EQUIOXX

Equioxx is a highly COX-2 selective NSAID for use in horses suffering from osteoarthritis

Relative COX selectivity of different equine NSAIDs:

Active ingredient / Brand names / Selectivity / Classification
Firocoxib / EQUIOXX / 643:1 / SELECTIVE
Phenylbutazone / Equipalazone, Pro-Dynam / 1.6:1 / Non-selective
Suxibuzone / Danilon / 1.6:1 / Non-selective
Flunixin / Finadye, Binixin, Meflosyl / 0.3:1 / Non-selective
Meloxicam / Metacam / 3.8:1 / Preferential
Vedaprofen / Quadrisol / 8:1 / Preferential
Carprofen / Rimadyl / 1.6:1 / Non-selective
Ketoprofen / Ketofen / ~1 / Non-selective

Significance of being highly selective:

Completely spares COX-1 at normal doses

COX enzymes:

The function of the COX enzymes is the production of various prostaglandins, many of which are needed for normal physiological function

COX-1 / COX-2
Responsible for production of “good” prostaglandins, needed for normal function, such as protection stomach and blood clotting / Responsible for production of “bad” prostaglandins which cause pain and inflammation
Examples- PGE2 in stomach, thromboxane in platelets / Example- PGE2 in joints with OA

NSAID side effects:

Gastrointestinal- stomach ulcers and damage to colon (particularly ‘bute)

Renal failure

Severe cases- death

Benefits of sparing COX-1

No inhibition of beneficial prostaglandins, so less likely to get GI side effects, even at high doses

Pharmacokinetics

After oral dose:

-  appears in plasma within 30 mins

-  peak plasma at 4 hrs

-  half-life= ~30hrs

-  7 doses to reach “steady state” in plasma (but will start working before this)

-  Good tissue penetration

Data sheet summary

Licensed claim

Alleviation of pain and inflammation associated with osteoarthritis and reduction of associated lameness in horses.

Dose

0.1mg/kg once daily for 14 days

Minimum age- 10 weeks

Adverse effects:

Lesions (erosion/ulceration) of the oral mucosa and of the skin around the mouth may occasionally be observed in treated animals. Typically, these lesions are mild and resolve without treatment, but oral lesions may be associated with salivation and labial and tongue oedema.

Contraindications:

Do not use in animals suffering from gastrointestinal disorders and haemorrhage, impaired hepatic, cardiac or renal function and bleeding disorders.

Do not use in breeding, pregnant or lactating animals.

Do not use concomitantly with corticosteroids or other NSAIDs.

Use in pregnancy?- NO, not licensed

Withdrawal period:

26 days for meat and milk

Racing- NO OFFICIAL DETECTION TIME YET- recommend 30 days

TRIAL SUMMARIES

Dose determination study

·  4 groups of 16 horses

·  Treated at 0.05mg/kg. 0.1mg/kg and 0.25mg/kg. Untreated control group

·  Treated for 14 days

·  Assessed by lameness score and force plate analysis

Key outcomes:

·  Similar results for 0.1 and 0.25mg/kg groups

·  Started working immediately- significant improvement seen within several hours

EQUIOXX versus Bute field trial

·  127 horses in EQUIOXX group, 126 horses in bute group

·  Treated for 14 days

·  Doses: 0.1mg/kg for Equioxx, 4.4mg/kg for bute (higher than usual dose in UK)

·  Assessed by:

-  lameness score

-  pain on manipulation of joint

-  joint swelling (subjective and objective)

-  range of motion

Key outcomes:

·  similar proportion of horses improved on lameness scores

·  significantly better results for Equioxx for joint swelling, range of motion and pain on manipulation

Significance:

Equioxx possibly more effective at reducing inflammation in joint

STRIDE Trial

·  very large trial (429 horses)

·  various ages (2-33) and weight (190-900kgs)

·  0.1mg/kg for 14 days

·  Assessed by vet lameness scoring and owner assessment

Key outcomes:

·  Good improvement in lameness grades after 14 days (25% with no lameness at all)

·  Owner scores- improved over time, highlighting benefits of giving full treatment course

COXIB issues in humans

·  Vioxx was withdrawn from market in 2004, ndue to increased incidence of heart attack/stroke in human patients

·  Due to underlying atherosclerosis

·  Atherosclerosis is not a problem in veterinary medicine, so being highly selective for COX-2 is not an issue

Presentations

·  Injectable for IV use, low dose volume (1ml/225kgs)

·  Oral paste syringe- one syringe treats up to 600kg horse, 100kg increments

Injectable dose rates

Drug / Dose (mls/kg) / Volume for 600kg horse
Equioxx / 1ml/225kgs / 2.67mls
Metacam / 1ml/45kgs / 13.2mls
Equipalazone / 1ml/33kgs / 18mls
Finadyne / 1ml/45kgs / 13.2mls

COLIC Paper summary

·  3 groups of 6 horses- saline control group, Equioxx group and flunixin group

·  Damage induced to small intestine by cutting off blood supply for two hours

·  Impact on gut healing assessed

·  Behavioural pain scoring also done to evaluate pain relief

Key outcomes

·  Pain scores similar in Equioxx and flunxin groups

·  Flunixin group had slower gut healing than Equioxx or control group

Significance:

Equioxx does not impact on healing of the small intestine and was an effective analgesic

Laminitis paper summary

·  Not a specific study assessing efficacy or safety in laminitis

·  Commentary by KOL on choosing an NSAID for laminitis

·  Quote:

“For horses being treated for laminitis and having significant risk for intestinal or renal injury from prolonged NSAID use, firocoxib could be a medically sound selection and, in a study of naturally occurring equine osteoarthritis, pain reduction with firocoxib was comparable to phenylbutazone”

Use in foals

·  Licensed from 10 weeks

·  Anecdotal data from USA and some safety trials in foals (from 36hrs old) suggest that dose of 0.1mg/kg is well tolerated

Oral ulcers

·  Ulcers were present in all horses prior to treatment in the safety studies (including the negative control group)

·  In the overdose groups (3 times and 5 times overdose), the incidence was slightly higher than in the control group by the end of the study, hence the label warning

·  In the field trials, out of approximately 600 horses treated with Equioxx, only one horse had mild transient hypersalivation and lip swelling for one day

·  A review of the pharmacovigilance data from the US shows that they did not have any reports of oral ulcers during 2010. In conclusion, a very uncommon and mild potential adverse effect

List prices

EQUIOXX Injection 25ml = £66.81

EQUIOXX Paste = £7.19

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