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British Journal of Clinical Pharmacology Jul 2022Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis....
AIMS
Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis. However, results have been contradictory. Thus, we quantified the risk of maculopathy with PPS with a focus on risk with duration of use.
METHODS
We used a new user, retrospective cohort study with an active comparator. We created a cohort of mutually exclusive 6221 PPS users and 89 744 amitriptyline users, a tricyclic antidepressant also used for the treatment of pain secondary to interstitial cystitis. Subjects were selected from the PharMetrics Plus database (IQVIA, Durham, NC) from 2006 to 2020. Cohort members were followed to the first event of the study outcome (maculopathy) or end of enrolment. A Cox regression model was constructed to adjust for potential confounders.
RESULTS
The mean follow-up was 3.0 years for PPS users and amitriptyline users. The adjusted hazard ratio (HR) for maculopathy in PPS users was 2.64 (95% confidence interval [CI]: 1.90-3.68). The HR for the sensitivity analysis that combined maculopathy and age-related macular degeneration (AMD) was 1.38 (95% CI: 1.16-1.65). A cumulative duration-response pattern was observed, with use greater than 3 years having a 9.5-fold risk of maculopathy (HR = 9.56, 95% CI: 3.60-25.37) compared to a 2.3-fold risk of maculopathy with use for 1 year or less (HR = 2.27, 95% CI: 1.50-3.43). The number needed to harm for the first 4 years of use was 250.
CONCLUSIONS
The results of this study suggest an increased risk of maculopathy with PPS use, particularly with longer duration of use.
Topics: Amitriptyline; Cystitis, Interstitial; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Retrospective Studies
PubMed: 35277990
DOI: 10.1111/bcp.15303 -
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 -
JAMA Ophthalmology Mar 2023
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Retinal Diseases
PubMed: 36729463
DOI: 10.1001/jamaophthalmol.2022.6158 -
Asia-Pacific Journal of Ophthalmology...Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder... (Review)
Review
Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder pain syndrome. A symptomatic pigmentary maculopathy associated with PPS was reported in 2018. Since then, recognition of this unique drug toxicity has increased rapidly. This potentially sight-threatening side effect prompted the FDA in June 2020 to update the label for PPS to warn about "retinal pigmentary changes." A challenging feature of pentosan maculopathy is its ability to mimic many other retinal conditions, including inherited retinal dystrophies such as pattern dystrophy, mitochondrially inherited diabetes and deafness, and Stargardt disease, and age-related macular degeneration. In this review, we discuss the history of PPS maculopathy and its implications for thousands of at-risk interstitial cystitis patients. We use published literature and an illustrative case from our institution to highlight the importance of diagnosing PPS maculopathy. We also compare PPS maculopathy to age-related macular degeneration, explain why differentiating between the 2 is clinically important, and highlight avenues for further research. Finally, we highlight the paucity of data on patients of color and why this lack of understanding may impact patient care.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Male; Pentosan Sulfuric Polyester; Retinal Dystrophies
PubMed: 35533330
DOI: 10.1097/APO.0000000000000504 -
Journal of Virology Aug 2019Human T-cell leukemia virus type 1 (HTLV-1) infection causes T-cell leukemia and inflammatory diseases, most notably including HTLV-1-associated myelopathy/tropical...
Human T-cell leukemia virus type 1 (HTLV-1) infection causes T-cell leukemia and inflammatory diseases, most notably including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The underlying mechanism for the pathogenesis of HAM/TSP remains unclear. According to a recent clinical trial, a humanized antibody that targets CCR4 cells ameliorates inflammation by reducing the number of infected cells in the central nervous system; this result suggests that the transmigration of HTLV-1-infected cells plays a crucial role in HAM/TSP. Partly due to the blood-brain barrier, current treatments for HAM/TSP are mostly palliative. Pentosan polysulfate (PPS), a semisynthetic glycosaminoglycan, has recently been used to treat HAM/TSP and was found to alleviate the symptoms. In this study, we investigated the effect of PPS on HTLV-1-infected cells and provide evidence for its efficacy in HAM/TSP. PPS was cytotoxic to certain HTLV-1-infected cells and significantly suppressed HTLV-1 virion production. PPS also efficiently inhibited HTLV-1 cell-cell transmission in T cells. In addition, PPS blocked HTLV-1 infection of primary endothelial cells (human umbilical vascular endothelial cells) and suppressed the subsequent induction of proinflammatory cytokine expression. Furthermore, PPS was found to inhibit the adhesion and transmigration of HTLV-1-infected cells. We also confirmed the anti-HTLV-1 effect of PPS using two mouse models. PPS blocked HTLV-1 infection in a mouse model with peripheral blood mononuclear cell (PBMC)-humanized NOD-scid IL2Rgamma (huPBMC NSG) mice. PPS was also found to suppress the development of dermatitis and lung damage in HTLV-1 bZIP factor (HBZ)-transgenic (HBZ-Tg) mice, an HTLV-1 transgenic mouse model in which the mice develop systemic inflammation. HTLV-1 is the first human retrovirus to have been identified and is endemic in certain areas worldwide. HTLV-1 infection leads to the development of an inflammatory disease called HAM/TSP, a myelopathy characterized by slowly progressive spastic paraparesis. There have been no effective therapeutics available for HAM/TSP, but recently, a semisynthetic glycosaminoglycan, named pentosan polysulfate (PPS), has been found to alleviate the symptoms of HAM/TSP. Here we conducted a comprehensive study on the effect of PPS both and PPS demonstrated anti-HTLV-1 potential in infected cell lines, as shown by its suppressive effects on HTLV-1 replication and transmission and on the transmigration of infected T cells. Moreover, results obtained from two HTLV-1 mouse models demonstrate that PPS inhibits HTLV-1 infection and inflammation development Our work offers insights into the treatment of HAM/TSP by PPS and also suggests its possible use for treating other HTLV-1-induced inflammatory diseases.
Topics: Animals; Antineoplastic Agents; Cell Adhesion; Cell Line, Tumor; Disease Models, Animal; Endothelial Cells; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukocytes, Mononuclear; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, Transgenic; Pentosan Sulfuric Polyester; T-Lymphocytes; Virus Replication
PubMed: 31167921
DOI: 10.1128/JVI.00413-19 -
Journal of Vitreoretinal Diseases 2023We investigated the potential for indication bias to be present in previous studies of pentosan polysulfate sodium (PPS) pigmentary retinopathy by comparing the...
We investigated the potential for indication bias to be present in previous studies of pentosan polysulfate sodium (PPS) pigmentary retinopathy by comparing the incidence and risk of retinopathy in patients with interstitial cystitis (IC) to matched controls. Adult women with IC from a multicenter database of electronic medical record data were matched to non-IC controls at a 1:4 ratio. The IC cohort was subdivided according to duration of PPS use: never, <5 years, and ≥5 years. Incidence and risk (estimated by Cox proportional hazards models) of retinopathy (defined by 6 , Ninth and Tenth Revision codes) were compared between groups. There were 22 060 women with IC and 88 240 women without IC. Average age was 53.92 years (SD, 16.22 years), and 96 110 (87.14%) patients were non-Hispanic White. Incidence of retinopathy per 100 000 person-years was 173.88 (95% CI, 162.78-185.53) for patients without IC, 226.63 (95% CI, 197.73-258.56) for IC without PPS use, 293.02 (95% CI 230.86-366.75) for IC with <5 years of PPS use, and 558.91 (95% CI, 399.29-761.07) for IC with ≥5 years of PPS use. Adjusted hazard ratios were 1.31 (95% CI, 1.13-1.51, < .001) for IC without PPS use, 1.70 (95% CI, 1.35-2.15, < .001) for IC with <5 years of PPS use, and 3.10 (95% CI, 2.26-4.27, < .001) for IC with ≥5 years of PPS use. Patients with IC had greater incidence and risk of retinopathy. PPS use further increased the incidence and risk of retinopathy.
PubMed: 37706083
DOI: 10.1177/24741264231190978 -
Research and Reports in Urology 2023Hemorrhagic cystitis (HC) can be one of the most challenging clinical scenarios for urologists to manage. It most commonly occurs as a toxicity of pelvic radiation... (Review)
Review
Hemorrhagic cystitis (HC) can be one of the most challenging clinical scenarios for urologists to manage. It most commonly occurs as a toxicity of pelvic radiation therapy or in patients treated with the oxazaphosphorine class of chemotherapy. Successful management of HC necessitates a stepwise approach with a thorough understanding of the various treatment options. Once ensuring hemodynamic stability, conservative management includes establishing bladder drainage, manual clot evacuation, and continuous bladder irrigation through a large-bore urethral catheter. If gross hematuria persists, operative cystoscopy with bladder clot evacuation is often required. There are multiple intravesical options for treating HC, including alum, aminocaproic acid, prostaglandins, silver nitrate, and formalin. Formalin is an intravesical option that has caustic effects on the bladder mucosa and is most often reserved as a last-line intravesical treatment. Non-intravesical management tools include hyperbaric oxygen therapy and oral pentosan polysulfate. If needed, nephrostomy tube placement or superselective angioembolization of the anterior division of the internal iliac artery can be performed. Finally, cystectomy with urinary diversion is a definitive, albeit invasive, treatment option for refractory HC. While there is no standardized algorithm, treatment modalities typically progress from less to more invasive. Clinical judgement and shared decision-making with the patient are required when choosing therapies for managing HC, as success rates are variable and some treatments may have significant or irreversible effects.
PubMed: 37404838
DOI: 10.2147/RRU.S320684 -
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 -
Ophthalmology Apr 2020To determine the association and cumulative dose-response pattern between pentosan polysulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy.
PURPOSE
To determine the association and cumulative dose-response pattern between pentosan polysulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy.
DESIGN
Large, multicenter, retrospective cohort study of commercially insured patients in the MarketScan database (Truven Health Analytics, San Jose, CA).
PARTICIPANTS
Two hundred twenty-seven thousand three hundred twenty-five patients with IC who were enrolled continuously in the MarketScan database.
METHODS
Cox proportional hazards models (controlling for patient gender, age at index diagnosis of IC, and diagnosis with diabetes mellitus) followed up patients from index diagnosis of IC for 5 years, or until patients discontinued insurance coverage, or until patients' first diagnosis with a maculopathy. As a sensitivity analysis, we re-estimate all models after excluding all patients with diabetes. To assess for dose response, we calculated the total days of PPS prescriptions filled and created a categorical variable indicating total exposure.
MAIN OUTCOME MEASURES
The primary outcome measure was association between binary PPS exposure and any maculopathy. Secondary outcome measures included exposure between binary and categorical, time-dependent, exposure to PPS and to drusen, nonexudative age-related macular degeneration (AMD), exudative AMD, hereditary maculopathy, and toxic maculopathy.
RESULTS
The most common diagnoses of maculopathy in patients with IC were exudative AMD (1.5%), drusen (0.8%), nonexudative AMD (0.3%), toxic maculopathy (0.1%), and hereditary dystrophy (0.04%). In unadjusted analyses, the percentage of patients who filled a PPS prescription and were diagnosed later with a maculopathy (2.37%) was very similar to the percentage of patients who did not fill a prescription (2.77%). Survival models using a binary variable indicating PPS exposure showed no significant associations between PPS exposure and diagnosis of drusen, nonexudative AMD, exudative AMD, toxic maculopathy, hereditary dystrophy, or an aggregate variable of any maculopathy. Similarly, there was no dose-dependent relationship between PPS exposure and diagnosis of any maculopathy. These findings remained stable in sensitivity analysis models that excluded patients with diabetes mellitus.
CONCLUSIONS
In this large, commercial claims database analysis, no association was found between PPS exposure and subsequent diagnosis of maculopathy.
Topics: Adult; Aged; Anticoagulants; Cystitis, Interstitial; Databases, Factual; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Insurance, Health; Macula Lutea; Male; Middle Aged; Pentosan Sulfuric Polyester; Proportional Hazards Models; Retinal Diseases; Retrospective Studies; Risk Factors; United States
PubMed: 31899034
DOI: 10.1016/j.ophtha.2019.10.036 -
Current Opinion in Urology Mar 2024Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new... (Review)
Review
PURPOSE OF REVIEW
Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new therapies. Our manuscript aims to review papers about BPS/IC treatments published in the last 2 years.
RECENT FINDINGS
During this period, several treatments were tested, most of them new and others combining treatments already used. Pentosan polysulfate, interleukin 1 antagonist, low energy shock wave, physical therapy, hypnosis, acupuncture, clorpactin, dimethyl sulfoxide and hyaluronic acid plus botulinum toxin-A showed positive results. ASP3652 and lidocaine-releasing intravesical systems failed to prove their efficacy.
SUMMARY
Validation of these studies is arduous due to the broad spectre of BPS/IC phenotypes, small number of patients enrolled, distinct outcome measures and short-term follow-up. It is also important to highlight that some authors combined therapies, and others split central and peripheric phenotypes before treatment. Therefore, soon, phenotyping and combining therapies with a step-by-step approach will be needed in BPS/IC treatment.
Topics: Humans; Cystitis, Interstitial; Quality of Life; Administration, Intravesical; Botulinum Toxins, Type A; Lidocaine
PubMed: 38168016
DOI: 10.1097/MOU.0000000000001159