Label: CLINDAMYCIN- clindamycin phosphate injection, solution, concentrate

  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated March 15, 2018

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  • BOXED WARNING (What is this?)

    WARNING

    Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Because clindamycin therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, as described in the INDICATIONS AND USAGE section. It should not be used in patients with nonbacterial infections such as most upper respiratory tract infections. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

    If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

  • DESCRIPTION

    Clindamycin Injection, USP, a water soluble ester of clindamycin and phosphoric acid, is a sterile solution for intramuscular or intravenous use.

    May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. pH is 6.5 range 5.5 to 7.0.

    Clindamycin is a semisynthetic antibiotic produced by a 7(S)-chloro- substitution of the 7 (R)‑hydroxyl group of the parent compound lincomycin.

    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 C 18H 34ClN 2O 8PS and the molecular weight is 504.97.

    The structural formula is represented below:

    structure

    Each mL contains clindamycin phosphate equivalent to 150 mg clindamycin, 0.5 mg disodium edetate and 9.45 mg benzyl alcohol added as a preservative.

  • CLINICAL PHARMACOLOGY

    Distribution

    Biologically inactive clindamycin phosphate is converted to active clindamycin.

    By the end of short-term intravenous infusion, peak serum levels of active clindamycin are reached.

    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 (see Excretion).

    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.

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

    Metabolism

    In vitro studies in human liver and intestinal microsomes indicated that clindamycin is predominantly metabolized by Cytochrome P450 3A4 (CYP3A4), with minor contribution from CYP3A5, to form clindamycin sulfoxide and a minor metabolite, N-desmethylclindamycin.

    Excretion

    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 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/mLTrough mcg/mL
    Healthy Adult Males (Post equilibrium)
    600 mg IV in 30 min q6h10.92
    600 mg IV in 30 min q8h10.81.1
    900 mg IV in 30 min q8h14.11.7
    600 mg IM q12h*9
    Pediatric Patients (first dose)*
    5-7 mg/kg IV in 1 hour10
    5-7 mg/kg IM8
    3-5 mg/kg IM4

    *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 USAGEsection.

    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)
    S I R S I R
    Staphylococcus spp. ≤0.51-2≥4≥2115-20≤14
    Streptococcus pneumoniae and other Streptococcus spp. ≤0.250.5≥1≥1916-18≤15
    Anaerobic Bacteria≤24≥8NANANA

    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 StrainAcceptable Quality Control Ranges
    Minimum Inhibitory
    Concentration Range
    (mcg/mL)
       Disk Diffusion Range 
    (Zone Diameters in mm)
       
    Enterococcus faecalis1
    ATCC 29212
    4-16NA
    Staphylococcus aureus
    ATCC 29213
    0.06-0.25NA
    Staphylococcus aureus
    ATCC 25923
    NA24-30
    Streptococcus pneumoniae
    ATCC 49619
    0.03-0.1219-25
    Bacteroides fragilis
    ATCC 25285
    0.5-2NA
    Bacteroides thetaiotaomicron 
    ATCC 29741
    2-8NA
    Clostridium difficile2
    ATCC 700057
    2-8NA
    Eggerthella lenta
    ATCC 43055
    0.06-0.25NA

    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

  • INDICATIONS AND USAGE

    Clindamycin Injection, USP is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.

    Clindamycin Injection, USP 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 BOXED WARNING, 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, USP 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.

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

  • CONTRAINDICATIONS

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

  • WARNINGS

    See BOXED WARNING.

    Clostridium difficile Associated Diarrhea

    Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

    If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. 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.

  • PRECAUTIONS

    General

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

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

    Clindamycin phosphate 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.

    Prescribing clindamycin 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.

    Information for Patients

    Patients should be counseled that antibacterial drugs including clindamycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When clindamycin 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 or other antibacterial drugs in the future.

    Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

    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.

    Clindamycin is metabolized predominantly by CYP3A4, and to a lesser extent by CYP3A5, to the major metabolite clindamycin sulfoxide and minor metabolite N-desmethylclindamycin. Therefore inhibitors of CYP3A4 and CYP3A5 may increase plasma concentrations of clindamycin and inducers of these isoenzymes may reduce plasma concentrations of clindamycin. In the presence of strong CYP3A4 inhibitors, monitor for adverse reactions. In the presence of strong CYP3A4 inducers such as rifampicin, monitor for loss of effectiveness.

    In vitro studies indicate that clindamycin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1 or CYP2D6 and only moderately inhibits CYP3A4.

    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/m 2) revealed no effects on fertility or mating ability.

    Pregnancy: Teratogenic Effects

    In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters, has not been associated with an increased frequency of congenital abnormalities.

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

    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/m 2, 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/m 2, respectively) revealed no evidence of teratogenicity.

    Clindamycin Injection USP contains benzyl alcohol. Benzyl alcohol can cross the placenta. See WARNINGS.

    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. Clindamycin has the potential to cause adverse effects on the breastfed infant’s gastrointestinal flora. If oral or intravenous clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. Monitor the infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.

    The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clindamycin and any potential adverse effects on the breastfed child from clindamycin or from the underlying maternal condition.

    Pediatric Use

    When clindamycin phosphate 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. See WARNINGS.

    The potential for the toxic effect in the pediatric population from chemicals that may leach from the single dose premixed IV preparation in plastic has not been evaluated. See WARNINGS.

    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.

    Infections and Infestations

    Clostridium difficile colitis

    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 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.

    Severe skin reactions such as Toxic Epidermal Necrolysis, some with fatal outcome, have been reported (see WARNINGS). Cases of Acute Generalized Exanthematous Pustulosis (AGEP), erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated 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). ­­­­­ ­­­­­

  • 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 2,618 mg/kg. In the mice, convulsions and depression were observed.

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

  • DOSAGE AND ADMINISTRATION

    If diarrhea occurs during therapy, this antibiotic should be discontinued. (See BOXED WARNING).

    Clindamycin phosphate IM administration should be used undiluted.

    Clindamycin phosphate IV administration should be diluted (see Dilution for IV use and IV infusion rates below).

    Adults

    Parenteral (IM or IV Administration):

    Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis, Peptococcus species and Clostridium species other than Clostridium perfringens):

    600 to 1,200 mg/day in 2, 3 or 4 equal doses

    More severe infections, particularly those due to proven or suspected Bacteroides fragilis, Peptococcus species, or Clostridium species other than Clostridium perfringens:

    1,200 to 2,700 mg/day in 2, 3 or 4 equal doses

    For more serious infections, these doses may have to be increased. In life threatening situations due to either aerobes or anaerobes these doses may be increased. Doses of as much as 4,800 mg daily have been given intravenously to adults. See Dilution for IV use and IV Infusion Rates section below.

    Single intramuscular injections of greater than 600 mg are not recommended.

    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/mL10 mg/min for 30 min0.75 mg/min
    Above 5 mcg/mL15 mg/min for 30 min1.00 mg/min
    Above 6 mcg/mL20 mg/min for 30 min1.25 mg/min

    Neonates (less than 1 month)

    15 to 20 mg/kg/day in three to four equal doses. The lower dosage may be adequate for small prematures.

    Pediatric patients (1 month of age to 16 years)

    Parenteral (IM or 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 clindamycin palmitate hydrochloride for oral solution 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 for IV use and IV Infusion Rates

    The concentration of clindamycin in diluent for infusion should notexceed 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 mg50 mL10 min
    600 mg50 mL20 min
    900 mg50-100 mL30 min
    1,200 mg100 mL40 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 phosphate 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

    Room Temperature: 6 mg/mL, 9 mg/mL, 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 mg/mL, 9 mg/mL, 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 mg/mL, 9 mg/mL 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.

  • HOW SUPPLIED

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

    Clindamycin Injection, USP (150 mg/mL) is supplied as follows:

    NDC No.Volume             Type ContainerClindamycin base Total Content
    47781-459-682 mL           Single-dose fliptop vial/25 vials per tray300 mg
    47781-460-684 mL           Single-dose fliptop vial/25 vials per tray600 mg
    47781-461-686 mL           Single-dose fliptop vial/25 vials per tray900 mg

    Store at 20 to 25°C (68 to 77°F) [see USP Controlled Room Temperature.]
    Do not refrigerate.


  • REFERENCES

    1. Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December 1982.

    2. CLSI. Performance Standards for Antimicrobial Susceptibility Testing: 26 th ed. CLSI supplement M100S. Wayne, PA: Clinical and Laboratory Standards Institute; 2016.

    3. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. CLSI document M07-A10. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.

    4. CLSI. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard-Eighth Edition. CLSI document M11-A8. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.

    5. CLSI. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard - Twelfth Edition. CLSI document M02-A12. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.

  • SPL UNCLASSIFIED SECTION

    Distributed by:
    Alvogen, Inc.
    Pine Brook, NJ 07058 USA

    Pl459-03
    Rev: 06/2017

  • PRINCIPAL DISPLAY PANEL

    2 mL Single-dose Fliptop Vial NDC 71872-7088-1 OUTER PACKAGE LABEL

    Clindamycin Injection, USP Rx only

    300 mg/2 mL (150 mg/mL)

    For I.M. or I.V. Use.

    Warning: Dilute Before I.V. Use.



    pdp

  • PRINCIPAL DISPLAY PANEL

    2 mL Single-dose Vial NDC 47781- 459-68 VIAL LABEL

    Rx only

    Clindamycin

    Injection, USP

    300 mg/2 mL

    (150 mg/mL)

    Alvogen, Inc., Pine Brook, NJ 07058 USA Rev. 08/2015

    label-300

  • INGREDIENTS AND APPEARANCE
    CLINDAMYCIN 
    clindamycin phosphate injection, solution, concentrate
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:71872-7088(NDC:47781-459)
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    CLINDAMYCIN PHOSPHATE (UNII: EH6D7113I8) (CLINDAMYCIN - UNII:3U02EL437C) CLINDAMYCIN PHOSPHATE150 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    EDETATE DISODIUM (UNII: 7FLD91C86K) 0.5 mg  in 1 mL
    BENZYL ALCOHOL (UNII: LKG8494WBH) 9.45 mg  in 1 mL
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:71872-7088-11 in 1 BAG03/05/2018
    12 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA06280006/03/2016
    Labeler - Medical Purchasing Solutions, LLC (601458529)
    Establishment
    NameAddressID/FEIBusiness Operations
    Medical Purchasing Solutions, LLC601458529repack(71872-7088)