CARBENICILLIN INDANYL SODIUM

By | 2010-07-05

For general information on the penicillins, including adverse effects, contraindications, overdosage, drug interactions and monitoring parameters, refer to the monograph: Penicillins, General Information.

Chemistry

An alpha-carboxypenicillin, carbenicillin is now available only as a an oral dosage form; the sodium salt of the indanyl ester of carbenicillin. It occurs as a bitter-tasting, white to off-white powder that is soluble in water and alcohol. Carbenicillin indanyl sodium may also be known as carindacillin sodium or indanylcarbenicillin sodium.

Storage – Stability – Compatibility

The oral indanyl sodium tablets should be stored in tight containers and protected from temperatures greater than 30°C The sodium injection powder for reconstitution should be stored at temperatures less than 30°C.

Pharmacology

The alpha-carboxypenicillins, sometimes called anti-pseudomonal penicillins, include both carbenicillin and ticarcillin. These agents have similar spectrums of activity as the aminopenicillins (ampicillin, etc.) including increased activity against many strains of gram negative aerobes not covered by either the natural penicillins or penicillinase-resistant penicillins, including some strains of E. coli, Klebsiella, and Haemophilus. Additionally, they have activity against several gram negative organisms of the family Enterobacteriaceae, including many strains of Pseudomonas aeruginosa and Acinetobacter. Like the natural penicillins they are susceptible to inactivation by beta-lactamase-producing bacteria (e.g., Staph aureus). Although not as active as the natural penicillins, they do have some activity against many anaerobic bacteria including Clostridial organisms.

Uses – Indications

As there are no veterinary-approved carbenicillin products, all uses of this drug are considered extra-label. Generally, carbenicillin is used parenterally in the treatment of systemic Pseudomonas aeruginosa infections in small animals, usually in combination with an appropriate aminoglycoside agent. Synergy may occur against some Pseudomonas strains when used in combination with aminoglycosides, but in vitro inactivation of the aminoglycoside may also occur (see Drug Interactions below) if the drugs are physically mixed together or in patients with severe renal failure.

Because the oral form is poorly absorbed and the drug has a rapid elimination half-life, oral therapy is only indicated for the treatment of susceptible urinary tract (and possibly prostate) infections as levels are too low in serum and other tissues for adequate therapy in other systemic Pseudomonas infections.

Pharmacokinetics (specific)

The oral form (indanyl sodium) of the drug is rapidly, but incompletely, absorbed (see above) with only 30-40% of an oral dose absorbed in humans. Peak levels of the indanyl sodium are attained in humans about 30 minutes after administration, but is rapidly hydrolyzed into the base.

Attainable serum levels after oral therapy are generally too low to treat systemic infections, but high levels are achieved in the urine. The volume of distribution is reportedly 0.18-0.2 L/kg in dogs and cats and 0.29-0.4 L/kg in the horse. The drug is 29-60% bound to serum proteins (human). Carbenicillin is thought to cross the placenta and is found in small quantities in milk. In cattle, mastitic milk levels of carbenicillin are approximately twice those found in normal milk, but are too low to treat most causal organisms.

Carbenicillin is eliminated primarily by the kidneys, via both tubular secretion and glomerular filtration. Concurrent probenecid administration can slow elimination and increase blood levels. In humans, about 2-5% of the drug is metabolized by hydrolysis to inactive compounds. The half-life in dogs and cats is reportedly 45-75 minutes and 60-90 minutes in the horse. Clearance is 1.8 ml/kg/min in the dog and 4.6 ml/kg/min in the horse.

Doses

Doses for dogs:

For susceptible infections:

a) For UTI: 15 – 50 mg/kg PO q6-8h

b) 15 mg/kg PO, IV tid

c) 55-110 mg/kg IV q8h or 55 mg/kg PO q8h

Doses for cats:

For susceptible infections:

a) For UTI: 15 – 50 mg/kg PO q6-8h

b) 15 mg/kg PO tid

c) 15 mg/kg IV q8h

d) 55 mg/kg PO q8h

Doses for birds

For susceptible infections in Psittacines:

a) 100 – 200 mg/kg PO bid; 1/3 tablet added to 4 oz drinking water. Crush tablets and gavage or hide in mash or palatable soft food item. If adding to drinking water, disguise bitter taste by adding Tang® or a Pina Colada mix to water.

b) 200 mg/kg PO for 5-10 days. Crush tablets and apply to favorite food (e.g., cooked sweet potato works well) or mix in mash or hand-feeding formula.

Dosage Forms/Preparations/FDA Approval Status

Veterinary-Approved Products:

None

Human-Approved Products:

Carbenicillin Indanyl Sodium Coated Oral Tablets 382 mg; Geocillin® (Roerig); (Rx)