Triamcinolone Acetonide: what the FDA reviewed for dog products

Medalone Cream NADA 200-275, Original approval, February 04, 2000; sponsor Med-Pharmex, Inc.; species: Dogs; foi_id 1032; FDA PDF

Indication

Topical treatment of allergic dermatitis and summer eczema in dogs.

Dose regimen

Cream rubbed into the affected areas (amount not specified), Topical, Two to four times daily; frequency may be decreased as improvement occurs, 4 to 10 days; not for ophthalmic use

The Recommended Dosage is that the cream is applied by rubbing into the affected areas two to four times daily for 4 to 10 days. Frequency of treatment may be decreased as improvement occurs.

Effectiveness

Bioequivalence waiver (generic ANADA; no in vivo study); same active and inactive ingredients in similar concentrations as the pioneer product; result: Waiver from an in vivo bioequivalence study granted on formulation characteristics; no new safety or effectiveness data.

The generic product is administered as a topical ointment and contains the same active and inactive ingredients in similar concentrations as the pioneer product.

Extraction notes: Generic (ANADA) approval; the summary contains only general information, the bioequivalence waiver statement and agency conclusions. The effectiveness entry records the waiver only. The pioneer product is not named in the extracted text.

Triamcinolone Acetonide Suspension NADA 138-869, Original approval, January 06, 1987; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs, cats and horses; foi_id 2551; FDA PDF

Indication

Treatment of inflammation and related disorders in dogs, cats and horses; management and treatment of acute arthritis and allergic and dermatologic disorders in dogs and cats.

Dose regimen

0.05 mg to 0.1 mg triamcinolone acetonide per pound body weight (dogs and cats, IM or SC); 0.1 mg per pound for dermatologic disorders, Intramuscular or subcutaneous (also intra-articular/intrasynovial in dogs, cats, horses and intralesional in dogs and cats), Single injection; may be repeated if symptoms recur (remission usually lasts 7 to 15 days), Intralesional: 1.2 to 1.8 mg total, not more than 0.6 mg per site or 6 mg total; intra-articular/intrasynovial: 1.0 to 3.0 mg (dogs and cats), 6.0 to 18.0 mg (horses); horses IM: 0.01 to 0.02 mg per pound (usually 12 to 20 mg)

Dogs and Cats: The recommended dosage is 0.05 mg to 0.1 mg triamcinolone acetonide per pound body weight as a single injection for the treatment of inflammatory or allergic disorders. For the treatment of dermatologic disorders, administer a single injection of 0.l mg per pound body weight. Remission of symptoms, if not permanent, usually lasts 7 to 15 days.

Pharmacokinetics

Effectiveness

Comparative bioavailability (pharmacodynamic) crossover study of Med-Tech Triamcinolone Acetonide Injection vs Squibb Vetalog® Parenteral (positive control); single IM injection of 0.1 mg/lb after a 12-hour fast; two groups of five males and five females; 5-week washout; serum glucose and direct eosinophil counts measured to 672 h; split-plot ANOVA on log-transformed data; n = Twenty healthy young adult Beagles (ten males and ten females); primary endpoint: Serum glucose and direct eosinophil count time-courses compared between products (Period by Group and Time by Period by Group terms); result: Eosinophil counts: overall means and curve shapes statistically different (p=0.0112, p=0.0007; 28.44% difference) mainly beyond 24 h; glucose: overall means not different (p=0.4806), curve shapes different (p=0.0003; -0.79%). Differences considered too small to be biomedically important; Med-Tech product judged medically bioequivalent to Squibb's product.

The study was of a crossover design utilizing twenty healthy young adult Beagles (ten males and ten females). The dogs were randomly assigned to one of two groups consisting of five males and five females each.

Extraction notes: 1987 NADA for a product relying on the NAS/NRC (DESI-type) effectiveness review of triamcinolone acetonide; the only study is a comparative bioavailability study using pharmacodynamic markers, recorded under effectiveness and as a single PK ('other') entry. The summary has no Species/Class field; species_class taken from the indication. Target animal safety section states only that the NAS/NRC review indicates the drug is safe at labeled dosages. The dosage text contains an OCR typo ('0.l mg per pound') retained verbatim in the quote. Sponsor in summary: Med-Tech, Inc. (catalogue sponsor now Cronus Pharma).

Genesis® Topical Spray NADA 141-210, Original approval, November 04, 2002; sponsor Virbac AH, Inc.; species: Dogs; foi_id 734; FDA PDF

Indication

Control of pruritus associated with allergic dermatitis in dogs.

Dose regimen

Sufficient pump sprays to uniformly wet the affected areas, up to the maximum number of pumps per application in Table 1 (28-day regimen), Topical (0.015% solution, pump spray), Twice daily for seven days, then once daily for seven days, then every other day for an additional 14 days, 28 days total; maximum allowable dosage 0.1 mg triamcinolone acetonide/kg/application (each pump about 0.9 mL = 0.135 mg); avoid eyes

Apply sufficient pump sprays to uniformly and thoroughly wet the affected areas while avoiding run-off of excess product. Avoid getting the spray in dog’s eyes. The recommended treatment schedule is twice daily for seven days, then once daily for seven days, then every other day for an additional 14 days (28 days total). To avoid overdosing the product, use Table 1 to determine the maximum number of pump sprays per treatment application.

Pharmacokinetics

Target-animal safety

dose multiples Approximately 5-6 times the maximum allowable dosage (15 mg triamcinolone daily via about 100 mL of 0.015% spray); duration Once daily for five consecutive days (days 0-4); plasma cortisol and ACTH-response measured to day 11; animals Six mongrel female dogs (two spray, two Vetalog® cream, two vehicle).

Six mongrel female dogs wei ghing 10.8-19.7 kg and free of exogenous corticosteroids for approximately four weeks were used in the study. Two were treated with the triamcinolone spray, two with triam cinolone cream and two with a placebo.

Effectiveness

Multi-center (5 US dermatology sites), double-blind, placebo (vehicle)-controlled field study, January 1999 to August 2000; 110 client-owned dogs enrolled, 105 completed; 28-day labeled regimen; investigator and owner scores at day 0 and day 28; n = 54 Genesis Topical Spray and 51 placebo (completed cases); primary endpoint: Treatment success: improvement of two or more grades in the investigator's overall clinical evaluation (0-5 scale) from pre-treatment to day 28; result: Success in 64.8% (35/54) of Genesis-treated dogs vs 23.5% (12/51) of placebo dogs, significant (p<0.05, Mantel-Haenszel stratified by investigator); investigator pruritus, erythema, eruption and overall scores and owner overall score also significantly better (p<0.05). Treated group had significantly fewer lymphocytes and eosinophils and higher serum albumin at day 28.

Success was defined for the individual animal as an improvement of two or more grades in the overall clinical score. Based on this definition, 64.8% (35/54) of the test cases were considered treatment successes compared to 23.5% (12/51) of the controls.

Adverse reactions

Extraction notes: Sections were not parsed for this summary (preamble only); extracted from raw text. PDF extraction inserted spaces inside words (e.g. 'wei ghing', 'triam cinolone', 'ma les'); quotes reproduce the extracted text. The target-animal-safety entry is the percutaneous absorption/HPA-axis laboratory study (Table 8 cortisol values) plus the literature review, not a conventional dose-multiple margin-of-safety study. Adverse-reaction rows quoted as flattened Table 7 rows: term, Genesis n (%), control n (%); the last two rows are pooled across groups. One dog inadvertently received about 8 times the maximum dosage for a week with only transient polyuria/polydipsia. Dosage characterization also includes an inflammatory-response study in 3 dogs and an uncontrolled exploratory field study in 17 dogs (12/17, 71%, at least moderately effective).