Clindamycin hydrochloride liquid
Clinsol Liquid (for use in dogs and cats) is 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
ecrophorum 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.
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,
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
Clinsol Liquid contains 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.
Clinsol Liquid (For Use in Dogs and Cats) is a palatable
formulation intended for oral administration. Each mL of Clinsol Liquid
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 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 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 50S
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 |
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 |
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 Clindamycin Hydrochloride to Dogs
Cat Serum Levels: Serum levels at or
above 0.5 µg/mL can be maintained by oral dosing at a rate of 5 mg/lb of
clindamycin hydrochloride liquid 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 Clinsol Liquid 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 clindamycin hydrochloride administration is due to the
parent molecule (clindamycin). Urine bioactivity, however, reflects a
mixture of clindamycin and active metabolites, especially N-dimethyl
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
capsules 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 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 gall bladder.
Safety in gestating bitches or breeding males has not
been established.
Cat Data: The recommended daily
therapeutic dose range for clindamycin hydrochloride (Clinsol Liquid) is
11 to 33 mg/kg/day (5 to 15 mg/lb/day) depending on the severity of the
condition. Clindamycin hydrochloride (Clinsol 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
(11mg/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) dose
level than for control cats. No other effects were noted. Safety in
gestating queens or breeding male cats has not been established.
CONTRAINDICATIONS
Clinsol Liquid is 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 clindamycin hydrochloride occasionally
results in overgrowth of non-susceptible organisms such as clostridia
and yeasts. Therefore, the administration of Clinsol Liquid 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, Clinsol Liquid 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 1-800-338-3659.
DOSAGE AND ADMINISTRATION
Dogs:
Infected Wounds, Abscesses, and Dental
Infections
Oral: 2.5-15.0 mg/lb (1-6 mL/10 lbs)
body weight every 12 hours.
Duration: Treatment with clindamycin
hydrochloride 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:
Clinsol Liquid, administer 1-6 mL/10
pounds body weight every 12 hours.
Dogs:
Osteomyelitis
Oral: 5.0-15.0 mg/lb (2-6 mL/10 lbs)
body weight every 12 hours.
Duration: Treatment with clindamycin
hydrochloride 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:
Clinsol Liquid, administer 2-6 mL/10
pounds body weight every 12 hours.
Cats:
Infected Wounds, Abscesses, and Dental
Infections
5.0-15.0 mg/lb (1-3 mL/5 lbs) body weight once every 24
hours depending on the severity of the condition.
Duration: Treatment with clindamycin
hydrochloride 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:
Clinsol Liquid, 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
Virbac: Clinsol 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-051311-500-25.
To report a suspected adverse reaction or to request a
material safety data sheet (MSDS), call 1-800-338-3659.
Store at controlled room temperature 20°
to 25° C (68° to 77° F) [see USP].
Caution: Federal (USA) law restricts
this drug to use by or on the order of a licensed veterinarian.
For Use in Animals Only