauck, Philip Kim, Michael Saulino, Mark S. Wallace, Eric Grigsby, I-zu Huang, Fannie Mori, Geertrui F. Vanhove, Gladstone McdowellAbstract:Background The Patient Registry of Intrathecal Ziconotide Management (PRIZM) evaluated long-term effectiveness, safety, and tolerability of intrathecal Ziconotide treatment in clinical practice. Methods Patient Registry of Intrathecal Ziconotide Management was an open-label, long-term, multicenter, observational study of adult patients with severe chronic pain. This interim analysis (data through July 10, 2015) of Ziconotide as the first vs. not first intrathecal agent in pump included change from baseline in the Numeric Pain Rating Scale (NPRS; primary efficacy measure) and Patient Global Impression of Change (PGIC) scores. Results Enrollment closed at 93 patients; data collection was ongoing at the time of this interim analysis. Fifty-one patients (54.8%) received Ziconotide as the first agent in pump (FIP+), whereas 42 (45.2%) did not (FIP−). Mean (SD) baseline NPRS scores were 7.4 (1.9) and 7.9 (1.6) in FIP+ and FIP− patients, respectively. Mean (SEM) percentage changes in NPRS scores were −29.4% (5.5%) in FIP+ patients (n = 26) and +6.4% (7.7%) in FIP− patients (n = 17) at month 6 and −34.4% (9.1%) in FIP+ patients (n = 14) and −3.4% (10.2%) in FIP− patients (n = 9) at month 12. Improvement from baseline, measured by PGIC score, was reported in 69.2% of FIP+ (n = 26) and 35.7% of FIP− (n = 14) patients at month 6 and 85.7% of FIP+ (n = 7) and 71.4% of FIP− (n = 7) patients at month 12. The most common adverse events (≥ 10% of patients overall as of the data cut) were nausea (19.6% vs. 7.1% of FIP+ vs. FIP− patients, respectively), confusional state (9.8% vs. 11.9%), and dizziness (13.7% vs. 7.1%). Conclusions Greater improvements in efficacy outcomes were observed when Ziconotide was initiated as first-line intrathecal therapy vs. not first intrathecal agent in pump. The adverse event profile was consistent with the Ziconotide prescribing information.
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Considerations and Methodology for Trialing Ziconotide
Pain physician, 2010Co-Authors: Allen W. Burton, Timothy R. Deer, Richard Rauck, Mark S. Wallace, Eric GrigsbyAbstract:BACKGROUND Before long-term intrathecal analgesic therapy is initiated, patients often undergo a spinal analgesia trial. Ziconotide is a nonopioid intrathecal analgesic used to manage severe chronic pain, and a variety of methods have been used to trial Ziconotide. OBJECTIVES The purpose of this review is to compare and discuss the different methods of Ziconotide trialing. METHODS Various databases (i.e., PubMed, Excerpta Medica, Cumulative Index to Nursing and Allied Health Literature, Biological Abstracts, Cochrane Database of Systematic Reviews, EMBASE, International Pharmaceutical Abstracts, and Google Scholar) and association meeting abstracts were searched with the use of the terms Ziconotide, Prialt, trial, and trialing. In addition, a search was conducted for abstracts/posters presented at a variety of association meetings. RESULTS Nine sources, including one expert opinion piece, were identified. Three methods of Ziconotide trialing were discovered: continuous infusion, limited-duration infusion, and bolus injection. Results indicate that patients often achieve analgesia during trialing, regardless of the trialing method. Adverse events reported during Ziconotide trialing studies were similar to those reported during Ziconotide clinical trials. Preliminary evidence suggests that both effectiveness and safety may be dose-related. In 3 studies the value of Ziconotide trialing in predicting long-term patient response to Ziconotide therapy was investigated; however, the results were preliminary. The expert opinion piece from 2008 recommended trialing Ziconotide via continuous infusion, using a starting dose of 1.2 mcg/d and dose increases of 1.2 mcg/d every 12 to 24 hours, for up to 3 days; the trial may be extended in some cases. LIMITATIONS Given the small samples size and lack of controlled Ziconotide trialing studies, it is currently not possible to determine the relative safety and effectiveness of different methods of Ziconotide trialing, nor is it possible to determine if trialing is predictive of patient response to long-term Ziconotide therapy. CONCLUSIONS All 3 methods of Ziconotide trialing appear to be viable options, and no method can be considered superior on the basis of the evidence presented in this review. Controlled studies comparing Ziconotide trialing methods may be warranted.
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Ziconotide combination intrathecal therapy: rationale and evidence.
The Clinical journal of pain, 2010Co-Authors: Mark S. Wallace, Richard Rauck, Timothy R. DeerAbstract:Background: Ziconotide is a nonopioid intrathecal analgesic used to manage moderate to severe chronic pain. Although Ziconotide is approved in the United States for intrathecal monotherapy only, it is often used in combination with other intrathecal drugs in clinical practice. Objectives: The need exists for a critical assessment of the currently available published literature on Ziconotide combination therapy. This review summarizes and evaluates the publications from preclinical and clinical peer-reviewed experiments that have investigated the safety and effectiveness of Ziconotide in combination with a variety of other drugs. Methods/Results: Eleven relevant publications were identified through a systematic search of multiple databases. Discussion: In preclinical studies, additive or synergistic antinociceptive effects were discovered when Ziconotide was used in combination with morphine, clonidine, or baclofen; however, no additional antinociceptive effects were observed when bupivacaine was added to Ziconotide therapy. Safety data from animal studies revealed that Ziconotide did not exacerbate morphine-induced respiratory depression, or clonidine-induced hypotension or bradycardia ; however, Ziconotide did potentiate morphine-induced hypotension and inhibition of gastrointestinal tract motility. Results from 2 open-label trials indicated that combination Ziconotide and morphine therapy produced greater analgesia than was produced by the use of either drug alone. Preliminary support for the use of Ziconotide in combination with morphine, baclofen, or hydromorphone was provided by case studies. Conclusions: Although clinical and preclinical studies provide some support for the use of Ziconotide in combination with morphine, hydromorphone, clonidine, or baclofen, strong evidence-based data are limited. Controlled, long-term clinical trials are warranted.
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Intrathecal Ziconotide for neuropathic pain: a review.
Pain practice : the official journal of World Institute of Pain, 2009Co-Authors: Richard Rauck, Mark S. Wallace, Allen W. Burton, Leonardo Kapural, James NorthAbstract:Neuropathic pain is a considerable burden that affects activities of daily living. The management of neuropathic pain can be challenging because of multiple etiologies and complex manifestations. Ziconotide is a nonopioid intrathecal (IT) analgesic option for patients with neuropathic pain refractory to conventional treatments. The objective of this article is to review the published literature on Ziconotide for the treatment of neuropathic pain. Relevant publications were identified through searches of all years of 6 databases, which included PubMed, EMBASE, and CINAHL. Search terms used were Ziconotide, SNX-111, MVIIA, Prialt, and neuropathic pain. Publications were included if Ziconotide was intrathecally administered (either alone or in combination with other IT agents) to treat neuropathic pain of any etiology and if pain assessment was an outcome measure. Data extracted included study design, IT drug doses, pain outcome measures, and adverse events (AEs). Twenty-eight articles met the inclusion criteria: 5 were preclinical studies and 23 were clinical studies. In the preclinical studies, Ziconotide demonstrated antiallodynic effects on neuropathic pain. Data from double-blind, placebo-controlled (DBPC) trials indicated that patients with neuropathic pain reported a mean percent improvement in pain score with Ziconotide monotherapy that ranged from 15.7% to 31.6%. A low starting dose and slow titration of Ziconotide resulted in an improved safety profile in the aforementioned trials. Common AEs associated with Ziconotide include nausea and/or vomiting, dizziness, confusion, urinary retention, and somnolence. Evidence from DBPC trials, open-label studies, case series, and case studies suggests that Ziconotide, as either monotherapy or in combination with other IT drugs, is a potential therapeutic option for patients with refractory neuropathic pain. Additional studies are needed to establish the long-term efficacy and safety of Ziconotide for neuropathic pain.
Timothy R. Deer - One of the best experts on this subject based on the ideXlab platform.
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Effectiveness and Safety of Intrathecal Ziconotide: Final Results of the Patient Registry of Intrathecal Ziconotide Management (PRIZM).
Pain medicine (Malden Mass.), 2020Co-Authors: Gladstone C. Mcdowell, Richard Rauck, Philip Kim, Michael Saulino, Mark S. Wallace, Eric Grigsby, I-zu Huang, Geertrui F. Vanhove, Robert Ryan, Timothy R. DeerAbstract:Background and objectives The Patient Registry of Intrathecal Ziconotide Management evaluated the long-term effectiveness and safety of intrathecal Ziconotide. Methods The study was a prospective, multicenter observational study of intrathecal Ziconotide in US clinical practice. Patients were adults with severe chronic pain that warranted intrathecal therapy. Ziconotide was initiated as the single agent in the pump; however, other intrathecal medications were permitted. The primary efficacy outcome was ≥30% reduction in numeric pain rating scale score from baseline at week 12. A secondary outcome was patient global impression of change. Adverse events were solicited at each visit. Results The registry enrolled 93 patients. Seventy-four and 28 patients completed 12 weeks and 18 months of treatment, respectively. In the overall patient population, 17.4% had ≥30% pain reduction from baseline at week 12, with a mean reduction in pain of 10.9%. At month 18, 38.5% of patients had ≥30% pain reduction from baseline, with a mean pain reduction of 24.7%. Patient-rated improvement was reported in 67% of patients at week 12 and 71% at month 18. Almost all patients experienced adverse events, the most common of which were nausea (25.8%), confusional state (22.6%), and dizziness (20.4%). Conclusions Final study analyses showed that intrathecal Ziconotide provided clinically meaningful pain relief in 17.4% and 38.5% of patients at week 12 and month 18, respectively. At these same time points, patient-rated improvement was reported in at least two-thirds of patients. The safety profile was consistent with that listed in the Ziconotide prescribing information.
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Intrathecal Therapy for Chronic Pain: A Review of Morphine and Ziconotide as Firstline Options.
Pain medicine (Malden Mass.), 2018Co-Authors: Timothy R. Deer, Michael Hanes, Jason E. Pope, Gladstone C. McdowellAbstract:Objectives To evaluate the evidence for morphine and Ziconotide as firstline intrathecal (IT) analgesia agents for patients with chronic pain. Methods Medline was searched (through July 2017) for "Ziconotide" or "morphine" AND "intrathecal" AND "chronic pain," with results limited to studies in human populations. Results The literature supports the use of morphine (based primarily on noncontrolled, prospective, and retrospective studies) and Ziconotide (based on randomized controlled trials and prospective observational studies) as first-choice IT therapies. The 2016 Polyanalgesic Consensus Conference (PACC) guidelines recommended both morphine and Ziconotide as firstline IT monotherapy for localized and diffuse chronic pain of cancer-related and non-cancer-related etiologies; however, one consensus point emphasized Ziconotide use, unless contraindicated, as firstline IT therapy in patients with chronic non-cancer-related pain. Initial IT therapy choice should take into consideration individual patient characteristics (e.g., pain location, response to previous therapies, comorbid medical conditions, psychiatric history). Trialing is recommended to assess medication efficacy and tolerability. For both morphine and Ziconotide, the PACC guidelines recommend conservative initial dosing strategies. Due to its narrow therapeutic window, Ziconotide requires careful dose titration. Ziconotide is contraindicated in patients with a history of psychosis. IT morphine administration may be associated with serious side effects (e.g., respiratory depression, catheter tip granuloma), require dose increases, and cause dependence over time. Conclusion Based on the available evidence, morphine and Ziconotide are recommended as firstline IT monotherapy for cancer-related and non-cancer-related pain. The choice of first-in-pump therapy should take into consideration patient characteristics and the advantages and disadvantages of each medication.
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Effectiveness and Safety of Intrathecal Ziconotide: Interim Analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM)
Pain practice : the official journal of World Institute of Pain, 2017Co-Authors: Timothy R. Deer, Richard Rauck, Philip Kim, Michael Saulino, Mark S. Wallace, Eric Grigsby, I-zu Huang, Fannie Mori, Geertrui F. Vanhove, Gladstone McdowellAbstract:Background The Patient Registry of Intrathecal Ziconotide Management (PRIZM) evaluated long-term effectiveness, safety, and tolerability of intrathecal Ziconotide treatment in clinical practice. Methods Patient Registry of Intrathecal Ziconotide Management was an open-label, long-term, multicenter, observational study of adult patients with severe chronic pain. This interim analysis (data through July 10, 2015) of Ziconotide as the first vs. not first intrathecal agent in pump included change from baseline in the Numeric Pain Rating Scale (NPRS; primary efficacy measure) and Patient Global Impression of Change (PGIC) scores. Results Enrollment closed at 93 patients; data collection was ongoing at the time of this interim analysis. Fifty-one patients (54.8%) received Ziconotide as the first agent in pump (FIP+), whereas 42 (45.2%) did not (FIP−). Mean (SD) baseline NPRS scores were 7.4 (1.9) and 7.9 (1.6) in FIP+ and FIP− patients, respectively. Mean (SEM) percentage changes in NPRS scores were −29.4% (5.5%) in FIP+ patients (n = 26) and +6.4% (7.7%) in FIP− patients (n = 17) at month 6 and −34.4% (9.1%) in FIP+ patients (n = 14) and −3.4% (10.2%) in FIP− patients (n = 9) at month 12. Improvement from baseline, measured by PGIC score, was reported in 69.2% of FIP+ (n = 26) and 35.7% of FIP− (n = 14) patients at month 6 and 85.7% of FIP+ (n = 7) and 71.4% of FIP− (n = 7) patients at month 12. The most common adverse events (≥ 10% of patients overall as of the data cut) were nausea (19.6% vs. 7.1% of FIP+ vs. FIP− patients, respectively), confusional state (9.8% vs. 11.9%), and dizziness (13.7% vs. 7.1%). Conclusions Greater improvements in efficacy outcomes were observed when Ziconotide was initiated as first-line intrathecal therapy vs. not first intrathecal agent in pump. The adverse event profile was consistent with the Ziconotide prescribing information.
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Intrathecal Pharmacology Update: Novel Dosing Strategy for Intrathecal Monotherapy Ziconotide on Efficacy and Sustainability.
Neuromodulation : journal of the International Neuromodulation Society, 2015Co-Authors: Jason E. Pope, Timothy R. DeerAbstract:Introduction Intrathecal drug delivery is a well-defined strategy to treat malignant and nonmalignant pain. Ziconotide is a well-studied intrathecal medicine option that has many attractive qualities, as it is non-granulomagenic, overdose or underdose is not associated with cardiopulmonary compromise or death, and is a non-opoid analgesic. However, it has had slow adoption into pain care algorithms because it has been historically plagued with the connotation of having a narrow therapeutic window and a low sustainability rate. We introduce a novel dosing strategy to improve patient outcomes and sustainability. Methods Patients were identified as being an intrathecal candidate and trialed with Ziconotide based on the current standard of care. Patient demographics, diagnosis, previous treatment failures, and pre-implant visual analog scale (VAS) scores were recorded. Once the trial was deemed successful, based on the dual bolusing strategy, the patient underwent device implantation. Consecutive patients were prospectively followed. Ziconotide was then initiated with a flex dosing strategy, weighted during nocturnal dosing. Outcome endpoints included: reduction in VAS, side effects, durability of therapy, and systemic opioid use prior to implant and at last visit were noted (calculated to daily morphine equivalents). Primary endpoint was tolerability of Ziconotide at three months following new dosing strategy. No industry support or funding was obtained for this project. Results All enrolled patients met the endpoint of the study of tolerability of Ziconotide at three months. Numbers declined to 75% of patients at four months, and 70% of patients at six months. The discontinuing side-effects were most commonly urinary retention and visual hallucinations. There were no serious adverse events and no unresolved complications reported. Numerical rating scale (NRS) decreased on average from 9.06 to 1.8. Opioid reduction in morphine equivalents averaged 91.5% Discussion The efficacy and tolerability of monotherapy Ziconotide may be improved by using a weighted bolus flex dosing strategy as compared with slow continuous infusions. Conclusion We present a novel strategy to deliver Ziconotide using a unique continuous infusion flex dosing strategy. Further randomized, prospective, higher-powered studies are needed to critically evaluate the conclusions suggested by this limited prospective case series.
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Considerations and Methodology for Trialing Ziconotide
Pain physician, 2010Co-Authors: Allen W. Burton, Timothy R. Deer, Richard Rauck, Mark S. Wallace, Eric GrigsbyAbstract:BACKGROUND Before long-term intrathecal analgesic therapy is initiated, patients often undergo a spinal analgesia trial. Ziconotide is a nonopioid intrathecal analgesic used to manage severe chronic pain, and a variety of methods have been used to trial Ziconotide. OBJECTIVES The purpose of this review is to compare and discuss the different methods of Ziconotide trialing. METHODS Various databases (i.e., PubMed, Excerpta Medica, Cumulative Index to Nursing and Allied Health Literature, Biological Abstracts, Cochrane Database of Systematic Reviews, EMBASE, International Pharmaceutical Abstracts, and Google Scholar) and association meeting abstracts were searched with the use of the terms Ziconotide, Prialt, trial, and trialing. In addition, a search was conducted for abstracts/posters presented at a variety of association meetings. RESULTS Nine sources, including one expert opinion piece, were identified. Three methods of Ziconotide trialing were discovered: continuous infusion, limited-duration infusion, and bolus injection. Results indicate that patients often achieve analgesia during trialing, regardless of the trialing method. Adverse events reported during Ziconotide trialing studies were similar to those reported during Ziconotide clinical trials. Preliminary evidence suggests that both effectiveness and safety may be dose-related. In 3 studies the value of Ziconotide trialing in predicting long-term patient response to Ziconotide therapy was investigated; however, the results were preliminary. The expert opinion piece from 2008 recommended trialing Ziconotide via continuous infusion, using a starting dose of 1.2 mcg/d and dose increases of 1.2 mcg/d every 12 to 24 hours, for up to 3 days; the trial may be extended in some cases. LIMITATIONS Given the small samples size and lack of controlled Ziconotide trialing studies, it is currently not possible to determine the relative safety and effectiveness of different methods of Ziconotide trialing, nor is it possible to determine if trialing is predictive of patient response to long-term Ziconotide therapy. CONCLUSIONS All 3 methods of Ziconotide trialing appear to be viable options, and no method can be considered superior on the basis of the evidence presented in this review. Controlled studies comparing Ziconotide trialing methods may be warranted.
Richard Rauck - One of the best experts on this subject based on the ideXlab platform.
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Effectiveness and Safety of Intrathecal Ziconotide: Final Results of the Patient Registry of Intrathecal Ziconotide Management (PRIZM).
Pain medicine (Malden Mass.), 2020Co-Authors: Gladstone C. Mcdowell, Richard Rauck, Philip Kim, Michael Saulino, Mark S. Wallace, Eric Grigsby, I-zu Huang, Geertrui F. Vanhove, Robert Ryan, Timothy R. DeerAbstract:Background and objectives The Patient Registry of Intrathecal Ziconotide Management evaluated the long-term effectiveness and safety of intrathecal Ziconotide. Methods The study was a prospective, multicenter observational study of intrathecal Ziconotide in US clinical practice. Patients were adults with severe chronic pain that warranted intrathecal therapy. Ziconotide was initiated as the single agent in the pump; however, other intrathecal medications were permitted. The primary efficacy outcome was ≥30% reduction in numeric pain rating scale score from baseline at week 12. A secondary outcome was patient global impression of change. Adverse events were solicited at each visit. Results The registry enrolled 93 patients. Seventy-four and 28 patients completed 12 weeks and 18 months of treatment, respectively. In the overall patient population, 17.4% had ≥30% pain reduction from baseline at week 12, with a mean reduction in pain of 10.9%. At month 18, 38.5% of patients had ≥30% pain reduction from baseline, with a mean pain reduction of 24.7%. Patient-rated improvement was reported in 67% of patients at week 12 and 71% at month 18. Almost all patients experienced adverse events, the most common of which were nausea (25.8%), confusional state (22.6%), and dizziness (20.4%). Conclusions Final study analyses showed that intrathecal Ziconotide provided clinically meaningful pain relief in 17.4% and 38.5% of patients at week 12 and month 18, respectively. At these same time points, patient-rated improvement was reported in at least two-thirds of patients. The safety profile was consistent with that listed in the Ziconotide prescribing information.
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Effectiveness and Safety of Intrathecal Ziconotide: Interim Analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM)
Pain practice : the official journal of World Institute of Pain, 2017Co-Authors: Timothy R. Deer, Richard Rauck, Philip Kim, Michael Saulino, Mark S. Wallace, Eric Grigsby, I-zu Huang, Fannie Mori, Geertrui F. Vanhove, Gladstone McdowellAbstract:Background The Patient Registry of Intrathecal Ziconotide Management (PRIZM) evaluated long-term effectiveness, safety, and tolerability of intrathecal Ziconotide treatment in clinical practice. Methods Patient Registry of Intrathecal Ziconotide Management was an open-label, long-term, multicenter, observational study of adult patients with severe chronic pain. This interim analysis (data through July 10, 2015) of Ziconotide as the first vs. not first intrathecal agent in pump included change from baseline in the Numeric Pain Rating Scale (NPRS; primary efficacy measure) and Patient Global Impression of Change (PGIC) scores. Results Enrollment closed at 93 patients; data collection was ongoing at the time of this interim analysis. Fifty-one patients (54.8%) received Ziconotide as the first agent in pump (FIP+), whereas 42 (45.2%) did not (FIP−). Mean (SD) baseline NPRS scores were 7.4 (1.9) and 7.9 (1.6) in FIP+ and FIP− patients, respectively. Mean (SEM) percentage changes in NPRS scores were −29.4% (5.5%) in FIP+ patients (n = 26) and +6.4% (7.7%) in FIP− patients (n = 17) at month 6 and −34.4% (9.1%) in FIP+ patients (n = 14) and −3.4% (10.2%) in FIP− patients (n = 9) at month 12. Improvement from baseline, measured by PGIC score, was reported in 69.2% of FIP+ (n = 26) and 35.7% of FIP− (n = 14) patients at month 6 and 85.7% of FIP+ (n = 7) and 71.4% of FIP− (n = 7) patients at month 12. The most common adverse events (≥ 10% of patients overall as of the data cut) were nausea (19.6% vs. 7.1% of FIP+ vs. FIP− patients, respectively), confusional state (9.8% vs. 11.9%), and dizziness (13.7% vs. 7.1%). Conclusions Greater improvements in efficacy outcomes were observed when Ziconotide was initiated as first-line intrathecal therapy vs. not first intrathecal agent in pump. The adverse event profile was consistent with the Ziconotide prescribing information.
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Considerations and Methodology for Trialing Ziconotide
Pain physician, 2010Co-Authors: Allen W. Burton, Timothy R. Deer, Richard Rauck, Mark S. Wallace, Eric GrigsbyAbstract:BACKGROUND Before long-term intrathecal analgesic therapy is initiated, patients often undergo a spinal analgesia trial. Ziconotide is a nonopioid intrathecal analgesic used to manage severe chronic pain, and a variety of methods have been used to trial Ziconotide. OBJECTIVES The purpose of this review is to compare and discuss the different methods of Ziconotide trialing. METHODS Various databases (i.e., PubMed, Excerpta Medica, Cumulative Index to Nursing and Allied Health Literature, Biological Abstracts, Cochrane Database of Systematic Reviews, EMBASE, International Pharmaceutical Abstracts, and Google Scholar) and association meeting abstracts were searched with the use of the terms Ziconotide, Prialt, trial, and trialing. In addition, a search was conducted for abstracts/posters presented at a variety of association meetings. RESULTS Nine sources, including one expert opinion piece, were identified. Three methods of Ziconotide trialing were discovered: continuous infusion, limited-duration infusion, and bolus injection. Results indicate that patients often achieve analgesia during trialing, regardless of the trialing method. Adverse events reported during Ziconotide trialing studies were similar to those reported during Ziconotide clinical trials. Preliminary evidence suggests that both effectiveness and safety may be dose-related. In 3 studies the value of Ziconotide trialing in predicting long-term patient response to Ziconotide therapy was investigated; however, the results were preliminary. The expert opinion piece from 2008 recommended trialing Ziconotide via continuous infusion, using a starting dose of 1.2 mcg/d and dose increases of 1.2 mcg/d every 12 to 24 hours, for up to 3 days; the trial may be extended in some cases. LIMITATIONS Given the small samples size and lack of controlled Ziconotide trialing studies, it is currently not possible to determine the relative safety and effectiveness of different methods of Ziconotide trialing, nor is it possible to determine if trialing is predictive of patient response to long-term Ziconotide therapy. CONCLUSIONS All 3 methods of Ziconotide trialing appear to be viable options, and no method can be considered superior on the basis of the evidence presented in this review. Controlled studies comparing Ziconotide trialing methods may be warranted.
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Ziconotide combination intrathecal therapy: rationale and evidence.
The Clinical journal of pain, 2010Co-Authors: Mark S. Wallace, Richard Rauck, Timothy R. DeerAbstract:Background: Ziconotide is a nonopioid intrathecal analgesic used to manage moderate to severe chronic pain. Although Ziconotide is approved in the United States for intrathecal monotherapy only, it is often used in combination with other intrathecal drugs in clinical practice. Objectives: The need exists for a critical assessment of the currently available published literature on Ziconotide combination therapy. This review summarizes and evaluates the publications from preclinical and clinical peer-reviewed experiments that have investigated the safety and effectiveness of Ziconotide in combination with a variety of other drugs. Methods/Results: Eleven relevant publications were identified through a systematic search of multiple databases. Discussion: In preclinical studies, additive or synergistic antinociceptive effects were discovered when Ziconotide was used in combination with morphine, clonidine, or baclofen; however, no additional antinociceptive effects were observed when bupivacaine was added to Ziconotide therapy. Safety data from animal studies revealed that Ziconotide did not exacerbate morphine-induced respiratory depression, or clonidine-induced hypotension or bradycardia ; however, Ziconotide did potentiate morphine-induced hypotension and inhibition of gastrointestinal tract motility. Results from 2 open-label trials indicated that combination Ziconotide and morphine therapy produced greater analgesia than was produced by the use of either drug alone. Preliminary support for the use of Ziconotide in combination with morphine, baclofen, or hydromorphone was provided by case studies. Conclusions: Although clinical and preclinical studies provide some support for the use of Ziconotide in combination with morphine, hydromorphone, clonidine, or baclofen, strong evidence-based data are limited. Controlled, long-term clinical trials are warranted.
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Intrathecal Ziconotide for neuropathic pain: a review.
Pain practice : the official journal of World Institute of Pain, 2009Co-Authors: Richard Rauck, Mark S. Wallace, Allen W. Burton, Leonardo Kapural, James NorthAbstract:Neuropathic pain is a considerable burden that affects activities of daily living. The management of neuropathic pain can be challenging because of multiple etiologies and complex manifestations. Ziconotide is a nonopioid intrathecal (IT) analgesic option for patients with neuropathic pain refractory to conventional treatments. The objective of this article is to review the published literature on Ziconotide for the treatment of neuropathic pain. Relevant publications were identified through searches of all years of 6 databases, which included PubMed, EMBASE, and CINAHL. Search terms used were Ziconotide, SNX-111, MVIIA, Prialt, and neuropathic pain. Publications were included if Ziconotide was intrathecally administered (either alone or in combination with other IT agents) to treat neuropathic pain of any etiology and if pain assessment was an outcome measure. Data extracted included study design, IT drug doses, pain outcome measures, and adverse events (AEs). Twenty-eight articles met the inclusion criteria: 5 were preclinical studies and 23 were clinical studies. In the preclinical studies, Ziconotide demonstrated antiallodynic effects on neuropathic pain. Data from double-blind, placebo-controlled (DBPC) trials indicated that patients with neuropathic pain reported a mean percent improvement in pain score with Ziconotide monotherapy that ranged from 15.7% to 31.6%. A low starting dose and slow titration of Ziconotide resulted in an improved safety profile in the aforementioned trials. Common AEs associated with Ziconotide include nausea and/or vomiting, dizziness, confusion, urinary retention, and somnolence. Evidence from DBPC trials, open-label studies, case series, and case studies suggests that Ziconotide, as either monotherapy or in combination with other IT drugs, is a potential therapeutic option for patients with refractory neuropathic pain. Additional studies are needed to establish the long-term efficacy and safety of Ziconotide for neuropathic pain.
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Ziconotide adverse events in patients with cancer pain: a multicenter observational study of a slow titration, multidrug protocol.
Pain physician, 2012Co-Authors: D. Dupoiron, François Boré, Daniele Lefebvre-kuntz, Olivier Brenet, Sabine Debourmont, F. Dixmerias, Nadia Buisset, Nathalie Lebrec, D. MonninAbstract:Background Ziconotide is a new analgesic agent administered intrathecally. It is challenging to use and can induce several and sometimes serious adverse events. A low initial dosage followed by slow titration may reduce serious adverse events. Objective To determine whether a low starting dosage of Ziconotide, followed by slow titration, decreases the incidence of major adverse events associated with Ziconotide when used for intractable cancer pain. Study design Observational cohort study. Setting Three French cancer centers. Methods Patients with incurable cancer causing chronic pain rated above 6/10 on a numerical scale while receiving high-dose opioid therapy (more than 200 mg/d of oral morphine equivalent) and/or exhibiting severe opioid-related adverse events received intrathecal infusions of Ziconotide combined with morphine, ropivacaine, and clonidine. Results Seventy-seven patients were included. Adverse events were recorded in 57% of them; moderate adverse events occurred in 51%. Adverse events required treatment discontinuation in 7 (9%) including 5 (6%) for whom a causal role for Ziconotide was highly likely; among them 4 (5%) were serious. All patients experienced a significant and lasting decrease in pain intensity (by 48%) in response to intrathecal analgesic therapy that included Ziconotide. Limitations Limitations include the nonrandomized, observational nature of the study. Determining the relative contributions of each drug to adverse events was difficult, and some of the adverse events manifested as clinical symptoms of a subjective nature. Conclusions The rates of minor and moderate adverse events were consistent with previous reports. However, the rate of serious adverse events was substantially lower. Our study confirms the efficacy of intrathecal analgesia with Ziconotide for relieving refractory cancer pain. These results indicate that multimodal intrathecal analgesia in patients with cancer pain should include Ziconotide from the outset in order to provide time for subsequent slow titration.
