Doses - OPIATE ANTIDIARRHEALS, PAREGORIC, DIPHENOXALATE HCL / ATROPINE SULFATE, LOPERAMIDE HCL

Dogs:

Paregoric:
a) For acute colitis: 0.06 mg/kg PO tid (DeNovo 1988)
b) For maldigestion/malabsorption/antidiarrheal: 0.05 - 0.06 mg/kg PO bid-tid (Chiapella1988), (Johnson 1984)
c) As an antidiarrheal: 2 - 15 ml PO q6h (Davis 1985a)
Diphenoxylate/Atropine:
a) For acute colitis/irritable colon syndrome: 0.1 mg/kg PO tid (DeNovo 1988)
b) As an antidiarrheal: 0.05 - 0.1 mg/kg qid PO; (not recommended for dogs weighing lessthan 10 kg) (Johnson 1984)
c) As an antidiarrheal: 0.1 - 0.2 mg/kg PO q8h (Jergens 1995)
Loperamide:
a) For acute colitis: 0.08 mg/kg PO tid (DeNovo 1988)
b) For maldigestion/malabsorption: 0.08 mg/kg PO qid (Chiapella 1988)
c) As an antidiarrheal: 1 capsule (2 mg) per 25 kg body weight qid PO; (not recommendedfor dogs weighing less than 10 kg) (Johnson 1984)
d) As an antidiarrheal: 0.1 - 0.2 mg/kg PO q8h (Jergens 1995)
Cats: Note: Use of antidiarrheal opiates in cats is controversial; this species may react with excitatory behavior.
Paregoric:
a) For maldigestion/malabsorption/antidiarrheal: 0.05 - 0.06 mg/kg PO bid-tid (Chiapella1988), (Johnson 1984)
Diphenoxylate/Atropine:
a) 0.063 mg/kg PO q8h (Davis 1985b)

Cattle:

Paregoric:
a) Calves: 15 - 30 ml PO (Cornell 1985)

Horses:

Paregoric:
a) Foals: 15 - 30 ml PO; Adults: 15 - 60 ml PO (Cornell 1985)
Monitoring Parameters -

1) Clinical efficacy

2) Fluid & electrolyte status in severe diarrhea

3) CNS effects if using high dosages
Client Information - If diarrhea persists, contact veterinarian. If animal appears listless or develops a high fever, contact veterinarian.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - Veterinary-Approved Products: None

Human-Approved Products:

Paregoric (camphorated tincture of opium) 2 mg of morphine equiv. per 5 ml; 45% alcohol.
Available in 60 ml, pints, and gallons & UD 5 ml; Generic; (Rx; Class-III controlled substance)
Diphenoxylate HCl 2.5 mg with 0.025 mg Atropine Sulfate Tablets (Class-V controlled substance; prescription only); Logen® (Goldline); Lomotil® (Searle); Lonox® (Geneva); Generic;(C-V)
Diphenoxylate HCl 2.5 mg with 0.025 mg Atropine Sulfate per 5 ml Oral Liquid in 60 mldropper bottles, UD 4 & 10 ml. (Class-V controlled substance; prescription only). There aremany trade names for this combination, included are: Lomotil® (Searle), Lonox® (Geneva),
Diphenatol® (Rugby); Lofene® (Lannett), Logen® (Goldline), Generic
Loperamide HCl 1 mg/5 ml (0.2 mg/ml) & 1 mg/ml Oral Liquid; Imodium® A-D (McNeil-CPC); Pepto Diarrhea Control® (Procter & Gamble); generic (OTC)
Loperamide HCl 2 mg Capsules & Tablets; Imodium ® (Janssen) (OTC); Kaopectate II
Caplets® (Upjohn) (OTC); Maalox Anti-Diarrheal Caplets® (R-P Rorer); Imodium A-D
Caplets® (McNeil-CPC) (OTC); Neo-Diaral® (Roberts) (OTC); generic (OTC)
ORBIFLOXACIN
Chemistry/

Storage, Stability, Compatibility

A 4-fluroquinolone antibiotic, orbifloxacin isslightly soluble in water at neutral pH. Solubility increases in either an acidic or basic medium. Thecommercially available tablets should be stored between 2-30°C (36-86°F) and protected fromexcessive moisture.

Pharmacology

Orbifloxacin is a concentration-dependent bactericidal agent. It acts by inhibitingbacterial DNA-gyrase (a type-II topoisomerase), thereby preventing DNA supercoiling and DNAsynthesis. The net result is disruption of bacterial cell replication.
Orbifloxacin has good activity against many gram negative and gram positive bacilli and cocci, including most species and strains of Klebsiella spp., Staphylococcus intermedius or aureus, E.coli, Enterobacter, Campylobacter, Shigella, Proteus, Pasturella species. Some strains of
Pseudomonas aeruginosa and Pseudomonas species are resistant and most Enterococcus spp. areresistant. Like other fluroquinolones, orbifloxacin has weak activity against most anaerobes and isnot a good choice when treating known or suspected anaerobic infections.
Development of bacterial resistance to 4-fluroquinolones can occur.
Uses, Indications - Orbifloxacin is indicated for treatment in dogs and cats for bacterial infectionssusceptible to it.

Pharmacokinetics

After oral administration in dogs or cats, orbifloxacin is apparently nearlycompletely absorbed. The drug is well distributed (Vd=1.4 L/kg in dogs and 1.4 L/kg in cats) andonly bound slight to plasma proteins (8% dogs; 15% cats). Orbifloxacin is eliminated primarily bythe kidneys. Approximately 50% of the drug is excreted unchanged. Serum half lives are about 6hours in both dogs and cats. Urine levels remain well above MIC's for susceptible organisms for atleast 24 hours after dosing.

Contraindications, Precautions, Reproductive Safety

Orbifloxacin, 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 is also contraindicated in dogs and cats known to be hypersensitive to orbifloxacin or other drugs in its class (quinolones).
The manufacturer states that orbifloxacin 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.
Safety in breeding or pregnant dogs or cats has not been established. It is not known whetherorbifloxacin enters maternal milk.

Adverse Effects, Warnings

While the manufacturer reports that no adverse effects were reportedduring clinical studies (at 2.5. mg/kg dosing) in adult animals, higher doses or additional experiencewith use of the drug may demonstrate additional adverse effects. Gastrointestinal effects (anorexia, vomiting, diarrhea) would most likely be the first adverse effects noted.
Overdosage - Dogs and cats receiving up to 5X (37.5mg/kg) for 30 days did not result in anysignificant adverse effects. Cats receiving the higher dosages exhibited soft feces and decreasedbody weight gains.

Drug Interactions

Antacids or other agents containing divalent or trivalent cations (Mg++,
Al+++, Ca++) may bind to orbifloxacin and prevent its absorption. Sucralfate may inhibit absorption of orbifloxacin; separate doses of these drugs by at least 2 hours.
Orbifloxacin administered with theophylline may increase theophylline blood levels.
Probenecid may block the tubular secretion of orbifloxacin 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 orbifloxacinapparently 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 of the fluroquinolones and their concomitant use is not recommended. Fluroquinolones may exacerbate the nephrotoxicity of cyclosporine (used systemically).