Pharmacia & Upjohn
brand of
clindamycin hydrochloride capsules, USP
Caution:
Federal (USA) law restricts this drug to use by or on the order of a
licensed veterinarian.
INDICATIONS
ANTIROBE (brand of
clindamycin hydrochloride) Capsules (for use in dogs only) and AQUADROPS
Liquid (for use in dogs and cats) are indicated for the treatment of
infections caused by susceptible strains of the designated microorganisms in
the specific conditions listed below: Dogs: Skin infections
(wounds and abscesses) due to coagulase positive staphylococci
(Staphylococcus aureus or
Staphylococcus intermedius). Deep wounds and abscesses
due to Bacteroides fragilis, Prevotella
melaninogenicus, Fusobacterium necrophorum and
Clostridium perfringens. Dental infections due to
Staphylococcus aureus, Bacteroides fragilis, Prevotella
melaninogenicus, Fusobacterium necrophorum and
Clostridium perfringens. Osteomyelitis due to
Staphylococcus aureus, Bacteroides fragilis, Prevotella
melaninogenicus, Fusobacterium necrophorum and
Clostridium perfringens.
Cats: Skin
infections (wounds and abscesses) due to
Staphylococcus aureus, Staphylococcus intermedius and
Streptococcus spp. Deep wounds and
infections due to Clostridium perfringens and
Bacteroides fragilis. Dental
infections due to Staphylococcus aureus,
Staphylococcus intermedius, Streptococcus spp.,
Clostridium perfringens and Bacteroides fragilis.
DESCRIPTION
ANTIROBE Capsules and ANTIROBE
AQUADROPS Liquid contain clindamycin hydrochloride which is the hydrated
salt of clindamycin. Clindamycin is a semisynthetic antibiotic produced by a
7(S)-chlorosubstitution of the 7(R)-hydroxyl group of a naturally produced
antibiotic produced by Streptomyces lincolnensis var.
lincolnensis.
ANTIROBE Capsules (For Use in
Dogs Only):
25 mg Capsule,
each yellow and white capsule contains clindamycin hydrochloride
equivalent to 25 mg of clindamycin.
75 mg Capsule,
each green capsule contains clindamycin hydrochloride equivalent to 75
mg of clindamycin.
150 mg
Capsule, each light blue and green capsule contains clindamycin
hydrochloride equivalent to 150 mg of clindamycin.
300 mg
Capsule, each light blue capsule contains clindamycin hydrochloride
equivalent to 300 mg of clindamycin.
ANTIROBE AQUADROPS Liquid (For
Use in Dogs and Cats) is a palatable formulation intended for oral
administration. Each mL of ANTIROBE AQUADROPS contains clindamycin
hydrochloride equivalent to 25 mg clindamycin; and ethyl alcohol, 8.64%.
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 5OS 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 subcellular elements at the
ribosomal level.
MICROBIOLOGY:
Clindamycin is a lincosaminide antimicrobial agent with activity against
a wide variety of aerobic and anaerobic bacterial pathogens. Clindamycin is
a bacteriostatic compound that inhibits bacterial protein synthesis by
binding to the 5OS ribosomal sub-unit. The minimum inhibitory concentrations
(MICs) of Gram-positive and obligate anaerobic pathogens isolated from dogs
and cats in the United States are presented in Table 1 and Table 2. Bacteria
were isolated in 1998-1999. All MICs were performed in accordance with the
National Committee for Clinical Laboratory Standards (NCCLS).
Table 1.
Clindamycin MIC Values (µg/mL) from Diagnostic Laboratory Survey Data
Evaluating Canine Pathogens in the U.S. During 1998-991
|
Organism |
Number of Isolates |
MIC50 |
MIC85 |
MIC90 |
Range |
|
Soft Tissue/Wound2 |
|
Staphylococcus aureus |
17 |
0.5 |
0.5 |
≥4.0 |
0.25-≥4.0 |
|
Staphylococcus intermedius |
28 |
0.25 |
0.5 |
≥4.0 |
0.125-≥4.0 |
|
Staphylococcus spp. |
18 |
0.5 |
0.5 |
≥4.0 |
0.25-≥4.0 |
|
Beta-hemolytic
streptococci |
46 |
0.5 |
0.5 |
≥4.0 |
0.25-≥4.0 |
|
Streptococcus spp. |
11 |
0.5 |
≥4.0 |
≥4.0 |
0.25-≥4.0 |
|
Osteomyelitis/Bone3 |
|
Staphylococcus aureus |
20 |
0.5 |
0.5 |
0.5 |
0.54 |
|
Staphylococcus intermedius |
15 |
0.5 |
≥4.0 |
≥4.0 |
0.25-≥4.0 |
|
Staphylococcus spp. |
18 |
0.5 |
≥4.0 |
≥4.0 |
0.25-≥4.0 |
|
Beta-hemolytic
streptococci |
21 |
0.5 |
2.0 |
2.0 |
0.25-≥4.0 |
|
Streptococcus spp. |
21 |
≥4.0 |
≥4.0 |
≥4.0 |
0.25-≥4.0 |
|
Dermal/Skin5 |
|
Staphylococcus aureus |
25 |
0.5 |
≥4.0 |
≥4.0 |
0.25-≥4.0 |
|
Staphylococcus intermedius |
48 |
0.5 |
≥4.0 |
≥4.0 |
0.125-≥4.0 |
|
Staphylococcus spp. |
32 |
0.5 |
≥4.0 |
≥4.0 |
0.25-≥4.0 |
|
Beta-hemolytic
streptococci |
17 |
0.5 |
0.5 |
0.5 |
0.25-0.5 |
1
The correlation between the in vitro susceptibility
data and clinical response has not been determined.
2
Soft Tissue/Wound: includes samples labeled wound, abscess, aspirate,
exudates, draining tract, lesion, and mass
3
Osteomyelitis/Bone: includes samples labeled bone, fracture, joint, tendon
4
No range, all isolates yielded the same value
5
Dermal/Skin: includes samples labeled skin, skin swab, biopsy, incision, lip
Table 2.
Clindamycin MIC Values (µg/mL) from Diagnostic Laboratory Survey Data
Evaluating Feline Pathogens from Wound and Abscess Samples in the U.S.
During 19981
|
Organism |
Number of Isolates |
MIC50 |
MIC90 |
Range |
|
Bacteroides/Prevotella |
30 |
0.06 |
4.0 |
≤0.015-4.0 |
|
Fusobacterium spp. |
17 |
0.25 |
0.25 |
≤0.015-0.5 |
|
Peptostreptococcus spp. |
18 |
0.13 |
0.5 |
≤0.015-8.0 |
|
Porphyromonas spp. |
13 |
0.06 |
0.25 |
≤0.015-8.0 |
1
The correlation between the in vitro susceptibility
data and clinical response has not been determined.
PHARMACOLOGY
Absorption:
Clindamycin hydrochloride is rapidly absorbed from the canine and feline
gastrointestinal tract.
Dog Serum
Levels: Serum levels at or above 0.5 µg/mL can be maintained by oral
dosing at a rate of 2.5 mg/lb of clindamycin hydrochloride every 12 hours.
This same study revealed that average peak serum concentrations of
clindamycin occur 1 hour and 15 minutes after oral dosing. The elimination
half-life for clindamycin in dog serum was approximately 5 hours. There was
no bioactivity accumulation after a regimen of multiple oral doses in
healthy dogs.
Clindamycin Serum
Concentrations 2.5 mg/lb (5.5 mg/kg) After B.I.D. Oral Dose of Antirobe
Capsules to Dogs
Cat Serum
Levels: Serum levels at or above 0.5 µg/mL can be maintained by oral
dosing at a rate of 2.5 mg/lb of clindamycin hydrochloride every 24
hours. The average peak serum concentration of clindamycin occurs
approximately 1 hour after oral dosing. The elimination half-life of
clindamycin in feline serum is approximately 7.5 hours. In healthy cats,
minimal accumulation occurs after multiple oral doses of clindamycin
hydrochloride, and steady-state should be achieved by the third dose.
Clindamycin Serum
Concentrations 5 mg/lb (11 mg/kg) After Single Oral Dose of Antirobe
Aquadrops to Cats
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 ANTIROBE product
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.
ANIMAL
SAFETY SUMMARY
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 (272.7 mg/lb/day) vomited, had anorexia, and subsequently lost
weight. At necropsy these dogs had erosive gastritis and focal areas of
necrosis of the mucosa of the gallbladder.
Safety in gestating
bitches or breeding males has not been established.
Cat Data:
The recommended daily therapeutic dose range for clindamycin
hydrochloride (ANTIROBE AQUADROPS Liquid) is 11 to 33 mg/kg/day (5 to 15
mg/lb/day) depending on the severity of the condition. Clindamycin
hydrochloride (ANTIROBE AQUADROPS Liquid) was tolerated with little
evidence of toxicity in domestic shorthair cats when administered orally
at 10x the minimum recommended therapeutic daily dose (11 mg/kg; 5
mg/lb) for 15 days, and at doses up to 5x the minimum recommended
therapeutic dose for 42 days. Gastrointestinal tract upset (soft feces
to diarrhea) occurred in control and treated cats with emesis occurring
at doses 3x or greater than the minimum recommended therapeutic dose (11
mg/kg/day; 5 mg/lb/day). Lymphocytic inflammation of the gallbladder was
noted in a greater number of treated cats at the 110 mg/kg/day (50
mg/lb/day) dose level than for control cats. No other effects were
noted. Safety in gestating queens or breeding male cats has not been
established.
CONTRAINDICATIONS
ANTIROBE Capsules and
ANTIROBE AQUADROPS Liquid are contraindicated in animals with a history
of hypersensitivity to preparations containing clindamycin or lincomycin.
Because of potential
adverse gastrointestinal effects, do not administer to rabbits,
hamsters, guinea pigs, horses, chinchillas or ruminating animals.
WARNINGS
Keep out of reach of
children. Not for human use.
PRECAUTIONS
During prolonged therapy
of one month or greater, periodic liver and kidney function tests and
blood counts should be performed.
The use of ANTIROBE
occasionally results in overgrowth of non-susceptible organisms such as
clostridia and yeasts. Therefore, the administration of ANTIROBE should
be avoided in those species sensitive to the gastrointestinal effects of
clindamycin (see CONTRAINDICATIONS). Should
superinfections occur, appropriate measures should be taken as indicated
by the clinical situation.
Patients with very severe
renal disease and/or very severe hepatic disease accompanied by severe
metabolic aberrations should be dosed with caution, and serum
clindamycin levels monitored during high-dose therapy. Clindamycin
hydrochloride has been shown to have neuromuscular blocking properties
that may enhance the action of other neuromuscular blocking agents.
Therefore, ANTIROBE should be used with caution in animals receiving
such agents.
Safety in gestating
bitches and queens or breeding male dogs and cats has not been
established.
ADVERSE
REACTIONS
Side effects occasionally
observed in either clinical trials or during clinical use were vomiting
and diarrhea. To report adverse reactions or a suspected adverse
reaction call 1-800-793-0596.
DOSAGE
AND ADMINISTRATION
Dogs:
Infected Wounds, Abscesses and Dental Infections
Oral:
2.5-15.0 mg/lb body weight every 12 hours.
Duration:
Treatment with ANTIROBE products may be continued up to a maximum of
28 days if clinical judgment indicates. Treatment of acute infections
should not be continued for more than three or four days if no response
to therapy is seen.
Dosage
Schedule:
Capsules
ANTIROBE
25 mg, administer 1-6 capsules every 12 hours for each 10 pounds of
body weight.
ANTIROBE
75 mg, administer 1-6 capsules every 12 hours for each 30 pounds of
body weight.
ANTIROBE
150 mg, administer 1-6 capsules every 12 hours for each 60 pounds of
body weight.
ANTIROBE
300 mg, administer 1-6 capsules every 12 hours for each 120 pounds
of body weight.
Liquid
ANTIROBE
AQUADROPS, administer 1-6 mL/10 lbs body weight every 12 hours.
Dogs:
Osteomyelitis
Oral:
5.0-15.0 mg/lb body weight every 12 hours.
Duration:
Treatment with ANTIROBE 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.
Dosage
Schedule:
Capsules
ANTIROBE
25 mg, administer 2-6 capsules every 12 hours for each 10 pounds of
body weight.
ANTIROBE
75 mg, administer 2-6 capsules every 12 hours for each 30 pounds of
body weight.
ANTIROBE
150 mg, administer 2-6 capsules every 12 hours for each 60 pounds of
body weight.
ANTIROBE
300 mg, administer 2-6 capsules every 12 hours for each 120 pounds
of body weight.
Liquid
ANTIROBE
AQUADROPS, administer 2-6 mL/10 lbs body weight every 12 hours.
Cats:
Infected Wounds, Abscesses, and Dental Infections
5.0 - 15.0 mg/lb body
weight once every 24 hours depending on the severity of the condition.
Duration:
Treatment with ANTIROBE AQUADROPS Liquid may be continued up to a
maximum of 14 days if clinical judgment indicates. Treatment of acute
infections should not be continued for more than three to four days if
no clinical response to therapy is seen.
Dosage
Schedule:
ANTIROBE
AQUADROPS, to provide 5.0 mg/lb, administer 1 mL/5 lbs body weight
once every 24 hours; to provide 15.0 mg/lb, administer 3 mL/5 lbs body
weight once every 24 hours.
HOW
SUPPLIED
ANTIROBE Capsules are
available as:
|
25 mg - bottles
of 600 |
NDC 0009-3043-01 |
|
75 mg - bottles
of 200 |
NDC 0009-3044-01 |
|
150 mg - bottles
of 100 |
NDC 0009-3045-01 |
|
150 mg - blister
packages of 100 |
NDC 0009-3045-08 |
|
300 mg - blister
packages of 100 |
NDC 0009-5015-01 |
|
ANTIROBE
AQUADROPS Liquid is available as 20 mL filled in 30 mL bottles
(25 mg/mL) supplied in packers containing 12 cartoned bottles
with direction labels and calibrated dosing droppers. |
NDC 0009-3179-01. |
To report a suspected
adverse reaction or to request a material safety data sheet (MSDS), call
1-800-793-0596.
Store at controlled room
temperature 20° to 25° C (68° to 77° F) [see USP].