fections caused by susceptible strains of the designated organisms in the conditions listed below: lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by anaerobes, streptococcus pneumoniae , other streptococci (except e. faecalis ), and staphylococcus aureus . skin and skin structure infections caused by streptococcus pyogenes , staphylococcus aureus , and anaerobes. gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes. intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms. septicemia caused by staphylococcus aureus , streptococci (except enterococcus faecalis ), and susceptible anaerobes. bone and joint infections including acute hematogenous osteomyelitis caused by staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms. to reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin injection, usp and other antibacterial drugs, clindamycin injection, usp should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

nued. appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of c. difficile , and surgical evaluation should be instituted as clinically indicated. anaphylactic and severe hypersensitivity reactions anaphylactic shock and anaphylactic reactions have been reported (see adverse reactions ). severe hypersensitivity reactions, including severe skin reactions such as toxic epidermal necrolysis (ten), drug reaction with eosinophilia and systemic symptoms (dress), and stevens-johnson syndrome (sjs), some with fatal outcome, have been reported (see adverse reactions ). in case of such an anaphylactic or severe hypersensitivity reaction, discontinue treatment permanently and institute appropriate therapy. a careful inquiry should be made concerning previous sensitivities to drugs and other allergens. benzyl alcohol toxicity in pediatric patients (“gasping syndrome”) this product contains benzyl alcohol as a preservative. the preservative benzyl alcohol has been associated with serious adverse events, including the “gasping syndrome”, and death in pediatric patients. although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. the risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys' capacity to detoxify the chemical. premature and low birth weight infants may be more likely to develop toxicity. usage in meningitis – since clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis.

ution for iv use and iv infusion rates ). alternatively, drug may be administered in the form of a single rapid infusion of the first dose followed by continuous iv infusion as follows: to maintain serum clindamycin levels rapid infusion rate maintenance infusion rate above 4 mcg/ml above 5 mcg/ml above 6 mcg/ml 10 mg/min for 30 min 15 mg/min for 30 min 20 mg/min for 30 min 0.75 mg/min 1 mg/min 1.25 mg/min neonates (less than 1 month) 15 to 20 mg/kg/day in 3 to 4 equal doses. the lower dosage may be adequate for small prematures. pediatric patients (1 month of age to 16 years) parenteral iv administration 20 to 40 mg/kg/day in 3 or 4 equal doses. the higher doses would be used for more severe infections. as an alternative to dosing on a body weight basis, pediatric patients may be dosed on the basis of square meters body surface: 350 mg/m 2 /day for serious infections and 450 mg/m 2 /day for more severe infections. parenteral therapy may be changed to oral clindamycin flavored granules (clindamycin palmitate hydrochloride) or clindamycin capsules (clindamycin hydrochloride) when the condition warrants and at the discretion of the physician. in cases of β-hemolytic streptococcal infections, treatment should be continued for at least 10 days. dilution for iv use and iv infusion rates clindamycin injection, usp must be diluted prior to iv administration. the concentration of clindamycin in diluent for infusion should not exceed 18 mg per ml. infusion rates should not exceed 30 mg per minute. the usual infusion dilutions and rates are as follows: dose diluent time 300 mg 600 mg 900 mg 1,200 mg 50 ml 50 ml 50 to 100 ml 100 ml 10 min 20 min 30 min 40 min administration of more than 1,200 mg in a single 1-hour infusion is not recommended. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. dilution and compatibility physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of clindamycin injection, usp in iv solutions containing sodium chloride, glucose, calcium or potassium, and solutions containing vitamin b complex in concentrations usually used clinically. no incompatibility has been demonstrated with the antibiotics cephalothin, kanamycin, gentamicin, penicillin or carbenicillin. the following drugs are physically incompatible with clindamycin phosphate: ampicillin sodium, phenytoin sodium, barbiturates, aminophylline, calcium gluconate, and magnesium sulfate. the compatibility and duration of stability of drug admixtures will vary depending on concentration and other conditions. for current information regarding compatibilities of clindamycin phosphate under specific conditions, please visit www.fresenius-kabi.us or call fresenius kabi usa, llc toll-free at 1-800-551-7176. physico-chemical stability of diluted solutions of clindamycin room temperature: 6, 9 and 12 mg/ml (equivalent to clindamycin base) in 5% dextrose injection, 0.9% sodium chloride injection, or lactated ringers injection in glass bottles or minibags, demonstrated physical and chemical stability for at least 16 days at 25°c. also, 18 mg/ml (equivalent to clindamycin base) in 5% dextrose injection, in minibags, demonstrated physical and chemical stability for at least 16 days at 25°c. refrigeration: 6, 9 and 12 mg/ml (equivalent to clindamycin base) in 5% dextrose injection, 0.9% sodium chloride injection, or lactated ringers injection in glass bottles or minibags, demonstrated physical and chemical stability for at least 32 days at 4°c. important: this chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time. good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible. frozen: 6, 9 and 12 mg/ml (equivalent to clindamycin base) in 5% dextrose injection, 0.9% sodium chloride injection, or lactated ringers injection in minibags demonstrated physical and chemical stability for at least eight weeks at -10°c. frozen solutions should be thawed at room temperature and not refrozen.

fusion rate maintenance infusion rate above 4 mcg/ml above 5 mcg/ml above 6 mcg/ml 10 mg/min for 30 min 15 mg/min for 30 min 20 mg/min for 30 min 0.75 mg/min 1 mg/min 1.25 mg/min

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soon after preparation as is feasible. frozen: 6, 9 and 12 mg/ml (equivalent to clindamycin base) in 5% dextrose injection, 0.9% sodium chloride injection, or lactated ringers injection in minibags demonstrated physical and chemical stability for at least eight weeks at -10°c. frozen solutions should be thawed at room temperature and not refrozen.

d with clindamycin. anaphylactic shock, anaphylactic reaction and hypersensitivity have also been reported (see warnings ). skin and mucous membranes pruritus, vaginitis, angioedema and rare instances of exfoliative dermatitis have been reported (see hypersensitivity reactions ). liver jaundice and abnormalities in liver function tests have been observed during clindamycin therapy. renal although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed. hematopoietic transient neutropenia (leukopenia) and eosinophilia have been reported. reports of agranulocytosis and thrombocytopenia have been made. no direct etiologic relationship to concurrent clindamycin therapy could be made in any of the foregoing. immune system drug reaction with eosinophilia and systemic symptoms (dress) cases have been reported. local reactions injection site irritation, pain, induration and sterile abscess have been reported after intramuscular injection and thrombophlebitis after intravenous infusion. reactions can be minimized or avoided by giving deep intramuscular injections and avoiding prolonged use of indwelling intravenous catheters. musculoskeletal polyarthritis cases have been reported. cardiovascular cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration (see dosage and administration ).

ive clindamycin is about 3 hours in adults and 2½ hours in pediatric patients. special populations renal/hepatic impairment the elimination half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function. hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. dosage schedules need not be modified in the presence of mild or moderate renal or hepatic disease. use in elderly pharmacokinetic studies in elderly volunteers (61 to 79 years) and younger adults (18 to 39 years) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentration-time curve) after iv administration of clindamycin phosphate. after oral administration of clindamycin hydrochloride, elimination half-life is increased to approximately 4.0 hours (range 3.4 to 5.1 h) in the elderly, compared to 3.2 hours (range 2.1 to 4.2 h) in younger adults. the extent of absorption, however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function 1 . serum assays for active clindamycin require an inhibitor to prevent in vitro hydrolysis of clindamycin phosphate. table 1. average peak and trough serum concentrations of active clindamycin after dosing with clindamycin phosphate dosage regimen peak mcg/ml trough mcg/ml healthy adult males (post equilibrium) 600 mg iv in 30 min q6h 10.9 2.0 600 mg iv in 30 min q8h 10.8 1.1 900 mg iv in 30 min q8h 14.1 1.7 pediatric patients (first dose)* 5 to 7 mg/kg iv in 1 hour 10 - *data in this group from patients being treated for infection. microbiology mechanism of action clindamycin inhibits bacterial protein synthesis by binding to the 23s rna of the 50s subunit of the ribosome. clindamycin is bacteriostatic. resistance resistance to clindamycin is most often caused by modification of specific bases of the 23s ribosomal rna. cross-resistance between clindamycin and lincomycin is complete. because the binding sites for these antibacterial drugs overlap, cross-resistance is sometimes observed among lincosamides, macrolides and streptogramin b. macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria. macrolide-resistant isolates of staphylococci and beta-hemolytic streptococci should be screened for induction of clindamycin resistance using the d-zone test. antimicrobial activity clindamycin has been shown to be active against most of the isolates of the following microorganisms, both in vitro and in clinical infections, as described in the indications and usage section. gram-positive bacteria staphylococcus aureus (methicillin-susceptible strains) streptococcus pneumoniae (penicillin-susceptible strains) streptococcus pyogenes anaerobic bacteria clostridium perfringens fusobacterium necrophorum fusobacterium nucleatum peptostreptococcus anaerobius prevotella melaninogenica at least 90% of the microorganisms listed below exhibit in vitro minimum inhibitory concentrations (mics) less than or equal to the clindamycin susceptible mic breakpoint for organisms of a similar type to those shown in table 2. however, the efficacy of clindamycin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials. gram-positive bacteria staphylococcus epidermidis (methicillin-susceptible strains) streptococcus agalactiae streptococcus anginosus streptococcus mitis streptococcus oralis anaerobic bacteria actinomyces israelii clostridium clostridioforme eggerthella lenta finegoldia (peptostreptococcus) magna micromonas (peptostreptococcus) micros prevotella bivia prevotella intermedia propionibacterium acnes susceptibility testing methods when available, the clinical microbiology laboratory should provide cumulative in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. these reports should aid the physician in selecting an antibacterial drug for treatment. dilution techniques quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (mics). these mics provide estimates of the susceptibility of bacteria to antimicrobial compounds. the mics should be determined using a standardized test method 2,3 (broth and/or agar). the mic values should be interpreted according to the criteria provided in table 2. diffusion techniques quantitative methods that require the measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. the zone size should be determined using a standardized method 2,5 . this procedure uses paper disks impregnated with 2 mcg of clindamycin to test the susceptibility of bacteria to clindamycin. the disk diffusion breakpoints are provided in table 2. anaerobic techniques for anaerobic bacteria, the susceptibility to clindamycin can be determined by a standardized test method 2,4 . the mic values obtained should be interpreted according to the criteria provided in table 2. table 2. susceptibility test interpretive criteria for clindamycin pathogen susceptibility interpretive criteria minimal inhibitory concentrations (mic in mcg/ml) disk diffusion ( zone diameters in mm) staphylococcus spp. s ≤ 0.5 i 1 to 2 r ≥ 4 s ≥ 21 i 15 to 20 r ≤ 14 streptococcus pneumoniae and other streptococcus spp. ≤ 0.25 0.5 ≥ 1 ≥ 19 16 to 18 ≤ 15 anaerobic bacteria ≤ 2 4 ≥ 8 na na na na=not applicable a report of susceptible (s) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. a report of intermediate (i) indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. this category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. this category also provides a buffer zone that prevents small, uncontrolled technical factors from causing major discrepancies in interpretation. a report of resistant (r) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the infection site; other therapy should be selected. quality control standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test 2,3,4,5 . standard clindamycin powder should provide the mic ranges in table 3. for the disk diffusion technique using the 2 mcg clindamycin disk the criteria provided in table 2 should be achieved. table 3. acceptable quality control ranges for clindamycin qc strain acceptable quality control ranges minimum inhibitory concentration range (mcg/ml) disk diffusion range ( zone diameters in mm) enterococcus faecalis 1 atcc 29212 4 to 16 na staphylococcus aureus atcc 29213 0.06 to 0.25 na staphylococcus aureus atcc 25923 na 24 to 30 streptococcus pneumoniae atcc 49619 0.03 to 0.12 19 to 25 bacteroides fragilis atcc 25285 0.5 to 2 na bacteroides thetaiotaomicron atcc 29741 2 to 8 na clostridium difficile 2 atcc 700057 2 to 8 na eggerthella lenta atcc 43055 0.06 to 0.25 na 1 enterococcus faecalis has been included in this table for quality control purposes only. 2 quality control for c. difficile is performed using the agar dilution method only, all other obligate anaerobes may be tested by either broth microdilution or agar dilution methods. na=not applicable atcc ® is a registered trademark of the american type culture collection.

positive bacteria staphylococcus aureus (methicillin-susceptible strains) streptococcus pneumoniae (penicillin-susceptible strains) streptococcus pyogenes anaerobic bacteria clostridium perfringens fusobacterium necrophorum fusobacterium nucleatum peptostreptococcus anaerobius prevotella melaninogenica at least 90% of the microorganisms listed below exhibit in vitro minimum inhibitory concentrations (mics) less than or equal to the clindamycin susceptible mic breakpoint for organisms of a similar type to those shown in table 2. however, the efficacy of clindamycin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials. gram-positive bacteria staphylococcus epidermidis (methicillin-susceptible strains) streptococcus agalactiae streptococcus anginosus streptococcus mitis streptococcus oralis anaerobic bacteria actinomyces israelii clostridium clostridioforme eggerthella lenta finegoldia (peptostreptococcus) magna micromonas (peptostreptococcus) micros prevotella bivia prevotella intermedia propionibacterium acnes susceptibility testing methods when available, the clinical microbiology laboratory should provide cumulative in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. these reports should aid the physician in selecting an antibacterial drug for treatment. dilution techniques quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (mics). these mics provide estimates of the susceptibility of bacteria to antimicrobial compounds. the mics should be determined using a standardized test method 2,3 (broth and/or agar). the mic values should be interpreted according to the criteria provided in table 2. diffusion techniques quantitative methods that require the measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. the zone size should be determined using a standardized method 2,5 . this procedure uses paper disks impregnated with 2 mcg of clindamycin to test the susceptibility of bacteria to clindamycin. the disk diffusion breakpoints are provided in table 2. anaerobic techniques for anaerobic bacteria, the susceptibility to clindamycin can be determined by a standardized test method 2,4 . the mic values obtained should be interpreted according to the criteria provided in table 2. table 2. susceptibility test interpretive criteria for clindamycin pathogen susceptibility interpretive criteria minimal inhibitory concentrations (mic in mcg/ml) disk diffusion ( zone diameters in mm) staphylococcus spp. s ≤ 0.5 i 1 to 2 r ≥ 4 s ≥ 21 i 15 to 20 r ≤ 14 streptococcus pneumoniae and other streptococcus spp. ≤ 0.25 0.5 ≥ 1 ≥ 19 16 to 18 ≤ 15 anaerobic bacteria ≤ 2 4 ≥ 8 na na na na=not applicable a report of susceptible (s) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. a report of intermediate (i) indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. this category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. this category also provides a buffer zone that prevents small, uncontrolled technical factors from causing major discrepancies in interpretation. a report of resistant (r) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the infection site; other therapy should be selected. quality control standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test 2,3,4,5 . standard clindamycin powder should provide the mic ranges in table 3. for the disk diffusion technique using the 2 mcg clindamycin disk the criteria provided in table 2 should be achieved. table 3. acceptable quality control ranges for clindamycin qc strain acceptable quality control ranges minimum inhibitory concentration range (mcg/ml) disk diffusion range ( zone diameters in mm) enterococcus faecalis 1 atcc 29212 4 to 16 na staphylococcus aureus atcc 29213 0.06 to 0.25 na staphylococcus aureus atcc 25923 na 24 to 30 streptococcus pneumoniae atcc 49619 0.03 to 0.12 19 to 25 bacteroides fragilis atcc 25285 0.5 to 2 na bacteroides thetaiotaomicron atcc 29741 2 to 8 na clostridium difficile 2 atcc 700057 2 to 8 na eggerthella lenta atcc 43055 0.06 to 0.25 na 1 enterococcus faecalis has been included in this table for quality control purposes only. 2 quality control for c. difficile is performed using the agar dilution method only, all other obligate anaerobes may be tested by either broth microdilution or agar dilution methods. na=not applicable atcc ® is a registered trademark of the american type culture collection.