V E T E R I N A R Y M E D I C A L S E R V I C E S
E X P L O R A T I O N S i n V e t e r i n a r y M e d i c i n e The Effect of ANTIROBE® Capsules (clindamycin hydrochloride) on Gingival Crevicular Fluid and Immune Mediators in Dogs
Source Material: Zetner K, Pum G, Rausch W-D, Rausch-Fan X-H,Hung ST. Effect of clindamycin hydrochloride on gingival crevicular fluidand immune mediators in beagles. Praktische Tierarzt. 2001;82(1):22-32;
T H E B I G P I C T U R E . Vet Therap. 2002;3(2):177-188. • Dental plaque and gingival indices T H E P R O C E S S O F D I S C O V E R Y . were significantly lower in dogs treated
Periodontitis is a common infection in veterinary practice and the leading
with ANTIROBE (P ≤ 0.0001).
cause of tooth loss in dogs. The condition begins with gingivitis, an inflammation of the gingiva and gums caused by accumulating bacteria. Left unchecked, the multiplying bacteria form plaque, which subsequently
• The volume of gingival crevicular fluid
mineralizes into tartar. Bacteria eventually invade the sulcus, the crevice
(GCF), a reliable indicator for the degree
between the gingiva and the root. (See Figure 1 on page 3.) As the gingivaregress, underlying periodontal structures detach from the root, and pockets
of inflammation, declined significantly
develop.Advancing periodontitis affects all of the periodontal structures,
including cementum, periodontal ligaments, and alveolar bone.
The presence of immune mediators provides early evidence of the inflammatory and degenerative processes of periodontal disease. • Levels of immune mediators decreased
The junctional epithelium and underlying gingival plexus play a vital
significantly after treatment with
role in local defense mechanisms, inflammatory reactions, and gingival
crevicular fluid (GCF) production. As soon as toxins cross the epithelial
junction, they activate the immune system. This provocation increases the volume of GCF and releases numerous immune mediators, includingleukotriene B4 (LTB4), prostaglandin E2 (PGE2), and polymorphonuclear(PMN) elastase. Leukotriene B4 is a powerful proinflammatory agent,especially in the early stage of gingivitis. Prostaglandin E2 increases 2-foldto 3-fold in the GCF of dogs with gingivitis and 5-fold to 6-fold duringactive stages of periodontitis. Along with other immune mediators,PGE2 increases bone destruction. Levels of PMN elastase increase in the GCF of dogs with gingivitis and, in humans, correlate with probedepth and loss of attachment. In this study, Zetner and colleagues evaluated the effect of ANTIROBE Capsules on immune mediators. H O W T H E S T U D Y W A S C O N D U C T E D . W H A T W A S L E A R N E D .
In a double-blind, crossover study, 10 dogs received ANTIROBE®
Compared with untreated controls, 2 weeks of treatment
Capsules (clindamycin hydrochloride) 11 mg/kg per day orally for
with ANTIROBE Capsules decreased the amount of GCF
14 days, and 10 dogs served as untreated controls. Five months later,
by 65% in the first series and 73% in the second series.The plaque
the treatments were reversed. Plaque and gingival indices were assessed
index fell 94% in the first series and 85% in the second series, and
on 6 reference teeth of each patient, and the volume of GCF was
the gingivitis index decreased by 88% in the first series and 87%
measured before and after the 2 study periods.The plaque index
in the second.These positive changes accompanied similar
was scored from 0 to 4,1 as was the gingivitis index.2 Concentrations
reductions in immune mediators.The mean reduction in PGE2
of PGE2, PMN elastase, and LTB4 were determined by ELISA.
was 33% in the first series and 40% in the second. Levels of LTB4
Calculus was removed ultrasonically and the teeth were polished at
declined by 18% in the first series and 24% in the second series.
Mean PMN elastase values were 45% higher before treatmentwith ANTIROBE than after. See Table 1. Table 1. Effects of oral treatment with clindamycin (11 mg/kg) on periodontal variables and immune mediators in beagles with periodontal disease. Control (n = 10) ANTIROBE (n = 10) Variable 32.55 ± 16.5*† 0.17 ± 0.38*† 0.27 ± 0.45*† 29.97 ± 5.38‡ 67.33 ± 7.51* 55.20 ± 8.85‡ Control (n = 10) ANTIROBE (n = 10) Variable 20.30 ± 9.45*† 0.37 ± 0.55*† 0.30 ± 0.46*† 68.62 ± 31.84* 41.21 ± 16.39‡ 65.82 ± 10.29* 50.12 ± 8.03‡ 74.76± 32.92* 41.38 ± 12.42‡
*Significantly different than control group value (P ≤ 0.05). † Significantly different than pretreatment value (P ≤ 0.0001).
‡Significantly different than pretreatment value (P ≤ 0.05). PMN = polymorphonuclear. Data are shown as mean ± standard deviation. R E F E R E N C E S . Figure 1. Illustration of tooth and surrounding structures.
1. Logan EI, Boyce EN. Oral health assessment in dogs: parameters
and methods. J Vet Dent. 1994;11:58-63. T A L K I T O U T .
2. Silness J, Loe H. Periodontal disease in pregnancy. II. Correlation
between oral hygiene and periodontal condition. Acta Odontol Scand. 1964;22:121-135.
Numerous researchers have documented the antimicrobial activity of ANTIROBE®in the mouth.3-5One group also noted
3. Henke CL, Colmery BH. Treating canine dental infections with oral
that ANTIROBE reduces bacteria in the surrounding air during
clindamycin hydrochloride. Vet Med. 1987;82:197-199.
ultrasonic removal of calculus.6 This excellent antimicrobial activity
4. Johnson DM, Erwin ME, Barrett MS, Gooding BB, Jones RN.
likely results from clindamycin’s superior penetration of oral tissues,
Antimicrobial activity of ten macrolide, lincosamine and streptogramin
including saliva, the gingival crevice, and bone.Tissue concentrations
drugs tested against Legionella species. Eur J Clin Microbiol Infect Dis. 1992;11(8):751-755.
of ANTIROBE have been shown to be higher than plasma concentrations.7,8 Professor Zetner postulates that the PGE
5. Mischke R, Amtsberg G, Beckmann G, Schmidt H, Nolte I.
may be a reflection of high concentrations of clindamycin in bone,
Wirksamkeit und Verträglichkeit von Clindamycin als BegleitendeTherapie von Gingivitis und Periodontitis nach Zahnsteinenfernung
which may help reduce decalcification and subsequent inflammation
beim Hund. Kleintierpraxis. 1992;37:423-492.
better than mechanical cleaning alone.ANTIROBE Capsules are contraindicated in animals with a history of hypersensitivity to clindamycin
6. Zetner K, Thiemann G. Die Bedeutung von Clindamycin und
Pilzen bie Oralen Infektionen. Kleintierpraxis. 1993;38:689-760.
7. Burrows GE. Pharmacotherapeutics of macrolides, lincomycins,
and spectinomycin. JAVMA. 1980;176:1072-1077. T H E F I N A L W O R D .
8. ANTIROBE Capsules package insert.
This study showed that treatment with ANTIROBE significantly
9. Gemmell CG, Peterson PK, Schmeling D, Mathews J, Quie PG.
reduced the indices of plaque and gingivitis while also significantly
Antibiotic-induced modification of Bacteroides fragilis and its susceptibility
decreasing levels of destructive immune mediators. ANTIROBE
to phagocytosis by human polymorphonuclear leukocytes. Eur J Clin
is beneficial as an adjunct to cleaning teeth and treating periodontal
disease, because of its direct antimicrobial effect and its ability to potentiate opsonization and phagocytosis.9
did not occur in the parameters evaluated to assess toxicity when comparing groups of treated animals withcontemporary controls. Rats administered clindamycin hydrochloride at 600 mg/kg/day (272.7 mg/lb/day) for six
NDC 0009-3043-01, NDC 0009-3044-01, NDC 0009-3045-01, NDC 0009-3045-08, NDC 0009-5015-01
months tolerated the drug well; however, dogs orally dosed at 600 mg/kg/day (272.7 mg/lb/day) vomited, had
brand of clindamycin hydrochloride capsules, USP
anorexia, and subsequently lost weight. At necropsy these dogs had erosive gastritis and focal areas of necrosisof the mucosa of the gall bladder. ANTIROBE AQUADROPS®
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
brand of clindamycin hydrochloride liquid
hydrochloride (ANTIROBE AQUADROPS Liquid) was tolerated with little evidence of toxicity in domestic shorthair
Caution: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.
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. DESCRIPTION
Gastrointestinal tract upset (soft feces to diarrhea) occurred in control and treated cats with emesis occurring
ANTIROBE Capsules and ANTIROBE AQUADROPS Liquid contain clindamycin hydrochloride which is the
at doses 3x or greater than the minimum recommended therapeutic dose (11 mg/kg/day; 5 mg/lb/day). Lymphocytic
hydrated salt of clindamycin. Clindamycin is a semisynthetic antibiotic produced by a 7(S)-chlorosubstitution of
inflammation of the gallbladder was noted in a greater number of treated cats at the 110 mg/kg/day (50 mg/lb/day)
the 7(R)-hydroxyl group of a naturally produced antibiotic produced by Streptomyces lincolnensis var. lincolnensis.
dose level than for control cats. No other effects were noted. Safety in gestating queens or breeding male cats
ANTIROBE Capsules (For Use in Dogs Only):
25 mg Capsule, each yellow and white capsule contains clindamycin hydrochloride equivalent to 25 mg of INDICATIONS
ANTIROBE (brand of clindamycin hydrochloride) Capsules (for use in dogs only) and AQUADROPS Liquid
75 mg Capsule, each green capsule contains clindamycin hydrochloride equivalent to 75 mg of clindamycin.
(for use in dogs and cats) are indicated for the treatment of infections caused by susceptible strains of the
150 mg Capsule, each light blue and green capsule contains clindamycin hydrochloride equivalent to 150 mg
designated microorganisms in the specific conditions listed below:
Dogs: Skin infections (wounds and abscesses) due to coagulase positive staphylococci (Staphylococcus 300 mg Capsule, each light blue capsule contains clindamycin hydrochloride equivalent to 300 mg of clindamycin. aureus or Staphylococcus intermedius). Deep wounds and abscesses due to Bacteroides fragilis, Prevotella
ANTIROBE AQUADROPS Liquid (For Use in Dogs and Cats) is a palatable formulation intended for oral
melaninogenicus, Fusobacterium necrophorum and Clostridium perfringens. Dental infections due to
administration. Each mL of ANTIROBE AQUADROPS contains clindamycin hydrochloride equivalent to 25 mg
Staphylococcus aureus, Bacteroides fragilis, Prevotella melaninogenicus, Fusobacterium necrophorum and
clindamycin; and ethyl alcohol, 8.64%. Clostridium perfringens. Osteomyelitis due to Staphylococcus aureus, Bacteroides fragilis, Prevotella melaninogenicus, Fusobacterium necrophorum and Clostridium perfringens. Site and Mode of Action: Clindamycin is an inhibitor of protein synthesis in the bacterial cell. The site of Cats: Skin infections (wounds and abscesses) due to Staphylococcus aureus, Staphylococcus intermedius
binding appears to be in the 5OS sub-unit of the ribosome. Binding occurs to the soluble RNA fraction of certain
and Streptococcus spp. Deep wounds and infections due to Clostridium perfringens and Bacteroides fragilis.
ribosomes, thereby inhibiting the binding of amino acids to those ribosomes. Clindamycin differs from cell wall
Dental infections due to Staphylococcus aureus, Staphylococcus intermedius, Streptococcus spp., Clostridium
inhibitors in that it causes irreversible modification of the protein-synthesizing subcellular elements at the ribosomal
perfringens and Bacteroides fragilis. CONTRAINDICATIONS MICROBIOLOGY: Clindamycin is a lincosaminide antimicrobial agent with activity against a wide variety of
ANTIROBE Capsules and ANTIROBE AQUADROPS Liquid are contraindicated in animals with a history of
aerobic and anaerobic bacterial pathogens. Clindamycin is a bacteriostatic compound that inhibits bacterial
hypersensitivity to preparations containing clindamycin or lincomycin.
protein synthesis by binding to the 50S ribosomal subunit. The minimum inhibitory concentrations (MICs) of
Because of potential adverse gastrointestinal effects, do not administer to rabbits, hamsters, guinea pigs, horses,
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 theNational Committee for Clinical Laboratory Standards (NCCLS). WARNINGS
Keep out of reach of children. Not for human use. Table 1. Clindamycin MIC Values (µg/mL) from Diagnostic Laboratory Survey Data Evaluating Canine PRECAUTIONS Pathogens in the U.S. During 1998-991
During prolonged therapy of one month or greater, periodic liver and kidney function tests and blood counts
Number of Organism Isolates
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 animalsreceiving 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 noresponse to therapy is seen. Dosage Schedule: Capsules
1 The correlation between the in vitro susceptibility data and clinical response has not been determined. ANTIROBE 25 mg, administer 1-6 capsules every 12 hours for each 10 pounds of body weight.
2 Soft Tissue/Wound: includes samples labeled wound, abscess, aspirate, exudates, draining tract, lesion, and mass
ANTIROBE 75 mg, administer 1-6 capsules every 12 hours for each 30 pounds of body weight.
3 Osteomyelitis/Bone: includes samples labeled bone, fracture, joint, tendon
ANTIROBE 150 mg, administer 1-6 capsules every 12 hours for each 60 pounds of body weight.
4 No range, all isolates yielded the same value
ANTIROBE 300 mg, administer 1-6 capsules every 12 hours for each 120 pounds of body weight.
5 Dermal/Skin: includes samples labeled skin, skin swab, biopsy, incision, lip
ANTIROBE AQUADROPS, administer 1-6 mL/10 lbs body weight every 12 hours. 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 Dogs: Osteomyelitis Oral: 5.0-15.0 mg/lb body weight every 12 hours. Number of Duration: Treatment with ANTIROBE is recommended for a minimum of 28 days. Treatment should not be Organism Isolates
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.
The correlation between the in vitro susceptibility data and clinical response has not been determined. PHARMACOLOGY ANTIROBE AQUADROPS, administer 2-6 mL/10 lbs body weight every 12 hours. Absorption: Clindamycin hydrochloride is rapidly absorbed from the Cats: Infected Wounds, Abscesses, and Dental Infections
canine and feline gastrointestinal tract.
5.0 - 15.0 mg/lb body weight once every 24 hours depending on the severity of the condition. Dog Serum Levels: Serum levels at or above 0.5 µg/mL can be Duration: Treatment with ANTIROBE AQUADROPS Liquid may be continued up to a maximum of 14 days if
maintained by oral dosing at a rate of 2.5 mg/lb of clindamycin
clinical judgment indicates. Treatment of acute infections should not be continued for more than three to four
hydrochloride every 12 hours. This same study revealed that average
days if no clinical response to therapy is seen.
peak serum concentrations of clindamycin occur 1 hour and 15 minutes
after oral dosing. The elimination half-life for clindamycin in dog serum
ANTIROBE AQUADROPS, to provide 5.0 mg/lb, administer 1 mL/5 lbs body weight once every 24 hours; to
was approximately 5 hours. There was no bioactivity accumulation after
provide 15.0 mg/lb, administer 3 mL/5 lbs body weight once every 24 hours.
a regimen of multiple oral doses in healthy dogs. Cat Serum Levels: Serum levels at or above 0.5 µg/mL can be HOW SUPPLIED
maintained by oral dosing at a rate of 2.5 mg/lb of clindamycin
hydrochloride every 24 hours. The average peak serum concentration
25 mg - bottles of 600 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 0009-3043-01
of clindamycin occurs approximately 1 hour after oral dosing. The
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.
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]. METABOLISM AND EXCRETION ANTIROBE Capsules ANTIROBE AQUADROPS
Extensive studies of the metabolism and excretion of clindamycin
hydrochloride administered orally in animals and humans have shown
Pharmacia & Upjohn Company Pharmacia & Upjohn Company
that unchanged drug and bioactive and bioinactive metabolites are
excreted in urine and feces. Almost all of the bioactivity detected in
By Patheon YM Inc.
serum after ANTIROBE product administration is due to the parent
813 805 712
molecule (clindamycin). Urine bioactivity, however, reflects a mixture of
clindamycin and active metabolites, especially N-dimethyl clindamycin
TOXICOLOGY AND SAFETY 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
2002 Pharmacia Corporation. All rights reserved.
1. Herrmann MK, Kertesz T, Gsänger T, Bloch E, Pollul G, Bouabdallaoui M, Strauss A, Herrmann M, Christiansen H, Wolff HA, Hess CF, Hille A . Gold marker displacement due to needle insertion during HDR-brachytherapy for treatment of prostate cancer: a prospective cone beam computed tomography and kilovoltage on-board imaging (kV-OBI) study. Radiat Oncol. 2012 Feb 20;7:24. 2. Schirmer MA,
Mom-to-Be Info We are pleased that you have chosen Southeast Women’s Center to work as a partner with you in providing your prenatal care. Good prenatal care is extremely important for a healthy, safe and happy pregnancy. It requires your knowledge and cooperation as well as the know-how and vigilance of your caregivers. You play the most important part in the health and well-being of bo