Clinacin Tablets (25 mg) (Canada)

Company: Merck Animal Health

(clindamycin hydrochloride tablets)

For Veterinary Use Only

Description

CLINACIN tablets contain clindamycin hydrochloride, which is the hydrated salt of clindamycin. Clindamycin is a semi-synthetic antibiotic produced by a 7 (S)-chloro-substitution of the 7 (R)-hydroxyl group of lincomycin, a naturally-produced antibiotic produced by Streptomyces lincolnensis var. lincolnensis.

ACTIONS:

Site and mode of action: Clindamycin is an inhibitor of protein synthesis in the bacterial cell. The site of binding appears to be in the 50S sub-unit of the ribosome. Binding occurs to the soluble RNA fraction of certain ribosomes, thereby inhibiting the binding of amino acids to those ribosomes. Clindamycin differs from cell wall inhibitors in that it causes irreversible modification of the protein-synthesizing sub-cellular elements at the ribosomal level.

MICROBIOLOGY:

The following clindamycin in vitro data are available but their clinical significance is unknown. Clindamycin has been shown to have in vitro activity against isolates of the following organisms:

Aerobic gram positive, including: Staphylococcus aureus (penicillinase and non-penicillinase producing strains), Staphylococcus intermedius, Staphylococcus simulans, Staphylococcus epidermidis, Streptococci (except S. faecalis), pneumococci.

Anaerobic gram-negative bacilli, including: Bacteroides species, Fusobacterium species.

Anaerobic gram-positive nonsporeforming bacilli, including Propionibacterium, Eubacterium, Actinomyces species.

Anaerobic and microaerophillic gram-positive cocci including: Peptococcus species, Peptostreptococcus species, microaerophillic streptococci.

Clostridia: Most C. perfringens are susceptible, but other species, e.g., C. sporogenes and C. tertium are frequently resistant to clindamycin.

Mycoplasma species: Most Mycoplasma species are susceptible to clindamycin.

Clindamycin and erythromycin show parallel resistance. Partial cross resistance has been demonstrated between clindamycin, erythromycin and macrolide antibiotics.

Pharmacology

Absorption: Clindamycin hydrochloride is rapidly absorbed from the canine gastrointestinal tract.

Dogs orally dosed with therapeutic amounts of clindamycin hydrochloride demonstrated antibacterial serum levels of the drug within 15 minutes post-dosing.

Canine serum levels: Therapeutically effective serum levels of clindamycin hydrochloride can be maintained by oral dosing at the rate of 5.5 mg/kg every 12 hours. Dogs orally dosed with clindamycin hydrochloride at 5.5 mg/kg every 12 hours during a 72-hour dosing regimen continuously maintained antibacterial serum levels of the drug. This same study revealed that average peak serum concentrations occurred 1 hour and 15 minutes after dosing. The biological half-life for clindamycin hydrochloride in dog serum was about 5 hours. There was no bioactivity accumulation after a regimen of multiple oral doses.

Metabolism and Excretion:

Extensive studies of the metabolism and excretion of clindamycin hydrochloride administered orally in animals and humans have shown that unchanged drug and bioactive and bioinactive metabolites are excreted in urine and feces. Almost all of the bioactivity detected in serum after Clinacin tablet administration is due to the parent molecule (clindamycin). Urine bioactivity, however, reflects a mixture of clindamycin and active metabolites, especially N-demethyl clindamycin and clindamycin sulfoxide.

TOXICOLOGY AND SAFETY:

Animal toxicity studies with clindamycin hydrochloride showed the following:

One year oral toxicity studies in rats and dogs at doses of 30, 100 and 300 mg/kg/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 for six months tolerated the drug well; however, dogs orally dosed at 600 mg/kg/day vomited, had anorexia, and subsequently lost weight.

Safety studies in gestating bitches or breeding males have not been run, however, teratology and reproductive studies in male and female rats at 50 mg/kg and higher showed no drug-related effects.

Clinacin Tablets (25 mg) Indications

For treatment of infected wounds, abscesses and dental infections caused by or associated with Streptococcus spp., Staphylococcus spp., Bacteroides spp., Fusobacterium necrophorum and Clostridium perfringens in dogs.

For treatment of osteomyelitis caused by Staphylococcus aureus in dogs.

Dosage and Administration

Canine infected wounds, abscesses and dental infections: 5.5 mg/kg body weight every 12 hours.

Treatment with CLINACIN tablets may be continued up to a maximum of 28 days if clinical judgement indicates. Treatment of acute infections should not be continued for more than three or four days if no response to therapy is seen.

Canine osteomyelitis: 11 mg/kg body weight every 12 hours.

Treatment with CLINACIN tablets is recommended for a minimum of 28 days. Treatment should not be continued for longer than 28 days if no response to therapy is seen.

In Vitro susceptibility testing:

Susceptibility tests should be done on samples collected prior to initiation of therapy with CLINACIN tablets. A standardized disk testing procedure¹ is recommended for determining susceptibility of aerobic bacteria to clindamycin. Using this method the laboratory can designate isolates as resistant, intermediate, or susceptible. Tube or agar dilution methods may be used for aerobic and anaerobic bacteria. MIC (minimal inhibitory concentration) of 1.6 mcg/ml may be considered susceptible; MICs of 1.6 to 4.8 mcg/ml may be considered intermediate and MICs greater than 4.8 mcg/ml may be considered resistant.

¹ Bauer, A.W., W.M. Kirby, J.C. Sherris and M. Turck. Antibiotic susceptibility testing by a standardized single disk method, Am. J. Clin. Path 45:493-496, 1966. Standardized Susceptibility Test, Federal Register 37:20527-29, 1972

Warning

KEEP OUT OF REACH OF CHILDREN.

Clinacin Tablets (25 mg) Caution

CLINACIN tablets are contraindicated in animals with a history of hypersensitivity to preparations containing clindamycin or lincomycin. In the event of a hypersensitivity reaction following the administration of this drug, immediate appropriate therapy should be instituted. The use of CLINACIN tablets occasionally results in overgrowth of non-susceptible organisms such as clostridia and yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation. Because of potential adverse gastrointestinal effects, do not administer to rabbits, hamsters, guinea pigs, chinchillas, ruminants and horses.

While high dose studies in rats suggest that clindamycin is not a teratogen and did not significantly affect the reproductive performance of males or females, safety in gestating bitches or breeding males has not been established.

Clindamycin hydrochloride has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, CLINACIN tablets should be used with caution in animals receiving such agents.

Partial cross-resistance has been demonstrated between clindamycin, erythromycin and macrolide antibiotics.

During prolonged therapy of one month or greater, periodic liver and kidney function tests and blood counts should be performed.

Patients with severe renal and/or very severe hepatic disturbances accompanied by severe metabolic aberrations should be dosed with caution and should be monitored by serum examination during high-dose clindamycin therapy.

PRESENTATION:

CLINACIN tablets 25 mg - each tablet contains clindamycin hydrochloride equivalent to 25 mg of clindamycin. Available in bottles of 200 tablets.

CLINACIN tablets 75 mg - each tablet contains clindamycin hydrochloride equivalent to 75 mg of clindamycin. Available in bottles of 200 tablets.

CLINACIN tablets 150 mg - each tablet contains clindamycin hydrochloride equivalent to 150 mg of clindamycin. Available in bottles of 100 tablets.

Storage

Store at controlled room temperature 15° - 30°C.

Manufactured by: Chanelle Pharmaceuticals Manufacturing Ltd., Ireland

Distributed by: Intervet Canada Corp., subsidiary of Merck & Co., Inc., 16750, route Transcanadienne, Kirkland, QC H9H 4M7

1 866 683-7838

DIN 02277719 (25 mg), 02277727 (75 mg), 02277735 (150 mg)

12-0060INS

CPN: 1208197.3