[1] Patients who have taken pentosan polysulfate orally report a variety of side effects, primarily gastrointestinal complaints such as diarrhea, heartburn, and stomach pain.

Recent report based on clinical observation hypothesizes that chronic exposure to pentosan polysulfate can cause retinal toxicity, mimicking pigmentary pattern dystrophy.

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.

[16] Read et al. (1996) [17] 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.

[18] 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.

[19] 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.

[21] 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.