Adequan Canine (polysulfated glycosaminoglycan) is recommended for intramuscular injection for the control of signs associated with non-infectious degenerative and/or traumatic arthritis of canine synovial joints. 

Why has my veterinarian prescribed Adequan Canine?

"This medication is a member of a unique class of drugs called Disease-Modifying Osteoarthritis Drugs."

Polysulfated glycosaminoglycan is used to control the signs associated with non-infectious degenerative and/or traumatic arthritis in dogs. This medication is a member of a unique class of drugs called Disease-Modifying Osteoarthritis Drugs (DMOAD).

How do I give Adequan Canine?

• This medication is administered as an intramuscular injection as directed by your veterinarian.
• Generally, one injection is required every 3 to 5 days over a specific period of time, or for a number of doses.

What do I do if I miss giving a dose?

Contact your veterinarian to set up a dosing schedule.

How do I store Adequan Canine?

• This medication should be stored in a cool place, at a temperature of 8 to 15° C.
• The manufacturer recommends discarding any unused portion.
• Keep this medicine out of reach of children.
• Do not store this medicine in the bathroom, near the kitchen sink or in damp places.

What are the potential side effects?

• Adverse reactions are unlikely when the intramuscular route is used. Possible side effects include pain at the injection site, vomiting, diarrhea, depression and abnormal bleeding.
• Other side effects may occur. If you notice anything unusual, contact your veterinarian.

Are there any possible drug interactions?

• Make sure to tell your veterinarian what other medication you are giving to your pet.
• Quite often, your veterinarian may prescribe two different medications, and sometimes a drug interaction may occur. In this case, your veterinarian may vary the dose and/or monitor your pet more closely.
• Your veterinarian will use this medication with caution if your pet is receiving non-steroidal anti-inflammatory drugs (NSAIDs), other steroids or anticoagulants.
• Contact your veterinarian if your pet experiences any unusual reactions when different medications are given together.

Polysulfated glycosaminoglycan (Rx)

Trade Names:

Adequan® Canine

General Description:

This drug is a medication that is used in dogs and cats to inhibit the destruction of cartilage and reduce the inflammation that is commonly associated with degenerative joint disease. Polysulfated glycosaminoglycan is available as an injectable.

What is this product?

• A cartilage protective agent
• Given by an injection into the muscle

Reasons for prescribing:

• To aid in the treatment of degenerative joint disease or arthritis

What dogs/cats should not use this medication?

• Animals with liver or kidney disease
• Animals with bleeding or clotting disorders
• Animals that will require surgery in the near future
• Animals that will be used for breeding
• Animals that may be pregnant or nursing
• Animals with a known hypersensitivity or allergy to this drug should not use this medication

Directions:

This medication is commonly given by your veterinarian. If you are giving this medication at home, follow your veterinarian's directions carefully. Give this medication for as long as your veterinarian directs. Do not skip doses or stop giving the medication without consulting your veterinarian.

Baseline blood work may be recommended to assess your pet's general health before starting this medication.

Periodic blood work to monitor its effects on the body may also be advised if long term therapy is necessary. Dose adjustments may be made based upon these results and an assessment of how your dog or cat is responding clinically.

Call ahead for refills.

Ideally, give this medication at the same time(s) daily.

When using an injectable:

Read the prescription label carefully

Follow the directions for injections given by your veterinarian

Give the exact amount prescribed and only as often as directed

Shake the vial to effectively suspend the medication in the liquid

Always use a clean needle and syringe

This medication is only to be given in the muscle, never give this medication into the vein

Follow local regulations when disposing of used needles and syringes

What if a dose is missed?

If a dose is missed, give it as soon as you can. If it is time already for the next dose, skip the missed dose and go back to the normal schedule. Do not give two doses at the same time.

What to tell/ask a veterinarian before giving this product?

Talk to your veterinarian about:

• When your pet will need to be rechecked
• What tests may need to be performed prior to and during treatment with this drug
• What are the risks and benefits of using this drug

Tell your veterinarian about:

• If your pet has experienced side-effects on other drugs/products
• If your pet has experienced digestive upset now or ever
• If your pet has experienced liver or kidney disease now or ever
• If your pet has experienced any other medical problems or allergies now or ever
• All medicines and supplements that you are giving your pet or plan to give your pet, including those you can get without a prescription. Your veterinarian may want to check that all of your pet's medications can be given together.
• If your pet is pregnant, nursing or if you plan to breed your pet

Storage and Warnings:

Polysulfated glycosaminoglycan should be stored in a childproof container in a cool, dry place at room temperature away from heat and direct sunlight.

Keep this and all medication out of reach of children and pets.

Call your physician immediately if you accidentally take this product.

Potential side effects:

• This medication can affect the bone marrow resulting in abnormal bruising and bleeding
• If these symptoms persist or you notice anything else unusual, contact your veterinarian

Can this product be given with other products/drugs?

• Yes, but possible interactions may occur when giving polysulfated glycosaminoglycan in conjunction with: heparin, nonsteroidal anti-inflammatories (ex. acetaminophen, deracoxib, carprofen, ibuprofen, meloxicam), and warfarin
• Drugs other than those listed may also interact with polysulfated glycosaminoglycan
• Do not give new food or medications without first talking to your veterinarian
• If your pet experiences any unusual reactions when taking multiple medications, contact your veterinarian

Overdosing?

Contact your veterinarian immediately if your pet receives more than the prescribed amount.

What else should I know?

Notify your veterinarian if your animal's condition does not improve or worsens despite this treatment.

As with all prescribed products/medicines, polysulfated glycosaminoglycan should only be given to the pet for which it was prescribed.

It should be given only for the condition for which it was prescribed.

This is just a summary of information about polysulfated glycosaminoglycan. If you have any questions or concerns about polysulfated glycosaminoglycan or the condition it was prescribed for, please contact your veterinarian.

ADEQUAN^® CANINE

Luitpold

Brand of Polysulfated Glycosaminoglycan Solution 100 mg/mL in a 5 mL preserved multiple dose vial for intramuscular use in dogs.

Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Description: The active ingredient in Adequan^® Canine is polysulfated glycosaminoglycan (PSGAG). Polysulfated glycosaminoglycan is a semi-synthetic glycosaminoglycan prepared by extracting glycosaminoglycans (GAGs) from bovine tracheal cartilage. GAGs are polysaccharides composed of repeating disaccharide units. The GAG present in PSGAG is principally chondroitin sulfate containing 3 to 4 sulfate esters per disaccharide unit. The molecular weight for PSGAG used in the manufacture of Adequan^® is 3,000 to 15,000 daltons. Each mL of Adequan^® Canine contains 100 mg of PSGAG, 0.9% v/v benzyl alcohol as a preservative, and water for injection q.s. to 1 mL. Sodium hydroxide and/or hydrochloric acid added when necessary to adjust pH.

Pharmacology: The specific mechanism of action of Adequan^® in canine joints is not known. PSGAG is characterized as a "disease modifying osteoarthritis drug." Experiments conducted in vitro have shown PSGAG to inhibit certain catabolic enzymes which have increased activity in inflamed joints, and to enhance the activity of some anabolic enzymes. For example, PSGAG has been shown to significantly inhibit serine proteinases. Serine proteinases have been demonstrated to play a role in the Interleukin-1 mediated degradation of cartilage proteoglycans and collagen. PSGAG is reported to be an inhibitor of Prostaglandin E2 (PGE2) synthesis. PGE2 has been shown to increase the loss of proteoglycan from cartilage. PSGAG has been reported to inhibit some catabolic enzymes such as elastase, stromelysin, metalloproteases, cathepsin B1, and hyaluronidases, which degrade collagen, proteoglycans, and hyaluronic acid in degenerative joint disease. Anabolic effects studied include ability to stimulate the synthesis of protein, collagen, proteoglycans, and hyaluronic acid in various cells and tissues in vitro. Cultured human and rabbit chondrocytes have shown increased synthesis of proteoglycan and hyaluronic acid in the presence of PSGAG. PSGAGs have shown a specific potentiating effect on hyaluronic acid synthesis by synovial membrane cells in vitro.

Absorption, distribution, metabolism, and excretion of PSGAG following intramuscular injection have been studied in several species, including rats, rabbits, humans, horses and dogs.

Studies in rabbits showed maximum blood concentrations of PSGAG following IM injection were reached between 20 to 40 minutes following injection, and that the drug was distributed to all tissues studied, including articular cartilage, synovial fluid, adrenals, thyroid, peritoneal fluid, lungs, eyes, spinal cord, kidneys, brain, liver, spleen, bone marrow, skin, and heart.

Following intramuscular injection of PSGAG in humans, the drug was found to be bound to serum proteins. PSGAG binds to both albumin and chi- and beta-globulins and the extent of the binding is suggested to be 30 to 40%. Therefore, the drug may be present in both bound and free form in the bloodstream. Because of its relatively low molecular weight, the synovial membrane is not a significant barrier to distribution of PSGAG from the bloodstream to the synovial fluid. Distribution from the synovial fluid to the cartilage takes place by diffusion. In the articular cartilage the drug is deposited into the cartilage matrix.

Serum and synovial fluid distribution curves of PSGAG have been studied in dogs and appear similar to those found in humans and rabbits.

In rabbits, metabolism of PSGAG is reported to take place in the liver, spleen, and bone marrow. Metabolism may also occur in the kidneys. PSGAG administered intramuscularly and not protein bound or bound to other tissues is excreted primarily via the kidneys, with a small proportion excreted in the feces.

Toxicity: In a subacute toxicity study, 32 adult beagle dogs (4 males and 4 females per treatment group) received either 0.9% saline solution or PSGAG at a dose of 5 mg, 15 mg, or 50 mg per kg of body weight (approximately 2.3, 6.8, or 22.7 mg/lb), via intramuscular injection twice weekly for 13 weeks. PSGAG doses represent approximately 1X, 3X, and 10X the recommended dosage of 2 mg/lb, and more than 3 times the recommended 4-week duration of treatment. Necropsies were performed 24 hours after the final treatment. During week 12, one dog in the 50 mg/kg dosage group developed a large hematoma at the injection site which necessitated euthanasia. No other mortalities occurred during the treatment period. Statistically significant changes in the 50 mg/kg group included increased prothrombin time, reduced platelet count, an increase in ALT and cholesterol, and increased liver and kidney weights. Increased cholesterol and kidney weights were also noted in the 15 mg/kg group. Microscopic lesions were noted in the liver (Kupffer cells containing eosinophilic foamy cytoplasm), kidneys (swollen, foamy cells in the proximal convoluted tubules), and lymph nodes (macrophages with eosinophilic foamy cytoplasm) in the 15 mg/kg and 50 mg/kg groups. Intramuscular inflammation, hemorrhage, and degeneration were seen in all 3 PSGAG treated groups; the incidence and severity appeared dose related.

Efficacy: Efficacy of Adequan^® Canine was demonstrated in two studies. A laboratory study using radiolabeled PSGAG established distribution of PSGAG into canine serum and synovial fluid following a single intramuscular injection of 2 mg/lb. A clinical field trial was conducted in dogs diagnosed with radiographically-confirmed traumatic and/or degenerative joint disease of 1 or 2 joints. Joints evaluated included hips, stifles, shoulders, hocks and elbows. Fifty-one dogs were randomly assigned to receive either Adequan^® Canine at 2 mg/lb of body weight or 0.9% saline. Both treatments were administered by intramuscular injection twice weekly for 4 weeks (8 injections total). Investigators administering treatment and evaluating the dogs were unaware of the treatment assignment. A total of 71 limbs in 51 dogs were evaluated. Of these, 35 limbs in 24 dogs were in the Adequan^® Canine treated group. Each lame limb was scored for lameness at a walk, lameness at a trot, pain, range of motion, and functional disability. The scores for the individual parameters were combined to determine a total orthopedic score. At the end of the treatment period, dogs treated with Adequan^® Canine showed a statistically significant improvement in range of motion and total orthopedic score over placebo treated control dogs.

Indications and Usage: Adequan^® Canine is recommended for intramuscular injection for the control of signs associated with non-infectious degenerative and/or traumatic arthritis of canine synovial joints.

Contraindications: Do not use in dogs showing hypersensitivity to PSGAG. PSGAG is a synthetic heparinoid; do not use in dogs with known or suspected bleeding disorders.

Reproductive Safety: Studies to establish the safety of Adequan^® Canine in breeding, pregnant, or lactating dogs have not been conducted.

Precaution: Use with caution in dogs with renal or hepatic impairment.

Adverse Reactions: In the clinical efficacy trial, 24 dogs were treated with Adequan^® Canine twice weekly for 4 weeks. Possible adverse reactions were reported after 2.1% of the injections. These included transient pain at the injection site (1 incident), transient diarrhea (1 incident each in 2 dogs), and abnormal bleeding (1 incident). These effects were mild and self-limiting and did not require interruption of therapy. To report suspected adverse reactions or for a copy of the Material Safety Data Sheet for this product, contact Novartis Animal Health US, Inc. at 1-800-637-0281.

Human Warning: Keep this and all medications out of the reach of children.

Dosage and Administration: 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). Do not exceed the recommended dose or therapeutic regimen. Do not mix Adequan^® Canine with other drugs or solvents.

Storage Conditions: Store at controlled room temperature up to 25°C (77°F) (See USP).

How Supplied: Adequan^® Canine Solution 100 mg/mL in a 5 mL preserved multiple dose vial.

NDC 10797-975-02

Manufactured by: LUITPOLD PHARMACEUTICALS, INC., Animal Health Division, Shirley, NY 11967

(631) 924-4000

1-800-458-0163

Marketed by: NOVARTIS ANIMAL HEALTH US, INC., Greensboro, NC 27408

NADA 141-038, Approved by FDA

Made in U.S.A.

Rev. 1/04

IN975

MG #12417

NAH/ADQ/VI/1