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JAMA Ophthalmology Jan 2022Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to...
IMPORTANCE
Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to quantify this association have yielded equivocal results.
OBJECTIVE
To estimate the association between PPS exposure and maculopathy.
DESIGN, SETTING, AND PARTICIPANTS
This disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from January 2013 through June 2020.
EXPOSURE
Adverse event reports for pentosan polysulfate were selected and compared with adverse event reports associated with drugs taken for the following indications: interstitial cystitis, cystitis, bladder disorder, or bladder pain.
MAIN OUTCOME MEASURES
Retinal adverse events were identified using the retinal disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query, which includes conditions associated with retinal damage attributable to blockage of its blood supply, nutritional deficiencies, toxins, and diseases affecting the retina.
RESULTS
There were 2775 reports available for analysis in the PPS group (of which 1966 were for women [70.9%]) and 6833 reports in the other drugs group (of which 4036 [59.1%] were for women). The proportion of adverse events for any macular event relative to all other events was elevated for the users of PPS compared with those using other interstitial cystitis and bladder pain drugs (proportionate reporting ratio [PRR], 1.21 [95% CI, 1.01-1.44]). With respect to specific retinal conditions, macular degeneration (20 [0.8%] vs 15 [0.2%]), maculopathy (83 [3.4%] vs 2 [0.03%]), retinal dystrophy (3 [0.1%] vs 0), retinal injury (5 [0.2%] vs 0), and retinal toxicity (3 [0.1%] vs 0) were proportionately more common among users of PPS compared with those using other interstitial cystitis and bladder pain drugs, respectively.
CONCLUSIONS AND RELEVANCE
The results of the current study add to the growing evidence that PPS use is associated with an increased risk of maculopathy. Studies that rule out prevalent retinal abnormalities prior to the initiation of PPS would strengthen the current body of literature.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Male; Pain; Pentosan Sulfuric Polyester; Retinal Dystrophies
PubMed: 34792558
DOI: 10.1001/jamaophthalmol.2021.4778 -
JFMS Open Reports 2021A 14-year-old male castrated Cornish Rex cat was referred for lethargy progressing rapidly to collapse in the hours following a subcutaneous injection of a product...
CASE SUMMARY
A 14-year-old male castrated Cornish Rex cat was referred for lethargy progressing rapidly to collapse in the hours following a subcutaneous injection of a product containing 100 mg/ml pentosan polysulfate sodium and 168 mg/ml glucosamine. Physical examination revealed the cat to be in hypotensive shock with swelling and interstitial oedema around the cranial thorax and caudal cervical regions without cutaneous haemorrhage. Initial diagnostics revealed a severe anaemia (packed cell volume 11%) which later deteriorated further, necessitating a blood transfusion and aggressive fluid therapy. Post-transfusion, the patient remained dyspnoeic and subsequent diagnostics found evidence of pre-existing cardiomyopathy and congestive heart failure. The cat was euthanased 24 h following presentation due to increasing dyspnoea. Post-mortem findings were of severe subcutaneous and intermuscular haemorrhage over the neck and thorax, among other changes. There were no detectable levels of coumarin anticoagulants in the liver.
RELEVANCE AND NOVEL INFORMATION
This is the first reported case of acute subcutaneous and intermuscular haemorrhage of this severity suspected to be related to the off-label use of an injectable product containing pentosan polysulfate in a cat. Given the popularity of its use for feline arthritis, there is a need for large-scale clinical trials to evaluate the safety and efficacy of products containing pentosan polysulfate for cats, and any side effects to be reported.
PubMed: 34777848
DOI: 10.1177/20551169211058650 -
Medical Hypotheses Dec 2021Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially...
Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially weight-bearing joints like knee, hip, backbone, and phalanges. NSAIDs that are used for the management of inflammation associated with osteoarthritis have high side effects related to gastric upset, gastric ulcer, and long term treatment associated with liver and kidney damage. Nanotechnology has gained a huge scope for the management of arthritis as it can reach out to the deep inside the cell and alter cellular physiology as desired. The present study hypothesizes the use of polyion complex nanoparticles of hyaluronic acid linked Pentosan polysulfate sodium, a disease-modifying agent for the treatment of osteoarthritis administered through transdermal route. The hypothesis involves the use of drug repurposing as the drug was initially approved for interstitial cystitis, a condition of the urinary bladder associated with pain and swelling. Being very low oral bioavailability and gastric irritation profile, the transdermal route would be beneficial. To overcome the problem associated with the oral route, there is a need for the targeted approach that will particularly reach at inflammatory sites. Thereby transdermal delivery of hyaluronic acid linked Pentosan polysulfate sodium through polyion complex nanoparticle therapy will be a novel therapeutic approach to combat osteoarthritis.
Topics: Cystitis, Interstitial; Drug Repositioning; Humans; Hyaluronic Acid; Nanoparticles; Osteoarthritis; Pentosan Sulfuric Polyester
PubMed: 34710749
DOI: 10.1016/j.mehy.2021.110713 -
Methods in Molecular Biology (Clifton,... 2022Capillary electrophoresis is a powerful methodology for quantification and structural characterization of highly anionic polysaccharides. Separation of saccharides under...
Capillary electrophoresis is a powerful methodology for quantification and structural characterization of highly anionic polysaccharides. Separation of saccharides under conditions of electrophoretic flow, typically achieved under low pH (Ampofo et al., Anal Biochem 199: 249-255, 1991; Rhomberg et al., Proc Natl Acad Sci U S A 95: 4176-4181, 1998) is charge-based. Resolution of components is often superior to flow-based techniques, such as liquid chromatography. During the heparin contamination crisis, capillary electrophoresis was one of the key methodologies used to identify whether or not heparin lots were contaminated (Guerrini et al., Nat Biotechnol 26: 669-675, 2008; Ye et al., J Pharm Biomed Anal 85: 99-107, 2013; Volpi et al., Electrophoresis 33: 1531-1537, 2012).Here we describe a method for the isolation of sulfated heparin/heparan sulfate saccharides from urine, their digestion by deployment of heparinase enzymes (Ernst et al., Crit Rev Biochem Mol Biol 30: 387-444, 1995) resolution of species through use of orthogonal digestions, and analysis of the resulting disaccharides by capillary electrophoresis.
Topics: Electrophoresis, Capillary; Heparin; Heparitin Sulfate; Pharmaceutical Preparations; Polysaccharides; Sulfates
PubMed: 34626391
DOI: 10.1007/978-1-0716-1398-6_27 -
Aktuelle Urologie Dec 2021It is currently assumed that interstitial cystitis/bladder pain syndrome is caused by damage to the glycosaminoglycane layer on the urothelium of the urinary bladder....
INTRODUCTION
It is currently assumed that interstitial cystitis/bladder pain syndrome is caused by damage to the glycosaminoglycane layer on the urothelium of the urinary bladder. This layer can be repaired by oral therapy with pentosan polysulfate sodium. The focus of this article is on the history of this drug, its efficacy, its valuation in guidelines and especially the possible correlation with maculopathy.
METHODS
Literature research in PubMed and Embase.
RESULTS
PPS has a US and European approval for the therapy of IC characterised by glomerulations or a Hunner lesion detected by endoscopy and bladder distension. Its efficacy was proven in randomised trials. This led to a recommendation as a basic pharmaceutical therapy (in addition to behavioural intervention, dietary therapy or other drug treatments such as pain therapy). After a treatment period of six months, efficacy should be re-evaluated. Side-effects include mild haemodilution, nausea and loss of hair. Two publications of a US eye clinic have recently postulated a correlation between prolonged high-dose therapy with PPS and a special kind of maculopathy. Although this correlation was rejected in a large-scale health service study in Germany, a "red-hand-letter" led to the recommendation to perform an ophthalmologic examination before and during the treatment with PPS. Due to a pending litigation between payers and the distributor, PPS is currently out of trade in Germany. However, PPS can still be prescribed but must be imported from adjacent European countries. Unfortunately, these modalities have led to a significant undersupply of patients with IC/BPS. It is feared that this undersupply will increase further as the litigation is ongoing.
CONCLUSION
Being the only causally acting compound in the therapy of IC/BPS, PPS has an exceptional status. Although an ongoing litigation is pending in Germany and the correlation with maculopathy is still unclear, PPS must remain part of the current and future therapy of IC/BPS.
Topics: Cystitis, Interstitial; Drug-Related Side Effects and Adverse Reactions; Germany; Humans; Pentosan Sulfuric Polyester; Urinary Bladder
PubMed: 34583396
DOI: 10.1055/a-1629-0199 -
International Urogynecology Journal Nov 2021Recent publications describe pigmentary changes in the retina associated with the use of pentosan polysulfate sodium, the only FDA-approved oral agent for relief of...
INTRODUCTION AND HYPOTHESIS
Recent publications describe pigmentary changes in the retina associated with the use of pentosan polysulfate sodium, the only FDA-approved oral agent for relief of bladder pain or discomfort associated with interstitial cystitis.
METHODS
To evaluate this association, we reviewed data from the FDA Adverse Event Reporting System and published case reports and observational studies.
RESULTS
The totality of clinical and epidemiology evidence does not resolve the question of causation between pentosan use and retinal pigmentary changes; however, several elements support a potential association.
CONCLUSION
Here, we provide our perspective on the available evidence the agency weighed when retinal pigmentary changes were added to pentosan labeling. It is important for urogynecologists prescribing pentosan to be aware of this potential association and be vigilant about assessing eye health in pentosan users.
Topics: Cystitis, Interstitial; Humans; Pelvic Pain; Pentosan Sulfuric Polyester; United States; United States Food and Drug Administration
PubMed: 34505923
DOI: 10.1007/s00192-021-04970-0 -
PloS One 2021Chikungunya virus (CHIKV) is an arthropod-borne virus that causes large outbreaks world-wide leaving millions of people with severe and debilitating arthritis....
Chikungunya virus (CHIKV) is an arthropod-borne virus that causes large outbreaks world-wide leaving millions of people with severe and debilitating arthritis. Interestingly, clinical presentation of CHIKV arthritides have many overlapping features with rheumatoid arthritis including cellular and cytokine pathways that lead to disease development and progression. Currently, there are no specific treatments or vaccines available to treat CHIKV infections therefore advocating the need for the development of novel therapeutic strategies to treat CHIKV rheumatic disease. Herein, we provide an in-depth analysis of an efficacious new treatment for CHIKV arthritis with a semi-synthetic sulphated polysaccharide, Pentosan Polysulfate Sodium (PPS). Mice treated with PPS showed significant functional improvement as measured by grip strength and a reduction in hind limb foot swelling. Histological analysis of the affected joint showed local inflammation was reduced as seen by a decreased number of infiltrating immune cells. Additionally, joint cartilage was protected as demonstrated by increased proteoglycan staining. Using a multiplex-immunoassay system, we also showed that at peak disease, PPS treatment led to a systemic reduction of the chemokines CXCL1, CCL2 (MCP-1), CCL7 (MCP-3) and CCL12 (MCP-5) which may be associated with the reduction in cellular infiltrates. Further characterisation of the local effect of PPS in its action to reduce joint and muscle inflammation was performed using NanoString™ technology. Results showed that PPS altered the local expression of key functional genes characterised for their involvement in growth factor signalling and lymphocyte activation. Overall, this study shows that PPS is a promising treatment for alphaviral arthritis by reducing inflammation and protecting joint integrity.
Topics: Animals; Anticoagulants; Arthritis, Rheumatoid; Chikungunya Fever; Chikungunya virus; Cytokines; Disease Models, Animal; Female; Inflammation; Intercellular Signaling Peptides and Proteins; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Pentosan Sulfuric Polyester
PubMed: 34492036
DOI: 10.1371/journal.pone.0255125 -
Central European Journal of Urology 2021Bladder pain syndrome/interstitial cystitis (BPS/IC) is a condition that is characterized by urgency, frequency and/or pelvic pain. The disease occurs mainly in women....
Safety and efficacy of pentosan polysulfate in patients with bladder pain syndrome/interstitial cystitis: a multicenter, double-blind, placebo-controlled, randomized study.
INTRODUCTION
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a condition that is characterized by urgency, frequency and/or pelvic pain. The disease occurs mainly in women. BPS/IC can be severe enough to have a significant impact on patients' quality of life, but it can also be associated with moderate symptoms that are equally debilitating.The aim of this article was to evaluate the possibility of the use of pentosan polysulfate sodium in patients in the complex treatment of BPS/IC.
MATERIAL AND METHODS
A multicenter, double-blind, placebo-controlled, randomized study was conducted in parallel groups in 7 Russian medical centers.
RESULTS
Efficacy and safety have been established as the main criteria. A total of 93 patients were screened. Statistical analysis was performed. It has been shown that pentosan therapy is more effective than in the placebo. Average change in the number of points on the scale O'Leary-Santa Interstitial Cystitis Symptom Index compared to baseline data in the pentosan group 4.93 ±3, 03, in the placebo group 1.66 ±3.19 (p = 0.014), and the adverse events and safety of pentosan are comparable to the placebo group.
CONCLUSIONS
Oral glycosaminoglycan (pentosan polusulfate sodium) is an effective and safe drug and should be included in the complex treatment of patients with bladder pain syndrome/interstitial cystitis.
PubMed: 34336239
DOI: 10.5173/ceju.2021.0340.R1 -
Journal of Vitreoretinal Diseases 2022This work describes characteristics of pentosan polysulfate sodium (PPS)-associated maculopathy and its similarities with common maculopathies in a retina practice...
PURPOSE
This work describes characteristics of pentosan polysulfate sodium (PPS)-associated maculopathy and its similarities with common maculopathies in a retina practice cohort.
METHODS
Thirty-two patients were identified through electronic medical record query who were exposed to PPS. One patient was excluded for lack of retinal imaging. Thirty-one patients (62 eyes) were included. A retrospective review was used to obtain patient characteristics, examination findings, and retinal imaging of the study patients. Classification into "likely," "unlikely," or "possible" to have PPS-associated maculopathy groups was based on the fundus photography and retinal imaging. Main outcome measures were best-corrected visual acuity, age, sex, diagnosis of reason for referral, allocation into designated maculopathy group, and presence of choroidal neovascularization.
RESULTS
Of 31 patients (62 eyes), the median age was 70 years (range, 24-104 years) and the majority were women (87%). Mean best-corrected visual acuity was 0.3 ± 0.4 logMAR at presentation. The most common reason for referral was age-related macular degeneration (29%). Maculopathy grades were "likely" (29%, 9 total patients), "possible" (26%, 8 total patients), or "unlikely" (45%, 14 total patients). Choroidal neovascularization was noted in 9.7% of all eyes and 11% of eyes in the "likely" group. The "possible" and "likely" groups had older ages of presentation ( < .05) compared with the "unlikely" group.
CONCLUSIONS
A high percentage (55%) of patients with a history of chronic PPS exposure showed features of "likely" or "possible" maculopathy. Similarities with common maculopathies such as age-related macular degeneration and the importance of screening and recognizing at-risk patients are highlighted.
PubMed: 37008666
DOI: 10.1177/24741264211020259 -
CMAJ : Canadian Medical Association... Jul 2021
Review
Topics: Humans; Macular Degeneration; Pentosan Sulfuric Polyester
PubMed: 34312174
DOI: 10.1503/cmaj.201900-f