New drugs in veterinary dermatology (Proceedings)

In the field of veterinary medicine we see a constant search for newer, more effective, and convenient but inexpensive drugs with lesser side effects. Not only new drugs are interesting, but old drugs are occasionally rediscovered for new indications. Although many of the new approved drugs available have been thoroughly investigated, reports of the use of older drugs or the use of a newer drugs for a different indication are often based on anecdotal reports and need to be further investigated in controlled studies.

Cefovecin sodium (Convenia; 80 mg/ml)

This is a semi-synthetic cephalosporin with bactericidal effect which inhibits bacterial cell wall syntheses and is relatively resistant to bacterial beta-lactamases. Its main antibacterial spectrum is: gram-negative bacteria (E. coli, Proteus, Klebsiella), gram-positive bacteria (Staphylococci & Streptococci.). Cefpodoxime is not effective against Pseudomonas aeruginosa, Enterococci and methicillin-resistant Staph. Poor efficacy has been shown against anaerobes.

     • Indication - dogs: skin infections (pyoderma, wounds, abscesses) with Staphylococcus intermedius and Streptococcus canis, cats: infections with Pasteurella multocida

     • Occasional GI signs (vomiting, diarrhea) may be seen.

     • Dosage: 8 mg/kg subcutaneous. Injection can be repeated after 7 to 14 days (very convenient!)

Cefpodoxime proxetil (Simplicef; 100 mg, 200 mg)

This 3rd generation cephalosporin (antimicrobial activity, see Cefovecin)

     • Indication: skin infections (pyoderma, wounds, abscesses) in dogs.

     • Drug is well tolerated. Occasionally GI signs may occur.

     • Dosage: 5-10 mg/kg orally every 24 hours

Chloramphenicol (Duricol; 50 mg, 100 mg or Viceton; 250 mg, 500 mg)

Broad spectrum antibiotic inhibiting bacterial protein synthesis. Gram-positive aerobic organisms (Streptococci, Staphylococci) are generally susceptible, and many anaerobic bacteria (Clostridium, Bacteroides, Fusobacterium) and organisms such as Nocardia, Mycoplasma, and Rickettsia are sensitive to chloramphenicol.

     • Indication: methicillin-resistant Staph. spp. infections

     • Usually well tolerated but dose-related bone marrow suppression (reversible) is occasionally seen with longterm use, as well as GI signs.

     • Dosage: 30-50 mg/kg orally every 8 hours

Cyclosporine (Atopica; 25 mg, 50 mg, 100 mg; Neoral; 100 mg/ml)

CsA is a naturally produced (fungus: Tolypocladium inflatum) calcineurin inhibitor with anti-inflammatory and immunosuppressive properties focused on cell-mediated immune response.

     •Indication: Perianal fistula, canine atopic dermatitis; may also be used for maintenance of auto-immune diseases (e.g. pemphigus foliaceus)

     • Since CsA is mainly metabolized through the liver it should be used with caution in patients with liver disease. Many drugs are metabolized through the same cytochrome P450 enzyme system and are able to reduce the metabolism of CsA. The use of ketoconazole at 5 mg/kg orally per day may help to reduce the CsA dose by up to 50%.

     • The most common side effects are vomiting, anorexia and diarrhea.

     • Dosage: 5 mg/kg orally every 24 hours

Tacrolimus (Protopic; 0.1% or 0.3% ointment)

This is a topical calcineurin inhibitor with similar mechanism as cyclosporine. Advantage of calcineurin inhibitors compared to steroids is their lack of cutaneous atrophy and metabolic effects.

     • Indication: localized atopy, discoid lupus erythematosus (DLE), pemphigus erythematosus (PE), pemphigus foliaceus (PF), cutaneous idiopathic vasculitis, alopecia areata, Vitiligo. May also be used for maintenance of perianal fistula.

     • Increased erythema and irritation can occasionally be observed after starting therapy, but the reaction is transient.

     • Dosage: apply daily on affected skin area.

Imiquimod (Aldara; 5% cream)

Imiquimod is an immune response modifier which is supposed to stimulate the patient's own immune system to release a variety of cytokines including interferon-alpha and interleukin-12. It does not have direct anti-viral effect, but the drug activates monocytes and macrophages to release cytokines that induce regression in viral protein production.

     • Indication: feline herpes virus dermatitis, actinic keratosis, squamous cell carcinoma and Bowen's disease, and viral papilloma.

     • Localized irritation and pruritus can occur.

     • Dosage: apply once daily to twice weekly on affected skin area.

Trilostane (Vetoryl; 30 mg, 60 mg)

Trilostane is a synthetic steroid analog that acts as a competitive inhibitor of 3-beta hydroxysteroid dehydrogenase, thereby reducing synthesis of cortisol, aldosterone, and adrenal androgens. Inhibition is reversible and dose dependant. Trilostane significantly reduces synthesis of progesterone and should not be used in pregnancy. The drug is usually well tolerated. Mild lethargy, electrolyte changes, and inappetence can occur initially.

     • Indication: pituitary-dependent or adrenal-dependent hyperadrenocorticism, Alopecia X.

     • Dosage: 2-20 mg/kg orally once daily with food. Monitor with ACTH-stim test, serum electrolytes (hyperkalemia), and adjust dose based on clinical response.

Spinosad (Comfortis; 140 mg, 270 mg, 560 mg, 810 mg, 1620 mg)

Activates the nicotinic acetylcholine receptors of the flea, resulting in paralysis and death. Kills up to 100% adult fleas within 4 hours. Side effects: a few reports of ivermectin toxicity if given in combination with off-label use daily oral ivermectin to treat generalized demodicosis. Should not be given to puppies <14 weeks of age.

     • Indication: Flea bite hypersensitivity; for dogs only.

     • Dosage: 30 mg/kg rally once monthly. Chewable beef flavored tablet

Metaflumizone/Amitraz (Promeris; 150 mg/ml)

Metaflumizone blocks influx of sodium required to propagate a nerve impulse along the axon and dendrite of the neuron causing a reduction in feeding, loss of coordination, paralysis and death of the flea. Amitraz is an insecticidal/miticidal agent, which is a monoamine oxidase (MAO) inhibitor (in mites) and may have effects on the CNS of susceptible organisms. It also appears to have alpha-2 adrenergic activity and inhibits prostaglandin synthesis.

Amitraz should not be given to animals with diabetes (increases plasma glucose levels by inhibiting insulin release via its alpha2-adrenergic activity. Yohimbine (alpha2 blocker) or atipamezole can antagonize this effect.

A few cases with pemphigus-like skin lesions triggered by the drug combination have been reported. The problem is usually mild and self-limiting. Transient sedation due to accidental oral uptake (licking application site) may occur.

     • Indication: To prevent/treat fleas, mites (Demodex, Sarcoptes, Cheyletiella, lice), ticks

     • Dosage: once monthly topical application at the base of the skull

Imidacloprid/Moxidectin (Advantage Multi)

Imidacloprid is a neonicotinoid, which is absorbed upon contact with the flea through the intersegmental membranes. It acts as an agonist on the postsynaptic nicotinic acetylcholine receptors of motor neurons in insects. Imidacloprid is an adulticide and a larvicide. Moxidectin binds to receptors on neuronal membranes of nematodes and muscle membranes of arthropods, causing increased permeability and an influx of chloride ions hyperpolarization paralysis death of parasite. Has also agonist activity at the GABA receptor complex of nematodes and arthropods.

     • Indication: - Imidacloprid: fleas

          - Moxidectin: adult nematodes, developmental stages of filarial nematodes (heartworms), mites

     • Dosage: once monthly for flea and heartworm prevention, twice monthly for the treatment of mite (e.g. Sarcoptes) infestation.