CLINDAMYCIN HYDROCHLORIDE Capsule [A-S Medication Solutions]

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. 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. 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). No significant levels of clindamycin are attained in the cerebrospinal fluid, even in the presence of inflamed meninges. 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. 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. 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. 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 some Gram-negative anaerobes. Clindamycin is bacteriostatic. Cross-resistance between clindamycin and lincomycin is complete. Antagonism has been demonstrated between clindamycin and erythromycin. Clindamycin inducible resistance has been identified in macrolide-resistant staphylococci and beta-hemolytic streptococci. Macrolide-resistant isolates of these organisms should be screened for clindamycin inducible resistance using the D-zone test. Clindamycin has been shown to be active against most of the isolates of the following microorganisms, both and in clinical infections, as described in the   section. (methicillin-susceptible strains) (penicillin-susceptible strains) At least 90% of the microorganisms listed below exhibit 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 1. However, the efficacy of clindamycin in treating clinical infections due to these microorganisms established in adequate and well-controlled clinical trials. (methicillin-susceptible strains) When available, the clinical microbiology laboratory should provide cumulative 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 the most effective antimicrobial. 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 based on dilution methods (broth, agar, or microdilution) or equivalent using standardized inoculum and concentrations of clindamycin. The MIC values should be interpreted according to the criteria provided in Table 1. Quantitative methods that require the measurement of zone diameters also pro­vide reproducible estimates of the susceptibility of bac­teria to antimicrobial compounds. The standardized procedure 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. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 2 mcg clindamycin disk should be interpreted according to the criteria in Table 1. Human Pharmacology
Absorption

Distribution

Excretion

Special Populations
Renal Impairment

Use in Elderly

Microbiology

in vitro

in vitroINDICATIONS AND USAGE
Gram-positive aerobes

Staphylococcus aureus

Streptococcus pneumoniae
Streptococcus pyogenes
Anaerobes

Prevotella melaninogenica

Fusobacterium necrophorum
Fusobacterium nucleatum
Peptostreptococcus anaerobius
Clostridium perfringens

in vitrohas not been
Gram-positive aerobes

Staphylococcus epidermidis

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

in vitro
Dilution Techniques

2,3
Diffusion Techniques

2,4

 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. 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. Standard clindamycin powder should provide the MIC ranges in Table 2. For the disk diffusion technique using the 2 mcg clindamycin disk the criteria provided in Table 2 should be achieved.

Quality Control

2,3,4,5

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CLINDAMYCIN HYDROCHLORIDE Capsule [A-S Medication Solutions]