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The Canadian Journal of Urology Dec 2023How should a conscientious physician advise patients with Interstitial Cystitis /Bladder Pain Syndrome (IC/BPS) when they want to know if taking Pentosan Polysulfate...
How should a conscientious physician advise patients with Interstitial Cystitis /Bladder Pain Syndrome (IC/BPS) when they want to know if taking Pentosan Polysulfate Sodium (PPS) will lead to loss of vision? Ever since the initial report from Pearce et al in 2018 suggesting that PPS usage can lead to the development of pigmented maculopathy (PM), my patients have been inundated with solicitations from attorneys looking to sign up clients for class action lawsuits.1 While there have been additional reports suggesting a relationship between PPS exposure and the development of PM, Ludwig et al found that there was no difference in the rate of macular disease between patients with documented IC/BPS who had taken PPS and those with IC/BPS with no history of PPS use.2 The large size of Ludwig's study certainly suggests that PPS may not cause PM to develop, and if the rate of PM in the IC population is higher than in controls, it may be due to the disease itself and not from the medication. In this manuscript, Proctor clearly describes the immune inflammatory response that is responsible for the development of the bladder damage seen with IC/BPS. Also, he describes how inflammatory mediators can enter the blood stream and might be a potential cause for the development of PM.3 This is a thought-provoking hypothesis that demands further evaluation. I have prescribed PPS since its approval and have many patients who feel it is an essential part of their IC treatment regimen. There is no other prescription medication that functions in the same fashion. I require them to follow the FDA recommendations for annual eye exams to look for PM development. I also advise patients that as they improve, we will discuss dose reduction and even discontinuation if their IC symptoms have abated. By following these suggestions, one should be able to continue to prescribe PPS for appropriate patients while carefully monitoring them for PM. I found this article extremely informative and will refer to it when counseling patients about IC/BPS and PPS.
Topics: Male; Humans; Pentosan Sulfuric Polyester; Cystitis, Interstitial; Macular Degeneration
PubMed: 38104331
DOI: No ID Found -
Ophthalmology. Retina Mar 2024To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used.
OBJECTIVE
To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used.
DESIGN
Population-based cohort study.
PARTICIPANTS
For evaluation of nationwide usage, 133 762 individuals who received PPS prescriptions between 2012 and 2021 were included. To investigate practice patterns, 55 487 individuals (referred to as overall users) who initiated PPS therapy between 2018 and 2020 were identified using the Health Insurance Review and Assessment database. After excluding patients with ophthalmic diseases before PPS administration, 34 857 PPS users without prior ophthalmic diseases were identified.
METHODS
Ophthalmic examinations performed after initiating PPS therapy were categorized as baseline and subsequent monitoring examinations. The timing and modalities employed for these examinations were analyzed. The annual trends in PPS utilization and maculopathy screening were evaluated by assessing the number of PPS users and determining the proportion of patients receiving retinal/macular examinations among these users.
MAIN OUTCOME MEASURES
Performance of baseline and subsequent monitoring examinations and timing and modalities used for screening.
RESULTS
The number of PPS users dramatically increased annually over the study period from 5494 in 2012 to 40 451 in 2021. However, the majority of PPS users did not undergo baseline or subsequent monitoring examinations for PPM. Only 27.2% and 12.4% of PPS users without prior ophthalmic disease underwent baseline and monitoring examinations, respectively. Funduscopy/fundus photography was the most commonly utilized, whereas OCT and fundus autofluorescence (FAF) were performed in only 45.2% and 5.3% of the PPS users without prior ophthalmic diseases for monitoring, respectively. The performance of the screening examinations differed significantly across the 3 different daily dose and duration groups (all P < 0.05).
CONCLUSIONS
This study highlights the lack of performance of baseline and monitoring examinations for maculopathy in most patients taking PPS in South Korea. The limited use of OCT and FAF suggests potential insensitivity in detecting PPM. These findings emphasize the need for improvements in screening practices, including increased awareness and referrals to ophthalmologists, utilization of more sensitive modalities, and regular monitoring to enable early detection of PPM.
FINANCIAL DISCLOSURE(S)
The authors have no proprietary or commercial interest in any materials discussed in this article.
Topics: Humans; Pentosan Sulfuric Polyester; Cohort Studies; Retinal Diseases; Macular Degeneration; Republic of Korea
PubMed: 37832716
DOI: 10.1016/j.oret.2023.10.005 -
BMJ Open May 2024Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain...
INTRODUCTION
Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia.
METHODS AND ANALYSIS
MaRVeL is a phase II, single-centre, parallel, superiority trial which will be conducted at Royal North Shore Hospital, Sydney, Australia. 92 participants (46 per arm) aged 40 and over with painful knee OA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) will be recruited from the community and randomly allocated to receive two cycles of either oral PPS or placebo for 5 weeks starting at baseline and week 11. Primary outcome will be the 16-week change in overall average knee pain severity measured using an 11-point Numeric Rating Scale. Main secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life and other structural changes. A biostatistician blinded to allocation groups will perform the statistical analysis according to the intention-to-treat principle.
ETHICS AND DISSEMINATION
The protocol has been approved by the NSLHD Human Research Ethics Committee (HREC) (2021/ETH00315). All participants will provide written informed consent online. Study results will be disseminated through conferences, social media and academic publications.
TRIAL REGISTRATION NUMBERS
Australian New Zealand Clinical Trial Registry (ACTRN12621000654853); U1111-1265-3750.
Topics: Humans; Osteoarthritis, Knee; Pentosan Sulfuric Polyester; Dyslipidemias; Quality of Life; Male; Treatment Outcome; Female; Middle Aged; Clinical Trials, Phase II as Topic; Australia; Pain Measurement; Adult
PubMed: 38777590
DOI: 10.1136/bmjopen-2023-083046 -
Ophthalmology. Retina Nov 2023
Topics: Humans; Pentosan Sulfuric Polyester; Visual Field Tests; Macular Degeneration; Retinal Diseases
PubMed: 37619623
DOI: 10.1016/j.oret.2023.08.009 -
Current Opinion in Ophthalmology May 2021The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS). (Review)
Review
PURPOSE OF REVIEW
The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS).
RECENT FINDINGS
PPS toxicity was described in 2018, and additional studies characterize it as dysfunction of the retinal pigment epithelium centered on the posterior pole, which can progress despite drug cessation. Requisite exposure can be as little as 0.325 kg and 2.25 years but averages closer to 1-2 kg and 10-15 years. Multimodal imaging should include near-infrared reflectance, optical coherence tomography, and fundus autofluorescence. Cross-sectional studies demonstrate evidence correlating cumulative dosing and the likelihood/severity of maculopathy. Early estimates of prevalence range from 12.7 to 41.7% depending on dosing, with overall rates around 20%.
SUMMARY
Reasonable evidence associates maculopathy with extended exposure to PPS, with an average reported incidence of around 20% in patients with long-term exposures. Patients with unexplained retinal pigment epithelium changes and difficulty with dark adaptation should be questioned regarding PPS exposure, and patients with known exposure to PPS should be examined. Further research is needed to refine screening protocols. Currently, providers should consider baseline examination and examination at 5 years and/or 500 g of exposure followed by yearly screening.
Topics: Anticoagulants; Drug-Related Side Effects and Adverse Reactions; Humans; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium
PubMed: 33710012
DOI: 10.1097/ICU.0000000000000754 -
The Analyst Aug 2019Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan,...
Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan, is the active pharmaceutical ingredient of the drug Elmiron™ used to treat interstitial cystitis. Unlike natural GAGs that can be enzymatically broken down into oligosaccharides for analysis, PPS is an unnatural polyanionic polysaccharide and is not amenable to such an analytical approach. Instead reactive oxygen species were used for the controlled depolymerization of PPS and the resulting oligosaccharide fragments were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to obtain bottom-up information on its composition. Because PPS has an average molecular weight ranging from 4000 to 6000 Da, similar to that of low molecular weight heparin, this suggested that it might be possible to use LC-MS on its intact chains and perform top-down analysis. The bottom-up and top-down analysis of PPS provides the first detailed compositional and structural information on PPS. Finally, we examined whether PPS would interfere with polysaccharide lyases and hydrolases, used in the analysis of natural GAGs such as chondroitin sulfates, heparan sulfate, and keratan sulfates. We found that PPS did not interfere with GAG analysis, suggesting that a combination of chemical and enzymatic treatment could be used to analyze samples containing both natural GAGs and PPS.
Topics: Chromatography, Liquid; Glycosaminoglycans; Hydrogen Peroxide; Mass Spectrometry; Oligosaccharides; Organometallic Compounds; Oxidation-Reduction; Pentosan Sulfuric Polyester
PubMed: 31287456
DOI: 10.1039/c9an01006h -
Fundamental & Clinical Pharmacology Oct 2022Pentosan polysulfate sodium (PPS) is a polysulfated glycosaminoglycan approved for the treatment of interstitial cystitis. It also showed renoprotective effects in...
Pentosan polysulfate sodium (PPS) is a polysulfated glycosaminoglycan approved for the treatment of interstitial cystitis. It also showed renoprotective effects in chronic kidney injury models, for example, 5/6 nephrectomy and diabetic nephropathy (DN). In the present study, we addressed to evaluate the therapeutic value of PPS in DN of rats in combination with losartan (LSR). Sixty male Sprague-Dawley rats were randomly divided into six groups: control group, untreated diabetic groups (8 and 16 weeks after diabetes induction by streptozotocin "STZ", 60 mg/kg, intraperitoneal [I.P.]), LSR-treated diabetic group (10 mg/kg/day, P.O.), PPS-treated diabetic group (25 mg/kg/day, P.O.), and combination-treated diabetic group. Drug treatment was started 8 weeks after induction of diabetes and continued for a further 8 weeks. Renal functions, albuminuria, renal IL-6, oxidative stress, and renal histopathology were evaluated. STZ-treated diabetic rats developed progressive albuminuria, renal dysfunction, and significant glomerular change 16 weeks after induction of diabetes. Administration of PPS, alone or in combination with LSR, showed some beneficial effects on DN evolution and significantly decreased renal inflammation as detected by IL-6 level. The best beneficial effect on DN evolution was obtained by PPS sole therapy based on albuminuria evaluation and renal histopathology. However, the combination of PPS and LSR did not show additive benefits. This study reported that the renoprotection of PPS in the setting of DN is evident by exerting anti-inflammatory and antioxidant effects, but this effect could be masked when combined with an angiotensin receptor blocker.
Topics: Albuminuria; Animals; Anti-Inflammatory Agents; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Interleukin-6; Kidney; Losartan; Male; Pentosan Sulfuric Polyester; Rats; Rats, Sprague-Dawley; Streptozocin
PubMed: 35434832
DOI: 10.1111/fcp.12781 -
Ophthalmic Surgery, Lasers & Imaging... Jul 2023To compare the risk factors for the development and progression of pigmentary retinopathy in patients exposed to pentosan polysulfate sodium (PPS).
BACKGROUND AND OBJECTIVE
To compare the risk factors for the development and progression of pigmentary retinopathy in patients exposed to pentosan polysulfate sodium (PPS).
MATERIALS AND METHODS
Retrospective cohort study of patients exposed to PPS with at least two follow-up visits with multimodal imaging.
RESULTS
A total of 97 patients were included (33 with PPS-associated retinopathy and 64 without). The average follow-up was 29.4 months, overall cumulative dose was 1,220 ± 910 g (1,730 ± 870 vs 959 ± 910; < 0.0001), and total PPS duration was 12.1 ± 7.1 years (16.0.2 ± 6.1 vs 10.1 ± 6.9; < 0.0001). The best-corrected visual acuity remained stable during follow-up. At presentation, the average area of the retinopathy in the worse eye was 54.1 ± 50 mm in the PPS-retinopathy group, worsening at a rate of 6.10 ± 10 mm/year. Patients who developed choroidal neovascular membranes (CNVMs) had faster rates of retinopathy progression (11.6 ± 12 vs 3.53 ± 7.6 mm/year, = 0.036). No patient had the exact same gene mutation.
CONCLUSION
PPS-associated pigmentary retinopathy can continue to progress over time, even after discontinuing the medication. CNVM development may be associated with faster rates of retinopathy progression. .
Topics: Humans; Pentosan Sulfuric Polyester; Follow-Up Studies; Retrospective Studies; Retinal Diseases; Retinitis Pigmentosa; Sodium
PubMed: 37310751
DOI: 10.3928/23258160-20230522-02 -
Canadian Journal of Ophthalmology.... Feb 2022To evaluate whether pentosan polysulfate maculopathy manifests distinctive imaging features that can be differentiated from those found in age-related macular...
OBJECTIVE
To evaluate whether pentosan polysulfate maculopathy manifests distinctive imaging features that can be differentiated from those found in age-related macular degeneration (AMD).
METHODS
Local databases were queried to identify patients with a diagnosis of interstitial cystitis who were seen at the Emory Eye Center between May 2014 and January 2019 and who had fundus imaging available for review. Ninety patients met the eligibility criteria. Masked graders categorized patients based on imaging characteristics as follows: category 1: pentosan polysulfate maculopathy; category 2: AMD or drusen; category 3: neither; and category 4: unsure. Pentosan polysulfate exposure characteristics were compared among groups.
RESULTS
Of the 90 subjects evaluated, 79 (88%) were female and the median age was 61.5 years (range, 30-89). Seventeen patients were placed in category 1; 25 in category 2; 47 in category 3, and; 1 in category 4. Among categories 1 to 4, respectively, 17 (100%), 15 (60%), 28 (60%), and 0 patients had exposure to pentosan polysulfate (p = 0.007). Mean cumulative exposure to pentosan polysulfate across the four categories was 2.1, 0.36, 0.34, and 0 kg, respectively (p < 0.00001). Eyes with pentosan polysulfate maculopathy did not have typical drusen in the macula.
CONCLUSION
Although pentosan polysulfate maculopathy resembles some aspects of AMD, the two conditions can be differentiated with the use of multimodal fundus imaging.
Topics: Anticoagulants; Female; Humans; Macula Lutea; Macular Degeneration; Male; Middle Aged; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Diseases
PubMed: 33722504
DOI: 10.1016/j.jcjo.2021.02.007 -
Clinical Ophthalmology (Auckland, N.Z.) 2021To evaluate the risk factors and fundus findings of patients with potential PPS-associated retinopathy.
PURPOSE
To evaluate the risk factors and fundus findings of patients with potential PPS-associated retinopathy.
PATIENTS AND METHODS
A retrospective chart review was performed of patients exposed to PPS who had a dilated fundus examination at a large retina-only practice from 2018-21. Multimodal images were evaluated by masked reviewers.
RESULTS
A total of 148 patients were included, of whom 33 (22%) had PPS-associated retinopathy, and 115 (78%) did not. The mean age was 60.3 years old, and the mean follow-up was 11.8 months. The PPS-associated retinopathy group had higher mean cumulative doses of PPS (1600g±849 vs 864g±852, < 0.0001, Mann-Whitney test) and longer duration of PPS use (13.6 years vs 7.48, < 0.0001). There was no statistically significant difference based on a history of kidney or liver disease or the dosage per day for the weight, body mass index, body surface area, or lean body weight. Of the patients with PPS-associated retinopathy whose genetic results were available, 15 of 16 (93%) were heterozygous for variants of uncertain significance.
CONCLUSION
A longer duration of PPS use and higher cumulative dosage of PPS were associated with an increased risk of developing PPS-associated pigmentary retinopathy. The role of genetic mutations in patients exposed to PPS is still to be determined.
PubMed: 34992341
DOI: 10.2147/OPTH.S340041