Polysulfated Glycosaminoglycan: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Polysulfated Glycosaminoglycan, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Adequan® Canine (NADA/ANADA 141-038)
Adequan® Canine NADA 141-038, Original approval, July 15, 1997; sponsor American Regent, Inc.; species: Dogs; foi_id 3696; FDA PDF
Indication
Control of signs associated with non-infectious degenerative and/or traumatic arthritis of canine synovial joints (intramuscular injection).
Dose regimen
2 mg/lb body weight (.02 mL/lb, or 1 mL per 50 lb), intramuscular injection only, twice weekly, for up to 4 weeks (maximum of 8 injections); do not exceed the recommended dose or regimen
The recommended dose of Adequan® Canine is 2 mg/lb body weight (.02 mL/lb, or 1 mL per 50 lb), by intramuscular injection only, twice weekly for up to 4 weeks (maximum of 8 injections).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | mean serum tritium-labeled PSGAG 4.43 µg PSGAG/mL at 2 hours, declining to 0.81 µg/mL at 72 hours | single IM injection of 2 mg/lb tritium-labeled PSGAG, 9 dogs with adjuvant-induced synovitis (scintillation) | TIME (HOURS) SERUM SYNOVIAL FULID: SHOULDER SYNOVIAL FULID: STIFLE 0 0 0 0 2 4.43 4.17 4.18 6 1.59 1.88 1.65 12 1.05 1.10 1.08 24 0.89 0.93 1.01 48 0.83 0.85 0.87 72 0.81 0.79 0.84 |
| other | mean synovial fluid tritium-labeled PSGAG 4.17 (shoulder) and 4.18 (stifle) µg PSGAG/mL at 2 hours; 0.79 and 0.84 at 72 hours | single IM 2 mg/lb, induced synovitis joints, 9 dogs | TIME (HOURS) SERUM SYNOVIAL FULID: SHOULDER SYNOVIAL FULID: STIFLE 0 0 0 0 2 4.43 4.17 4.18 6 1.59 1.88 1.65 12 1.05 1.10 1.08 24 0.89 0.93 1.01 48 0.83 0.85 0.87 72 0.81 0.79 0.84 |
| other | mean articular cartilage tritium-labeled PSGAG 0.17 (stifle, induced synovitis), 0.16 (shoulder, induced synovitis), 0.10 (hip, normal), 0.08 (elbow, normal) µg PSGAG/g | 72 hours after single IM 2 mg/lb, 9 dogs | JOINT PSGAG LEVEL STIFLE (INDUCED SYNOVITIS) 0.17 SHOULDER (INDUCED SYNOVITIS) 0.16 HIP (NORMAL) 0.10 ELBOW (NORMAL) 0.08 |
| other | reaches synovial fluid within 2 hours; detectable in synovial fluid and cartilage up to 72 hours | single IM 2 mg/lb | These data indicate that, after an intramuscular injection of PSGAG at 2 mg/lb in dogs, PSGAG reaches synovial fluid within 2 hours and detectable levels are maintained in synovial fluid and articular cartilage for up to 72 hours. |
Target-animal safety
dose multiples ~1X (5 mg/kg), ~3X (15 mg/kg), ~10X (50 mg/kg); duration IM twice weekly for 13 weeks (~3 times the recommended 4-week duration); necropsy 24 h after final dose; animals 16 of each sex; 4 groups of 4 males and 4 females.
Thirty-two adult beagle dogs (16 of each sex) served as test animals. After a 4 week acclimation period, the dogs were stratified by sex and weight and assigned to 4 groups of 4 males and 4 females each.
| Finding | Quote |
|---|---|
| Transient injection site pain in three 50 mg/kg dogs and one 15 mg/kg dog | Transient injection site pain was noted on one occasion each in three 50 mg/kg dogs and one 15 mg/kg dog. |
| One 50 mg/kg dog euthanized after a large hematoma in week 12 | One 50 mg/kg dog was euthanized after development of a large hematoma during week 12 of the treatment. |
| Reduced prothrombin time and platelet counts at 50 mg/kg (week 12) | A statistically significant reduction of prothrombin time and platelet counts in the 50 mg/kg group at week 12 was detected. |
| Increased ALT at 50 mg/kg and cholesterol at 15 and 50 mg/kg | Significantly increased serum alanine aminotransferase (ALT, SGPT) values in the 50 mg/kg group and cholesterol values in the 15 and 50 mg/kg groups were noted at weeks 6 and 12. |
| Increased liver and kidney weights at 50 mg/kg; kidney weights at 15 mg/kg; histologic changes in liver, kidney, mesenteric lymph nodes at 15 and 50 mg/kg | There were significant increases in liver and kidney weights in the 50 mg/kg group and significant increases in kidney weights in the 15 mg/kg group. Treatment related changes in the liver, kidneys and mesenteric lymph nodes were detected histologically in the 15 and 50 mg/kg groups. |
| Conclusion: labeled regimen unlikely to produce adverse effects; kidney, liver and coagulation effects possible at higher doses/longer duration | These data indicate that the proposed dosage regimen for Adequan® Canine (2 mg/lb body weight twice weekly for 4 weeks) is unlikely to produce adverse effects in dogs. At higher doses and for longer treatment periods, effects on the kidney, liver, and blood coagulation are possible. |
Effectiveness
Blinded, placebo (0.9% saline)-controlled, randomized field trial at 3 US small animal practices; Adequan Canine 2 mg/lb IM twice weekly for 4 weeks (8 injections) in dogs with lameness from radiographically confirmed traumatic or degenerative joint disease in 1-2 joints; n = 51 dogs (24 Adequan, 27 placebo); 71 limbs; primary endpoint: Percent change from baseline in orthopedic scores (lameness at walk/trot, pain on manipulation, range of motion, functional disability, total orthopedic score) at interim (after 5th injection) and final (1 week after 8th injection); responder analysis (>30% improvement in all limbs); result: Significant improvement for Adequan in range of motion (final p = 0.007) and total orthopedic score (final p = 0.025); lameness at trot p = 0.053; responders at final 67% Adequan vs 33% placebo (p = 0.0025)
The final data analysis included data from 71 limbs in 51 dogs. Of these, 35 limbs in 24 dogs were in the Adequan® Canine treated group, and 36 limbs in 27 dogs were in the placebo treated group.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Preputial bleeding (field trial; investigator considered unrelated) | 1 incident (treatment group not stated) | a. preputial bleeding (1 incident; the investigator did not believe the bleeding was related to the experimental treatment) | |
| Transient injection site pain (field trial) | 1 incident (treatment group not stated) | b. transient injection site pain (1 incident) | |
| Transient diarrhea (field trial) | 1 incident each in 2 dogs (treatment group not stated) | c. transient diarrhea (1 incident each in 2 dogs) |
Extraction notes: 1997 summary; no species field, 'Dogs' inferred from 'canine'. PK values are tissue-distribution data for tritium-labeled PSGAG (Tables 1-2), not classical PK parameters; no half-life, Cmax or bioavailability reported. Dose written as '.02 mL/lb' exactly as printed. Field-trial adverse reactions are listed without treatment-group assignment; the safety study used Arteparon powder (human product) reconstituted in saline rather than the final Adequan formulation. Effectiveness p-values come from the ANOVA table and responder table on pages 17 of 23.
Reproduce: foi_structured_search(query="Polysulfated Glycosaminoglycan") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).