Clindamycin Hydrochloride
FDA Label NDC 67296-0315

To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin hydrochloride and other antibacterial drugs, clindamycin hydrochloride should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.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.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. 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.Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of therapy with clindamycin.

Clindamycin hydrochloride is the hydrated hydrochloride salt of clindamycin. 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 for clindamycin hydrochloride 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 monohydrochloride. The structural formula is represented below: C18H33ClN2O5S•HCl                                                                                          M.W. 461.45Clindamycin hydrochloride capsules, USP contain clindamycin hydrochloride equivalent to 150 mg or 300 mg of clindamycin. Each capsule also contains the following inactive ingredients: lactose monohydrate, corn starch, talc, and magnesium stearate. The empty hard gelatin capsule shell consists of FD and C Blue No. 1, titanium dioxide, gelatin and sodium lauryl sulphate. In addition 150 mg also contains yellow iron oxide. The capsules are printed with edible ink containing black iron oxide and shellac.

Human Pharmacology
Serum level studies with a 150 mg oral dose of clindamycin hydrochloride in 24 normal adult volunteers showed that clindamycin was rapidly absorbed after oral administration. An average peak serum level of 2.5 mcg/mL was reached in 45 minutes; serum levels averaged 1.51 mcg/mL at 3 hours and 0.7 mcg/mL at 6 hours. Absorption of an oral dose is virtually complete (90%), and the concomitant administration of food does not appreciably modify the serum concentrations; serum levels have been uniform and predictable from person to person and dose to dose. Serum level studies following multiple doses of clindamycin hydrochloride for up to 14 days show no evidence of accumulation or altered metabolism of drug.
 
Serum half-life of clindamycin is increased slightly in patients  with  markedly  reduced renal function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.
 
Concentrations of clindamycin in the serum increased linearly with increased dose. Serum levels exceed the MIC (minimum inhibitory concentration) for most indicated organisms for at least six hours following administration of the usually recommended doses. Clindamycin is widely distributed in body fluids and tissues (including bones). The average biological half-life is 2.4 hours. Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the feces; the remainder is excreted as bioinactive metabolites.
 
Doses of up to 2 grams of clindamycin per day for 14 days have been well tolerated by healthy volunteers, except that the incidence of gastrointestinal side effects is greater with the higher doses.
 
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 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.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 1.
 
Diffusion Techniques
 
Quantitative methods that require the measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure^2,3 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 1.     

Table 1. Susceptibility 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.	≤0.5	1-2	≥4	≥21	15-20	≤14
Streptococcus pneumoniae and     other Streptococcus spp.	≤0.25a	0.5	≥1	≥19b	16-18	≤15
Anaerobic Bacteriac	≤2	4	≥8	NA	NA	NA

^a 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.
^b 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.
^c These interpretive criteria are for all anaerobic bacterial pathogens; no organism specific interpretive criteria are available.
NA=Not applicable
 
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 2. 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. Acceptable Quality Control Ranges for Clindamycin to be Used in Validation of Susceptibility Test Results

QC Strain	Acceptable Quality Control Ranges
Minimum Inhibitory Concentrations (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 49619d	0.03–0.12e	19–25f
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

NA=Not applicable
^d This organism may be used for validation of susceptibility test results when testing Streptococcus spp. other than S. pneumoniae.
^e This quality control range for S. pneumoniae is 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.
^f 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.
 
ATCC^® is a registered trademark of the American Type Culture CollectionINDICATIONS AND USAGE
Clindamycin hydrochloride capsules are indicated in the treatment of serious infections caused by susceptible anaerobic