CLINDAMYCIN- clindamycin phosphate injection
For Intravenous Use Only
NOT FOR DIRECT INFUSION
PHARMACY BULK VIAL
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.
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.
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 C18 H34 ClN2 O8 PS 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.)
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 function1.
Serum assays for active clindamycin require an inhibitor to prevent in vitro hydrolysis of clindamycin phosphate.
|Healthy Adult Males (Post equilibrium) 600 mg IV in 30 min q6h600 mg IV in 30 min q8h900 mg IV in 30 min q8h Pediatric Patients (first dose)*5-7 mg/kg IV in 1 hour|| |
Although clindamycin phosphate is inactive in vitro , rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Clindamycin has been shown to have in vitro activity against isolates of the following organisms:
Aerobic gram positive cocci , including:
- Staphylococcus aureus (penicillinase and non-penicillinase producing strains). When tested by in vitro methods, some staphylococcal strains originally resistant to erythromycin rapidly develop resistance to clindamycin.
- Staphylococcus epidermidis (penicillinase and non-penicillinase producing strains). When tested by in vitro methods, some staphylococcal strains originally resistant to erythromycin rapidly develop resistance to clindamycin.
- Streptococci (except Enterococcus faecalis)
Anaerobic gram negative bacilli , including:
- Bacteroides species (including Bacteroides fragilis group and Bacteroides melaninogenicus group)
- Fusobacterium species
Anaerobic gram positive nonsporeforming bacilli , including:
- Actinomyces species
Anaerobic and microaerophilic gram positive cocci , including
- Peptococcus species
- Peptostreptococcus species
- Microaerophilic streptococci
Clostridia: Clostridia are more resistant than most anaerobes to clindamycin. Most Clostridium perfringens are susceptible, but other species, e.g., Clostridium sporogenes and Clostridium tertium are frequently resistant to clindamycin. Susceptibility testing should be done.
Cross resistance has been demonstrated between clindamycin and lincomycin.
Antagonism has been demonstrated between clindamycin and erythromycin.
In vitro Susceptibility Testing: Disk diffusion technique—Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure2 has been recommended for use with disks to test susceptibility to clindamycin.
Reports from a laboratory using the standardized single-disk susceptibility test1 with a 2 mcg clindamycin disk should be interpreted according to the following criteria:
Susceptible organisms produce zones of 17 mm or greater, indicating that the tested organism is likely to respond to therapy.
Organisms of intermediate susceptibility produce zones of 15 to 16 mm, indicating that the tested organism would be susceptible if a high dosage is used or if the infection is confined to tissues and fluids (e.g., urine), in which high antibiotic levels are attained.
Resistant organisms produce zones of 14 mm or less, indicating that other therapy should be selected.
Standardized procedures require the use of control organisms. The 2 mcg clindamycin disk should give a zone diameter between 24 and 30 mm for S. aureus ATCC 25923.
Dilution techniques—A bacterial isolate may be considered susceptible if the minimum inhibitory concentration (MIC) for clindamycin is not more than 1.6 mcg/mL. Organisms are considered moderately susceptible if the MIC is greater than 1.6 mcg/mL and less than or equal to 4.8 mcg/mL. Organisms are considered resistant if the MIC is greater than 4.8 mcg per mL.
The range of MICs for the control strains are as follows:
S. aureus ATCC 29213, 0.06 to 0.25 mcg/mL.
E. faecalis ATCC 29212, 4.0 to 16 mcg/mL.
For anaerobic bacteria the minimum inhibitory concentration (MIC) of clindamycin can be determined by agar dilution and broth dilution (including microdilution) techniques3. If MICs are not determined routinely, the disk broth method is recommended for routine use. THE KIRBY-BAUER DISK DIFFUSION METHOD AND ITS INTERPRETIVE STANDARDS ARE NOT RECOMMENDED FOR ANAEROBES.
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