Doses - DIETHYLSTILBESTROL, (DES)

Dogs:

For pregnancy avoidance after mismating:
a) 0.1 - 1 mg PO for 5 days if animal is presented 24-48 hours after coitus. If animal ispresented later than 5 days post-coitus: 1 - 2 mg PO for 5 days after ECP therapy(0.044 mg/kg (ECP) IM once during 3-5 days of standing heat or within 72 hours ofmismating) (Woody 1988)
For treatment of perianal gland adenomas and prostatic hyperplasias:
a) 0.1 - 1 mg PO q24-48h (Thompson 1989)
b) 1 mg PO q72h; or 1.1 mg/kg once. Do not administer more than 25 mg. (Rosenthal1985)
For treatment of estrogen-responsive incontinence:
a) Initially 0.1 - 1 mg PO daily for 3-5 days, followed by maintenance therapy of approximately 1 mg PO per week. Some animals may require much higher initial dosagesto obtain a response. Maximum initial doses of 0.1 - 0.3 mg/kg once daily for 7 days, then reduce to once weekly. All maintenance doses should be gradually reduced to thelowest effective dose. (Polzin and Osborne 1985)
b) 0.1 - 1 mg PO per day for 3-5 days, then 1 mg once weekly (LaBato 1988)
c) 0.1 - 1 mg PO for 3-5 days followed by 1 mg every week or less often. Some animals may require more than 1 mg weekly to maintain. (Chew, DiBartola, and Fenner 1986)
Monitoring Parameters - When therapy is either at high dosages or chronic; see Adverse effects for more information.
Done at least monthly:

1) Packed Cell Volumes (PCV)

2) White blood cell counts (CBC)

3) Platelet counts
Baseline, one month after therapy, and repeated 2 months after cessation of therapy if abnormal:
1) Liver function tests
Client Information - Contact veterinarian if signs and symptoms of lethargy, diarrhea, vomiting, abnormal discharge from vulva, excessive water consumption and urination or abnormal bleeding occur.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - Veterinary-Approved Products: None
Human-Approved Products: At the time of writing, no commercially available regular oral DES products are available in the USA, however compounded preparations may be available from a variety of compounding pharmacies.
Diethylstilbestrol Diphosphate Injection 50 mg/ml in 5 ml amps: .i.Stilphostrol;® (Miles) (Rx)Diethylstilbestrol Diphosphate 50 mg Tablets; Stilphostrol® (Miles) (Rx)
DIFLOXACIN HCL
Chemistry/

Storage, Stability, Compatibility

A 4-fluroquinolone antibiotic, difloxacin HClcommercially available tablets should be stored between 15-30°C (59-86°F) and protected fromexcessive heat.

Pharmacology

Like other drugs in its class, difloxacin is a concentration-dependent bactericidalagent. It acts by inhibiting bacterial DNA-gyrase (a type-II topoisomerase), thereby preventing
DNA supercoiling and DNA synthesis. The net result is disruption of bacterial cell replication.
Difloxacin has good activity against many gram negative and gram positive bacilli and cocci, including most species and strains of Klebsiella spp., Staphylococcus spp., E. coli, Enterobacter,
Campylobacter, Shigella, Proteus, Pasturella species. Some strains of Pseudomonas aeruginosaand Pseudomonas species are resistant and most Enterococcus spp. are resistant. Like otherfluroquinolones, difloxacin has weak activity against most anaerobes and is not a good choice whentreating known or suspected anaerobic infections.
Development of bacterial resistance to 4-fluroquinolones can occur.
Uses, Indications - Difloxacin is indicated for treatment in dogs for bacterial infections susceptibleto it.

Pharmacokinetics

After oral administration in dogs, difloxacin serum levels peak about 3 hourspost dosing. The drug is well distributed (Vd=2.8 L/kg) in dogs and marginally bound to plasmaproteins (16-52% in dogs). Difloxacin is eliminated by the kidneys and high levels are attained inthe urine. Serum half life is about 9 hours in dogs. Urine levels remain well above MIC's forsusceptible organisms for at least 24 hours after dosing.

Contraindications, Precautions, Reproductive Safety

Difloxacin, like other fluroquinolonescan cause arthropathies in immature, growing animals. Because dogs appear to be more sensitive tothis effect, the manufacturer states that the drug is contraindicated in immature dogs during therapid growth phase (between 2-8 months in small and medium-sized breeds and up to 18 months inlarge and giant breeds). The drug should also be considered to be contraindicated in dogs known tobe hypersensitive to difloxacin or other drugs in its class (quinolones).
The manufacturer states that difloxacin should be used with caution in animals with known orsuspected CNS disorders (e.g., seizure disorders) as rarely drugs in this class have been associatedwith CNS stimulation and seizures.
While difloxacin may find use in other species, early anecdotal reports are that it can cause nausea and vomiting in cats.
Safety in breeding or pregnant dogs has not been established. It is not known whether orbifloxacin enters maternal milk.

Adverse Effects, Warnings

While the manufacturer reports that only self-limited gastrointestinaleffects (anorexia, vomiting, diarrhea) were reported during clinical studies (at 5 mg/kg dosing) inadult animals, higher doses or additional experience with use of the drug may demonstrateadditional adverse effects.
Overdosage - Dogs receiving up to 2.5X (25 mg/kg) for 30 days did not demonstrate overlysignificant adverse effects. Facial erythema/edema, diarrhea, decreased appetite and weight loss werenoted.

Drug Interactions

Antacids or other agents containing divalent or trivalent cations (Mg++,
Al+++, Ca++) may bind to difloxacin and prevent its absorption. Sucralfate may inhibit absorption of difloxacin; separate doses of these drugs by at least 2 hours, if both are required.
Difloxacin administered with theophylline may increase theophylline blood levels.
Probenecid may block the tubular secretion of difloxacin and may increase its blood level andhalf-life.
Synergism may occur, but is not predictable, against some bacteria (particularly Pseudomonasaeruginosa or other Enterobacteriaceae) with these compounds and aminoglycosides, 3rd generation cephalosporins agents, and extended-spectrum penicillins. Although difloxacin apparently has minimal activity against anaerobes, in vitro synergy has been reported when otherfluroquinolones have been used with clindamycin against strains of Peptostreptococcus,
Lactobacillus and Bacteroids fragilis. Nitrofurantoin may antagonize the antimicrobial activity ofthe fluroquinolones and their concomitant use is not recommended. Fluroquinolones may exacerbate the nephrotoxicity of cyclosporine (used systemically).
The manufacturer reports that difloxacin was used concurrently in field trials with a variety ofdrugs including heartworm preventative, thyroid hormones, ectoparasiticides, antiseizure drugs, anesthetics, antihistamines, and topical antibiotic/antiinflammatory preps without untoward effects.