Hubbry Logo
Pentosan polysulfatePentosan polysulfateMain
Open search
Pentosan polysulfate
Community hub
Pentosan polysulfate
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Pentosan polysulfate
Pentosan polysulfate
Pentosan polysulfate
View on Wikipedia
from Wikipedia

Pentosan polysulfate
Clinical data
Trade namesElmiron, Zycosan
Other namesPPS, (1->4)-β-Xylan 2,3-bis(hydrogen sulfate) with a 4 O-methyl-α-D-glucuronate
AHFS/Drugs.comMonograph
License data
Routes of
administration		By mouth, intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
ExcretionFeces, urine[1]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H18O21S4
Molar mass602.47 g·mol−1
3D model (JSmol)
  • O[C@@H]1CO[C@@H](O[C@@H]2CO[C@@H](O)[C@H](OS(O)(=O)=O)[C@H]2OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O
  • InChI=1S/C10H18O21S4/c11-3-1-26-10(8(31-35(22,23)24)5(3)28-32(13,14)15)27-4-2-25-9(12)7(30-34(19,20)21)6(4)29-33(16,17)18/h3-12H,1-2H2,(H,13,14,15)(H,16,17,18)(H,19,20,21)(H,22,23,24)/t3-,4-,5+,6+,7-,8-,9-,10+/m1/s1
  • Key:FCCNSUIJIOOXEZ-SJYYZXOBSA-N
  (verify)

Pentosan polysulfate, sold under the brand name Elmiron among others, is a medication used for interstitial cystitis.[1] Evidence of benefit, however, is mixed as of 2024.[2] It is recommended that the medication be stopped if there is no improvement within 6 months.[3] It was approved for medical use in the United States in 1996.[1][4][5]

Medical uses

[edit]

Pentosan polysulfate sodium is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.[1][6][7][8] Evidence of benefit, however, is mixed as of 2024 with some studies finding benefit and others not.[2]

Side effects

[edit]

People who have taken pentosan polysulfate by mouth report a variety of side effects, primarily gastrointestinal complaints such as diarrhea, heartburn, and stomach pain.[9] Hair loss, headache, rash, and insomnia have also been reported.[9] Due to anticoagulant effects, some report bruising more easily. In some cases, people are asked to stop taking the medication before major surgery to reduce the likelihood of bleeding.

Maculopathy

[edit]

Pentosan polysulfate maculopathy (PPSM) is a slowly worsening eye condition that affects the retinal pigment epithelium (RPE) and can lead to vision problems. It has been strongly linked to long-term use of pentosan polysulfate sodium (PPS), a drug commonly prescribed for interstitial cystitis.[10][11]

A 2025 review of data from over 140,000 patients found that the risk of developing PPSM increases with the total amount of PPS taken, with a 0.1% rise in relative risk for each gram of the drug used.[12][13] People who took at least 2000 grams of PPS (roughly equal to 18 years of typical treatment) had a 8 times higher risk of developing PPSM than non-users, while even low exposures (<500g) were linked to a 2 times higher risk.[12][13] Multimodal imaging techniques can detect specific signs of the condition, such as mottled areas in the RPE, patches of abnormal autofluorescence, and deposits beneath the retina. These features can help distinguish PPSM from inherited maculopathies with >99% accuracy.[10][14]

Even after stopping the drug, about 20% of people continue to show worsening changes in the macula, which is why baseline and yearly eye exams—including optical coherence tomography and fundus autofluorescence—if PPS has been used.[10][11] Current recommendations advise reducing the PPS dose to the lowest amount that reduces symptoms and watching carefully for early signs of eye damage.[12][13]

Mechanism of action

[edit]

In interstitial cystitis, pentosan polysulfate is believed to work by providing a protective coating to the damaged bladder wall. Pentosan polysulfate is similar in structure to the natural glycosaminoglycan coating of the inner lining of the bladder, and may replace or repair the lining, reducing its permeability.[15]

History

[edit]

The calcium salt of pentosan polysulfate was one of the first reported disease-modifying osteoarthritis drugs (DMOAD).[16]

Society and culture

[edit]

Names

[edit]

The IUPAC name for pentosan polysulfate is [(2R,3R,4S,5R)-2-hydroxy-5-[(2S,3R,4S,5R)-5-hydroxy-3,4-disulfooxyoxan-2-yl]oxy-3-sulfooxyoxan-4-yl] hydritalicogen sulfate.[17]

There are 40 synonyms listed for pentosan polysulfate on PubChem including BAY-946, HOE-946, pentosan sulfuric polyester, polypentose sulfate, polysulfated xylan, PZ-68, SP-54, xylan SP54 and xylan sulfate.[18]

Various brand names include Elmiron (as sodium salt), Hemoclar, Anarthron, Fibrase, Fibrocid, Thrombocid and SP54. Pentosan polysulfate capsules are sold in India under the brand names Comfora, Pentossan-100, Cystopen and For-IC. In the veterinary field, pentosan polysulfate is sold as Cartrophen Vet and Sylvet by Biopharm Australia, Pentosan by Naturevet Australia, Anarthron by Randlab Australia and Zydax by Parnell.[19]

Research

[edit]

Osteoarthritis

[edit]

Pentosan polysulfate has been studied in knee osteoarthritis, though evidence to support such use is poor as of 2003.[20] There is some theoretical evidence that it should help.[21]

Transmissible spongiform encephalopathies

[edit]

Pentosan polysulfate is being studied as a potential treatment of Creutzfeldt–Jakob disease (CJD). The rationale for this treatment was unclear but it was subsequently shown in prion-infected mouse neuroblastoma cells that pentosan polysulfate could rapidly reduce the levels of abnormal (scrapie) prion without affecting the normal cellular isoform.[22] As pentosan polysulfate can bind to the cellular isoform of the prion protein, it may stabilise this form and prevent its conversion to the pathological (scrapie) isoform.[23]

The treatment[24] of one patient in Northern Ireland and around six other patients in mainland Britain was reported in the press.[25]

Veterinary uses

[edit]

Dogs

[edit]

Read et al. (1996) [26] used three different doses of sodium pentosan polysulfate to treat 40 geriatric dogs with well-established clinical signs of chronic osteoarthritis (OA) with a subcutaneous injection. The 3 mg/kg dose was the most effective. In a study conducted with 10 elderly dogs with osteoarthritis given calcium pentosan polysulfate (3 mg/kg intramuscularly) once weekly for four weeks, the improvement in symptoms (seen at 1, 2, 3 and 7 weeks after initiation of therapy) was found to correlate with plasma indices of fibrinolytic activity and lipid profiles.[27] In a study in dogs with OA secondary to cranial cruciate ligament deficiency, although no differences were identified in either functional outcome or radiographic progression using the oral calcium pentosan polysulfate compared with placebo, there were significantly lower levels of proteoglycan breakdown products in the synovial fluid of the osteoarthritic joints.[28] The efficacy of subcutaneous sodium pentosan polysulfate (3 mg/kg) was tested in 40 dogs with cranial cruciate ligament instability and found to hasten recovery, as measured by more rapidly improved ground reaction forces, over 48 weeks.[29]

Horses

[edit]

Zycosan, for horses, is a heparin-like compound and is the first injectable pentosan product to receive approval by the US Food and Drug Administration (FDA).[30]

In December 2022, the US Food and Drug Administration (FDA) approved pentosan polysulfate (Zycosan) for the control of clinical signs associated with osteoarthritis in horses.[30] Zycosan is for intramuscular use in horses only and is not for use in humans.[30] Zycosan is sponsored by Anzac Animal Health LLC, based in Maryland Heights, Missouri.[30]

Pentosan polysulfate is being used for this osteoarthritis in Australia. When administered to racing thoroughbreds with chronic osteoarthritis (2 to 3 mg/kg, intramuscularly, once weekly for 4 weeks, then as required), pentosan polysulfate treatment improved but did not eliminate clinical signs of joint disease.[31] Articular cartilage fibrillation was substantially reduced by similar NaPPS treatment intramuscularly in nine horses with experimentally-induced carpal osteoarthritis.[32]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Pentosan polysulfate

View on Grokipedia
from Grokipedia
Pentosan polysulfate sodium (PPS) is a semi-synthetic, sulfated derived from beechwood hemicellulose, functioning as a heparin-like compound with , fibrinolytic, and properties. It is primarily indicated for the relief of bladder pain and discomfort associated with interstitial cystitis (IC), a characterized by and urgency. First developed in the as a thrombolytic agent, PPS was approved by the U.S. () in 1996 under the brand name Elmiron for oral use in treating IC symptoms. Chemically, PPS is a low molecular weight (4,000–6,000 Daltons) resembling glycosaminoglycans, with a structure based on sulfated units that mimic the protective lining of the . Its exact mechanism in IC remains unclear, but it is believed to adhere to the wall, buffering against irritants, reducing permeability, and inhibiting inflammatory mediators like fibroblast growth factors. Orally administered at doses of 100 mg three times daily, PPS has low bioavailability (approximately 6%), with most of the drug excreted unchanged in feces and a plasma of 20–27 hours. In addition to human use, PPS has established veterinary applications, particularly for managing in animals. The FDA approved an injectable formulation, Zycosan, in 2022 for controlling clinical signs of in , where it promotes repair and reduces . It has also been studied and used off-label in dogs and cats for joint disorders and lower urinary tract conditions, leveraging its chondroprotective and tissue-repair effects. Research continues into its potential for other conditions, such as , though these remain investigational. Long-term use of PPS in humans has been associated with serious risks, including pigmentary maculopathy—a potentially irreversible retinal condition characterized by vision changes like or difficulty reading. The FDA added a for this risk in 2020. Common side effects include alopecia, , , and , while rare but notable issues involve risks due to its properties. Patients are advised to undergo baseline and periodic ophthalmologic monitoring, and the drug is contraindicated in those with known to pentosan polysulfate sodium. It should be used with caution in patients at risk of bleeding.

Pharmacology

Chemical structure and properties

Pentosan polysulfate is a semi-synthetic derived from beechwood , primarily consisting of a linear backbone of β-D- units with occasional 4-O-methyl-α-D-glucuronic acid side chains attached at the 2-position of some residues. The molecule features multiple ester groups, typically two per monomer, conferring a polyanionic character that mimics sulfated glycosaminoglycans. Its average molecular weight ranges from 4,000 to 6,000 Da, reflecting a heterogeneous mixture of chain lengths. Physically, pentosan polysulfate sodium presents as a white to off-white, odorless, hygroscopic powder that is freely soluble in , forming solutions up to 50% concentration at neutral . It remains stable under standard storage conditions (dry, ) but can degrade under extreme environments, such as strong acids or bases, due to potential desulfation or hydrolysis of glycosidic bonds. Classified as a heparinoid, pentosan polysulfate exhibits structural and functional analogies to , including a high degree of sulfation that accounts for approximately 16% content by weight (corresponding to about two groups per unit). This sulfation enhances its polyanionic properties, enabling electrostatic interactions similar to those of natural glycosaminoglycans. The compound is synthesized by first extracting , a , from beechwood or other plant sources, followed by chemical sulfation using chlorosulfonic acid, often in the presence of or as solvents to facilitate esterification at hydroxyl groups. The process yields a polydisperse product that is neutralized with to form the sodium salt, ensuring the desired degree of sulfation and molecular weight distribution.

Mechanism of action

Pentosan polysulfate (PPS) primarily exerts its therapeutic effects in the by adhering to the damaged uro and replenishing the defective () layer, thereby forming a protective barrier that shields the underlying epithelium from urinary irritants such as potassium ions and protons. This replenishment mimics the natural GAG components, including and , restoring the impermeability of the bladder mucosa and reducing symptoms associated with epithelial permeability defects. Emerging research as of 2025 suggests PPS may also alleviate IC symptoms by modulating metabolism and activating the TGR5 receptor. In addition to its barrier function, PPS demonstrates anti-inflammatory properties by stabilizing mast cells, inhibiting histamine release, and modulating cytokine production to favor anti-inflammatory responses. It interferes with inflammatory mediators, increasing levels of the anti-inflammatory cytokine interleukin-10 while decreasing proinflammatory factors, which collectively dampen local inflammation and leukocyte activation. These effects help mitigate the recruitment and migration of leukocytes to inflamed tissues. PPS also possesses anticoagulant properties akin to those of heparin, albeit with lower potency, by binding to antithrombin III and thereby enhancing the inhibition of coagulation factors Xa and thrombin. This interaction accelerates the inactivation of thrombin and factor Xa, reducing fibrin formation and clot propagation, though the clinical anticoagulant effect is milder compared to unfractionated heparin due to differences in sulfation patterns and molecular weight. The multifaceted interactions of PPS stem from its highly sulfated structure, which imparts a strong negative charge enabling electrostatic binding to positively charged proteins and cellular components, such as those in the uroepithelium and inflammatory mediators. This charge-driven affinity underlies its adhesion to biological surfaces and modulation of enzymatic activities.

Medical uses

Interstitial cystitis

Pentosan polysulfate sodium, marketed as Elmiron, received FDA approval in 1996 as the only oral therapy for the relief of bladder pain and discomfort associated with interstitial cystitis (IC), also known as bladder pain syndrome (BPS). This approval was based on clinical evidence demonstrating its potential to alleviate key symptoms such as pain, urgency, and frequency in patients with this chronic condition. As of 2025, it remains the sole FDA-approved oral medication for IC/BPS, distinguishing it from other treatments like intravesical therapies or analgesics. The standard dosing regimen for IC/BPS is 100 mg orally three times daily, totaling 300 mg per day, taken with water at least one hour before or two hours after meals to optimize absorption. Symptom improvement, particularly in pain and urgency, typically emerges after 3 to 6 months of continuous use, with urinary frequency potentially requiring up to 6 to 9 months for noticeable relief. If no symptomatic benefit is observed after 6 months, discontinuation is recommended to avoid unnecessary long-term exposure. Efficacy data from clinical trials support its use in select patients. In a blinded, randomized, placebo-controlled study involving 151 patients, 38% of those receiving pentosan polysulfate experienced greater than 50% improvement in pain after 3 months, compared to 18% on (p=0.005). An open-label physician's usage study of 2,499 patients further indicated that 29% reported pain improvement by one to two categories at 3 months. These benefits are attributed to the drug's ability to restore the protective (GAG) layer on the , which is often compromised in IC/BPS, thereby reducing irritation from urine components. Pentosan polysulfate is particularly suitable for patients with moderate to severe IC/BPS who have not responded to conservative therapies such as dietary modifications, , or first-line oral analgesics. Long-term use requires careful patient selection and ongoing monitoring to assess response and manage potential issues. Recent 2025 guidelines from Urological Association emphasize the importance of prior to initiating pentosan polysulfate, highlighting the need to discuss associated risks, including potential vision-related concerns from prolonged exposure. However, these guidelines conditionally recommend against its use () due to limited and potential for serious adverse effects. Clinicians should ensure patients understand these factors, especially for extended therapy durations.

Other approved indications

In the European Union, pentosan polysulfate is approved in gel form for the topical treatment of thrombophlebitis, contusions, and varicose veins, owing to its mild anticoagulant effects that help reduce inflammation and clotting in superficial vascular issues. It has also been approved and employed in Europe for thrombosis prophylaxis, particularly to mitigate the risk of postoperative deep vein thrombosis in settings like orthopedic surgery, where its anti-factor Xa activity aids in preventing clot formation without the bleeding risks associated with stronger anticoagulants. These approvals stem from its historical development as an antithrombotic agent, with initial regulatory recognitions in Europe dating to the 1970s for vascular conditions like phlebitis, prior to a greater emphasis on urological uses. In contrast, as of November 2025, the U.S. has not granted approvals for pentosan polysulfate beyond its indication for interstitial cystitis, though formulations like Zycosan have been approved for veterinary management of in (see Veterinary applications). For vascular indications in approved regions, administration often involves subcutaneous injections of 50 mg twice daily or topical gel application, differing from the standard 300 mg daily oral regimen for bladder conditions; dosage adjustments are made based on patient weight and treatment duration to monitor effects via aPTT levels. Limited approvals and use persist in select countries for postoperative in orthopedic procedures, reflecting its established safety profile in short-term prophylaxis.

Adverse effects

Common side effects

Common side effects of pentosan polysulfate sodium are generally mild and transient, affecting a minority of patients treated for interstitial cystitis. Gastrointestinal disturbances are among the most frequently reported, including (occurring in approximately 4% of patients), (4%), dyspepsia (2%), and (2%), which are often dose-related and resolve with continued use or dose adjustment. Headache is reported in about 3% of users, while occurs in around 1%, both typically self-limiting without requiring intervention. , or , affects approximately 4% of patients and is usually mild, reversible, and limited to localized areas such as on the scalp, often appearing within the first few weeks of therapy. is another common dermatological reaction, noted in 3% of cases in clinical trials. Post-marketing surveillance data through 2025 continues to identify alopecia and as frequently reported mild adverse events, consistent with earlier clinical findings. Management of these side effects generally involves symptomatic treatment, such as antiemetics for or analgesics for , and dose reduction if symptoms persist, with most resolving spontaneously as the body adjusts.

Serious adverse effects

One of the most significant serious adverse effects associated with long-term use of pentosan polysulfate sodium (PPS) is pigmentary , a progressive toxicity characterized by pigmentary changes in the , often linked to cumulative doses exceeding 1 kg. Symptoms typically include , prolonged dark adaptation, and , with potential progression to macular atrophy even after drug cessation. A 2021 study reported a of approximately 23% among long-term interstitial cystitis patients exposed to PPS, highlighting the dose-dependent nature of this risk. PPS has also been associated with colopathy, including new-onset or exacerbated (IBD), with 2025 cohort studies demonstrating a strong link, where 69% of long-term users (median exposure 2.04 kg) developed IBD diagnoses. These effects show a dose-response relationship, with higher cumulative exposures correlating to increased risk of flares, gastrointestinal symptoms, and in severe cases, . Additional serious risks include rare hepatic elevations, observed in up to 1.2% of patients at standard doses, necessitating caution in those with hepatic impairment due to PPS's partial in the liver. Due to its weak properties (about 1/15th that of ), PPS can precipitate events, such as rectal hemorrhage in 6.3% of users at mg/day, particularly in patients with coagulopathies or concurrent therapy. To mitigate these risks, baseline and annual ophthalmologic screening, including funduscopy, , and autofluorescence imaging, is recommended for all PPS users, especially those approaching 500 g cumulative dose. The FDA updated warnings in 2020 (with ongoing through 2025 studies) to emphasize risks, advising immediate discontinuation if maculopathy is suspected; early intervention may allow partial reversibility, though advanced cases often progress irreversibly.

History and development

Discovery and synthesis

Pentosan polysulfate was first synthesized in 1947 by Dr. Wilhelm Benend, a German working in the , as a semi-synthetic heparinoid derived from plant sources to address the limitations of animal-derived anticoagulants like , which faced supply shortages during and after . Benend developed a standardized process for producing sodium pentosan polysulfate (NaPPS) by extracting , a , from the bark of beech trees () and subjecting it to sulfation to enhance its biological activity. This extraction involved alkaline of beechwood to isolate pentosan fractions, followed by chemical sulfation using agents such as chlorosulfonic acid or in organic solvents, resulting in a polyanionic compound with and properties. The compound's development was spurred by wartime needs for synthetic alternatives to heparin, and Benend secured key patents for its production methods in the late 1940s. By 1949, following the establishment of Dr. Wilhelm Benend K.G., commercial sales of NaPPS began in Germany under the brand name SP 54, initially marketed for its antithrombotic potential in preventing thromboembolism. In the , early confirmed pentosan polysulfate's and effects, demonstrating reduced formation and in models of vascular injury, though its oral limited its potency as a direct substitute. These preclinical trials, including those referenced in foundational work from the era, highlighted its fibrinolytic activity and tissue-protective qualities without the bleeding risks associated with higher-potency anticoagulants. Research in the in shifted focus toward its broader therapeutic applications, with studies exploring its protective effects on mucosal tissues, including initial investigations into lining integrity for urological conditions. By the , the first clinical uses emerged for treating vascular disorders, such as thromboembolic events, based on these accumulated findings.

Regulatory approvals

Pentosan polysulfate sodium was first approved in in 1949 for indications such as prevention of , with the injectable formulation SP-54 receiving marketing authorization from bene-Arzneimittel for vascular conditions including . This approval built on earlier synthesis work in the , enabling its commercial use as an agent across several European countries, where it remains available for such purposes as of 2025. In the United States, the (FDA) granted approval for the oral formulation of pentosan polysulfate sodium, marketed as Elmiron by , on September 26, 1996, specifically for the relief of bladder pain associated with interstitial cystitis (IC), also known as bladder pain syndrome. The has not approved the drug for any other indications, limiting its labeled use to IC despite exploratory research in other areas. Post-approval, the FDA mandated significant labeling updates due to emerging safety concerns. In June 2020, the agency approved revisions to the Elmiron label, including a warning highlighting the risk of pigmentary maculopathy and recommending baseline and periodic ophthalmologic examinations for patients on long-term , as cumulative dose was identified as a key . Further scrutiny of ocular adverse events led to ongoing FDA considerations for enhanced warnings. In the , the oral formulation Elmiron received centralized marketing authorization from the on June 2, 2017 for the symptomatic relief of IC in adults, remaining active as of 2025. Internationally, variations exist; in , the listed Elmiron on the Australian Register of Therapeutic Goods in 1994 for IC treatment, with no formal approvals for (OA) but ongoing special access provisions for adjunctive use in OA under 2025 regulatory updates via the Special Access Scheme. While concerns over side effects, particularly maculopathy, have prompted market restrictions or heightened monitoring in select regions, such as enhanced pharmacovigilance in since 2021, pentosan polysulfate has not faced global delisting or widespread withdrawals and continues to be marketed where approved.

Society and culture

Brand names

Pentosan polysulfate sodium is primarily marketed under the brand name Elmiron in the , , and several European countries for the treatment of interstitial cystitis, with , a of , as the original developer and manufacturer. In , additional brands include SP-54, which has been used for its and fibrinolytic properties in vascular conditions. Generics of pentosan polysulfate sodium became available in around 2010, marketed under names such as Cystopen for cystitis. The U.S. patent for Elmiron expired in January 2010, which opened the possibility for generic entry, though market limitations due to the drug's niche indications have resulted in few generics being introduced globally. For veterinary applications, pentosan polysulfate is sold under brands such as Cartrophen Vet (primarily for dogs and horses in , , and the ) and Zycosan (approved for horses in the U.S. for ). Compounding of pentosan polysulfate for veterinary use, particularly in dogs, has also become common in some regions where branded formulations are unavailable. As of 2025, no major new human brands have emerged, and generic availability remains limited outside select markets like .

Availability and regulation

Pentosan polysulfate, marketed primarily as Elmiron in many countries, is classified as a prescription-only worldwide, requiring oversight by healthcare professionals due to its potential side effects. In , it is designated as a Schedule 4 substance under the , restricting it to prescription use and prohibiting over-the-counter sales. In the United States, following a 2020 label update by the , prescribers are advised to implement periodic ophthalmologic monitoring for patients on long-term to detect pigmentary maculopathy, with guidelines emphasizing baseline and follow-up eye examinations that have been reinforced in subsequent clinical recommendations. In the United States, pentosan polysulfate is widely available through pharmacies for the treatment of interstitial cystitis, though prescription volumes have declined since the identification of ocular risks in the late , with usage dropping as awareness of maculopathy grew. In , it is authorized under the brand Elmiron by the primarily for interstitial cystitis relief. No widespread bans have been imposed, but regulatory scrutiny has intensified, including label updates for maculopathy risks and recommendations for screening, contributing to reduced prescribing trends across regions. The cost of pentosan polysulfate in the averages approximately $1,300 for a 30-day supply of 90 capsules (300 mg daily dose) without as of 2025, though assistance programs and generic availability can lower this to $500–$600 per month for eligible individuals. coverage is generally provided for its approved use in interstitial cystitis under most commercial plans and , but off-label applications are often not reimbursed, leading to higher out-of-pocket expenses. Pentosan polysulfate is derived semisynthetically from beech wood plant extracts (), with production relying on established supply agreements that have prevented reported shortages globally. As of November 2025, faces numerous lawsuits in the United States alleging failure to warn patients about the risk of vision impairment from long-term use of Elmiron, with some settlements reached since 2023.

Research directions

Osteoarthritis

Pentosan polysulfate (PPS) has been investigated for its potential in treating (OA), particularly knee OA, through intra-articular or . The rationale for its use stems from its chondroprotective properties, where PPS promotes repair by stimulating (GAG) synthesis, including proteoglycans and hyaluronan, while inhibiting enzymatic degradation via suppression of matrix metalloproteinase-3 (MMP-3) and inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). Additionally, PPS exhibits anti-inflammatory effects by reducing mediators like IL-6 and (NGF) in , alongside improving subchondral blood flow to enhance joint nutrition. Key clinical trials have explored subcutaneous PPS dosing at 2 mg/kg weekly or twice-weekly for 6 weeks. An exploratory phase 2, randomized, double-blind, placebo-controlled trial (NCT04809376) in patients with Kellgren-Lawrence grade 2-4 knee OA demonstrated significant improvements in and function with twice-weekly dosing, showing a 49.5% reduction in WOMAC scores compared to 29.7% with (p=0.050), and a 50.0% improvement in function versus 24.9% (p=0.017); notably, 60% of treated patients achieved ≥50% improvement. An earlier open-label study in 20 patients with mild knee reported 64.7% reduction on visual analog scale (VAS) after walking and 59.3% for stair climbing at 52 weeks (p<0.05), alongside a 19.7% decrease in breakdown marker . Ongoing phase 3 studies, such as NCT06917404 (recruiting as of November 2025), continue to evaluate subcutaneous PPS versus for and function in knee OA, with dosing at 2 mg/kg weekly. In , PPS is accessible via the Therapeutic Goods Administration's Special Access Scheme for adjunctive therapy, though not formally approved for this indication. Efficacy data from small cohorts indicate 30-50% symptom improvements in and function, supported by reductions in synovial biomarkers of (e.g., TNF-α, IL-6) and chondrodegradation (e.g., COMP, ARGS), with increases in protective markers like TIMP-1. The MaRVeL trial protocol (oral PPS at 10 mg/kg twice-weekly in cycles) targets knee OA with dyslipidaemia, assessing via numeric rating scale and structural changes via MRI, building on pilot data showing symptomatic relief. However, PPS remains unapproved by the FDA for , limited to interstitial cystitis treatment, and long-term safety concerns include potential retinal toxicity from cumulative exposure observed in other indications. Ongoing research in 2025, including Paradigm Biopharma's placebo-controlled dose-response trial for knee OA pain using up to ten sites in and the , focuses on optimizing injectable PPS regimens. Recent publications emphasize imaging biomarkers, such as MRI assessments of and lesions, to correlate dose-response with structural modifications and clinical outcomes in small cohorts.

Neurological disorders

Pentosan polysulfate (PPS) has been investigated for its potential in treating diseases, particularly variant Creutzfeldt-Jakob disease (vCJD), due to its ability to interfere with protein conversion. In the early , compassionate use programs administered subcutaneous or intraventricular PPS to patients with vCJD, aiming to block the conversion of normal protein (PrP^C) to its pathogenic form (PrP^Sc). A notable case involved continuous intraventricular at 11 μg/kg/day in a young patient, which appeared to temporarily stabilize disease progression. However, observational studies conducted in the UK and from 2007 to 2010 demonstrated limited efficacy, with no significant halt in neurological deterioration despite some prolongation of survival in select cases. As of November 2025, no active clinical trials for PPS in diseases are ongoing, reflecting the historical challenges of high associated with high-dose regimens, which often led to complications such as hemorrhage or at infusion sites. Retrospective analyses indicate that while PPS delayed progression in a subset of vCJD patients under compassionate use, the overall risk-benefit profile precluded further advancement, with survival extensions rarely exceeding months. These outcomes underscore PPS's mechanism, akin to its anticoagulant-like binding to proteins, in modulating pathological protein interactions but highlight delivery limitations in the . Beyond prions, preclinical research has explored PPS for , where it inhibits -β (Aβ) aggregation and protects the blood-brain barrier from Aβ-induced toxicity in endothelial cell models. Studies demonstrate that PPS reduces Aβ peptide cytotoxicity and preserves barrier integrity, suggesting a neuroprotective role against pathology.

PPS has shown promise in preclinical and early clinical studies for (MPS), a group of lysosomal storage disorders. In animal models of MPS IIIA and MPS VI, oral PPS reduced neuroinflammation, GAG accumulation, and improved behavioral outcomes by promoting and inhibiting inflammatory pathways. A phase 1/2 trial in MPS I, II, and VI patients demonstrated and preliminary in reducing joint inflammation and improving mobility after 24 weeks of oral dosing at 20-40 mg/kg/day. As of 2025, phase 2 studies continue to evaluate long-term effects on skeletal and neurological symptoms. Key challenges in advancing PPS for neurological disorders include its poor penetration of the blood-brain barrier, necessitating invasive routes like intraventricular delivery, and dosing constraints imposed by systemic side effects such as . These barriers have limited progression from preclinical promise to clinical viability, particularly for chronic conditions requiring long-term administration. Ethically, PPS's use in rare prion diseases has benefited from frameworks, facilitating compassionate access despite the absence of formal approval for these indications, emphasizing the need for balanced in ultra-rare settings.

Veterinary applications

Use in dogs

Pentosan polysulfate is primarily used in for the treatment of and in dogs. The standard protocol involves at a dosage of 3 mg/kg body weight, given every 5 to 7 days for a total of four weeks. Veterinary studies have demonstrated its efficacy in reducing lameness and improving mobility, with clinical studies reporting positive responses in a majority of treated dogs based on and owner assessments. This improvement is attributed to its role in protecting by inhibiting inflammatory mediators and promoting synthesis. In clinical practice, pentosan polysulfate is available under veterinary-specific formulations such as Cartrophen Vet and Zydax in , while in the , it is often used off-label or as compounded preparations like those from Wedgewood Pharmacy, with Elmiron (the human formulation) occasionally employed similarly. As of 2025, it is widely adopted in for canine joint disorders and increasingly utilized off-label in the , though veterinarians monitor for potential gastrointestinal side effects such as or , which occur in a small percentage of cases. Due to its mild properties, pentosan polysulfate is contraindicated in dogs with bleeding disorders, coagulation abnormalities, or recent trauma, and caution is advised in those on concurrent therapy.

Use in cats

Pentosan polysulfate is used off-label in cats primarily for managing and idiopathic lower urinary tract disease, such as feline idiopathic cystitis. Dosing regimens are similar to those in dogs, typically 3 mg/kg subcutaneously weekly for four weeks for joint conditions, though oral formulations like Elmiron have been explored for urinary issues at lower doses (e.g., 50 mg/cat twice daily). Clinical evidence is limited, with studies showing potential benefits in reducing urinary symptoms and improving mobility, but safety data are incomplete, including risks of hemorrhage in some cases. It is not FDA-approved for cats, and use requires veterinary discretion, especially avoiding in breeding, pregnant, or lactating animals.

Use in

Pentosan polysulfate sodium (PPS) is primarily used in for the management of (OA), a common degenerative disease that causes lameness, stiffness, and reduced performance. In 2022, the U.S. approved Zycosan, the first injectable formulation of PPS specifically for , indicated for controlling clinical signs associated with OA, such as , , and lameness. This approval was based on a multicenter field study involving 219 client-owned aged 3 to 32 years with radiographic evidence of OA in a single , where PPS demonstrated significant improvements in lameness scores compared to saline controls. In Australia, injectable formulations of pentosan polysulfate, such as Pentosan Equine and Cartrophen Equine Forte, are commonly used for the management of non-infectious inflammatory joint disease in horses, including osteoarthritis. Veterinarians frequently recommend combining these injections with daily oral joint supplements for enhanced therapeutic outcomes, including improved anti-inflammatory effects, cartilage protection, and long-term joint health. Examples include 4CYTE Epiitalis Forte, a daily oral gel or powder containing Epiitalis® to reduce inflammation and support cartilage repair, and Joint Guard from Ceva Animal Health, which contains glucosamine, chondroitin sulfate, manganese, and vitamin C to support cartilage maintenance. Such combinations are part of a multi-modal approach to joint disease management and should always be determined and supervised by a veterinarian to ensure appropriate, individualized treatment. The standard dosage for PPS in horses is 3 mg/kg body weight administered intramuscularly once weekly for four consecutive weeks, typically injected into the neck muscle to minimize discomfort. This regimen has shown disease-modifying effects in experimental models of equine OA, including reduced cartilage fibrillation, decreased synovial inflammation, and elevated levels of 846 epitopes in , which indicate improved cartilage metabolism. In the pivotal field trial, 60% of treated achieved treatment success—defined as at least a one-grade improvement in lameness—versus 36% in the control group, with benefits observed in joints like the hocks, stifles, and tarsi. PPS is believed to exert its effects through actions, inhibition of proteolytic enzymes that degrade , and stimulation of synthesis, thereby supporting lubrication and tissue repair. Safety profiles from clinical studies indicate PPS is well-tolerated in , with no clinically relevant adverse effects on or systemic health. Common side effects are limited to transient injection-site reactions, such as mild swelling, heat, or pain, occurring in less than 10% of cases and resolving within five days without intervention. Prolonged activated (aPTT) and (PT) may occur due to PPS's properties, but no bleeding events were reported in trials. It is available only by veterinary prescription and is not approved for use in horses intended for production. While primarily studied for OA, ongoing research explores PPS in combination therapies, such as with N-acetyl glucosamine and hyaluronan, which have shown reductions in radiographic and macroscopic joint pathology in induced OA models.

References

  1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020193s014lbl.pdf
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC2873929/
  3. https://medlineplus.gov/druginfo/meds/a602007.html
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC10893900/
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC7171972/
  6. https://go.drugbank.com/drugs/DB00686
  7. https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-injectable-pentosan-osteoarthritis-horses
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC10315557/
  9. https://pubmed.ncbi.nlm.nih.gov/8683953/
  10. https://pmc.ncbi.nlm.nih.gov/articles/PMC4827827/
  11. https://www.sciencedirect.com/science/article/pii/S2162098923006898
  12. https://pubmed.ncbi.nlm.nih.gov/11218575/
  13. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/020193Orig1s014.pdf
  14. https://pdf.hres.ca/dpd_pm/00058196.PDF
  15. https://sitem.herts.ac.uk/aeru/vsdb/Reports/1754.htm
  16. https://file.medchemexpress.com/batch_PDF/HY-A0203/Pentosan-Polysulfate-SDS-MedChemExpress.pdf
  17. https://www.researchgate.net/publication/12111951_Studies_on_the_Structural_Variations_of_Pentosan_Polysulfate_Sodium_NaPPS_from_Different_Sources_by_Capillary_Electrophoresis
  18. https://www.ncbi.nlm.nih.gov/books/NBK589706/
  19. https://pubchem.ncbi.nlm.nih.gov/compound/Elmiron
  20. https://patents.google.com/patent/WO2012101544A1/en
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC1476002/
  22. https://pmc.ncbi.nlm.nih.gov/articles/PMC1079893/
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC4708541/
  24. https://pubmed.ncbi.nlm.nih.gov/40747461/
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC4708535/
  26. https://pmc.ncbi.nlm.nih.gov/articles/PMC4505659/
  27. https://pubmed.ncbi.nlm.nih.gov/16706553/
  28. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020193s009lbl.pdf
  29. https://pmc.ncbi.nlm.nih.gov/articles/PMC10132487/
  30. https://pubmed.ncbi.nlm.nih.gov/2442830/
  31. https://pmc.ncbi.nlm.nih.gov/articles/PMC3369482/
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC8250366/
  33. https://www.cua.org/system/files/Guideline-Files/9182.pdf
  34. https://www.io.nihr.ac.uk/wp-content/uploads/2022/01/13742-Pentosan.pdf
  35. https://paradigmbiopharma.com/product-development/
  36. https://obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.13686
  37. https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-025-08605-z
  38. https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20193s003lbl.pdf
  39. https://www.drugwatch.com/elmiron/
  40. https://www.drugs.com/monograph/pentosan-polysulfate.html
  41. https://www.drugs.com/sfx/pentosan-polysulfate-sodium-side-effects.html
  42. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020193s015lbl.pdf
  43. https://www.sciencedirect.com/science/article/pii/S1350946225000734
  44. https://www.mayoclinicproceedings.org/article/S0025-6196%2821%2900312-8/fulltext
  45. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1494467/full
  46. https://pubmed.ncbi.nlm.nih.gov/40792210/
  47. https://eyewiki.org/Pentosan_Polysulfate_Maculopathy
  48. https://www.bene-arzneimittel.de/en/about-bene
  49. https://www.bene-pharmachem.de/en/company/history/
  50. https://patents.justia.com/patent/20180134813
  51. https://paradigmbiopharma.com/wp-content/uploads/2022/05/Baker-Young-Research-Report-February-2021-.pdf
  52. https://www.bene-arzneimittel.de/en/business-partners/company/company-history
  53. https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-003573-41/GB
  54. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=1784
  55. https://www.ema.europa.eu/en/medicines/human/EPAR/elmiron
  56. https://www.tga.gov.au/resources/artg/48446
  57. https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/pentosan-polysulfate-sodium-elmiron
  58. https://www.tga.gov.au/news/safety-updates/pentosan-polysulfate-sodium-and-pigmentary-maculopathy
  59. https://www.ema.europa.eu/en/documents/product-information/elmiron-epar-product-information_en.pdf
  60. https://www.drugs.com/international/pentosan-polysulfate.html
  61. https://pubmed.ncbi.nlm.nih.gov/2418527/
  62. https://www.genericmedsaustralia.com/product/cystopen-100-mg/
  63. https://www.drugs.com/availability/generic-elmiron.html
  64. https://www.icnetwork.org/economic-toll-elmiron/
  65. https://vcahospitals.com/know-your-pet/pentosan-polysulfate-sodium
  66. https://veterinarypartner.vin.com/default.aspx?pid=19239&catId=254070&id=4951467
  67. https://www.healthdirect.gov.au/medicines/brand/amt%2C39734011000036107/elmiron
  68. https://retinatoday.com/articles/2022-mar/beware-of-pigmentary-retinopathy-with-pentosan-polysulfate-sodium
  69. https://pubmed.ncbi.nlm.nih.gov/40962246/
  70. https://www.singlecare.com/prescription/elmiron
  71. https://journals.lww.com/fpmrs/fulltext/2023/02000/an_analysis_of_stated_insurance_coverage_and.27.aspx
  72. https://pmc.ncbi.nlm.nih.gov/articles/PMC5417682/
  73. https://www.drugwatch.com/elmiron/lawsuits/
  74. https://www.oarsijournal.com/article/S1063-4584(23)00086-9/fulltext
  75. https://clinicaltrials.gov/study/NCT04809376
  76. https://clinicaltrials.gov/study/NCT06917404
  77. https://www.drdavidsamra.com.au/pentosan
  78. https://bmjopen.bmj.com/content/14/5/e083046
  79. https://pubmed.ncbi.nlm.nih.gov/40074062/
  80. https://www.clinicaltrialsarena.com/news/advanced-clinical-paradigm-trial/
  81. https://www.sciencedirect.com/science/article/abs/pii/S0163445304001860
  82. https://jnnp.bmj.com/content/85/8/921
  83. https://www.cureffi.org/2012/12/13/the-rise-and-fall-of-pentosan-polysulfate-in-prion-disease/
  84. https://www.ucl.ac.uk/national-prion-clinic/drug-treatments
  85. https://www.skpharmteco.com/news-insights/blog/rare-diseases-part-ix-a-look-at-prion-diseases/
  86. https://pmc.ncbi.nlm.nih.gov/articles/PMC1513442/
  87. https://journals.sagepub.com/doi/10.3233/JAD-2010-100759
  88. https://pubmed.ncbi.nlm.nih.gov/24671717/
  89. https://pubmed.ncbi.nlm.nih.gov/23300225/
  90. https://www.orpha.net/en/drug/substance/412265
  91. http://www.cartrophen.com/en/for-vets/dosage-usage/
  92. http://www.cartrophen.com/for-vets/safety-and-efficacy/
  93. https://avmajournals.avma.org/view/journals/javma/230/4/javma.230.4.514.xml
  94. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2022.830098/full
  95. https://www.wedgewood.com/medications/pentosan-polysulfate/
  96. https://theanimalpharmacy.com.au/zydax-100-20ml/
  97. https://monbulkvetcentre.com.au/arthritis-in-dogs-and-cats/
  98. https://chanellepharma.com/wp-content/uploads/2019/06/Osteopen-Licence_VPA10987-131-001_20072018151541.pdf
  99. https://www.noahcompendium.co.uk/?id=-472056
  100. https://pubmed.ncbi.nlm.nih.gov/18996037/
  101. https://journals.sagepub.com/doi/10.1177/20551169211058650
  102. https://www.vetwest.com.au/pet-library/arthritis-and-cats/
  103. https://thehorse.com/1121431/pentosan-polysulfate-safe-effective-for-arthritic-horses/
  104. https://www.cartrophen.com/en/for-horse-owners-and-trainers/what-is-cartrophen-vet-cartrophen-equine-forte/
  105. https://www.ceva.com.au/Products/Products-list/Pentosan-Equine-Injection
  106. https://www.westvets.com.au/prevention-and-treatment-for-arthritis-in-horses/
  107. https://au.4cyte.global/horses/
  108. https://pubmed.ncbi.nlm.nih.gov/22533393/
  109. https://pubmed.ncbi.nlm.nih.gov/24819506/
Add your contribution
Related Hubs
User Avatar
No comments yet.