Issued: May 2014
AN: 00708/2013
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
Osphos 60 mg/ml Solution for Injection for Horses
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml contains:
Active substance:
Disodium Clodronate 60 mg
as Clodronic acid 51 mg
For the full list of excipients, see section6.1.
3. PHARMACEUTICAL FORM
Solution for injection.
Clear and colourless, aqueous solution.
4. CLINICAL PARTICULARS
4.1 Target species
Horses
4.2 Indications for use, specifying the target species
For the control of clinical signs associated with the bone resorptive processes of navicular syndrome in horses.
4.3 Contraindications
In the absence of any data relating to use in growing animals, do not administer to horses less than 4 years of age.
Do not administer to horses with impaired renal function.
4.4 Special warnings for each target species
None.
4.5 Special precautions for use
Special precautions for use in animals:
The clinical effect of the product depends on the presence of osteolytic processes causing pain and leading to lameness. The product should be used only after a proper diagnosis combining a complete orthopaedic clinical examination including local analgesia and appropriate imaging techniques in order to identify the cause of pain and the nature of bone lesions.
Special precautions to be taken by the person administering the veterinary medicinal product to animals:
Care should be taken when handling the product to avoid self-injection especially by pregnant women. In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician.
Accidental spillage on the skin or eyes should be washed off with plenty of water.
4.6 Adverse reactions (frequency and seriousness)
The most common adverse reactions associated with treatment with clodronic acid at the recommended dose were nervousness, lip licking, yawning, pawing, tongue rolling, head bobbing/shaking, injection site swelling, and mild colic signs.
In the field effectiveness study with 146 horses, ten horses had clinical signs of discomfort or nervousness, or experienced cramping (mild colic) immediately post-treatment. All horses recovered shortly after treatment; 8 of the 10 horses had resolution of clinical signs with hand walking only; one horse had resolution of clinical signs without intervention. One horse developed urticaria (hives) which responded to treatment with anti-inflammatory medication. Injection site swelling was noted in 0.8% (two) of 248clodronic acid injection sites. Clinical signs of colic were observed following 1.6% (four) of the 248 treatments with clodronic acid, including 3 of the 10 horses with clinical signs immediately post-treatment.
4.7 Use during pregnancy, lactation or lay
The safety of the veterinary medicinal product has not been established during pregnancy or lactation.
Use only accordingly to the benefit-risk assessment by the responsible veterinarian.
Laboratory studies in rats and rabbits have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects.
4.8 Interaction with other medicinal products and other forms of interaction
Medications such as aminoglycosides whose toxicity can be exacerbated by a reduction in serum calcium, and medications such as tetracyclines that can reduce serum calcium should not be given for 72 hours after administration with clodronic acid.
Use of the product with concurrent administration of phenylbutazone has been shown to be well tolerated.
4.9 Amounts to be administered and administration route
By intramuscular injection, 1.80 mg Disodium clodronate (1.53 mg Clodronic acid) per kg bodyweight, corresponding to 3 ml per 100 kg body weight. Divide the total volume evenly for administration at 2 to 3 separate injection sites.
The maximum dose is 900 mg Disodium clodronate per horse (one 15 ml vial per horse >500 kg).
Treatment may be repeated after 3 months as needed to control the clinical signs associated with navicular syndrome in horses.
In a clinical trial, lameness in 74.7% of 114 horses was improved by at least 1 grade on the AAEP
5 point scale by day 56. By day 180, 65.8% were improved. Therefore treatment may be repeated after 3 months as needed to control the clinical signs associated with navicular syndrome in horses.
4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
There is no experience with massive overdose. The risk of experiencing adverse reactions at exaggerated doses (2X to 5X the recommended dose) may however increase when the animal is overdosed. Signs of adverse reactions at exaggerated doses are primarily gastrointestinal and central nervous system related and transient in nature.
At exaggerated doses (2X to 5X the recommended dose), adverse reactions included: flehming, head shaking, neck retching, pawing, agitation, depression, muscle fasiculations and colic. Signs of colic included rolling, full body stretching, repetitive lying down and rising, kicking at the abdomen and other typical signs of acute gastrointestinal discomfort. At 5X dosing of clodronic acid, 3 out of 6horses developed temporary gait abnormalities including hypermetria, spasticity or mild ataxia.
Horses treated with clodronic acid at escalating doses (2X, 3X, and 5X the recommended dose) showed a dose related trend for increases in BUN and creatinine post-treatment.
4.11 Withdrawal period(s)
Not to be used in horses intended for human consumption.
Treated horses may never be slaughtered for human consumption.
The horse must have been declared as not intended for human consumption under the national horse passport legislation.
5. PHARMACOLOGICAL IMMUNOLOGICAL PROPERTIES
Pharmacotherapeutic group: Biphosphonate.
ATCvet code: QM05BA02
5.1 Pharmacodynamic properties
Clodronic acid is a geminal bisphosphonate that inhibits bone resorption by binding to hydroxyapatite crystals (inhibiting their formation and dissolution), and by direct cellular effects on osteoclasts (inhibiting osteoclast cell function). It has a high affinity for solid-phase calcium phosphate and therefore accumulates in bone, where it inhibits the formation, aggregation and dissolution of calcium phosphate crystals. Bound to bone matrix, clodronic acid enters resorbing osteoclasts, alters their morphology and reduces the number of active osteoclasts, regardless of the cause of osteoclast activity. Clodronic acid increases bone mass by inhibiting bone resorption and retarding bone turnover.
5.2 Pharmacokinetic particulars
The pharmacokinetic profile after a single intramuscular administration in horses diagnosed with navicular syndrome at doses of 255mg, 765mg and 1275mg of clodronic acid is characterized by rapid absorption of clodronic acid and a longer terminal elimination phase. The area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) increased proportionally with dosage. The plasma half-life of 765 mg clodronic acid administered intramuscularly is approximately 11.8 hours ± 12.5 hours, Cmax is 7.5 ± 1.7 µg/mL (765mg dose clodronic acid) and time to maximum concentration (Tmax) is approximately 0.6 hours.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium hydroxide
Water for Injections
6.2 Incompatibilities
None known.
6.3 Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 2years.
6.4. Special precautions for storage
Do not store above 30°C.
6.5 Nature and composition of immediate packaging
Cardboard carton containing a clear 15ml Type I glass vial with a grey siliconised rubber stopper and aluminium seal.
6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
Dechra Limited
Dechra House
Jamage Industrial Estate
Talke Pits
Stoke-on-Trent
Staffordshire
ST7 1XW
UK
8. MARKETING AUTHORISATION NUMBER
Vm 10434/4085
9. DATE OF FIRST AUTHORISATION
30 April 2014
10. DATE OF REVISION OF THE TEXT
April 2014
APPROVED 30 April 2014
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