Clindamycin

Generic Name: Clindamycin phosphate
Dosage Form: Injection

For Intravenous Use Only

NOT FOR DIRECT INFUSION

PHARMACY BULK VIAL

Rx ONLY

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Clindamycin injection and other antibacterial drugs, Clindamycin injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Clindamycin Description

Clindamycin Injection contains Clindamycin phosphate, a water-soluble ester of Clindamycin and phosphoric acid. Each mL contains the equivalent of 150 mg Clindamycin, 0.5 mg disodium edetate and 9.45 mg benzyl alcohol added as preservative. Clindamycin is a semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent compound lincomycin. The pH range is 5.5 to 7.0.

The chemical name of Clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl- trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate).

The molecular formula is C18H34ClN2O8PS and the molecular weight is 504.97. The structural formula is represented below:

A Pharmacy Bulk Package is a container of a sterile preparation for intravenous use that contains many single doses. The contents are intended for use in a pharmacy admixture service program, utilizing a sterile transfer device and are restricted to the preparation of admixtures for intravenous infusion. FURTHER DILUTION IS REQUIRED BEFORE USE. (See DOSAGE AND ADMINISTRATION.)

Clindamycin - Clinical Pharmacology

Biologically inactive Clindamycin phosphate is rapidly converted to active Clindamycin.

By the end of short-term intravenous infusion, peak serum levels of active Clindamycin are reached. Biologically inactive Clindamycin phosphate disappears rapidly from the serum; the average elimination half-life is 6 minutes; however, the serum elimination half-life of active Clindamycin is about 3 hours in adults and 2 1/2 hours in pediatric patients.

After intramuscular injection of Clindamycin phosphate, peak levels of active Clindamycin are reached within 3 hours in adults and 1 hour in pediatric patients. Serum level curves may be constructed from IV peak serum levels as given in Table 1 by application of elimination half-lives listed above.

Serum levels of Clindamycin can be maintained above the in vitro minimum inhibitory concentrations for most indicated organisms by administration of Clindamycin phosphate every 8 to 12 hours in adults and every 6 to 8 hours in pediatric patients, or by continuous intravenous infusion. An equilibrium state is reached by the third dose.

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.

No significant levels of Clindamycin are attained in the cerebrospinal fluid even in the presence of inflamed meninges.

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.

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

* Data in this group from patients being treated for infection.
Dosage Regimen	Peak mcg/mL	Trough mcg/mL
Healthy Adult Males (Post equilibrium) 600 mg IV in 30 min q6h 600 mg IV in 30 min q8h 900 mg IV in 30 min q8h Pediatric Patients (first dose)* 5-7 mg/kg IV in 1 hour	10.9 10.8 14.1 10	2.0 1.1 1.7

Microbiology

Clindamycin inhibits bacterial protein synthesis by binding to the 50S subunit of the ribosome. It has activity against Gram-positive aerobes and anaerobes as well as the Gram-negative anaerobes. Clindamycin is bacteriostatic. Cross-resistance between Clindamycin and lincomycin is complete. Antagonism in vitro has been demonstrated between Clindamycin and erythromycin.

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 aerobes

 

Staphylococcus aureus (methicillin-susceptible strains)

 

Streptococcus pneumoniae (penicillin-susceptible strains)

 

Streptococcus pyogenes

Anaerobes

 

Prevotella melaninogenica

 

Fusobacterium necrophorum

 

Fusobacterium nucleatum

 

Peptostreptococcus anaerobius

 

Clostridium perfringens

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Clindamycin. However, the safety and effectiveness of Clindamycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Gram-positive aerobes

 

Staphylococcus epidermidis (methicillin-susceptible strains)

 

Streptococcus agalactiae

 

Streptococcus anginosus

 

Streptococcus oralis

 

Streptococcus mitis

Anaerobes

 

Prevotella intermedia

 

Prevotella bivia

 

Propionibacterium acnes

 

Micromonas (“Peptostreptococcus”) micros

 

Finegoldia (“Peptostreptococcus”) magna

 

Actinomyces israelii

 

Clostridium clostridioforme

 

Eubacterium lentum

SUSCEPTIBILITY TESTING METHODS

NOTE: Susceptibility testing by dilution methods requires the use of Clindamycin susceptibility powder.

When available, the results of in vitro susceptibility tests should be provided 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 the most effective antimicrobial.

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 procedure. Standardized procedures are based on a dilution method (broth and agar) 1, 2, 3 or equivalent with standardized inoculum concentrations and standardized concentrations of Clindamycin powder. The MIC values should be interpreted according to the criteria provided in Table 2.

Diffusion Techniques: Quantitative methods that required the measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2, 3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 2 mcg of Clindamycin to test the susceptibility of microorganisms to Clindamycin. The disk diffusion interpretive criteria are provided in Table 2.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” 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” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of quality control microorganisms to control the technical aspects of the test procedures. Standard Clindamycin powder should provide the following range of values noted in Table 3. NOTE: Quality control microorganisms are specific strains of organisms with intrinsic biological properties relating to resistance mechanisms and their genetic expression within bacteria; the specific strains used for microbiological quality control are not clinically significant.

Table 2. Susceptibility interpretive Criteria for Clindamycin

* These interpretive standards for S. pneumoniae and other Streptococcus spp. are applicable only to tests performed by broth microdilution using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood inoculated with a direct colony suspension and incubated in ambient air at 35°C for 20 to 24 hours. † These zone diameter interpretive standards are applicable only to tests performed using Mueller-Hinton agar supplemented with 5% sheep blood inoculated with a direct colony suspension and incubated in 5% CO2 at 35°C for 20 to 24 hours. ‡ These interpretive criteria are for all anaerobic bacterial pathogens; no organism specific interpretive criteria are available. NA= not applicable.
Pathogen	Susceptibility Interpretive Criteria
	Minimal Inhibitory Concentrations (MIC in mcg/mL)			Disk Diffusion (Zone Diameters in mm)
	S	I	R	S	I	R
Staphylococcus spp.	≤0.5	1-2	≥4	≥21	15-20	≤14
Streptococcus pneumoniae and other Streptococcus spp.	≤0.25*	0.5	≥1	≥19†	16-18	≤15
Anaerobic Bacteria‡	≤2	4	≥8	NA	NA	NA

 Table 3. Acceptable Quality Control Ranges for Clindamycin to be Used in Validation of Susceptibility Test Results

NA = Not applicable
* This organism may be used for validation of susceptibility test results when testing Streptococcus spp. other than S. pneumoniae. † This quality control range for S. pneumoniaeis applicable only to tests performed by broth microdilution using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood inoculated with a direct colony suspension and incubated in ambient air at 35°C for 20 to 24 hours. ‡ This quality control zone diameter range is applicable only to tests performed using Mueller-Hinton agar supplemented with 5% sheep blood inoculated with a direct colony suspension and incubated in 5% CO2 at 35°C for 20 to 24 hours.
QC Strain	Acceptable Quality Control Ranges
	Minimum Inhibitory Concentration (MIC in mcg/mL)	Disk Diffusion (Zone Diameters in mm)
When Testing Aerobic Pathogens
Staphylococcus aureus ATCC 29213	0.06-0.25	NA
Staphylococcus aureus ATCC 25923	NA	24-30
Streptococcus pneumoniae ATCC 49619*	0.03-0.12†	19-25‡
When Testing Strict Anaerobes
Bacteroides fragilis ATCC 25285	0.5-2	NA
Bacteroides thetaiotaomicron ATCC 29741	2-8	NA
Eubacterium lentum ATCC 43055	0.06-0.25	NA

ATCC® is a registered trademark of the American Type Culture Collection

Indications and Usage for Clindamycin

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Clindamycin injection and other antibacterial drugs, Clindamycin injection 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.

Clindamycin injection is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.

Clindamycin injection is also indicated in the treatment of serious infections due to susceptible strains of streptococci, pneumococci, and staphylococci. Its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgment of the physician, a penicillin is inappropriate. Because of the risk of antibiotic-associated pseudomembranous colitis, as described in the WARNING box, before selecting Clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).

Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to Clindamycin.

Indicated surgical procedures should be performed in conjunction with antibiotic therapy.

Clindamycin injection is indicated in the treatment of serious infections 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.

Contraindications

This drug is contraindicated in individuals with a history of hypersensitivity to preparations containing Clindamycin or lincomycin.

Warnings

See WARNING box.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Clindamycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis.

A careful inquiry should be made concerning previous sensitivities to drugs and other allergens.

This product contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants. (See PRECAUTIONS– Pediatric Use.)

Usage in Meningitis–Since Clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis.

SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN AND INTRAVENOUS CORTICOSTEROIDS SHOULD ALSO BE ADMINISTERED AS INDICATED.

Precautions

General

Prescribing Clindamycin injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Review of experience to date suggests that a subgroup of older patients with associated severe illness may tolerate diarrhea less well. When Clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency.

Clindamycin injection should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Clindamycin injection should be prescribed with caution in atopic individuals.

Certain infections may require incision and drainage or other indicated surgical procedures in addition to antibiotic therapy.

The use of Clindamycin injection may result in overgrowth of nonsusceptible organisms–particularly yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation.

Clindamycin injection should not be injected intravenously undiluted as a bolus, but should be infused over at least 10 to 60 minutes as directed in the DOSAGE AND ADMINISTRATION section.

Clindamycin dosage modification may not be necessary in patients with renal disease. In patients with moderate to severe liver disease, prolongation of Clindamycin half-life has been found. However, it was postulated from studies that when given every eight hours, accumulation should rarely occur. Therefore, dosage modification in patients with liver disease may not be necessary. However, periodic liver enzyme determinations should be made when treating patients with severe liver disease.

Information for Patients

Patients should be counseled that antibacterial drugs including Clindamycin injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Clindamycin injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Clindamycin injection or other antibacterial drugs in the future.

Laboratory Tests

During prolonged therapy periodic liver and kidney function tests and blood counts should be performed.

Drug Interactions

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

Antagonism has been demonstrated between Clindamycin and erythromycin in vitro. Because of possible clinical significance, the two drugs should not be administered concurrently.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed with Clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 1.1 times the highest recommended adult human dose based on mg/m2) revealed no effects on fertility or mating ability.

Pregnancy

Teratogenic Effects; Pregnancy Category B

Reproduction studies performed in rats and mice using oral doses of Clindamycin up to 600 mg/kg/day (2.1 and 1.1 times the highest recommended adult human dose based on mg/m2, respectively) or subcutaneous doses of Clindamycin up to 250 mg/kg/day (0.9 and 0.5 times the highest recommended adult human dose based on mg/m2, respectively) revealed no evidence of teratogenicity.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Clindamycin has been reported to appear in breast milk in the range of 0.7 to 3.8 mcg/mL at dosages of 150 mg orally to 600 mg intravenously.

Because of the potential for adverse reactions due to Clindamycin in neonates (see Pediatric Use), the decision to discontinue the drug should be made, taking into account the importance of the drug to the mother.

Pediatric Use

When Clindamycin injection is administered to the pediatric population (birth to 16 years) appropriate monitoring of organ system functions is desirable.

Usage in Newborns and Infants

This product contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants.

Geriatric Use

Clinical studies of Clindamycin did not include sufficient numbers of patients age 65 and over to determine whether they respond differently from younger patients. However, other reported clinical experience indicates that antibiotic-associated colitis and diarrhea (due to Clostridium difficile) seen in association with most antibiotics occur more frequently in the elderly (>60 years) and may be more severe. These patients should be carefully monitored for the development of diarrhea.

Pharmacokinetic studies with Clindamycin have shown no clinically important differences between young and elderly subjects with normal hepatic function and normal (age-adjusted) renal function after oral or intravenous administration.

Adverse Reactions

The following reactions have been reported with the use of Clindamycin.

Gastrointestinal: Antibiotic-associated colitis (see WARNINGS), pseudomembranous colitis, abdominal pain, nausea, and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS). An unpleasant or metallic taste occasionally has been reported after intravenous administration of the higher doses of Clindamycin phosphate.

Hypersensitivity Reactions: Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with Clindamycin. A few cases of anaphylactoid reactions have been reported. If a hypersensitivity reaction occurs, the drug should be discontinued. The usual agents (epinephrine, corticosteroids, antihistamines) should be available for emergency treatment of serious reactions.

Skin and Mucous Membranes: Pruritus, vaginitis, 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 in rare instances.

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.

Local Reactions: 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: Rare instances of polyarthritis have been reported.

Cardiovascular: Rare instances of cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration. (See DOSAGE AND ADMINISTRATION section.)

Overdosage

Significant mortality was observed in mice at an intravenous dose of 855 mg/kg and in rats at an oral or subcutaneous dose of approximately 2618 mg/kg. In the mice, convulsions and depression were observed.

Hemodialysis and peritoneal dialysis are not effective in removing Clindamycin from the serum.

Clindamycin Dosage and Administration

If diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING box).

Adults: Parenteral (IV Administration)

Serious infections: 600 to 1200 mg/day in 2, 3, or 4 equal doses.

More severe infections: 1200 to 2700 mg/day in 2, 3, or 4 equal doses.

In life-threatening situations due to either aerobes or anaerobes these doses may be increased. Doses of as much as 4800 mg daily have been given intravenously to adults. See Dilution and Infusion Rates section below.

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 1.00 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/m2/day for serious infections and 450 mg/m2/day for more severe infections.

Parenteral therapy may be changed to oral Clindamycin palmitate hydrochloride or Clindamycin hydrochloride capsules 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 and Infusion Rates

Clindamycin phosphate 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 1200 mg	50 mL 50 mL 50-100 mL 100 mL	10 min 20 min 30 min 40 min

Administration of more than 1200 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 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.

Physico-Chemical Stability of diluted solutions of Clindamycin Injection

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.

DIRECTIONS FOR DISPENSING

Pharmacy Bulk Vial – Not for Direct Infusion

The Pharmacy Bulk Vial is for use in a Pharmacy Admixture Service only under a laminar flow hood. Entry into the vial should be made with a small diameter sterile transfer set or other small diameter sterile dispensing device, and contents dispensed in aliquots using aseptic technique. Use of a syringe with needle is not recommended. Multiple entries increase the potential of microbial and particulate contamination. AFTER ENTRY USE ENTIRE CONTENTS OF VIAL PROMPTLY. ANY UNUSED PORTION MUST BE DISCARDED WITHIN 4 HOURS AFTER INITIAL ENTRY.

NOTE: Parenteral drug products should be inspected visually for particulates and discoloration whenever solution and container permit.

How is Clindamycin Supplied

Each mL of Clindamycin Injection contains Clindamycin phosphate equivalent to 150 mg Clindamycin; 0.5 mg disodium edetate; 9.45 mg benzyl alcohol added as preservative. When necessary, pH is adjusted with sodium hydroxide and/or hydrochloric acid.

Clindamycin Injection USP is available as follows:

60 mL Pharmacy Bulk Vial NDC 55390-109-01; individually boxed.

Store at 20° to 25°C (68° to 77°F). See USP controlled room temperature. Do not refrigerate.

Animal Toxicology

One year oral toxicity studies in Spartan Sprague-Dawley rats and beagle dogs at dose levels up to 300 mg/kg/day (approximately 1.1 and 3.6 times the highest recommended adult human dose based on mg/m2, respectively) have shown Clindamycin to be well tolerated. No appreciable difference in pathological findings has been observed between groups of animals treated with Clindamycin and comparable control groups. Rats receiving Clindamycin hydrochloride at 600 mg/kg/day (approximately 2.1 times the highest recommended adult human dose based on mg/m2) for 6 months tolerated the drug well; however, dogs dosed at this level (approximately 7.2 times the highest recommended adult human dose based on mg/m2) vomited, would not eat, and lost weight.

REFERENCES

1. NCCLS. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-5th ed. NCCLS document M7-A5, 2000. NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898.
2. NCCLS. Performance Standards for Antimicrobial Susceptibility Testing: 13th Informational Supplement. NCCLS document M100- S13 (M2 & M7), 2003. NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898.
3. NCCLS. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria 5th ed. Approved Standard. NCCLS document M11-A5, 2001. NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898.
4. NCCLS. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard-8th ed. NCCLS document M2-A8 (ISBN 1-56238-393-0), 2003. NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898.

Manufactured by:                                         Manufactured for:
Ben Venue Laboratories, Inc.                      Bedford Laboratories™
Bedford, OH 44146                                      Bedford, OH 44146

August 2006                                                 CLND - P01

Clindamycin (Clindamycin Phosphate)

PRODUCT INFO Product Code 55390-109 Dosage Form INJECTION Route Of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Clindamycin phosphate (Clindamycin) Active 150 MILLIGRAM  In 1 MILLILITER Benzyl alcohol Inactive 9.45 MILLIGRAM  In 1 MILLILITER EDETATE DISODIUM Inactive 0.5 MILLIGRAM  In 1 MILLILITER Hydrochloric acid Inactive   Sodium hydroxide Inactive

IMPRINT INFORMATION Characteristic Appearance Characteristic Appearance Color Score Shape Symbol Imprint Code Coating Size

PACKAGING # NDC Package Description Multilevel Packaging 1 55390-109-01 1 VIAL In 1 BOX, UNIT-DOSE contains a VIAL 1 60 MILLILITER In 1 VIAL This package is contained within the BOX, UNIT-DOSE (55390-109-01)

Revised: 02/2007