Ketoprofen  431

Drug Interactions
Ketoconazole is a potent inhibitor of hepatic and intestinal cytochrome P450 enzymes
and P-glycoprotein and will inhibit metabolism of other drugs (anticonvulsants, cyclo-
sporine, warfarin, and cisapride). Particular caution should be exercised when adminis-
tering ketoconazole with ivermectin. This combination may produce ivermectin toxicity
by decreasing clearance and enhancing penetration across the blood–brain barrier.

Instructions for Use

Oral absorption depends on acidity in the stomach. Do not administer with antise-
cretory drugs or antacids. Because of endocrine effects, ketoconazole has been used
for short-term treatment of hyperadrenocorticism. However, many experts believe
that ketoconazole is not an effective long-term treatment for canine Cushing disease.
Patient Monitoring and Laboratory Tests
Monitor liver enzymes (alanine aminotransferase [ALT], alkaline phosphatase [ALP])
for evidence of toxicity. Ketoconazole will lower serum cortisol levels.
Formulations
• Ketoconazole is available in 200-mg tablets and 100-mg/mL oral suspension (Canada).
Stability and Storage K
Store in a tightly sealed container, protected from light, and at room temperature.
Ketoconazole is practically insoluble in water but is soluble in ethanol. When ketoconazole
was compounded extemporaneously from tablets with syrups and flavorings, it was stable
for 60 days. However, ketoconazole requires acidity for solubility and may not be ab-
sorbed from these formulations. If compounded in alkaline conditions, it may precipitate.
Small Animal Dosage
Dogs
• 10-15 mg/kg q8-12h PO.
• Malassezia infection: 5 mg/kg q24h PO every 3 weeks.
• Hyperadrenocorticism: Start with 5 mg/kg q12h initially, then increase after
7 days to 12-15 mg/kg q12h PO.
Cats
• 5-10 mg/kg q8-12h PO.
Large Animal Dosage
Horses
Poorly absorbed. Fluconazole, itraconazole, or voriconazole is more completely
absorbed.
Regulatory Information
Withdrawal times are not established for animals that produce food. For extralabel use
withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

Ketoprofen
kee-toe-proe9fen
Trade and other names: Orudis-KT (human over-the-counter [OTC] tablet), Ketofen
(veterinary injection), and Anafen (outside the US.)
Functional classification: Nonsteroidal anti-inflammatory drug (NSAID)
432  Ketoprofen

Pharmacology and Mechanism of Action

Ketoprofen, like other NSAIDs, produces analgesic and anti-inflammatory effects by
inhibiting the synthesis of prostaglandins. The enzyme inhibited by NSAID is the
cyclo-oxygenase (COX) enzyme. The COX enzyme exists in two isoforms: COX-1 and
COX-2. COX-1 is primarily responsible for synthesis of prostaglandins important for
maintaining a healthy GI tract, renal function, platelet function, and other normal physi-
ologic functions. COX-2 is induced and responsible for synthesizing prostaglandins that
are important mediators of pain, inflammation, and fever. However, it is known that
there is some crossover of COX-1 and COX-2 effects in some situations, and COX-2
activity is important for some biological effects. Ketoprofen is a nonselective inhibitor of
COX-1 and COX-2. There is weak evidence of its ability to inhibit lipoxygenase.
Indications and Clinical Uses
Ketoprofen is an NSAID and is used for treatment of moderate pain and inflammation. It
has a half-life in most animals of less than 2 hours, but it has a duration of action for up to
24 hours. Ketoprofen is not approved in the United States for small animals, but has been
labeled for dogs and cats in other countries. It has been given by injection for acute treat-
ment and by tablet for long-term use. In dogs and cats, it has been shown effective for
treating pyrexia. In horses, ketoprofen is used for musculoskeletal inflammation and pain,
abdominal pain, and other inflammatory conditions. Ketoprofen also has been used in cat-
tle, goats, sheep, and pigs. In cattle, it has been effective for fever, pain, and inflammation
associated with mastitis. It is approved for use in cattle in Canada but not in the US.

Precautionary Information
Adverse Reactions and Side Effects
All NSAIDs share the similar adverse effect of GI toxicity. The most common
side effect is vomiting. Gastrointestinal ulceration is possible in some animals.
Ketoprofen has been administered for 5 consecutive days in dogs without serious
adverse effects, but longer treatment should be avoided. Dogs that received
ketoprofen for 30 consecutive days (0.25 mg/kg per day) induced pyloric lesions
and fecal occult blood. In horses, ketoprofen has been less ulcerogenic than phen-
ylbutazone or flunixin meglumine in one study. Bleeding problems can occur if
ketoprofen is administered before or after surgery.
Contraindications and Precautions
Do not administer to animals prone to GI ulcers. Do not administer with other
ulcerogenic drugs such as corticosteroids. Do not use extended-release formula-
tions of ketoprofen.
Drug Interactions
Do not administer with other NSAIDs or with corticosteroids. Corticosteroids have
been shown to exacerbate the GI adverse effects. Some NSAIDs may interfere with
the action of diuretic drugs and angiotensin-converting enzyme (ACE) inhibitors.

Instructions for Use

Although not approved in the US, ketoprofen is approved for small animals in other
countries. Doses listed are based on approved use in those countries. It is available as
an OTC drug for humans in the US. In the US if it is used in small animals, either
the large-animal injectable formulation or the human oral OTC tablets are used.
Patient Monitoring and Laboratory Tests
Monitor patient for signs of GI intoxication (vomiting and diarrhea). Monitor renal
function during chronic treatment.
 Ketorolac Tromethamine  433

Formulations
• Ketoprofen is available in 12.5-mg tablets (OTC); 25, 50, and 75 mg (human
preparation); and 100-mg/mL injection for horses. It is available in 10 mg/mL
outside the US.
Stability and Storage
Store in a tightly sealed container, protected from light, and at room temperature.
Ketoprofen is insoluble in water, but it is soluble in ethanol. Stability of oral com-
pounded formulations has not been evaluated.
Small Animal Dosage
Dogs and Cats
• 1 mg/kg q24h PO for up to 5 days. Initial dose can be given via injection at up
to 2 mg/kg SQ, IM, or IV.
Large Animal Dosage
Horses
• 2.2-3.3 mg/kg/day IV or IM.
Pigs
• 3 mg/kg/day, PO, IV or IM. K
Cattle and Small Ruminants
• 3 mg/kg/day IV or IM for up to 3 days.
Regulatory Information
Extralabel use in US: Withdrawal time of at least 7 days for meat and 24-48 hours
for milk at a dose of 3.3 mg/kg q24h IM or IV. However, in other countries the
withdrawal times are shorter. For example, it is approved in Canada.
For swine and cattle with a meat withdrawal time of 1 day.
RCI classification: 4

Ketorolac Tromethamine
kee-toe9role-ak troe-meth9eh-meen
Trade and other names: Toradol
Functional classification: Nonsteroidal anti-inflammatory drug

Pharmacology and Mechanism of Action

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that is a derivative of hetero-
aryl acetic acid. Ketorolac, like other NSAIDs, produces analgesic and anti-inflammatory
effects by inhibiting the synthesis of prostaglandins. The enzyme inhibited by NSAIDs is
the COX enzyme. The COX enzyme exists in two isoforms: COX-1 and COX-2. COX-1
is primarily responsible for synthesis of prostaglandins important for maintaining a healthy
GI tract, renal function, platelet function, and other normal physiologic functions. COX-2
is induced and responsible for synthesizing prostaglandins that are important mediators
of pain, inflammation, and fever. However, it is known that there is some crossover of
COX-1 and COX-2 effects in some situations, and COX-2 activity is important for some
biological effects. Ketorolac is a nonselective inhibitor of COX. There is some evidence
that ketorolac also may affect opioid receptors centrally to produce analgesia, but it does
not directly bind to opioid receptors. In some human studies it has had comparable effi-
cacy to morphine. The pharmacokinetics have been studied in dogs, but not other species.