23 NSAIDs and Steroids in Food Animals

NSAIDs and Steroids in Food Animals

• Goal is to ensure "Primum Non Nocere" or "First, do no harm."

Learning Objectives

• Identify which NSAIDs and steroids are used in food animals and which are labeled for this usage.
• Dexamethasone usage should be considered for "brainers" and cattle intended for reproduction.
• Evaluate the routine use of NSAIDs after calving to prevent LDAs or as ancillary therapy in infectious diseases like:
  • Acute metritis
  • Respiratory disease
  • Neonatal diarrhea

NSAID and Steroid Goals

• Analgesic
• Anti-inflammatory
• Antipyretic
• Improve treatment response

NSAID Food Animal Options

• Flunixin meglumine (Banamine, generics) can be used in swine and cattle.
• Phenylbutazone ("Bute") is all ELDU.
• Ketoprofen (Ketofen) is labeled in combination with tulathromycin for BRD and reduces pyrexia associated with BRD.
• Aspirin is marketed under an over-the-counter monograph but is not approved for use through water in swine.
• Meloxicam is all ELDU.
• Ibuprofen can be used through the water in swine, with ELDU.

Steroid Food Animal Options

• Dexamethasone (Azium, "Dex") is an option.
• Isoflupredone acetate (Predef 2x) is an option.

The Steer "Dipstick"

• A client contacts you about a steer named Dipstick, destined for the county fair in 3 weeks.
• The youth has been working hard on showmanship every day.
• Dipstick, weighing 1475#, has become progressively more lame on his hind legs.
• Dipstick has a conformational problem and is "post legged," with little angle through his hock and fetlock.
• The steer will go to slaughter and carcass competition after the fair
• The challenge is to manage Dipstick's condition through the fair, considering he has a conformational disaster

How to Choose an Anti-inflammatory

• Efficacy
• ELDU rules
• Withdrawal times
• Owner compliance
  • Route of administration which can cause tissue damage
  • Frequency of administration (duration of effect)

Phenylbutazone

• Administration should be IV only for injection due to tissue irritation.
• Oral administration would be the only option for swine and an option for cattle.
• The half-life in cattle is 36-65 hours.
• Can be given IV or orally every other day.
• AMDUCA prohibits ELDU in dairy cattle over 20 months of age.
• Contact FARAD for meat withdrawal (WDI) information.
• A 2008 FARAD Digest suggested a minimum 55-day WDI.

Flunixin Meglumine

• Approved for use in cattle in the United States.
• Available as Banamine Transdermal and Banamine Injectable Solution.
• Effective as an analgesic, anti-inflammatory, and antipyretic.

Flunixin Transdermal Solution

• Labeled for controlling pain due to foot rot.
• Labeled for controlling fever due to bovine respiratory disease and acute mastitis.
• Slaughter WDT is 8 days.
• Not for use in suckling beef calves, dairy calves, and veal calves.

Flunixin Injectable Solution

• Labeled for controlling inflammation in endotoxemia.
• Labeled for controlling pyrexia due to bovine respiratory disease, endotoxemia, and acute mastitis.
• Slaughter withdrawal of 4 days, an exaggerated WDT for this use is required.

Pharmacokinetics Comparison - Flunixin

• Dose 2.2mg/kg for Flunixin IV, Resflor IM/SQ, and Hexasol IM/SQ.
  • Dose 3.3 mg/kg for Flunixin TD.
• Half life IV 3.5 hrs, TD 6 hrs, Resflor IM 5.2 hrs, Resflor SQ 7.5 hrs, Hexasol IM 4.1 hrs, Hexasol SQ 6 hrs
• AUC0-inf:
  • Flunixin IV: 13.9
  • Flunixin TD: 10.1
  • Resflor IM: 10.25
  • Resflor SQ: 9.8
  • Hexasol IM: 7.96
  • Hexasol SQ: 7.49
• Tmax:
  • Flunixin TD: 2 hr
  • Resflor IM: 0.33 hr
  • Resflor SQ: 1.6 hr
  • Hexasol IM: 0.5 hr
  • Hexasol SQ: 3.5 hr

Flunixin Transdermal PGE2 Suppression

• A study in 2017 showed PGE2 suppression for approximately 30 hours with flunixin transdermal in 2-month-old calves.

Flunixin Meglumine

• Must be given IV (or topical) in cattle.
  • IM administration has a bioavailability of around 75% due to muscle damage.
• IM administration is used in swine.
• Injectable solution has about 4-6 hours of efficacy based on plasma concentrations.
  • Administer 2-3 times a day for full effect.
• Label slaughter withdrawal time:
  • 4 days in cattle
  • 12 days in swine
• Bovine milk discard time is 36 hours (has a lactating dairy cow label).

Ketoprofen

• T1/2 is approximately is 3 hours.
• 48 hr withdrawal time
• Ketoprofen is used for the control of pyrexia associated with Bovine Respiratory Disease (BRD) in beef heifers, beef steers, beef calves 2 months of age and older, beef bulls, replacement dairy heifers, and dairy bulls.
  • Should not be used in reproducing animals over one year of age, in dairy calves, or in veal calves, and in lactating dairy cattle or calves <2 months old.

Salicylic Acid Derivatives

• Aspirin products have historically been marketed using over-the-counter labeling that is not an approval such as an ANADA or NADA.
• Aspirin products cannot be used with ELDU.
• FARAD meat withdrawal in food animals was previously 24 hours but is now not recommended.

FDA on Aspirin Products in Lactating Dairy Cattle

• There are no FDA-approved aspirin products for use in cattle.
• Extralabel use of unapproved drugs in food-producing species is prohibited.
• Approved animal products for pyrexia and pain should have a label that states "Approved by FDA under NADA # XXX-XXX" for brand-name drugs or "Approved by FDA under ANADA # XXX-XXX" for generic drugs.
• Veterinarians and dairy farmers should stop using unapproved aspirin in lactating dairy cattle and use FDA-approved products to control pyrexia and pain.

Meloxicam

• Meloxicam has 100% oral bioavailability.
• Human generic tablets cost 3-4 cents/15mg tab or $0.15-0.20/100 lbs.
• Oral meloxicam at 1mg/kg has a half-life of 27 hours.
• The EU meat withdrawal period is 15 days (0.5 mg/kg IM).
• The Canadian withdrawal period is 20 days.
• A common treatment is 0.5 to 1.0 mg/kg orally in feed or as tablets in gel caps.
• 30 days ELDU WDT is needed.
  • A 96-hour milk hold is suggested after a 1 mg/kg oral dose.
• It can be given every day for a couple of days, and then every other day.
• Treatments of 3-4 weeks have been completed with no detected ill effects.

Meloxicam Research

• Meloxicam maintains effective analgesic concentrations for 3-5 days following a single oral 1 mg/kg dose.
• Reduces stress associated with cautery dehorning at 1 mg/kg orally, whether given before or during the procedure.
• Reduces BRD after castration when given at 1 mg/kg orally prior to the procedure.
• Decreases the severity of induced lameness in beef calves when given at 0.5 mg/kg PO once daily for 4 days.

AMDUCA Levels

• Use of a labeled product for the specified indication.
• Use a food animal labeled product in an extra-label manner.
• Use a non-food animal veterinary product or human labeled product in an extra-label manner.
• Compound from a labeled veterinary or human product.

Dexamethasone

• Antipyretic and anti-inflammatory
• Protein catabolic, which increases blood calcium due to breakdown of bone protein matrix.
• Can cause transient hyperglycemia due to gluconeogenesis.
• Label dose is 5-20 mg in cows, given IM or IV, with no withdrawal time on the label.
• Induces monocytes to produce a protein factor that inhibits neutrophil activity and antibody responses to antigens.
• It inhibits Interleukin-1 production by macrophages.
  • chemotactic agent for leukocytes
  • activates T lymphocytes
  • increases acute-phase protein production
• Shown to completely inhibit bovine neutrophil function in ex-vivo assays at 0.04 mg/kg (IM Q24H for 3 days).
  • A single dose may also have this effect.
• Pigs are more refractive to the immunosuppressive effects.
  • 2 mg/kg in swine has been documented to not have the same immunosuppressive effect as above in cattle.
• The following are adverse effects that can result from usage:
  • Bull sterility due to semen defects for approximately 6 weeks
  • Abortion in cows
  • Potential immunosuppression

Isoflupredone Acetate

• Predef 2X (Zoetis) is an aqueous suspension of isoflupredone acetate labeled for IM or intrasynovial use in cattle.
• Used in the treatment of the following conditions:
  • Bovine ketosis
  • Musculoskeletal conditions
  • Allergic reactions
  • Overwhelming infections with severe toxicity, shock, and other conditions
• Has 50 times the anti-inflammatory potency of hydrocortisone (compared to 70-80 times for dexamethasone).
• Labeled dose is 10 to 20 mg for cattle, 5 mg for 300 lb pig, repeated in 12-24 hours if needed.
• Meat withdrawal is 7 days for all species, and no milk withdrawal time is required.
• It is not abortigenic in pregnant cattle.

General Info

• NSAIDs and dexamethasone are commonly used with antibiotics in food animals to treat infectious diseases.
• Flunixin treatment following parturition for pain mitigation has no significant effect on milk yield, milk fever, abomasal displacement, clinical ketosis, or mastitis.
  • However, it increases the likelihood of retained placenta (2.5x) and metritis (1.5x).
• Calves with fecal blood treated with a single dose of flunixin meglumine (and an oral antibiotic) received fewer antimicrobial treatments and had fewer morbid days compared to controls (oral antibiotic only).
• Multiple doses of flunixin showed numerically lower morbidity days, but were not significantly different from the controls
• Flunixin treated calves had a 10% (4/38) death loss in one treatment and 8% (3/37) for the other compared to 2% (1/40) for the controls.
• NSAIDs appear beneficial for pain mitigation associated with surgical procedures like castration and dehorning, but require additional logistical considerations and add cost.
• Not all NSAIDs provide the same amount of pain mitigation, and they may not mitigate pain associated with all procedures equally.