KNOW ABOUT ONE DRUG EVERY DAY - ENROFLOXACIN

KNOW ABOUT ONE DRUG EVERY DAY

ENROFLOXACIN

Pharmacology

• Bactericidal by inhibition of microbial DNA gyrase, thus preventing DNA supercoiling and DNA synthesis.
• Concentration-dependent killing mechanism.
• Cell death of susceptible bacteria within 20 to 30 minutes of exposure.
• Significant post-antibiotic effect for Gram-positive and Gram-negative bacteria.
• Active in both the growth phase and the stationary phase of bacterial replication.

Activity

• Active against a wide range of Gram-negative bacteria including Pseudomonas aeruginosa and Klebsiella.
• Active against many Gram-negative bacilli and cocci, including most Pseudomonas aeruginosa, Klebsiella spp., Escherichia coli, Enterobacter, Shigella, Salmonella, Aeromonas, Haemophilus, Proteus, Yersinia, Serraria and Vibrio spp.
• Active against some Gram-positive micro-organisms.
• Generally active against Brucella spp., Chlamydia trachomatis, Staphylococcus spp., Mycoplasma and Mycobacterium spp. (not Mycobacterium paratuberculosis).
• Active against Mycoplasma spp.

Appropriate Use

• Enrofloxacin-sensitive infections.
• Tend to "spare" the normal gut flora.

Limitations

• Inactive against obligate anaerobes.
• Not particularly active against streptococci (Streptococcus spp.) or enterococci.; variable activity against Streptococci.
• Resistance occurs through mutations. This may be seen particularly with Pseudomonas aeruginosa, Klebsiella pneumonia, Acinetobacter spp. and enterococci.

Pharmacokinetics and Drug Interactions

Oral Absorption

• Good absorption; in dogs about 80% bioavailability following oral dosing, in sheep about 65-75%.
• Percentage absorption not decreased by the presence of food in the stomach.
• 50% of peak levels within 15 minutes and peak level within one hour.
• Rate may be decreased by the presence of food in the stomach.

Distribution

• Throughout the body.
• Volume of distribution in dogs about 3-4 L/kg; in cattle about 1.5 L/kg, in sheep 0.4 L/kg.
• Highest concentrations in bile, kidney, liver, lungs, reproductive system (including prostate), with therapeutic levels in bone, synovial fluid, skin, muscle, aqueous humour of the eye, pleural fluid.
• Reported to concentrate in macrophages.
• CSF concentrations low (6-10% of serum levels).

Plasma Protein binding / Storage

• About 27% bound to plasma proteins in the dog.

Elimination Route

• 15 to 50% excreted unchanged in urine (by tubular secretion and glomerular filtration).
• Partially (10-40% in most species) metabolised to ciprofloxacin (active metabolite); both enrofloxacin and ciprofloxacin are metabolised to various less active compounds which are excreted in urine and faeces.
• Conversion to ciprofloxacin may be minimal or zero in foals, pigs and some lizards.

Elimination half-life / Clearance Rate

• Half life approximately: dogs four to five hours, cats six hours, sheep 1.5-4.5 hours, horses six hours "turtles" 18 hours, "alligators" 55 hours.
• Half-life and serum level may be slightly increased in patients with severely reduced renal function, but without necessitating dosage adjustment.

Drug Interactions

• Absorption may be prevented by the presence of antacids containing cations such as Mg⁺⁺, Al⁺⁺⁺, Ca⁺⁺ which may bind to the drug.
• Absorption may be inhibited by the presence of sucralfate: give doses of the two compounds at least two hours apart from one another.
• If administered with theophyline, the blood levels of theophyline may be increased.
• If administered with probenecid, blood level and half-life of enrofloxacin may be increased as probenecid blocks the tubular secretion of enrofloxacin and ciprofloxacin.
• Synergistic effects may be seen if used together with aminoglycosides, third generation cephalosporins or extended-spectrum penicillins against some bacteria particularly Pseudomonas aeruginosa and other Enterobacteriaceae. However this effect is not predictable.
• In vitro synergy reported in combination with Clindamycin against strains of Peptostreptococcus, Lactobacillus, Bacteroides.
• Antagonism of the anti-microbial action of enrofloxacin may occur if nitrofurantoin is administered concomitantly.
• Exacerbation of the nephrotoxicity of systemically administered cyclosporine may occur from concomitant use.

Contraindications / Precautions        

• Should not be used in growing dogs (under 12-18 months old) or cats (under eight weeks old) as it may inhibit growth of load-bearing articular cartilage.
• Contraindicated at two to eight months in small and medium sized dogs and for longer in large and giant breed individuals.
• Caution in patients with epilepsy as this drug may predispose to seizure activity.
• Increasing incidence of resistance in some organisms including  Escherichia coli, Salmonella spp. and Camplylobacter spp.: preferably perform antimicrobial sensitivity tests before use, or use only for treatment of intractable Gram-negative infections which are potentially life-threatening or resistant to other antibacterial drugs e.g. due to insufficient penetration to the site of infection.
• Do not allow patients to become dehydrated as occasional crystalluria has been noted with use of ciprofloxacin in humans. 
• Safety in pregnant or lactating non-domestic animals has not been established; care should be taken in such animals.
• Contraindicated in patients with known hypersensitivity to quinolones.
• In dogs: "not generally recommended to be used in pregnancy unless the benefits of therapy clearly outweigh the risks", due to the potential risk of cartilage abnormalities in young animals.
• In cats: safety for use during breeding, pregnancy and lactation has not been established.

Adverse Effects / Side Effects / Warnings

• Occasional skin reactions may occur in kennelled greyhounds.
• Occasional muscle bruising following injection in reptiles or birds.
• Cats: 
• rarely: ocular toxicity with mydriasis, retinal degeneration and blindness. Occurred only at higher dose rates (>15mg/kg/day).
• rarely: vomiting, anorexia, hepatic enzyme elevation, diarrhoea, ataxia, seizures, depression/lethargy, vocalisation, aggression.
•  Dogs:
• rarely: hepatic enzyme elevation, ataxia, seizures, depression/lethargy, nervousness.
• Potentially hypersensitivity reactions.
• Potentially crystalluria.
• Humans: fluoroquinolones have caused mild increases in liver enzymes, blood urea nitrogen (BUN) and creatinine, and decreases in haematocrit.
• Rabbits: 
• Arthropathy may occur in juveniles.
• Inappetance or transient mild diarrhoea occur in some rabbits.

Operator Warnings

• Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding operator safety/warnings.
• Hallucinations, vivid dreams and headache may occur if enrofloxacin is given to humans.

Overdose / Acute Toxicity

• May result in anorexia and vomiting.

Possibly other effects as indicated in Adverse Effects / Side Effects / Warnings above.

Acute Toxicity

Dog:

• Ten times recommended dose for at least fourteen days resulted in only vomiting and anorexia.
• Twenty five times recommended dose for eleven days resulted in some deaths.

Reproductive effects

Dog:

• No treatment related effects following administration of up to 15mg/kg per day to breeding, pregnant and lactating dogs.
• No effects on male breeding performance (limited studies).

Organ toxicity

• Articular cartilage: bubble-like changes noted in dogs given two to five times recommended dose for 30 days; clinical signs seen only with five times recommended dose.