CLINDAMYCIN HCL, CLINDAMYCIN PALMITATE HCL, CLINDAMYCIN PHOSPHATE

Chemistry - A semisynthetic derivative of lincomycin, clindamycin is available as the hydrochloride hydrate, phosphate ester, and palmitate hydrochloride. Potency of all three salts are expressed as milligrams of clindamycin. The hydrochloride occurs as a white to practically white, crystalline powder. The phosphate occurs as a white to off-white, hygroscopic crystalline powder.
The palmitate HCl occurs as a white to off-white amorphous powder. All may have a faint characteristic odor and are freely soluble in water. With the phosphate, about 400 mg are soluble in one ml of water. Clindamycin has a pKa of 7.45. The commercially available injection has a pH of 5.5-7.

Storage, Stability, Compatibility

Clindamycin capsules and the palmitate powder for oral solution should be stored at room temperature (15-30°C). After reconstitution, the palmitate oral solution (human-product) should not be refrigerated or thickening may occur. It is stable for 2 weeks at room temperature. The veterinary oral solution should be stored at room temperature and has an extended shelf-life.
Clindamycin phosphate injection should be stored at room temperature. If refrigerated or frozen, crystals may form which resolubolize upon warming.
Clindamycin for injection is reportedly compatible for at least 24 hours in the following IV infusion solutions : D5W, Dextrose combinations with Ringer's. lactated Ringer's, sodium chloride,
D10W, sodium chloride 0.9%, Ringer's injection, and lactated Ringer's injection. Clindamycin forinjection is reportedly compatible with the following drugs: amikacin sulfate, ampicillin sodium, aztreonam, carbenicillin disodium, cefamandole naftate, cefazolin sodium, cefonicid sodium, cefoperazone sodium, cefotaxime sodium, ceftazidime sodium, ceftizoxime sodium, cefuroximesodium, cephalothin sodium, cimetidine HCl, gentamicin sulfate, heparin sodium, hydrocortisonesodium succinate, kanamycin sulfate, methylprednisolone sodium succinate, magnesium sulfate, meperidine HCl, metoclopramide HCl, metronidazole, morphine sulfate, penicillin Gpotassium/sodium, piperacillin sodium, potassium chloride, sodium bicarbonate, tobramycin HCl(not in syringes), verapamil HCl, and vitamin B-complex with C.
Drugs that are reportedly incompatible with clindamycin include: aminophylline, ranitidine HCl, and ceftriaxone sodium. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for more specificinformation (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).

Pharmacology - CLINDAMYCIN HCL, CLINDAMYCIN PALMITATE HCL, CLINDAMYCIN PHOSPHATE

The lincosamide antibiotics, lincomycin and clindamycin, share mechanisms ofaction and have similar spectrums of activity, although lincomycin is usually less active againstsusceptible organisms. Complete cross-resistance occurs between the two drugs, and at least partialcross-resistance occurs between the lincosamides and erythromycin. They may act as bacteriostaticor bactericidal agents, depending on the concentration of the drug at the infection site, and thesusceptibility of the organism. The lincosamides are believed to act by binding to the 50S ribosomalsubunit of susceptible bacteria, thereby inhibiting peptide bond formation.
Most aerobic gram positive cocci are susceptible to the lincosamides (Strep. faecalis is not) including Staphylococcus, and Streptococci. Other organisms that are generally susceptible include:
Corynebacterium diphtheriae, Nocardia asteroides, Erysepelothrix, Toxoplasma, and Mycoplasma sp. Anaerobic bacteria that are generally susceptible to the lincosamides include:
Clostridium perfringens, C. tetani (not C. difficile), Bacteroides (including many strains of B.fragilis), Fusobacterium, Peptostreptococcus, Actinomyces, and Peptococcus.
Uses, Indications - Clindamycin products are approved for use in dogs and humans. The labeledindications for dogs include wounds, abscesses and osteomyelitis caused by Staphylococcus aureus. Because clindamycin also has excellent activity against most pathogenic anaerobic organisms, it is also used extensively for those infections. For further information refer to the Dosage or Pharmacology sections.

Pharmacokinetics - CLINDAMYCIN HCL, CLINDAMYCIN PALMITATE HCL, CLINDAMYCIN PHOSPHATE

The pharmacokinetics of clindamycin have apparently not been extensivelystudied in veterinary species. Unless otherwise noted, the following information applies to humans.
The drug is rapidly absorbed from the gut and about 90% of the total dose is absorbed. Fooddecreases the rate of absorption, but not the extent. Peak serum levels are attained about 45-60minutes after oral dosing. IM administration gives peak levels about 1-3 hours post injection.
Clindamycin is distributed into most tissues. Therapeutic levels are achieved in bone, synovialfluid, bile, pleural fluid, peritoneal fluid, skin and heart muscle. Clindamycin also penetrates wellinto abscesses and white blood cells. CNS levels may reach 40% of those in the serum if meningesare inflamed. Clindamycin is about 93% bound to plasma proteins. The drug crosses the placentaand also can be distributed into milk at concentrations equal to those in the plasma.
Clindamycin is partially metabolized in the liver to both active and inactive metabolites. Unchangeddrug and metabolites are excreted in the urine, feces and bile. Half-lives can be prolonged inpatients with severe renal or hepatic dysfunction. The elimination half-life of clindamycin in dogs isreportedly 3-5 hours after oral administration and 10-13 hours after subcutaneous administration.

Contraindications, Precautions, Reproductive Safety

Although there have been case reportsof parenteral administration of lincosamides to horses, cat le and sheep, the lincosamides areconsidered to be contraindicated for use in rabbits, hamsters, guinea pigs, horses, and ruminantsbecause of serious gastrointestinal effects that may occur, including death. Clindamycin is contraindicated in patients with known hypersensitivity to it or lincomycin.
Clindamycin should be used cautiously in cats with pulmonic toxoplasmosis. Preliminary reportsof ongoing research has indicated that several cats with experimentally-induced toxoplasmosis diedafter being given clindamycin parenterally.
The manufacturer recommends using the drug with caution in atopic animals. Patients with verysevere renal and/or hepatic disease should receive the drug with caution and the manufacturersuggests monitoring serum clindamycin levels during high-dose therapy in these patients.
Clindamycin crosses the placenta, and cord blood concentrations are approximately 46% of thosefound in maternal serum. Safe use during pregnancy has not been established, but neither has thedrug been implicated in causing teratogenic effects.
Because clindamycin is distributed into milk, nursing puppies or kittens of mothers taking clindamycin may develop diarrheas.

Adverse Effects, Warnings

Adverse effects reported in dogs and cats include gastroenteritis(emesis, loose stools, and infrequently bloody diarrhea in dogs). IM injections reportedly causepain at the injection site.
Overdosage, Acute Toxicity - There is little information available regarding overdoses of thisdrug. In dogs, oral doses of up to 300 mg/kg/day for up to one year did not result in toxicity. Dogsreceiving 600 mg/kg/day developed anorexia, vomiting and they lost weight.

Drug Interactions

Clindamycin possesses intrinsic neuromuscular blocking activity and shouldbe used cautiously with other neuromuscular blocking agents.
Erythromycin and clindamycin have shown antagonism in vitro. Chloramphenicol and clindamycin may also be antagonistic, but this has not been confirmed. Unlike lincomycin, clindamycin absorption does not appear to be significantly altered by kaolin.
Drug/Laboratory Interactions - Slight increases in liver function tests (AST, ALT, Alk.
Phosph.) may occur. There is apparently not any clinical significance associated with these increases.