(clindamycin hydrochloride,   clindamycin phosphate [for injection])

Brands

Veterinary: Antirobe, Clinitabs, Clinicaps, Aquadrops, Clindadrops (Clindamycin Hydrochloride Oral Liquid)

Veterinary Availability:

• Tablets: 25 mg, 75 mg, 150 mg
• Capsules: 25 mg, 75 mg, 150 mg, 300 mg
• Liquid: Clindadrops (Clindamycin Hydrochloride Oral Liquid) is available as 20 mL filled in 30 mL bottles (25 mg/mL)

Brands

Human:  Cleocin, Cleocin Pediatric, Cleocin Phosphate

Human Availability:

• Granules:  Cleocin Pediatric (Clindamycin palmitate HCL granules for oral solution): 75 mg/5mL (15mg/mL) in 100 mL
• Injectable:  Cleocin Phosphate (Clindamycin Phosphate) 150 mg/mL in vial volumes 2 mL, 4 mL, 6 mL, 60 mL, 100 mL

Pharmacology

Clindamycin, a lincosamide, is a derivative of lincomycin that exhibits activity against a wide variety of aerobic and anaerobic bacterial pathogens. Clindamycin inhibits protein synthesis in bacterial cells. The site of binding is in the 50S ribosomal subunit. Binding occurs to the soluble RNA fraction of certain ribosomes, which allows it to inhibit binding of amino acids to those ribosomes. Clindamycin differs from antibiotics that inhibit cell wall formation, instead, causing irreversible modification of the protein-synthesizing subcellular elements at the ribosomal level. Clindamycin may act as a bactericidal or a bacteriostatic agent depending upon the susceptibility of the organism and the concentration of the drug at the site of infection.

Clindamycin has shown in vitro activity against most aerobic gram positive cocci, including Streptococci (except Enterococcus faecalis), and Staphylococci (including penicillin-resistant staphylococci). It also shows activity against many of the anaerobic organisms such as Clostridium perfringens, Bacteroides and Actinomyces. Other organisms that show some susceptibility include: Corynebacteria and Mycoplasma spp.

Rapidly absorbed in the gut, clindamycin is widely distributed into most tissues such as lungs, bone and joint, skin, heart muscle, and into body fluids with the exception of CSF (cerebrospinal fluid), as well as penetrating abscesses and white blood cells. Only minimal concentrations of the drug are found in the CNS (central nervous system) in the presence of inflamed meninges. Clindamycin is distributed into breast milk. Although clindamycin has been shown to cross the placenta it revealed no evidence of impaired fertility, or harm to the fetus in rats or rabbits during reproductive toxicity studies, except at doses high enough to cause maternal toxicity ³.

The lincosamide class of antibiotics is one most associated with pseudomembranous colitis, when primarily given orally. Their use may result in overgrowth of non-susceptible organisms such as clostridia and yeasts. However, in studies clindamycin has been shown to offer more complete and predictable absorption from the gastrointestinal tract, than does lincomycin, which is thought to reduce the chance of diarrhea by its use.

Even so, it is recommended to avoid administration of clindamycin in those species sensitive to the gastrointestinal effects of clindamycin, and in those species that are more tolerant of the drug (such as the rat) to administer probiotics concomitantly during and following treatment (refer to Considerations at the end of the monograph).

Clindamycin is metabolized in the liver to active and inactive metabolites and excreted in urine and feces.
Since clindamycin is also known to be distributed in breast milk it is not recommended that it be given to animals that are nursing young due to the potential for GI effects.

*Note: Rat and Dog Data: One year oral toxicity studies in rats and dogs at doses of 30, 100 and 300 mg/kg/day (13.6, 45.5 and 136.4 mg/lb/day) have shown clindamycin hydrochloride to be well tolerated. Differences did not occur in the parameters evaluated to assess toxicity when comparing groups of treated animals with contemporary controls. Rats administered clindamycin hydrochloride at 600 mg/kg/day (272.7 mg/lb/day) for six months tolerated the drug well; however, dogs orally dosed at 600 mg/kg/day (272.7mg/lb/day) vomited, had anorexia, and subsequently lost weight. ¹

Indications

Used in bone and joint infections, wound infections (e.g., MRSA), abscesses, oral infections, and respiratory infections susceptible to clindamycin.

Drug Interactions or Contraindications

• Lincomycin and clindamycin show complete cross resistance, and partial cross resistance has been noted between clindamycin, erythromycin and macrolide antibiotics. It is suggested that concomitant use be cautious or avoided altogether.
• Clindamycin hydrochloride has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, caution should be exercised if administering concomitantly.
• Clindamycin half-life may be prolonged in the presence of hepatic disease. Use cautiously in rats with hepatic disorders.
• Avoid use or select a more appropriate alternative antibiotic for use in rats that are nursing young.

Adverse Reactions

Esophageal: irritation, strictures

GI: colitis, diarrhea

*Note: in the event of diarrhea, it is advised to stop the antibiotic and contact the veterinarian. Do not give anti-diarrhea medications without first contacting a veterinarian.

Dosage Recommendations

7.5 mg/kg, SQ, q12hr  ^{34, 35, 41, 44}

or

7.5 mg/kg to 25 mg/kg, PO, q24hr  ⁴²

or

7.5 mg/kg to 25 mg/kg, PO, BID or TID  ³³ (as determined by veterinarian based on severity of disease being treated)

*Note: duration of treatment with clindamycin hydrochloride products may be continued up to a maximum of 28 days (or longer in penicillin-resistant staphylococcal infection) if clinical judgment indicates. However, it has been recommended that treatment of acute infections should not be continued for more than three or four days, based upon assessment by a veterinarian, if no response to therapy is seen.

Considerations

• While lincosamides, such as clindamycin, have the potential for causing fatal clostridial enterotoxemia in some species, and should avoid being administered to rabbits, hamsters, guinea pigs, horses, chinchillas or ruminating animals, the rat is very tolerant of its use. It is, however, strongly recommended to include the administration of a probiotic concurrently, in the rat, while on clindamycin, and to continue the probiotic for 2 to 3 weeks following completion of treatment.
• Irritation and scarring of esophageal tissue, by administering tablets or capsules dry, has been known to occur in cats (though not reported in the rat). It remains advisable to dissolve the tablet or capsule contents well into food or fluids prior to administering.
• In treating suspected polymicrobial infections, where a broader coverage may be needed, synergistic or combination drugs may be used. The following drugs may be seen used simultaneously with clindamycin: fluoroquinolones (e.g., enrofloxacin), or amikacin, or gentamicin, or the penicillins, or third generation cephalosprins  ³⁴ , or doxycycline ³⁹.
• Store injectable, capsules, veterinary oral solution, and powder for reconstitution at room temperature 15°-30°C (59°-86°F). Powder following reconstitution (mixed as suspension) is stable at room temperature for 2 weeks.
• Due to the bitter taste of lincosamides, refrigerating clindamycin oral liquid may ease some of the unpleasantness of the taste. Some thickening of the liquid may occur upon refrigeration. Refrigeration is, however, not required for storing the drug.

Consultant

• Nathalie Baldwin, DVM. Village Gate Animal Hospital and Pet Resort, Columbus, OH

Reference

1. Clindamycin Hydrochloride Oral Drops- clindamycin hydrochloride liquid. (July, 2011). Food and Drug Administration. Retrieved January 15, 2014, from http://www.accessdata.fda.gov/spl/data/5996f67c-7e13-43f7-84d1-b82948103802/5996f67c-7e13-43f7-84d1-b82948103802.xml
2. Antirobe- clindamycin hydrochloride capsule. (March, 2010). Food and Drug Administration. Retrieved January 16, 2014, from http://www.accessdata.fda.gov/spl/data/461d2e78-8a3d-43a5-be73-e8010eb1c30a/461d2e78-8a3d-43a5-be73-e8010eb1c30a.xml
3. Cleocin Pediatric (clindamycin palmitate hydrochloride) granule, for solution. DailyMed. Retrieved January 16, 2014, from http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1ef87b6c-9d32-44ac-8c55-8bf01424cc45
4. Clindamycin (clindamycin phosphate) injection, solution. DailyMed. Retrieved January 16, 2014, from http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b8133f76-8880-4b91-a451-b3f831ad6853
5. Gray, J., Weaver, R., Bollert, J. and Feenstra, E., 1972. The oral toxicity of clindamycin in laboratory animals. Toxicology and Applied Pharmacology, 21(4), pp.516-531.
   https://doi.org/10.1016/0041-008X(72)90008-7